Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with abacavir would be possible from a pharmacokinetic standpoint. Coadministration of abacavir with dolutegravir/lamivudine/tenofovir-DF has not been studied, but a clinically significant interaction is unlikely. Coadministration of abacavir (300 mg single dose) and tenofovir-DF (300 mg once daily) had no effect on tenofovir AUC or Cmax, and abacavir AUC; abacavir Cmax increased by 12%. Note, the bioavailability of lamivudine solution has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in liquid formulations such as abacavir oral solution.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abatacept is a fusion protein consisting of the extracellular domain of human CTLA-4 linked to a modified Fc portion of human IgG1 and is likely to be eliminated via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abemaciclib is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Abemaciclib has no inhibitory or inducing effects on drug metabolizing enzymes. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone is metabolised by CYP3A4 and SULT2A1. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to affect abiraterone metabolism. Abiraterone is not expected to have inhibitory or inducing effects on drug metabolizing enzymes. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abrocitinib is mainly metabolised by CYP2C19 and CYP2C9, and to a lesser extent by CYP3A4 and CYP2B6. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Abrocitinib is not expected to have a clinically relevant effect on UGTs or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acalabrutinib is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Acalabrutinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acamprosate is eliminated unchanged in the urine both via glomerular filtration and active secretion (exact transporter unknown, possibly OATs or OCTs). No interaction is expected with dolutegravir. Given the potential limited role of OCT or OAT in acamprosate’s elimination and considering the therapeutic index of acamprosate, no clinically relevant interaction with lamivudine or tenofovir is anticipated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Acenocoumarol is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion. No interaction is expected with dolutegravir. In vitro studies have shown acetazolamide may competitively inhibit the renal transporters OAT1, OAT3 and OAT4 and thereby impair tenofovir renal elimination. Close monitoring of renal function is recommended. A clinically relevant drug interaction is unlikely with lamivudine as it is excreted by different renal transporters.

Coadministration has not been studied. Aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Dolutegravir is not expected to inhibit OAT1 and lamivudine is eliminated by different renal transporters. However, tenofovir derived from tenofovir-DF may compete with aciclovir for active tubular secretion which could lead to increased levels of either drug. Closely monitor renal function.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acitretin undergoes isomerisation and glucuronidation. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce UGTs at clinically relevant concentrations. Acitretin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aclidinium bromide is rapidly and extensively hydrolyzed (non-enzymatic and enzymatic transformation by esterases and butylrylcholineesterases) to its pharmacologically inactive metabolites with only a minor role for CYP metabolism. Dolutegravir, lamivudine and tenofovir-DF are not expected to affect aclidinium bromide metabolism.

Coadministration has not been studied. Activated charcoal absorbs substances in the stomach and intestines and may decrease absorption of orally administered medicines. If coadministration is required, administration of activated charcoal and dolutegravir should be separated by 4 hours. [Note: this interaction is not specific for dolutegravir, lamivudine or tenofovir-DF, but for any oral medication taken with activated charcoal.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adalimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied and is not recommended. Adefovir is eliminated renally via glomerular filtration and active renal secretion by OAT1. Dolutegravir is not expected to inhibit this renal transporter. Coadministration of adefovir dipivoxil (10 mg) and lamivudine (100 mg) did not alter the pharmacokinetic profile of either drug. Coadministration of adefovir alone (10 mg single dose) and tenofovir-DF (300 mg once daily) decreased adefovir Cmax and AUC by 7% and 11%; tenofovir Cmax and AUC decreased by 1% and 2% (n=22). However, adefovir and tenofovir-DF are both nephrotoxic and should not coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adrenaline is rapidly inactivated, mostly in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Afatinib is mainly eliminated unchanged in the faeces. Dolutegravir is metabolised mainly by UGT1A1 and to a lesser extent by CYP3A4. Afatinib does not inhibit or induce UGTs or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. African potato was shown to inhibit CYP3A4 and P-gp in vitro and to activate PXR suggesting that inhibition may occur initially followed by induction of CYP3A4 and P-gp when used for extended periods. Use with caution as African potato could decrease concentrations of dolutegravir. Therapeutic drug monitoring of dolutegravir is recommended. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly by CYP1A2. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Agomelatine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolised by CYP3A4 and by the flavine-containing monooxygenase system. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Albendazole is unlikely to affect UGT1A1 or CYP3A4. There is little potential for an interaction via competition with lamivudine or tenofovir for renal elimination pathways.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with albuvirtide would be possible from a pharmacokinetic standpoint. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. In vitro human microsomal studies and limited in vivo drug-drug interaction data indicate that albuvirtide has no inhibiting or inducing properties on CYP enzymes. Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. No interaction is expected with dolutegravir, lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcohol is metabolised by alcohol dehydrogenase and aldehyde dehydrogenase. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. The chronic use of alcohol may induce CYP2E1 and to a lesser extent CYP3A4, however, no interaction with dolutegravir is expected as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Alcuronium is predominantly excreted unchanged via the kidneys. As there are no available data determining whether excretion is via active tubular secretion or glomerular filtration, there is some potential for exposure of alcuronium to be increased since dolutegravir inhibits the renal transporter OCT2. There is also potential for competition with lamivudine or tenofovir for active renal transport mechanisms, which may lead to increased levels of alcuronium, lamivudine or tenofovir. Caution is advised as alcuronium has a narrow therapeutic window.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alectinib is metabolised by CYP3A4 to an active metabolite (M4), which is also metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Alectinib does not inhibit or induce CYP3A4 to a clinically relevant extent. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alemtuzumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. CYP-mediated drug interactions are not expected with alemtuzumab. Note, use of alemtuzumab (marketed as Lemtrada) for the treatment of relapsing remitting multiple sclerosis is contraindicated in patients with HIV infection as it causes prolonged reductions of CD4+ lymphocyte counts.

Coadministration has not been studied. If taken at the same time, it is likely that food and beverages (including mineral water), calcium supplements, antacids, and some oral medicinal products will interfere with absorption of alendronate. Therefore, patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes CYP3A4 metabolism. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Alfentanil is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised mainly by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Alfuzosin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alirocumab is a monoclonal antibody eliminated through binding to PCSK9 at low concentrations and through a proteolytic pathway at higher concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. P-gp is a major determinant of aliskiren bioavailability. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes or P-gp at clinically relevant concentrations. Aliskiren is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Almotriptan is partly eliminated unchanged in the urine and partly metabolised (mainly via monoamine oxidase-A and to a lesser extent by CYP3A4, CYP2D6 and flavin monooxygenase). Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected affect almotriptan metabolism. Almotriptan is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Aloe vera is only a weak inhibitor of CYPs in vitro and therefore is unlikely to cause clinically significant interactions. It does not inhibit P-gp and there is no evidence to suggest it impacts UGTs. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism. Alogliptin was shown to have no inhibitory or inducing effect on CYPs at concentrations achieved with the recommended dose of 25 mg alogliptin. Furthermore, alogliptin was shown to be neither a substrate nor an inhibitor of the renal transporters OAT1, OAT3 or OCT2 and to cause no interactions with P-glycoprotein substrates.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that alosetron is metabolised by CYPs 2C9, 3A4 and 1A2, with in vivo data suggesting that CYP1A2 plays a more prominent role. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Alosetron is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alpelisib is primarily metabolised by enzymatic hydrolysis to an inactive metabolite, with a minor contribution from CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to affect alpelisib metabolism. Alpelisib is unlikely to inhibit or induce UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Alprazolam is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following administration, ~80% of circulating alprostadil is rapidly metabolised in the lungs primarily by beta- and omega- oxidation and the resulting metabolites are mainly excreted in urine. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Alprostadil is unlikely to affect CYP or UGT enzymes. No interaction is expected with lamivudine. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied. Amantadine is mainly eliminated in the kidney by glomerular filtration and active secretion via OCT2. There is potential for dolutegravir to increase amantadine exposure via inhibition of OCT2 but the clinical relevance of this is unknown. There is also potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug. No interaction is expected with tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ambrisentan is mainly glucuronidated by UGT1A9, UGT2B7, UGT1A3 and is metabolised to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce P-gp, UGT or CYP enzymes at clinically relevant concentrations. Ambrisentan is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amikacin is eliminated renally by glomerular filtration. Dolutegravir and lamivudine do not interact with amikacin. However, tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely.

