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).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion and in vitro studies have shown it may competitively inhibit the renal transporters OAT1, OAT3 and OAT4. In vitro data suggest that dolutegravir inhibits OCT2 therefore a drug-drug interaction is unlikely as those drugs act on different renal transporters.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Aciclovir is eliminated renally via glomerular filtration and active renal secretion by OAT1, however, dolutegravir is not expected to inhibit this renal transporter.

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.

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 has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely, Adefovir is eliminated renally via glomerular filtration and active renal secretion by OAT1, however, dolutegravir is not expected to inhibit this renal transporter.

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.

Coadministration has not been studied but based on metabolism and clearance, as well as limited drug-drug interaction data, a clinically significant interaction is unlikely. Dolutegravir is metabolized by UGT1A1, with some contribution from CYP3A. Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. In vitro human microsomal studies and limited in vivo drug-drug interaction data indicate that albuvirtide has no inhibiting or inducing properties on P450 enzymes.

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 the metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Dolutegravir does not interfere with this metabolic pathway.

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

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.

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 metabolized to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Dolutegravir does not interfere with ambrisentan metabolism.

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

Coadministration has not been studied. Amiloride is eliminated unchanged by the kidney with in vitro data indicating that it is a substrate of OCT2. In vitro data indicate that dolutegravir inhibits OCT2 and may increase amiloride exposure.

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 metabolized by CYP1A2, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

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, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration with amodiaquine alone has not been studied. Amodiaquine is metabolized mainly by CYP2C8, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Co-administration 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ampicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that dolutegravir inhibits OCT2 but is unlikely to cause a clinically relevant drug interaction with due to ampicillin’s large therapeutic index.

Dolutegravir should be administered 2 hours before or 6 hours after taking medications containing polyvalent cations, such as antacids. Simultaneous coadministration of a magnesium/aluminium containing antacid (Maalox) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 72%, 74% and 74%, respectively. When antacid was administered 2 hours after dolutegravir (50 mg once daily, n=16), dolutegravir Cmax, AUC and Ctrough decreased by 18%, 26% and 30%, respectively. Coadministration with antacids containing calcium carbonate has not been studied. Medicinal products that reduce dolutegravir exposure (e.g. antacids) should be avoided in the presence of integrase class resistance.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolized by CYP3A4 and to a lesser extent CYP1A2, CYP2C8, CYP2C9 and CYP2C19, but dolutegravir is mainly metabolized by UGT1A1.

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. Drug-drug interactions studies performed with substrates of different cytochromes and P-glycoprotein (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.

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 are rapidly excreted in the urine when in excess of the requirements of the body. A pharmacokinetic interaction is unlikely with vitamin C itself. However, vitamin C can be found in multivitamin preparations. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations. Medicinal products that reduce dolutegravir exposure (e.g. multivitamins) should be avoided in the presence of integrase class resistance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to salicylic acid and then further metabolized mainly by glucuronidation (by several UGT, major UGT1A6).

Coadministration of atazanavir (400 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 50% and 91%, with Ctrough increasing by 2.8-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. No dosage adjustment is necessary. The European SmPC for dolutegravir advises that dolutegravir should not be dosed higher than 50 mg twice daily in combination with atazanavir due to lack of data.

Coadministration with atazanavir/cobicistat has not been studied. Coadministration of atazanavir/ritonavir (300/100 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 34% and 62%, and increased Ctrough by 2.21-fold (due to inhibition of UGT1A1 by atazanavir). Similarly, co-administration with atazanavir/cobicistat is expected to increase dolutegravir plasma concentrations. Dolutegravir is not expected to affect the pharmacokinetics of atazanavir/cobicistat. No dose adjustment is required for dolutegravir if co-administered with atazanavir/cobicistat. The European SmPC for dolutegravir advises that dolutegravir should not be dosed higher than 50 mg twice daily in combination with atazanavir due to lack of data.

Coadministration of atazanavir/ritonavir (300/100 mg once daily) and dolutegravir (30 mg once daily) increased dolutegravir Cmax and AUC by 34% and 62%, and increased Ctrough by 2.21-fold. Compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of atazanavir. No dosage adjustment is necessary. The European SmPC for dolutegravir advises that dolutegravir should not be dosed higher than 50 mg twice daily in combination with atazanavir due to lack of data.