Coadministration has not been studied. Amiloride is eliminated unchanged by the kidney and in vitro data indicate that it is a substrate of OCT2. In vitro data indicate that dolutegravir inhibits OCT2 and may increase amiloride exposure. Amiloride may potentially compete with lamivudine for renal elimination transport mechanisms which may lead to increased concentrations of either drug. Tenofovir is unlikely to interfere with amiloride elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolised by CYP1A2. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Theophylline is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Amiodarone is metabolised by CYPs 3A4 and 2C8. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Amiodarone is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine. However, tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as amiodarone could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolised and is primarily eliminated renally, possibly via OCT. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction with amisulpride. There is little potential for an interaction with lamivudine or tenofovir-DF via competition for active renal transport mechanisms given the possible limited role of OCT in amisulpride’s elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Amitriptyline is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amivantamab is a monoclonal IgG1 and is eliminated primarily via intracellular catabolism similarly to endogenous IgG. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Amlodipine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amodiaquine is mainly metabolised by CYP2C8 to N-desethylamodiaquine, an active metabolite but less potent than the parent compound. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Coadministration of dolutegravir and artesunate-amodiaquine had no significant effect on the AUC of amodiaquine or on the AUCs of artesunate and its metabolites. Standard doses of artesunate-amodiaquine can be used in patients receiving 50 mg dolutegravir once daily. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxapine is mainly metabolised by CYP2D6. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir does not inhibit or induce CYP2D6. Amoxapine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected lamivudine or tenofovir-DF

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3, dolutegravir is not expected to affect this renal transporter. Lamivudine and tenofovir are secreted by other renal transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphetamine is metabolised by CYP2D6. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Amphetamine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amphotericin is not appreciably metabolised and is eliminated to a large extent in the bile. No interaction is expected with dolutegravir or lamivudine. However, the use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product (such as amphotericin B). If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely.

Coadministration has not been studied. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion. About 20 to 40% of an oral dose may be excreted unchanged in the urine in 6 hours. After parenteral use about 60 to 80% is excreted in the urine within 6 hours. No interaction is expected with dolutegravir. As lamivudine and tenofovir are eliminated by renal tubular secretion, there is potential for competition with ampicillin for renal transporters, which could lead to increased drug concentrations when ampicillin is administered intravenously. When administered orally, there is little potential for significant interactions.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anakinra is an IL-1 receptor antagonist which is predominantly cleared renally by glomerular filtration and subsequent tubular metabolism. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Anakinra, per se, has no inhibitory or inducing effects on cytochromes. Anakinra will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated by UGT1A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Anastrozole is unlikely to inhibit or induce UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperature.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied. Dolutegravir/lamivudine/tenofovir-DF should be administered 2 hours before or 6 hours after taking medications containing polyvalent cations, such as antacids. Simultaneous coadministration of dolutegravir (50 mg once daily) and a magnesium/aluminium containing antacid (Maalox) decreased dolutegravir Cmax, AUC and Ctrough by 72%, 74% and 74%, respectively. When antacid was administered 2 hours after dolutegravir (50 mg once daily), dolutegravir Cmax, AUC and Ctrough decreased by 18%, 26% and 30%, respectively. Coadministration with antacids containing calcium carbonate has not been studied. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thymoglobulins are cleared by the reticuloendothelial system.

Coadministration has not been studied. Apalutamide is primarily metabolised by CYP2C8 and CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Apalutamide is a strong inducer of CYP3A4 and can also induce UGT1A1. Coadministration is expected to decrease dolutegravir concentrations, thus dolutegravir should be administered at 50 mg twice daily in the absence of integrase class resistance. In the presence of integrase class resistance this combination should be avoided. Apalutamide has a long half-life (3 days), therefore the dolutegravir dose should be kept at 50 mg twice daily for a minimum of 2 weeks (but preferably 4 weeks) following cessation of enzalutamide due to the persisting inducing effect upon discontinuation of a strong inducer. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolised by CYP3A4 and to a lesser extent CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Telithromycin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apomorphine is metabolised by several pathways including glucuronidation, sulfation and to a lesser extent N-demethylation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apremilast is metabolised by multiple pathways involving hydrolysis, glucuronidation and oxidation by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent CYP3A4. Apremilast has no inhibitory or inducing effects on drug metabolizing enzymes or drug transporters. Lamivudine and tenofovir-DF do not interfere with apremilast’s elimination pathways. Note: severe diarrhoea, nausea and vomiting can occur within the first few weeks after initiating apremilast treatment. Patients should be instructed to contact their healthcare provider if they experience severe diarrhoea, nausea or vomiting as this could potentially alter the absorption of orally administered antiretroviral drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and does not inhibit or induce CYPs at clinically relevant concentrations. Aprepitant shows an initial inhibitory effect on CYP3A4 followed by a weak inducing effect on CYP3A4 and UGT on day 8 which is clinically insignificant by two weeks. Any transient change in dolutegravir exposure is unlikely to be clinically significant. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Argatroban undergoes metabolism in the liver via hydroxylation and aromatization. In vitro studies indicate that CYP3A4 plays a role in argatroban metabolism, however, human drug-drug interactions studies suggest that metabolism via CYP3A4 is not a major elimination pathway in vivo. Drug-drug interactions studies performed with substrates of different cytochromes and P-gp (i.e., acetaminophen, lidocaine, warfarin, digoxin) indicate that argatroban has a low potential to cause drug-drug interactions and therefore is unlikely to alter the exposure of dolutegravir, lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Aripiprazole is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Arsenic trioxide is hydrolysed to arsenious acid (the pharmacologically active metabolite) which is then methylated to less cytotoxic metabolites primarily in the liver (non-CYP mediated). Arsenious acid is also oxidated to arsenic acid, which may occur in numerous tissues via enzymatic or nonenzymatic processes. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir is unlikely to affect arsenic trioxide metabolism. Arsenic trioxide is unlikely to affect UGT1A1 and does not inhibit or induce CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Artemisinins undergo rapid metabolism via several CYPs (3A4, 2A6, 2B6) and the active metabolite (dihydroartemisinin, which has greater potency than the parent drug) is further metabolised via UGT1A9 and 2B7. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Artemisinins induce CYP3A4 and could potentially decrease dolutegravir concentrations, but this is unlikely to be clinically relevant due to the short treatment duration for artemisinins. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asciminib is metabolised by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Asciminib is a weak CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses of ascorbic acid may cause the urine to become acidic causing unexpected renal tubular reabsorption of acidic drugs, thus producing an exaggerated response. Conversely basic drugs may exhibit decreased reabsorption resulting in a decreased therapeutic effect. No interaction is expected with dolutegravir. Lamivudine and tenofovir-DF are predominantly via active renal tubular secretion, however unless treatment with ascorbic acid involves large doses of prolonged duration, significant interactions are not expected.

Coadministration has not been studied. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses of ascorbic acid may cause the urine to become acidic causing unexpected renal tubular reabsorption of acidic drugs, thus producing an exaggerated response. Conversely basic drugs may exhibit decreased reabsorption resulting in a decreased therapeutic effect. Lamivudine and tenofovir-DF are predominantly eliminated via active renal tubular secretion, however unless treatment with ascorbic acid involves large doses of prolonged duration, significant interactions are not expected. A pharmacokinetic interaction is unlikely with dolutegravir and vitamin C itself as dolutegravir does not interfere with this metabolic pathway. However, vitamin C can be found in multivitamin preparations. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir/lamivudine/tenofovir-DF should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolised by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major) and CYP3A4, 2D6 (minor). Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Asenapine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ashwagandha extracts had no effect on CYP enzymes in vitro.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data suggest that asparaginase is likely to be eliminated by the reticuloendothelial system. Less than 0.1% of a total injected dose is recovered in urine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Aspirin is rapidly deacetylated to salicylic acid and then further metabolised mainly by glucuronidation (by several UGT, major UGT1A6). Dolutegravir is unlikely to inhibit or induce UGTs at clinically relevant concentrations. No interaction is expected with lamivudine. However, coadministration could potentially increase the risk of nephrotoxicity with tenofovir-DF. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is coadministered with an NSAID, renal function should be monitored adequately.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid which is further glucuronidated by several UGTs (major UGT1A6). Dolutegravir and lamivudine do not interact with aspirin metabolism. Aspirin used as an antiplatelet agent at 100 mg once daily in chronic use is unlikely to increase the risk of tenofovir-DF nephrotoxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolised by CYP2D6, CYP2J2 and CYP3A4. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with other antiretroviral agents is not recommended. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir would be possible from a pharmacokinetic standpoint. Coadministration of atazanavir/ritonavir and dolutegravir increased dolutegravir AUC, Cmax and Ctrough by 62%, 34% and 121%, respectively. There was no effect on atazanavir or ritonavir. No interaction is expected with lamivudine. In a combined analysis of several clinical studies with tenofovir-DF (300 mg) and atazanavir/ritonavir (300/100 mg), tenofovir AUC, Cmax and Cmin increased by 37%, 34% and 29%, respectively; atazanavir AUC, Cmax and Cmin decreased by 25%, 28% and 26%, respectively. Patients should be closely monitored for tenofovir-associated adverse events, including renal disorders. Atazanavir/ritonavir should be dosed at 400/100 mg once daily in presence of tenofovir-DF and an H2-receptor antagonist due to the resulting decrease in atazanavir exposure.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with other antiretroviral agents is not recommended. Atazanavir alone should not be coadministered as tenofovir-DF may decrease atazanavir concentrations and the atazanavir product labels recommend boosted atazanavir with tenofovir-DF. Coadministration of tenofovir-DF (300 mg once daily) with atazanavir/ritonavir 300/100 mg once daily) decreased atazanavir AUC, Cmax and Cmin 22%, 16% and 23%, respectively.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with atazanavir/cobicistat would be possible from a pharmacokinetic standpoint, but with close monitoring for tenofovir-associated adverse events. Atazanavir/cobicistat is expected to increase dolutegravir concentrations, but dolutegravir is not expected to affect the pharmacokinetics of atazanavir/cobicistat. No interaction is expected with lamivudine. Boosted PIs were shown to increase tenofovir-DF and there are currently inadequate data to determine whether tenofovir-DF plus cobicistat is associated with a greater risk of renal adverse reactions than tenofovir-DF without cobicistat. The European SmPC for tenofovir-DF advises close renal monitoring of patients receiving tenofovir-DF with a cobicistat-boosted protease inhibitor. The US Prescribing Information for cobicistat does not recommend coadministration of cobicistat and tenofovir-DF in combination with concomitant or recent use of a nephrotoxic agent. Note, cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine and should not be initiated in patients with creatinine clearance less than 70 ml/min if tenofovir-DF requires dose adjustment based on creatinine clearance. A similar recommendation is to be observed for atazanavir/cobicistat. It is not recommended to take both tenofovir-DF and an H2-receptor antagonist with atazanavir, due to the resulting decrease in atazanavir exposure.