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. Therefore there is potential for dolutegravir to increase atenolol exposure via inhibition of OCT2. Based on the drug-drug interaction study with 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. 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 the metabolism/elimination and toxicity profiles of both drugs there is little potential for interaction when 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. There is, therefore, little potential for clinically significant interactions with dolutegravir via modulation of, or competition for, metabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avanafil is primarily metabolized by CYP3A4 and does not inhibit or induce CYPs or UGTs. Dolutegravir is mainly metabolized by UGT1A1 and is not expected to inhibit or induce CYP enzymes at clinically relevant concentrations.

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 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. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat which is eliminated predominantly renally.

Coadministration has not been studied but based on the 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%). There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes. Similarly, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

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. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction via competition for renal elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betahistine is metabolized by monoamine oxidase. Betahistine does not induce or inhibit CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Betamethasone is a moderate inducer of CYP3A4, however, no clinically significant interaction is expected as CYP3A4 does not play a major role in dolutegravir metabolism.

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 and dolutegravir does not inhibit or induce P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as bevacizumab is metabolized via proteolytic catabolism.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as half of bezafibrate dose is eliminated unchanged in the urine.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and should not be administered with other antiretroviral products. 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 limited information concerning the metabolism and clearance of biperiden, there is little potential for clinically significant interaction. 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. No effect on dolutegravir is expected as in vitro studies suggest black cohosh is unlikely to affect UGT1A1 at clinically relevant concentrations.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9. Bosentan could potentially decrease dolutegravir exposure although to a moderate extent as CYP3A4 does not play a major role in dolutegravir metabolism. No a priori dosage adjustment is required.

Coadministration 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 not expected to inhibit or induce CYP450 or UGTs enzymes at clinically relevant concentrations.

Coadministration has not been studied. Calcium folinate is the calcium salt of 5-formyl tetrahydrofolic acid, an active metabolite of folinic acid. 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.

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. Dolutegravir should be administered 2 hours before or 6 hours after taking medications containing polyvalent cations, such as calcium supplements. The US Prescribing information suggests that, alternatively, dolutegravir and calcium supplements can be taken together with food. Medicinal products that reduce dolutegravir exposure (e.g. calcium supplements) should be avoided in the presence of integrase class resistance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4 which are not affected by dolutegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19 and is unlikely to significantly inhibit CYP3A4, UGT1A1 or intestinal transporters in the range of doses in clinical use. Dolutegravir does not inhibit or induce P450 enzymes.

Coadministration has not been studied. Capreomycin is predominantly excreted via the kidneys as unchanged drug, partly by glomerular filtration and possibly partly by tubular secretion (renal transporter not identified). There is some potential for exposure of capreomycin to be increased since dolutegravir inhibits the renal transporter OCT2. Renal function should be monitored as clinically appropriate.

Coadministration of carbamazepine (300 mg twice daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Cmin by 33%, 49% and 73%, respectively. The recommended dose of dolutegravir is 50 mg twice daily when coadministered with carbamazepine in treatment-naive or treatment experienced, INSTI-naive patients. 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. Alternatives to carbamazepine should be used where possible for INSTI resistant patients. Limited data from a small number of patients showed TDM 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carboplatin is excreted primarily by renal glomerular filtration and therefore there is little potential for a pharmacokinetic interaction.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cat’s claw was demonstrated to strongly inhibit CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. No interaction is expected as CYP3A4 does not play a major role in dolutegravir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ceftazidime is excreted predominantly by renal glomerular filtration.

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 the metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly metabolized by glucuronidation via UGT2B7 whereas dolutegravir is mainly eliminated by glucuronidation via UGT1A1. Dolutegravir is not expected to inhibit UGTs at clinically relevant concentrations. Although, in vitro studies have shown that chloramphenicol inhibits CYP3A4 and CYP2C19, CYP3A4 does not play a major role in dolutegravir metabolism. 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 the metabolism and clearance a clinically significant drug-drug interaction is unlikely. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

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 does not interact with ciclesonide metabolism.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3, however, dolutegravir is not expected to inhibit these renal transporters.

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 metabolized and partially cleared through the bile and intestine. Dolutegravir is not expected to inhibit OAT3.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%), however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

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

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. Clobazam is a weak inducer and could potentially decrease dolutegravir exposure although to a limited extent.

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. Three metabolites, two glucuronides, have been identified in urine, As glucuronidation has a minor role in clofazimine elimination, an interaction with dolutegravir via this mechanism is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYP3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

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 CYP450 enzymes at clinically relevant concentrations.

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. There is little potential for an interaction with dolutegravir via modulation of, or competition for, metabolic pathways. No interaction is expected with vitamin D when 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 should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations. Medicinal products that reduce dolutegravir exposure (e.g. multivitamins) should be avoided in the presence of integrase class resistance.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. There is no evidence to suggest that Piper cubeba impacts UGTs.

Coadministration has not been studied. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. No interaction is expected with 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; simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations. Medicinal products that reduce dolutegravir exposure (e.g. multivitamins) should be avoided in the presence of integrase class resistance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolized by CYP3A4.

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 increased by 33%, 29% and 45%, respectively). No dose adjustment of daclatasvir or dolutegravir is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9 which is not affected by dolutegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapsone is mainly metabolized by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darifenacin is metabolized by CYP3A4 and CYP2D6.

Coadministration of dolutegravir (50 mg once daily) and darunavir/cobicistat (800/150 mg once daily) decreased dolutegravir Cmax, AUC, and C24 by 11%, 16% and 19%, respectively (n=9). Darunavir Cmax, AUC, and C24 decreased 21%, 13% and 18%, respectively, and cobicistat Cmax, AUC and C24h decreased by 14%, 12% and 2%, respectively. Dolutegravir and darunavir/cobicistat can be administered without dose adjustments.

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) 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 dolutegravir 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 C24 by 11%, 16% and 19%, respectively (n=9). Darunavir Cmax, AUC, and C24 decreased 21%, 13% and 18%, respectively, and cobicistat Cmax, AUC and C24h decreased by 14%, 12% and 2%, respectively. Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) increased tenofovir AUC and Cmax by 25% and 10% (n=10). No significant effects were observed on dolutegravir pharmacokinetics relative to historical controls.

Darunavir/ritonavir had no clinically significant effect on the pharmacokinetics of dolutegravir. Coadministration of darunavir/ritonavir (600/100 mg twice daily) and dolutegravir (30 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 11%, 22% and 38%, respectively. Coadministration with darunavir/ritonavir and etravirine had no significant effect on dolutegravir exposure (AUC, Cmax and Ctrough decreased by 25%, 12% and 37%, respectively). There was no effect on darunavir or ritonavir exposure. No dose adjustment is necessary.

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

Coadministration 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 does not affect CYP enzymes.

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 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 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. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Dolutegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied but based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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 CYP450 enzymes at clinically relevant concentrations.

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 does not inhibit or induce these UGTs.

Coadministration has not been studied. Disopyramide is metabolized 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.

Coadministration has not been studied and 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%).

The dolutegravir dose (50 mg) in Triumeq is insufficient when coadministered with some medications that may decrease dolutegravir concentrations. The European product label for Triumeq does not recommend coadministration with these medications. However, the US product label for Triumeq recommends that if additional dolutegravir is required, a dolutegravir 50 mg tablet, separated by 12 hours from Triumeq, should be taken.

The dolutegravir dose (50 mg) in Dovato is insufficient when coadministered with some medications that may decrease dolutegravir concentrations. An additional 50 mg tablet of dolutegravir, separated by 12 hours from Dovato (dolutegravir/lamivudine), is recommended with these medications.

The dolutegravir dose (50 mg) in Juluca may be insufficient when coadministered with some medications that may decrease dolutegravir concentrations. If additional dolutegravir is required, a dolutegravir 50 mg tablet, separated by 12 hours from Juluca could be taken.

Coadministration of dolutegravir (50 mg once daily) and doravirine (200 mg once daily) did not significantly alter doravirine exposure. Dolutegravir AUC, Cmax and Cmin were increased by 36%, 43% and 27%, respectively (n=11). These changes are not considered as clinically significant thereby supporting the coadministration of dolutegravir and doravirine.

Delstrigo (doravirine, 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 dolutegravir would be possible from a pharmacokinetic standpoint. Coadministration of dolutegravir (50 mg once daily) and doravirine (200 mg once daily) did not significantly alter doravirine exposure. Dolutegravir AUC, Cmax and Cmin were increased by 36%, 43% and 27%, respectively. These changes are not considered as clinically significant thereby supporting the coadministration of dolutegravir and doravirine. Similarly, no clinically significant interactions were observed or are anticipated with tenofovir-DF or lamivudine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.)

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No significant metabolism of doxycycline occurs and it is cleared intact by renal and biliary mechanisms.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir does not interact with these metabolic pathways. Dolutegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Dolutegravir does not interact with this metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dulaglutide is presumed to be degraded by general protein catabolism pathways. Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, interaction studies did not result in any clinically relevant effects and no dose adjustment of comedications is recommended.