Coadministration has not been studied. Atenolol is mainly eliminated by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. Dolutegravir may increase atenolol exposure via inhibition of OCT2. Based on the drug-drug interaction study with dolutegravir and metformin (another drug transported by OCT2 and MATE1), the increase in atenolol exposure is expected to be ~80% or ~110% when dolutegravir is administered once daily and twice daily, respectively. Furthermore, competition with atenolol and lamivudine for elimination via renal transport proteins may lead to increased concentrations of either drug. No interaction is expected with tenofovir-DF. It is recommended to start atenolol at a lower dose and adjust dosage until the desired clinical effect is achieved.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atogepant is metabolised primarily by CYP3A4 and is a substrate of OATP. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Atogepant is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atomoxetine is metabolised by CYP2D6. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Atomoxetine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atorvastatin is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atovaquone is mainly eliminated unchanged in the faeces.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atropine is used either systemically or as eye drops. Although metabolism of atropine is not fully elucidated, up to 50% is excreted unchanged via the kidneys. No interaction is expected with dolutegravir. There is little potential for an interaction via competition with lamivudine or tenofovir-DF for active renal transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avanafil is primarily metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Avanafil is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Avapritinib was shown to inhibit and induce CYP3A4 in vitro but the net effect in vivo has not been studied. However, avapritinib is unlikely to cause a significant effect on dolutegravir metabolism given that CYP3A4 is a minor pathway. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avatrombopag is mainly metabolised by CYP2C9 and CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Avatrombopag is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avelumab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Axitinib is metabolised primarily by CYP3A4 and to a lesser extent by CYP1A2, CYP2C19 and UGT1A1. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Axitinib does not inhibit or induce UGTs or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are both eliminated renally

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. In vitro data suggest that some harma alkaloids found in ayahuasca preparations have a weak/moderate inhibitory effect on CYP3A4, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally

Coadministration has not been studied. Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Urinary excretion is the primary route of elimination of azacitidine and/or its metabolites. Following cellular uptake, azacitidine is sequentially phosphorylated via phosphokinases activities to azacitidine triphosphate which is able to incorporate into DNA and RNA. Phosphorylation of lamivudine occurs via the same enzymes and competition may occur for this activation path. However, the clinical relevance of this interaction is unknown. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Azacitidine does not inhibit or induce UGT or CYP enzymes. No interaction is expected with tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is metabolised to 6-mercaptopurine which is further inactivated by xanthine oxidase and thiopurine methyltransferase.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azilsartan is metabolised mainly by CYP2C9. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Azilsartan is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-glycoprotein and MRP2. In vitro data indicate that dolutegravir does not inhibit P-glycoprotein and MRP2 at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Baclofen is primarily eliminated by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Baricitinib is mainly eliminated renally through glomerular filtration and active secretion via OAT3, P-gp, BCRP and MATE2-K, with CYP3A4 metabolism representing less than 10% of its overall metabolism. Dolutegravir is unlikely to affect baricitinib elimination. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by CYP or UGT enzymes. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Barnidipine is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir does not inhibit or induce CYP3A4. Barnidipine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Basiliximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolised by CYP3A4, CYP1A2 and are glucuronidated. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Bazedoxifene and conjugated estrogens are unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine and tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beclometasone is a pro-drug which is not metabolised by CYP450, but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone -17-monopropionate.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bedaquiline is metabolised by CYP3A4 and mainly eliminated in faeces. Bedaquiline is unlikely to be affected by dolutegravir, lamivudine or tenofovir-DF. There are no clinical data on the safety and efficacy of bedaquiline when co-administered with antiretroviral agents.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belatacept is a protein that undergoes non-CYP mediated metabolism in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Patients requiring treatment with belimumab may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Belimumab was shown to lower IFN and IL-6/10 and is expected to normalize metabolism but no significant effect on dolutegravir is expected and no a priori dose adjustment is required when initiating or discontinuing belimumab. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bempedoic acid is glucuronidated by UGT2B7 and also converted to an active metabolite by aldo-keto reductase. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce UGTs at clinically relevant concentrations. Bempedoic acid does not inhibit or induce UGTs. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat which is eliminated predominantly renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to affect bendamustine metabolism. Bendamustine does not inhibit or induce CYP enzymes and is unlikely to affect UGTs. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is eliminated by hepatic metabolism (70%, exact pathway not known) and excreted unchanged in the urine (30%) via OAT1 and OAT3. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. There is no evidence that bendroflumethiazide inhibits or induces CYP or UGT enzymes. A drug interaction with lamivudine is unlikely as lamivudine and bendroflumethiazide are eliminated by different renal transporters. In vitro data indicate that bendroflumethiazide inhibits OAT1 and OAT3 but a clinically relevant drug interaction with tenofovir is unlikely in the range of observed clinical concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benserazide is hydrolysed to trihydroxybenzylhydrazine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benznidazole undergoes non-CYP mediated metabolism and partly CYP mediated metabolism. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction with lamivudine or tenofovir-DF via competition for renal elimination pathways. A case study of a patient taking an antiretroviral regimen of tenofovir-DF, emtricitabine and raltegravir reported no clinical or laboratory adverse events when the patient received benznidazole 5 mg/kg daily for 90 days. At the end of treatment, the patient’s viral load remained undetectable, and CD4 count was maintained.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benzonatate is metabolized by plasma butyrylcholinesterase. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir is unlikely to affect benzonatate metabolism. Benzonatate is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bepridil is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beta-alanine is a non-essential amino acid and dietary supplements enter the same physiological processes as endogenous beta-alanine. Excess beta-alanine is excreted in the urine by the kidneys. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Beta-alanine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betahistine is metabolised by monoamine oxidase.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betamethasone is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Betamethasone is a moderate inducer of CYP3A4 but a clinically significant effect on dolutegravir is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but no clinically relevant drug interactions are expected with the topical use of betamethasone (for example, ointment, cream, lotion, emollient, foam).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. In vitro date indicate that dolutegravir is not expected to inhibit or induce P-gp. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bevacizumab is metabolised via proteolytic catabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bexarotene is mainly metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Half of bezafibrate dose is eliminated unchanged in the urine. No interaction is expected with dolutegravir or with lamivudine as it is excreted by different renal transporters. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1 but a clinically relevant drug interaction with tenofovir is unlikely in the observed range of clinical concentrations.

Coadministration has not been studied. Bicalutamide is metabolised by CYP3A4 and UGT1A9. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Bicalutamide does not inhibit or induce UGT or CYP enzymes. No interaction is expected with lamivudine which is eliminated renally. Bicalutamide is a weak inhibitor of P-gp in vitro and could potentially increase the absorption of tenofovir-DF (the prodrug of tenofovir) although only to a limited extent.

Dolutegravir/lamivudine/tenofovir-DF and Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, products containing lamivudine should not be administered with products containing emtricitabine due to the risk for intracellular interactions between cytidine analogues such as emtricitabine and lamivudine. Furthermore, coadministering two integrase inhibitors (i.e., bictegravir and dolutegravir) is unlikely to be of clinical benefit.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bilastine is mainly excreted unchanged and is a substrate of P-gp and OATP1A2. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Bilastine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bimekizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Binimetinib is primarily metabolised by UGT1A1 and the active metabolite M3 is metabolised by CYP1A2 and CYP2C19. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce UGT or CYP enzymes at clinically relevant concentrations. Binimetinib is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

Coadministration has not been studied. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas. No interaction is expected with lamivudine or tenofovir-DF. A pharmacokinetic interaction is unlikely with dolutegravir and biotin alone. However, biotin administered in multivitamin preparations may decrease dolutegravir exposure. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir/lamivudine/tenofovir-DF should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited human data suggest biperiden undergoes hydroxylation in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following sublingual administration, birch tree pollen allergen is actively taken up through the oral mucosa by dendritic cells, in particular Langerhans cells. Allergen which is not absorbed is expected to be hydrolysed to amino acids and small polypeptides in the gastrointestinal tract and there is no evidence to suggest absorption into the vascular system to any significant extent. No interaction trials have been conducted in humans and no potential drug interactions have been identified from any source.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisacodyl is converted to an active metabolite by intestinal and bacterial enzymes. Absorption from the gastrointestinal tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide. Significant interactions are not expected with dolutegravir, lamivudine or tenofovir-DF.