Coadministration has not been studied but based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Dutasteride is mainly metabolized by CYP3A4, however, dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Dolutegravir does not interact with these metabolic pathways. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is a substrate for P-gp but dolutegravir does not inhibit or induce P-gp.

Coadministration decreases dolutegravir exposure and a dose increase of dolutegravir is recommended. Coadministration of efavirenz (600 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 39%, 57% and 75%, respectively. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of efavirenz. In treatment-naïve or INSTI-naïve patients, a dose adjustment of dolutegravir to 50 mg twice daily is recommended. Alternative combinations that do not include metabolic inducers should be considered where possible for INSTI-experienced patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance. Switching from efavirenz to dolutegravir decreased dolutegravir Ctrough by 60% and 85% in CYP2B6 normal and slow/intermediate metabolizers, respectively. CYP2B6 slow metabolizers experienced more prolonged subtherapeutic dolutegravir concentrations. When switching from efavirenz to dolutegravir, consider administering dolutegravir 50 mg twice daily for 2 weeks  in patients who are not virologically suppressed, or who have resistance to efavirenz, or in patients who are CYP2B6 slow metabolizers.

Coadministration of multiple doses of elbasvir/grazoprevir and dolutegravir had no clinically relevant effect on the pharmacokinetics of grazoprevir, elbasvir or dolutegravir. No dose adjustments are required. Coadministration of dolutegravir (50 mg single dose) and elbasvir + grazoprevir (50 + 200 mg once daily) to 12 subjects decreased elbasvir AUC, Cmax and C24 by 2%, 3% and 2%, respectively, and decreased grazoprevir AUC, Cmax and C24 by 19%, 36% and 14%, respectively. Dolutegravir AUC, Cmax and Ctrough increased by 16%, 22% and 14%, respectively.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., dolutegravir and elvitegravir) is unlikely to be of clinical benefit.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., dolutegravir and elvitegravir) is unlikely to be of clinical benefit.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Empagliflozin is mainly glucuronidated by UGTs 1A3, 1A8, 1A9 and 2B7. It is a substrate of P-gp and BCRP, and also a substrate of the renal transporter OAT3 and the hepatic transporters OATP1B1 and OATP1B3. Dolutegravir is unlikely to affect the metabolism of empagliflozin and empagliflozin is unlikely to affect dolutegravir concentrations as it does not inhibit or induce CYPs and does not inhibit UGTs. 

Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) increased tenofovir AUC and Cmax by 25% and 10% (n=10). No significant effects were observed on dolutegravir pharmacokinetics relative to historical controls. Coadministration of dolutegravir (50 mg once daily) and tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (10/200/150/150 mg) had no significant effect on the pharmacokinetics of dolutegravir and tenofovir alafenamide. The recommended dose of Descovy for HIV-1 treatment is 200/25 mg once daily.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Based on metabolism and elimination a clinically significant interaction with emtricitabine is unlikely. No clinically significant pharmacokinetic interaction was observed between tenofovir-DF and dolutegravir. Coadministration of tenofovir-DF (300 mg once daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax and Ctrough by 3% and 8%, and increased AUC by 1%. Tenofovir Cmax, AUC and Ctrough increased by 9%, 12% and 19%, respectively. Coadministration with emtricitabine has not been studied but based on metabolism and elimination no clinically significant interaction is likely. No dosage adjustment is necessary.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Entecavir is eliminated renally via glomerular filtration and active renal secretion by both organic anions and cations transporters. Dolutegravir is not expected to inhibit OATs. In vitro data indicate that dolutegravir inhibits OCT, but is unlikely to cause a clinically relevant drug interaction with entecavir.

This interaction has not been studied. Ephedrine is predominantly eliminated unchanged via the kidneys possibly via the renal transporter OCT2. In vitro data indicate that dolutegravir inhibits OCT2 and may increase the exposure of ephedrine.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Eplerenone is metabolized by CYP3A4 but dolutegravir does not inhibit or induce CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epoprostenol is rapidly hydrolyzed in the blood.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor role.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolized by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration has not been studied but is expected to decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by eslicarbazepine. Interaction studies with dolutegravir and rifampicin (a strong inducer) showed that the effect of induction on dolutegravir concentrations can be overcome by administering an additional 50 mg dose of dolutegravir. Although no dosing recommendations are provided for eslicarbazepine, the European and US product labels for dolutegravir recommend dolutegravir 50 mg twice daily in presence of carbamazepine (another anticonvulsant with inducing properties) in treatment-naive or treatment experienced, INSTI-naive patients. This dose adjustment should be maintained for approximately 2 weeks after stopping eslicarbazepine as the inducing effect may persist after discontinuation of a strong inducer. Alternatives to eslicarbazepine should be used where possible for INSTI resistant patients.