Coadministration has not been studied. Bismuth subsalicylate is largely hydrolysed in the stomach to form salicylic acid, which is rapidly absorbed, and insoluble bismuth salts, which are excreted unchanged in faeces. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Bismuth subsalicylate is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally. However, dolutegravir may be subject to chelation by high concentrations of trivalent bismuth cations which may result in reduced dolutegravir concentrations. Dolutegravir/lamivudine/tenofovir-DF should be taken 2 hours before or 6 hours after bismuth subsalicylate.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bisoprolol is unlikely to affect UGT1A1 or CYP3A4. Lamivudine is eliminated by OCT2 and in vitro data indicate that bisoprolol inhibits OCT2. However, the clinical relevance of an interaction via OCT is unknown given the good tolerability of lamivudine. No interaction is expected with tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. No effect on dolutegravir exposure is expected as in vitro studies suggest black cohosh is unlikely to affect CYP3A4 or UGT1A1 at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bleomycin is inactivated by a cytosolic enzyme, bleomycin hydrolase. Furthermore, ~67% of the administered drug is excreted unchanged in urine probably by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An indirect effect of blinatumomab on CYPs may occur due to transient release of cytokines during the first days of therapy which can inhibit CYP450 metabolism, however a clinically relevant interaction is unlikely. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bortezomib is mainly metabolised by CYP3A4 and 2C19 and to a lesser extent CYP1A2, 2D6 and 2C9. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bortezomib does not inhibit or induce CYP3A4 and is unlikely to affect UGT1A1. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Bosentan is a substrate of CYP3A4 and CYP2C9. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bosentan could potentially decrease dolutegravir exposure although a significant effect is not expected as CYP3A4 does not play a major role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosutinib is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bosutinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Branched chain amino acids (BCAAs) mainly undergo intracellular catabolism in skeletal muscle. Excess BCAAs and BCAA-derived metabolic products are excreted in the urine by the kidneys. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. BCAAs are unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brentuximab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with dolutegravir. MMAE is a substrate of CYP3A4 and P-gp but no interaction is expected as dolutegravir is not expected to inhibit or induce CYPs or P-gp at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brexpiprazole is predominantly metabolised by CYP3A4 and CYP2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Brexpiprazole is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brigatinib is metabolised by CYP2C8 and CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Brigatinib is a weak CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brimonidine is metabolised mainly by aldehyde oxidase.

Coadministration has not been studied. Brincidofovir is a prodrug converted to cidofovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Dolutegravir and lamivudine are not expected to affect this elimination pathway. Unlike cidofovir, brincidofovir is not a substrate of OATs and is less likely to accumulate in the kidney thereby reducing the potential for nephrotoxicity. Administration of oral brincidofovir leads to cidofovir plasma concentrations less than 1% of those observed after IV cidofovir. Tenofovir is primarily eliminated by the kidneys, notably via OAT1, however given that brincidofovir is not a substrate of this transporter no pharmacokinetic interaction is expected. In addition, the potential risk of nephrotoxicity with tenofovir-DF is expected to be lower with brincidofovir given that it results in lower cidofovir concentrations. Brincidofovir inhibits BCRP but not P-gp and therefore could increase tenofovir-DF exposure although only to a limited extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brinzolamide is mainly metabolised by CYP3A4, and to a lesser extent by CYPs 2A6, 2C8 and 2C9. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir does not inhibit or induce CYPs. Brinzolamide is unlikely to affect UGT1A1 and does not inhibit or induce CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may also play a role. Dolutegravir is metabolised by UGT1A1 and to lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bromazepam is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromocriptine is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bromocriptine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Budesonide is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bulevirtide is catabolized by peptidases and elimination occurs through binding to NTCP (a bile salt liver transporter serving as HDV/HBV entry receptor). Dolutegravir, lamivudine and tenofovir-DF do not interfere with this elimination pathway. Coadministration of tenofovir-DF and bulevirtide in healthy volunteers had no effect on tenofovir pharmacokinetics (AUC and Cmax decreased by ~4% and ~15%, n=12).

Coadministration has not been studied. Bumetanide is hepatically metabolised and approximately 50-80% of bumetanide is excreted in the urine by OAT1 and OAT3, mainly as unchanged drug (~50%). Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. In vitro data suggest that bumetanide inhibits OAT1 but no interaction is expected with lamivudine as it is eliminated by other renal transporters. However, coadministration is expected to affect tenofovir renal elimination and increase the risk of renal toxicity. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupivacaine is predominantly metabolised via CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bupivacaine is unlikely to affect UGT1A1 or CYP3A4. Renal excretion of unchanged bupivacaine is thought to account for approximately 1% of a dose and there is little potential for an interaction with lamivudine or tenofovir-DF via competition for renal elimination pathways.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Norbuprenorphine, an active metabolite, can further undergo glucuronidation (via UGT1A3 and UGT1A1). Dolutegravir is unlikely to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Buprenorphine and norbuprenorphine are unlikely to affect dolutegravir metabolism. The interaction between buprenorphine and lamivudine or tenofovir-DF was investigated in HIV-negative, buprenorphine/naloxone maintained subjects. When compared to values obtained from control subjects not receiving buprenorphine, no significant changes in buprenorphine pharmacokinetics were observed. When compared to controls, buprenorphine had no statistically significant effect on NRTI concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolised by CYP2B6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Bupropion is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Buspirone is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Busulfan is metabolised through conjugation with glutathione (spontaneous and GST-mediated) and then by hepatic oxidation (likely CYP3A4-mediated). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir is unlikely to affect busulfan metabolism. Busulfan is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabazitaxel is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cabazitaxel has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolised by the liver predominantly via hydrolysis (non-CYP mediated metabolism) and does not inhibit or induce drug metabolizing enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolised by the liver predominantly via hydrolysis (non-CYP mediated metabolism) and does not inhibit or induce drug metabolizing enzymes.

Cabotegravir used as PrEP is not expected to be coadministered with antiretrovirals except in the case of breakthrough infection when an antiretroviral treatment should be initiated. Residual concentrations of cabotegravir may remain in the systemic circulation for prolonged periods (up to 12 months or longer) but are not expected to affect the exposure of antiretroviral drugs initiated after discontinuation of cabotegravir for PrEP.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to cabotegravir should be considered as coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Cabotegravir is not expected to alter concentrations of other antiretroviral products.

Dolutegravir/lamivudine/tenofovir-DF and Cabenuva (cabotegravir LA, rilpivirine LA) are indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., cabotegravir and dolutegravir) is unlikely to be of clinical benefit. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for a prolonged period after discontinuation of intramuscular cabotegravir/rilpivirine but are not expected to affect exposure of antiretroviral drugs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabozantinib is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cabozantinib has no inhibitory or inducing effects on drug metabolizing enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Caffeine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Caffeine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcitonin is primarily metabolised via proteolysis in the kidney. Dolutegravir, lamivudine and tenofovir-DF do not interfere with this pathway.