Coadministration with estradiol as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Preliminary data with estradiol administered as feminizing hormone therapy (FHT) to trans women with HIV taking FHT and integrase inhibitors (bictegravir/emtricitabine/tenofovir alafenamide, n=8; dolutegravir/abacavir/lamivudine, n=2) suggest a low probability of clinically relevant drug-drug interactions between FHT and unboosted integrase inhibitor-based ART.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolized by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and in the urine (50%).

Dolutegravir has no clinically relevant effect on the pharmacokinetics of ethinyl estradiol. Coadministration of ethinyl estradiol (0.035 mg) and dolutegravir (50 mg twice daily) decreased ethinyl estradiol Cmax by 1% and increased AUC and Ctrough by 3% and 2%, respectively. Dolutegravir had no pharmacodynamic effect on luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone. No dose adjustment of oral contraceptives is necessary when co-administered with dolutegravir. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolized in the liver with animal studies suggesting involvement of flavin-containing monooxygenases.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethosuximide is mainly metabolized by CYP3A4 and does not induce metabolizing enzymes. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etidocaine is metabolized by CYP3A4, but dolutegravir does not inhibit or induce drug metabolizing enzymes.

The effect of dolutegravir on etonogestrel exposure (administered as subdermal implant at a dose of 68 mg) was evaluated in HIV-infected Kenyan women on dolutegravir containing treatment and HIV-negative women not on antiretroviral drugs (control group). Etonogestrel exposure in the dolutegravir-containing treatment group was shown to be 19-54% higher compared to the control group. This modest increase in etonogestrel exposure is not considered to be clinically relevant. A study in Botswanan HIV-infected women with etonogestrel implants showed that all women receiving dolutegravir-based antiretroviral treatment (n=30) had etonogestrel concentrations above 90 pg/mL, the threshold for ovulation suppression.

Coadministration with etonogestrel as a combined vaginal ring (CVR) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. Dolutegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate.

Etravirine significantly reduced plasma concentrations of dolutegravir, but the effect of etravirine was mitigated by coadministration of lopinavir/ritonavir or darunavir/ritonavir, and is expected to be mitigated by atazanavir/ritonavir. The etravirine product labels and the US Prescribing Information for dolutegravir do not recommend the use of dolutegravir and etravirine without coadministration of atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. However, the European SPC for dolutegravir suggests a dose of dolutegravir of 50 mg twice daily when coadministered with etravirine without boosted protease inhibitors to patients without INSTI resistance, but recommends dolutegravir and etravirine should be administered with atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir in INSTI-resistant patients. Coadministration of etravirine (200 mg twice daily) and dolutegravir (50 mg once daily) decreased dolutegravir Cmax, AUC and Ctrough by 52%, 71% and 88%, respectively. When the same doses were coadministered in the presence of ritonavir-boosted darunavir or lopinavir, dolutegravir Cmax, AUC and Ctrough decreased by 12%, 25% and 37%, respectively, with darunavir/lopinavir and increased by 7%, 11% and 28%, respectively, with lopinavir/ritonavir. When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of etravirine.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. There is no evidence to suggest that eucalyptus impacts UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Evolocumab 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 as exenatide is cleared mainly by glomerular filtration.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Famciclovir is converted to penciclovir by aldehyde oxidase which is then eliminated in the urine, possibly by OAT1. Dolutegravir is not expected to inhibit this renal transporter.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucloxacillin is mainly eliminated renally partly by glomerular filtration and partly by active secretion via OAT1. Flucloxacillin is thought to be a weak inducer of CYP3A4 particularly at higher doses (>2-3 g daily) and could potentially decrease dolutegravir concentrations, but this is unlikely to be of clinical significance as CYP3A4 does not play a major role in dolutegravir metabolism.

Coadministration has not been studied. Fluconazole is a moderate inhibitor of CYP3A4 but a clinically significant interaction is not expected as CYP3A4 does not play a major role in dolutegravir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolized in the liver to inactive metabolites, possibly via CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide undergoes CYP3A4-mediated metabolism. Dolutegravir does not interact with flunisolide metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. There is therefore little potential for an interaction with dolutegravir via modulation of, or competition for, metabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases.