Coadministration has not been studied. Calcium folinate is the calcium salt of 5-formyl tetrahydrofolic acid, an active metabolite of folinic acid. No interaction is expected with lamivudine or tenofovir-DF. In theory, calcium could chelate with dolutegravir and potentially decrease the amount of dolutegravir available to bind to the active site of the HIV integrase. However, given that the extent of chelation is dependent on the amount of calcium, this risk is predicted to be low when administering calcium folinate in small doses at frequent intervals. Since calcium is distributed rapidly, separating the intake of dolutegravir from the IV administration of calcium folinate by 2 hours should eliminate any risk of chelation.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied. Calcium is eliminated through faeces, urine and sweat. No interaction is expected with lamivudine or tenofovir-DF. Simultaneous coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) to fasting subjects decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. When taken with food, dolutegravir/lamivudine/tenofovir-DF and supplements containing calcium can be taken at the same time. Under fasting conditions, dolutegravir/lamivudine/tenofovir-DF should be taken 2 hours before or 6 hours after taking supplements containing calcium.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. The metabolism of canagliflozin is primarily mediated by UGT1A9 and UGT2B4. Dolutegravir, lamivudine and tenofovir-DF are unlikely to inhibit or induce UGTs at clinically relevant concentrations. However, since an increased risk for bone fractures has been reported with canagliflozin (particularly in patients with a history of, or at high risk of, cardiovascular disease), caution is recommended when coadministering canagliflozin in the long term with tenofovir-DF due to potential additive bone toxicities.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canakinumab is an IL-1 beta monoclonal antibody and is eliminated via intracellular catabolism. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Canakinumab, per se, has no inhibitory or inducing effects on cytochromes. Canakinumab will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolised by CYP3A4 and CYP2C19. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cannabidiol is unlikely to significantly inhibit CYP3A4, UGT1A1 or intestinal transporters in the range of doses in clinical use. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetrahydrocannabinol (THC, the psychoactive component of cannabis), is metabolised mainly by CYP2C9 and to a lesser extent by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. THC is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Nucleoside/tide analogues such as lamivudine or tenofovir-DF may compete for these metabolic pathways. The clinical relevance of this interaction is unknown. No interaction is expected with dolutegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capmatinib is primarily metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Capmatinib is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Capreomycin is predominantly excreted in the urine as unchanged drug. There is some potential for exposure of capreomycin to be increased since dolutegravir inhibits the renal transporter OCT2. There may also be potential competition with lamivudine and tenofovir for renal elimination transport mechanisms resulting in increased drug concentrations. In addition, renal toxicity has been reported during capreomycin treatment. Tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is largely excreted in the urine by OAT1 (40-50% as unchanged drug, the rest as disulfide and other metabolites). Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied. No significant interaction is expected with lamivudine or tenofovir. However, the dolutegravir dose (50 mg) is insufficient when coadministered with certain drugs (such as carbamazepine) that may decrease dolutegravir concentrations. Coadministration of carbamazepine (300 mg twice daily) and dolutegravir alone (50 mg once daily) decreased dolutegravir AUC, Cmax and Cmin by 49%, 33% and 73%, respectively. Product labels for the dolutegravir/lamivudine/tenofovir fixed dose combination recommend that an additional 50 mg tablet of dolutegravir, separated by 12 hours from the fixed dose combination, should be taken when given with carbamazepine. This dose adjustment should be maintained for approximately 2 weeks after stopping carbamazepine as the inducing effect may persist after discontinuation of a strong inducer. Considering the limited experience when coadministering inducers with combination antiretroviral regimens, close monitoring of HIV infection is recommended. Limited data from a small number of patients showed evaluations for carbamazepine and oxcarbazepine were within the therapeutic ranges and trough concentrations for dolutegravir were ~83% lower when compared with HIV-infected patients not treated with antiepileptic drugs. A case report describes a person living with HIV on dolutegravir/lamivudine/tenofovir-DF (50/300/245 mg once daily) and carbamazepine (400 mg once daily) who remained virologically suppressed. The extrapolated dolutegravir concentration 24 h post-dose was estimated to be 670 ng/mL (clinical target concentration 300 ng/mL). The magnitude of the interaction with carbamazepine in this patient was less pronounced than in a published drug interaction study and is likely due to the lower dose of carbamazepine in this patient (400 mg) compared to the dose used in the interaction study (600 mg) given that carbamazepine induction is dose/concentration dependent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbidopa is partly metabolised and partly eliminated unchanged (30% of the total urinary excretion).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbimazole is a pro-drug which undergoes rapid and virtually complete metabolism to the active metabolite, thiamazole (also known as methimazole). Despite this potential hepatic metabolism very few data exist on carbimazole drug interactions and a marked interaction is not expected with dolutegravir, lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbocisteine is metabolized in the liver via acetylation, decarboxylation and sulfoxidation with up to 60% excreted unchanged in the urine. The likelihood of a clinically significant drug interaction is low and no studies have been performed. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Carboplatin is excreted primarily by renal glomerular filtration. Dolutegravir does not interfere with carboplatin elimination. There is little potential for competition for active renal elimination mechanisms by carboplatin and lamivudine or tenofovir-DF. However, carboplatin and tenofovir-DF both have nephrotoxic potential and use of tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic medicinal product. If coadministration is unavoidable, renal function should be monitored closely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carfilzomib is rapidly metabolised, mainly by peptidase cleavage and epoxide hydrolysis with CYP-mediated metabolism representing a minor pathway. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to affect carfilzomib metabolism. Carfilzomib is not expected to have a clinically relevant effect on drugs metabolised by CYPs or UGT1A1. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cariprazine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Carvedilol is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. In vitro data indicate that caspofungin is a substrate of the hepatic transporter OATP1B1. There is no evidence that dolutegravir inhibits OATP1B1. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Cat’s claw was demonstrated to strongly inhibit CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. However, cat's claw is unlikely to significantly affect dolutegravir exposure as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cedazuridine is eliminated renally and converted to its epimer (which is then renally excreted). Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Cedazuridine does not inhibit or induce UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Cefalexin is predominantly eliminated unchanged via the kidneys (by glomerular filtration and tubular secretion via OAT1 and MATE1). Dolutegravir is not expected to inhibit these renal transporters and lamivudine is eliminated by different renal transporters. However, there is potential competition for renal transporters with cefalexin and tenofovir, which could lead to increased concentrations of either drug.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. Dolutegravir is unlikely to interfere with cefazolin elimination. There is little potential for an interaction with lamivudine or tenofovir via competition for active renal elimination transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefixime is renally excreted predominantly by glomerular filtration, with no significant active renal tubular secretion. Dolutegravir is unlikely interfere with cefixime elimination. There is little potential for an interaction with lamivudine or tenofovir via competition for active renal elimination transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is partially metabolised by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine (about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite). In vitro studies indicate that OAT3 participates in the renal elimination of cefotaxime. Dolutegravir is unlikely to interfere with cefotaxime elimination. There is little potential for an interaction with lamivudine or tenofovir via competition for active renal elimination transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftazidime is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion. Dolutegravir is unlikely to interfere with ceftazidime elimination. There is little potential for an interaction with lamivudine or tenofovir via competition for active renal transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is excreted predominantly by renal glomerular filtration with minimal active renal tubular secretion. Dolutegravir is unlikely to interfere with ceftriaxone elimination. There is little potential for an interaction with lamivudine or tenofovir via competition for active renal transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefuroxime is not metabolised and is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Celecoxib is metabolised mainly by CYP2C9. Dolutegravir is unlikely to inhibit or induce CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. However, coadministration could potentially increase the risk of nephrotoxicity with tenofovir-DF. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is coadministered with an NSAID, renal function should be monitored adequately.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cemiplimab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied. Cenobamate is primarily glucuronidated by UGT2B7 and to a lesser extent by UGT2B4. CYP3A4 contributes to cenobamate metabolism but to a minor extent. Dolutegravir is primarily metabolised by UGT1A1, with a minor contribution from CYP3A4. Dolutegravir has no inhibitory or inducing effects on drug metabolizing enzymes. Cenobamate is a dose-dependent inducer of CYP3A4 and was shown to reduce exposure of midazolam (a CYP3A4 substrate) by 72% at a dose of 200 mg daily and by 27% at a dose of 100 mg daily. Cenobamate is dose-titrated until the 200 mg maintenance dose is reached. Cenobamate at a daily dose of 200 mg or greater could potentially decrease dolutegravir concentrations. If coadministration with cenobamate at doses of 200 mg daily or greater is necessary, a dose adjustment of dolutegravir to 50 mg twice daily is recommended in the absence of integrase class resistance. This dose adjustment should be maintained for approximately 2 weeks after stopping cenobamate as the inducing effect may persist after discontinuation of a strong inducer. In the presence of integrase class resistance this combination should be avoided. Cenobamate inhibits OAT3 but this does not impact lamivudine elimination. Tenofovir is mainly eliminated by OAT1 and to a lesser extent by OAT3. Inhibition of OAT3 by cenobamate could potentially increase tenofovir exposure, although only to a limited extent.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceritinib is metabolised by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Ceritinib is a strong CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Certolizumab pegol is an antibody Fab’ fragment conjugated with polyethylene glycol (PEG). The Fab’ fragment is expected to be degraded to peptides and amino acids by proteolysis; the PEG moiety is mainly excreted in urine without further metabolism. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Patients requiring treatment with certolizumab pegol may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Certolizumab pegol will normalize cytochrome activity (via reduction of cytokines) but no significant effect on dolutegravir is expected and no a priori dose adjustment is required when initiating or discontinuing certolizumab pegol. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. No interaction is expected with dolutegravir or tenofovir-DF. Lamivudine is eliminated by OCT2 and in vitro data indicate that cetirizine inhibits OCT2. However, the clinical relevance of an interaction via OCT is unknown and given the good tolerability of lamivudine, no a priori dose adjustment of lamivudine is needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetuximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorambucil is almost completely metabolised (little is known about chlorambucil metabolism in humans, most probably non CYP mediated) and has extremely low urinary excretion.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly metabolised by glucuronidation via UGT2B7. Dolutegravir is unlikely to inhibit or induce UGT enzymes at clinically relevant concentrations. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Chloramphenicol is unlikely to affect UGT1A1. Although, in vitro studies have shown that chloramphenicol inhibits CYP3A4, CYP3A4 only plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlordiazepoxide is extensively metabolised by hepatic microsomal enzymes. Dolutegravir is metabolised by UGT1A1 and to lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Chlordiazepoxide is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration with a chlormadinone-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Ethinylestradiol is mainly metabolised by hydroxylation and glucuronidation. Dolutegravir is not expected to interact with these metabolic pathways and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Chlormadinone and ethinylestradiol are unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine and tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloroquine undergoes CYP mediated metabolism by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Chloroquine is unlikely to affect UGT1A1 or CYP3A4. Due to the multiple elimination pathways, a clinically significant interaction with lamivudine or tenofovir-DF is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolised in the liver via CYP2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Chlorphenamine is unlikely to affect UGT1A1 or CYP3A4. Approximately 22% of a chlorphenamine dose is excreted unchanged in the urine and there is little potential for an interaction with lamivudine or tenofovir-DF via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Chlorpromazine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlortalidone is mainly excreted unchanged in the urine and faeces.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4 mediated metabolism. Dolutegravir is not expected to affect ciclesonide metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration of a dolutegravir containing regimen and ciclosporin was evaluated in a clinical study in which 19 transplant recipients with HIV (63% liver recipients) were switched from a raltegravir to a dolutegravir containing regimen (dolutegravir plus abacavir/lamivudine or lamivudine/tenofovir-DF) while on ciclosporin treatment. No participants experienced acute rejection or virological failure and CD4 cell counts remained unchanged during the follow-up. Pharmacokinetic data were available in 2 participants receiving ciclosporin. The switch in antiretroviral treatment did not result in clinically significant changes in ciclosporin Cmax, AUC and Cmin (-64%, -47% and +14%, respectively). No interaction is expected with lamivudine which is eliminated renally. However, tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as ciclosporin could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended, especially as ciclosporin can also impair renal function.

Coadministration has not been studied. Cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Dolutegravir is not expected to inhibit these renal transporters. No interaction is expected with lamivudine. Since tenofovir is primarily eliminated by the kidneys, coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir or the coadministered drug. Tenofovir-DF should be avoided with concurrent or recent use of a nephrotoxic agent. If concomitant use of tenofovir-DF and nephrotoxic agents is unavoidable, renal function should be monitored closely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cinacalcet is metabolised by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cinacalcet is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged through the kidneys (by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is also metabolised and partially cleared through the bile and intestine. Dolutegravir is unlikely to interfere with ciprofloxacin elimination. There is little potential for an interaction with lamivudine or tenofovir via competition for active renal elimination transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisapride is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cisapride is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisatracurium undergoes mainly (80% of overall elimination) spontaneous degradation in plasma and tissues at physiological pH and temperature (Hofmann elimination).

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1. OCT2 facilitates the entry of cisplatin in the tubular cell whereas MATE1 facilitates its elimination in the urine. In vitro data indicate that dolutegravir is a moderate inhibitor of OCT2 but causes no clinically significant inhibition of MATE1. Inhibition of OCT2 will lead to lower concentrations of cisplatin inside the tubular cell which represents an advantage as this may reduce the risk of cisplatin related nephrotoxicity. However, cisplatin may impair renal function which may alter the elimination of lamivudine. Closely monitor creatinine clearance. Based on metabolism and clearance a pharmacokinetic interaction is unlikely with tenofovir as it is eliminated by other renal transporters, however, coadministration may increase the risk of nephrotoxicity. If coadministration is necessary with tenofovir-DF, close monitoring of renal function is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolised by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied. Clarithromycin is a strong CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine. However, tenofovir-DF is a substrate of P-gp and inhibitors of P-gp such as clarithromycin could potentially increase the absorption of tenofovir-DF, thereby increasing the systemic concentration of tenofovir. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clavulanic acid is extensively metabolised (likely by a non-CYP mediated pathway) and excreted in the urine by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is extensively metabolised in the liver but the enzymes responsible are undefined. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir is unlikely to affect clemastine metabolism. Clemastine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolised by CYP3A4 with some metabolites having antibacterial activity. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Clindamycin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19. Dolutegravir is metabolised by UGT1A1 and to lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Clobazam is a weak inducer and could potentially decrease dolutegravir exposure although only to a limited extent. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically relevant drug interaction is unlikely with the topical use of clobetasol.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Two glucuronide metabolites have been identified in urine. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. As glucuronidation has a minor role in clofazimine elimination, an interaction with dolutegravir is unlikely. Clofazimine is a moderate CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. An interaction with lamivudine or tenofovir via competition for renal elimination pathways is unlikely as renal excretion has a minor role in clofazimine elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolyzed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Dolutegravir is not expected to inhibit OAT1. No interaction is expected with lamivudine as it is excreted by different renal transporters. No clinically relevant increase in clofibrate and tenofovir is anticipated as a result of competition for renal secretion via OAT1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP2D6 is thought to have a role in clomifene metabolism and renal excretion of clomifene is thought to account for approximately 8% of an oral dose. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Clomifene is unlikely to affect UGT1A1 or CYP3A4. There is little potential for an interaction with lamivudine or tenofovir-DF via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolised by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Clomipramine and desmethylclomipramine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clonazepam is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Clonazepam is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in form of the unchanged parent drug (40-60% of the dose). No interaction is expected with dolutegravir. Clonidine is a weak inhibitor of OCT2 and is unlikely to significantly interact with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug that is converted to its active metabolites via CYPs 3A4, 2B6, 2C19 and 1A2. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolised to oxazepam by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Clorazepate is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clotrimazole undergoes hepatic metabolism (likely via CYP3A4). Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Clotrimazole is unlikely to affect UGT1A1. Clotrimazole is a moderate CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but a clinically significant interaction is unlikely with the topical use of clotrimazole as it is minimally absorbed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted via glomerular filtration and tubular secretion. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction as total renal elimination of cloxacillin represents approximately 35% of a dose. There is little potential for significant interactions with lamivudine or tenofovir-DF via competition for renal transport.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolised by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Clozapine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Cobimetinib is unlikely to have a clinically relevant effect on CYP3A4 or UGTs. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cocaine is metabolised by several non CYP mediated pathways, with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cocaine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Codeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 10-15% of the overall metabolism. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is unlikely to inhibit or induce UGT or CYP enzymes at clinically relevant concentrations. Codeine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The major route of elimination for coenzyme Q10 is by biliary and faecal excretion; only a small fraction is eliminated in the urine. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs or P-gp. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Colchicine is a substrate of CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Colchicine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. There is little potential for an interaction with dolutegravir, lamivudine or tenofovir-DF via modulation or competition for vitamin D metabolism.

Coadministration has not been studied. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally. No interaction is expected with dolutegravir and vitamin D given as a single agent (i.e. not with calcium or in a multivitamin preparation) or as an injection. However, colecalciferol can be found in multivitamin preparations. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir/lamivudine/tenofovir-DF should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract, is not metabolised and does not affect CYP enzymes. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. However, given that colesevelam can reduce the gastrointestinal absorption of some drugs, colesevelam should be administered at least four hours before or after dolutegravir/lamivudine/tenofovir-DF to minimize the risk of reduced absorption.

Coadministration has not been studied. Colestyramine may delay or reduce the absorption of drugs. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for dolutegravir, lamivudine and tenofovir-DF but for any medication taken with colestyramine.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Collagen hydrolysate is digested and absorbed as essential amino acids for use in essential physiological processes. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Collagen hydrolysate is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Conjugated estrogens are metabolised by CYP3A4, CYP1A2 and are glucuronidated. Dolutegravir does not inhibit or induce CYP enzymes at clinically relevant concentrations. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Conjugated estrogens are unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally. In addition, no interaction is expected with progestogens administered as part of HRT. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Copanlisib is metabolised by CYP3A (~90%) and CYP1A1 (~10%). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir does not inhibit or induce CYPs. Copanlisib does not inhibit or induce UGT1A1 or CYP3A4. Copanlisib is an inhibitor of MATE2-k and may increase lamivudine concentrations but a clinically relevant interaction is not expected given the multiple transporters involved in the elimination of lamivudine and the good tolerability of lamivudine. No interaction is expected with tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cortisone is rapidly converted in the liver to its active metabolite, hydrocortisone (cortisol); cortisone and hydrocortisone are metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cortisone is rapidly converted in the liver to its active metabolite, hydrocortisone (cortisol); cortisone and hydrocortisone are metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Creatine monohydrate is not degraded during normal digestion and nearly 99% of orally ingested creatine monohydrate is either taken up by muscle or excreted in urine. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Creatine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Crizotinib is mainly metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Crizotinib is a moderate CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Several constituents of Piper cubeba were shown to inhibit CYP3A4, but a clinically significantly effect on dolutegravir exposure is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. Piperine, a component of Piper cubeba, inhibits intestinal P-gp. No interaction is expected with lamivudine. However, tenofovir-DF is a substrate of P-gp and its absorption could potentially increase, thereby increasing tenofovir systemic concentrations. Monitoring of tenofovir-associated adverse reactions, including frequent renal monitoring, is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

Coadministration has not been studied. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. No interaction is expected with lamivudine or tenofovir-DF. No interaction is expected with dolutegravir and vitamin B12 when given as a single agent (i.e. not in a multivitamin preparation) or as an injection. However, vitamin B12 can be found in multivitamin preparations and simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir/lamivudine/tenofovir-DF should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of cyclizine has not been fully described but may involve CYP2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cyclizine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclobenzaprine is primarily metabolized by CYP3A4 and CYP1A2 and to a lesser extent by CYP2D6. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir does not inhibit or induce CYP enzymes. Cyclobenzaprine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is activated (major pathway) to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cobimetinib is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration. No interaction is expected with dolutegravir and there is little potential for an interaction via competition with lamivudine or tenofovir for active renal transport mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Cyproterone acetate is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytarabine is metabolised by cytidine deaminase. No interaction is expected with dolutegravir, lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytisine is primarily excreted renally as unchanged drug. There are no reports of CYP or transporter involvement and significant pharmacokinetic interactions are unlikely. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabigatran is not metabolised by CYP enzymes and is mainly cleared by glomerular filtration. The prodrug of dabigatran is a substrate of P-gp and in vitro data indicate that dolutegravir does not inhibit P-gp at clinically relevant concentrations. There is little potential for an interaction via competition with lamivudine or tenofovir-DF for active renal transport mechanisms.