Coadministration has not been studied. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases. A pharmacokinetic interaction is unlikely with folic acid itself. However, folic acid may be administered in a multivitamin preparation which may also contain polyvalent cations. Simultaneous coadministration of a multivitamin preparation decreased dolutegravir exposure by ~33%. Dolutegravir should be administered 2 hours before or 6 hours after medications containing polyvalent cations, such as multivitamin preparations. Medicinal products that reduce dolutegravir exposure (e.g. multivitamins) should be avoided in the presence of integrase class resistance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as foscarnet is cleared mainly by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosinopril is hydrolysed by esterases in the GI mucosa and liver. Fosinopril does not inhibit or induce CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gabapentin is cleared mainly by glomerular filtration.

Coadministration has not been studied. Garlic supplements have been shown to decrease unboosted saquinavir AUC by 50% in a clinical trial and there is a case report of treatment failure due to garlic cloves (six garlic cloves three times weekly) decreasing ritonavir-boosted atazanavir trough concentrations by ~70%. Similarly, concentrations of dolutegravir could be decreased via induction of CYP3A4 and/or P-gp. Patients should be advised against the use of garlic supplements.

Coadministration has not been studied but based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for interaction. Gefitinib is metabolized by CYP3A4 and CYP2D6. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gentamicin is eliminated unchanged predominantly via glomerular filtration.

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Ethinylestradiol is mainly metabolized by hydroxylation. Dolutegravir does not inhibit or induce CYP450 enzymes at clinically relevant concentrations. Dolutegravir had no clinically relevant effect on the pharmacokinetics of ethinylestradiol when administered with a COC containing ethinylestradiol/norgestimate.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. There is no evidence to suggest that ginger inhibits or induces UGTs.

Coadministration has not been studied but may decrease dolutegravir concentrations through induction of CYP3A4 by Ginkgo biloba. The magnitude and clinical relevance of this potential interaction is difficult to predict as CYP3A4 does not play a major role in dolutegravir metabolism. No a priori dose adjustment is recommended.

Coadministration with dolutegravir alone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of dolutegravir and glecaprevir/pibrentasvir was evaluated as part of a Phase 1 study with Triumeq (abacavir/dolutegravir/lamivudine) and showed no clinically significant interaction with glecaprevir/pibrentasvir. No dose adjustment is required when glecaprevir/pibrentasvir is coadministered with dolutegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glyceryl trinitrate is metabolised by aldehyde dehydrogenase-2. Glyceryl trinitrate is not known to induce or inhibit CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycopyrronium bromide is mainly eliminated renally (active secretion via organic cation transporter) and is also partly hydroxylated via multiple CYPs. Inhibition or induction of its metabolism is unlikely to result in a significant change in exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Goldenseal has been shown to inhibit CYP3A4 in vitro but not in vivo; in addition CYP3A4 does not play a major role in dolutegravir metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Goserelin is mainly hydrolyzed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system.

Coadministration has not been studied. In vitro data indicate that extracts of hops activate PXR and induce expression of CYP3A4, CYP2B6 and MDR1 genes to a degree similar to that of St John's wort. However, a pharmacokinetic study with a standardised hop extract showed no clinically relevant effect on CYPs 2C9, 1A2, and 2D6 and suggested only minor induction of CYP3A4/5 (AUC of alprazolam, a CYP3A4/5 substrate, decreased by ~8%). Based on these results, hop extracts are unlikely to have a clinically significant effect on dolutegravir.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea undergoes metabolism via non-CYP mediated metabolism and is unlikely to affect concentrations of dolutegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Dolutegravir undergoes hepatic metabolism whereas ibalizumab, a monoclonal antibody binding to the CD4 receptor, is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies. Dose modifications of ibalizumab are not required when administered with any other antiretroviral.

Coadministration has not been studied. Ibandronic acid should be taken after an overnight fast (at least 6 hours) and before the first food or drink of the day. Medicinal products and supplements should be similarly avoided prior to taking ibandronic acid. Fasting should be continued for at least 30 minutes after taking ibandronic acid.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloprost is extensively metabolized via beta oxidation of the carboxyl side chain with only a minor role for CYP metabolism.

Coadministration has not been studied. Imatinib is primarily metabolized by CYP3A4 and to a lesser extent CYPs 1A2, 2D6, 2C9, 2C19. In vitro data indicate that imatinib inhibits CYPs 3A4, 2D6, 2C9, 2C19. A clinically significant interaction is not expected as CYP3A4 does not play a major role in dolutegravir metabolism.