Coadministration has not been studied. Dabrafenib is metabolised by CYP3A4 and CYP2C8 and the active metabolites are metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. However, dabrafenib is a strong inducer of CYP3A4 and may induce UGTs and therefore has the potential to decrease dolutegravir exposure. Based on the drug-drug interaction study with rifampicin (a strong inducer), a dose adjustment of dolutegravir to 50 mg twice daily is recommended when coadministered with dabrafenib in the absence of integrase class resistance. This dose adjustment should be maintained for approximately 2 weeks after stopping dabrafenib as the inducing effect may persist after discontinuation of a strong inducer. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Dacarbazine is activated to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dacarbazine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine. However, dacarbazine could compete with tenofovir for renal active secretion, increasing exposure of either drug. No a priori dosage adjustment is recommended but renal function and haematological parameters should be monitored.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daclatasvir is partly metabolised by CYP3A4 and mainly eliminated unchanged in bile. No interaction with lamivudine is expected. Coadministration of dolutegravir (50 mg once daily) and daclatasvir (60 mg once daily) had no significant effect on daclatasvir AUC (2% decrease), Cmax (3% increase) or Cmin (6% increase). There was no clinically relevant change in dolutegravir exposure AUC, Cmax and Cmin which increased by 33%, 29% and 45%, respectively. Coadministration of tenofovir-DF (300 mg once daily) and daclatasvir (60 mg once daily) had no clinically relevant effect on daclatasvir AUC, Cmax or Cmin which increased by 10%, 6% and 15%, respectively. There was no clinically relevant effect on tenofovir AUC (10% increase), Cmax (5% decrease) or Cmin (17% increase).

Coadministration has not been studied. Dacomitinib is metabolised by CYP2D6 (~26%) to O-desmethyl dacomitinib, an active metabolite with similar activity to dacomitinib, whilst CYP3A4 (~6%) contributes to the formation of other minor metabolites. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dacomitinib does not inhibit or induce CYP3A4, but inhibits UGT1A1 and could increase dolutegravir exposure, although only to a modest extent. No dose adjustment is needed. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dactinomycin is minimally metabolised, is concentrated in nucleated cells and does not penetrate the blood-brain barrier. Dolutegravir, lamivudine and tenofovir-DF do not interfere with dactinomycin elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce UGT enzymes at clinically relevant concentrations. Dapagliflozin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Dapivirine used as PrEP is not expected to be coadministered with antiretrovirals. Dapivirine is unlikely to affect the exposure of antiretroviral drugs initiated after discontinuation of dapivirine for PrEP.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapoxetine is metabolised by CYP2D6, CYP3A4 and flavin monooxygenase 1. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dapoxetine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapsone is mainly metabolised by N-acetylation with a component of N-hydroxylation, and is via multiple CYP enzymes. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dapsone is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daptomycin is eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daratumumab, is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The mechanisms of darbepoetin alfa clearance and the site of degradation have not been fully determined but are likely to involve uptake and degradation via epoetin receptor expressing cells and degradation or metabolism via cells in the reticuloendothelial scavenging pathway or lymphatic system. Clinical results to date do not indicate any interaction of darbepoetin with other medicinal products.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daridorexant is mainly metabolised by CYP3A4. Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4. Daridorexant is unlikely to have a significant effect on UGT1A1. Daridorexant is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on dolutegravir as CYP3A4 plays a minor role in dolutegravir metabolism. Dolutegravir does not inhibit or induce CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darifenacin is metabolised by CYP3A4 and CYP2D6. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Darifenacin is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP or UGT enzymes or P-gp at clinically relevant concentrations. Darolutamide is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on dolutegravir exposure. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration of darunavir/ritonavir would be possible from a pharmacokinetic standpoint, but with close monitoring for tenofovir-associated adverse events. Coadministration of darunavir/ritonavir and dolutegravir decreased dolutegravir AUC (22%), Cmax (11%) and Ctrough (38%); there was no effect on darunavir or ritonavir. No interaction is expected with lamivudine. Coadministration of tenofovir-DF (300 mg once daily) and darunavir/ritonavir (300/100 mg twice daily) increased darunavir Cmax (16%), AUC (21%) and C24h (24%). Tenofovir Cmax, AUC and Cmin increased by 24%, 22% and 37%, respectively. No dose adjustments is necessary, however, a higher risk of renal impairment has been reported in patients receiving tenofovir-DF and a ritonavir or cobicistat boosted protease inhibitor. Close monitoring of renal function and for tenofovir-associated adverse reactions is required in these patients.

Dolutegravir/lamivudine/tenofovir-DF and Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, Symtuza contains emtricitabine and tenofovir alafenamide and must not be administered with products containing lamivudine and tenofovir-DF.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with darunavir/cobicistat would be possible from a pharmacokinetic standpoint. Coadministration of dolutegravir (50 mg once daily) and darunavir/cobicistat (800/150 mg once daily) decreased dolutegravir Cmax, AUC, and C24h by 11%, 16% and 19%, respectively. Darunavir Cmax, AUC, and C24h decreased by 21%, 13% and 18%, respectively. Cobicistat Cmax, AUC and C24h decreased by 14%, 12% and 2%, respectively. No interaction is expected with lamivudine. Boosted PIs were shown to increase tenofovir-DF levels and there are currently inadequate data to determine whether tenofovir-DF plus cobicistat is associated with a greater risk of renal adverse reactions than tenofovir-DF without cobicistat. The European SPC for tenofovir-DF advises close renal monitoring of patients receiving tenofovir-DF with a cobicistat-boosted protease inhibitor. The US Prescribing Information for cobicistat does not recommend coadministration of cobicistat and tenofovir-DF in combination with concomitant or recent use of a nephrotoxic agent. Note, cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine and should not be initiated in patients with creatinine clearance less than 70 ml/min if tenofovir-DF requires dose adjustment based on creatinine clearance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dasatinib is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dasatinib is a CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No interaction is expected with dolutegravir or tenofovir-DF. A clinical study reported that antiretroviral regimens containing lamivudine had no effect on the pharmacokinetics of liposomal daunorubicin.

Coadministration has not been studied. The primary route of decitabine metabolism is likely by cytidine deaminase. Decitabine is a prodrug and is activated intracellularly through sequential phosphorylation via phosphokinases activities to the active triphosphate. Phosphorylation of lamivudine occurs via the same enzymes and competition may occur for this activation path. However, the clinical relevance of this interaction is unknown. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Decitabine does not inhibit or induce UGT1A1 or CYP3A4. No interaction is expected with tenofovir-DF which is eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Deferasirox is mainly glucuronidated by UGT1A1 and to a lesser extent by UGT1A3; CYP-mediated metabolism appears to be minor (~8%). Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Deferasirox is a weak inducer of CYP3A4 and was shown to reduce midazolam exposure by 17%, although it is unlikely to significantly decrease dolutegravir concentrations. No interaction is expected with lamivudine and tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Deflazacort is immediately metabolised by plasma esterases to the active metabolite (21-desdeflazacort) which is then metabolised mainly by CYP3A4 to several inactive metabolites which are excreted in the urine (~70%) and faeces (~30%). Dolutegravir is mainly metabolized by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Deflazacort and 21-desdeflazacort do not inhibit or induce UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration with a fixed dose combination of dolutegravir, lamivudine and tenofovir-DF has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Dolutegravir is not expected to inhibit or induce CYPs at clinically relevant concentrations. No interaction is expected with lamivudine and no clinically relevant interaction was observed with tenofovir-DF. Coadministration of delamanid (100 mg twice daily) and tenofovir-DF (300 mg once daily) decreased delamanid Cmax and AUC by 16% and 4% and decreased tenofovir Cmax and AUC decreased by 11% and 9% (n=13).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Denosumab is not eliminated via hepatic metabolism but follows the immunoglobulin clearance pathway. (Note, caution is required if denosumab is given with calcium supplements as dolutegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced dolutegravir concentrations.)

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desflurane is almost exclusively eliminated unchanged by the lungs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is metabolised by CYP2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Desipramine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desloratadine is metabolised to the active metabolite 3-hydroxydesloratadine, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of the active metabolite have not been identified, but no clinically relevant interactions have been observed with inhibitors of CYP enzymes. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Desloratadine does not inhibit or induce UGT1A1 or CYP3A4. No interaction is expected with lamivudine and tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desmopressin undergoes no significant hepatic metabolism and is not a substrate for CYP enzymes. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally.

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolised by CYP3A4. Ethinylestradiol is mainly metabolised by hydroxylation. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations and had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Desogestrel and ethinylestradiol are unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19) which is then metabolised by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Desogestrel is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desvenlafaxine is mainly metabolised by glucuronidation and to a minor extent through oxidative metabolism by CYP3A4 and CYP2C19. Renal elimination of unchanged desvenlafaxine also constitutes an important route of elimination. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Desvenlafaxine is not expected to significantly inhibit or induce CYP3A4 at the dose in clinical use. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg. Dexamethasone could potentially decrease dolutegravir concentrations, but this is unlikely to be of clinical significance as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is metabolised by CYP3A4. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dexamethasone is weak CYP3A4 inducer at a low dose and is unlikely to have a clinically significant effect on dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dexketoprofen is mainly excreted as glucuronide conjugates; CYP2C8/9 plays a minor role in metabolism. Dolutegravir is unlikely to inhibit or induce UGT or CYP enzymes at clinically relevant concentrations. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Dexketoprofen is unlikely to affect UGT1A1 or CYP3A4. Lamivudine and tenofovir (derived from tenofovir-DF) are eliminated renally. No interaction is expected with lamivudine. However, coadministration could potentially increase the risk of nephrotoxicity with tenofovir-DF. The risk is increased if an NSAID is used for a long duration, if the patient has a pre-existing renal dysfunction, has a low body weight, or receives other drugs that may increase tenofovir exposure. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in patients treated with tenofovir-DF and with risk factors for renal dysfunction. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction. If tenofovir-DF is coadministered with an NSAID, renal function should be monitored adequately.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Data from an interaction study with omeprazole suggest that solubility of dolutegravir is not influenced by changes in gastric pH. Dolutegravir may be coadministered with PPIs or H2-antagonists without dose adjustment or separation. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexmedetomidine undergoes extensive hepatic metabolism through direct glucuronidation (mainly via UGT1A4, 2B10) and CYP450s (mainly CYP2A6). Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is unlikely to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Dexmedetomidine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextromethorphan is metabolized by CYP2D6. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Dolutegravir does not inhibit or induce CYP2D6. Dextromethorphan is unlikely to affect UGT1A1 and does not inhibit or induce CYP3A4. No interaction is expected with abacavir or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is mainly metabolised by CYP3A. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dextropropoxyphene is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diamorphine is rapidly metabolised by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is unlikely to inhibit or induce CYP or UGT enzymes at clinically relevant concentrations. Diamorphine and morphine are unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolised to nordiazepam (by CYP3A4 and 2C19) and to temazepam (mainly by CYP3A4). Dolutegravir is metabolised by UGT1A1 and to lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Diazepam is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9 (catalyzes the major route of diclofenac oxidative metabolism). Dolutegravir is not expected to inhibit or induce UGT or CYP enzymes at clinically relevant concentrations. No interaction is expected with lamivudine. However, coadministration could potentially decrease renal elimination of tenofovir (thereby increasing the risk of nephrotoxicity) as diclofenac is a strong inhibitor of MRP4. A retrospective analysis showed that patients treated with diclofenac together with tenofovir-DF containing regimens were at higher risk of developing an acute kidney injury when compared to patients treated with tenofovir-DF-sparing regimens. Since diclofenac can exacerbate tenofovir-DF nephrotoxicity, diclofenac should preferably be avoided or otherwise used with caution and close monitoring of renal function is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diethylcarbamazine is mainly excreted unchanged in the urine. There is little potential for an interaction with dolutegravir, lamivudine or tenofovir-DF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Digoxin is eliminated renally via the renal transporters OATP4C1 and P-glycoprotein. In vitro data indicate that dolutegravir does not inhibit P-gp at clinically relevant concentrations. Lamivudine and tenofovir are excreted by different renal transporters so no interactions are expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine is converted to dihydromorphine (active metabolite) via CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine via CYP3A4. Dolutegravir is unlikely to inhibit or induce UGT or CYP enzymes at clinically relevant concentrations. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Dihydrocodeine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydroergotamine is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Dihydroergotamine is a CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diloxanide furoate is largely hydrolysed under the combined action of bacterial and gut esterases and consequently glucuronidated. No clinically-significant drug interactions are known, and significant interactions with antiretrovirals are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diltiazem is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Diltiazem is a strong CYP3A4 inhibitor, but a clinically significant interaction is unlikely as CYP3A4 plays a minor role in dolutegravir metabolism. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dimethyl fumarate is metabolised by esterases before entering the blood stream. Further metabolism occurs though the TCA cycle. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Dimethyl fumarate is unlikely to have a clinically significant effect on substrates of CYPs, UGTs and P-gp. No interaction is expected with lamivudine which is eliminated renally. However, coadministration with tenofovir-DF may increase the risk of nephrotoxicity. If concomitant use of tenofovir-DF and dimethyl fumarate is unavoidable, renal function should be monitored closely.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolised by CYP2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Diphenhydramine is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce UGT enzymes at clinically relevant concentrations. Dipyridamole is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied. Disopyramide is metabolised by CYP3A4 (25%) whereas 50% of the drug is eliminated unchanged in the urine (possibly via OCT2). In vitro data indicate that dolutegravir inhibits OCT2 and may increase disopyramide exposure. Caution is warranted and clinical monitoring is recommended if coadministered. Data from animal studies indicate that disopyramide is a weak inhibitor of the renal transporter OCT2. Since OCT2 may contribute to the renal elimination of disopyramide, there is potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug. No interaction via OCT2 is expected with tenofovir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disulfiram is reduced to diethyldithiocarbamic acid, is conjugated with glucuronic acid, oxidised to sulphate, methylated and decomposed to diethylamine and carbon disulphide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Docetaxel is metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Docetaxel is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Docusate has been reported to undergo extensive first-pass metabolism and metabolism in the liver, but the metabolic pathway remains unclear. Dolutegravir is mainly metabolised by UGT1A1 and to a lesser extent by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Docusate is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

Coadministration has not been studied but is contraindicated. Dofetilide is mainly excreted unchanged in urine. Renal elimination involves both glomerular filtration and active tubular secretion (via cation transport system). Dolutegravir is an inhibitor of OCT2 and therefore can increase dofetilide exposure and thereby increase the risk of cardiac arrhythmias. There is also potential for competition with lamivudine for active renal transport mechanisms, which may lead to increased levels of either drug. Tenofovir is not eliminated by organic cation transporters and therefore does not interfere with the elimination of dofetilide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolised by CYP2D6 (10-20%) and CYP3A4 (<1%). Dolutegravir is not expected to inhibit or induce UGT or CYP enzymes at clinically relevant concentrations. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4. Dolasetron is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF.

The dolutegravir dose (50 mg) in a fixed dose combination of dolutegravir/lamivudine/tenofovir-DF can be insufficient when coadministered with some medications that may decrease dolutegravir concentrations. An additional 50 mg tablet of dolutegravir, separated by 12 hours from the fixed dose combination, is recommended with these medications.

Dolutegravir/lamivudine/tenofovir-DF and Triumeq (dolutegravir, abacavir, lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both regimens contain dolutegravir and lamivudine and should not be taken with any other medicinal products also containing dolutegravir and lamivudine.

Dolutegravir/lamivudine/tenofovir-DF and Dovato (dolutegravir, lamivudine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both regimens contain dolutegravir and lamivudine and should not be taken with any other medicinal products also containing dolutegravir and lamivudine.

Dolutegravir/lamivudine/tenofovir-DF and Juluca (dolutegravir, rilpivirine) are both indicated for use as complete regimens for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. In addition, both regimens contain dolutegravir and should not be taken with any other medicinal products also containing dolutegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Domperidone is mainly metabolised by CYP3A4. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Domperidone is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Donepezil is metabolised by CYP3A4 and to a lesser extent by CYP2D6. Dolutegravir is metabolised by UGT1A1 and to a lesser extent by CYP3A4 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations. Donepezil is unlikely to affect UGT1A1 or CYP3A4. No interaction is expected with lamivudine or tenofovir-DF which are eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase to inactive compounds. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals. Renal elimination of unchanged dopamine is minimal. There is little potential for dopamine to affect the disposition of antiretrovirals, or to be affected if co-administered with antiretrovirals.