Liverpool HIV Interactions

Potential Interaction

Rilpivirine (RPV)

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Rilpivirine at a dose of 25 mg once daily is unlikely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but these are unlikely to occur during coadministration with ondansetron. However, given the known QT prolongation risk associated with ondansetron, caution is recommended.

Description:

There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and medicinal products that prolong the QTc interval of the ECG. In a study of healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram (ECG). Rilpivirine at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. Rilpivirine should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes.

Edurant Summary of Product Characteristics, Janssen-Cilag Ltd, January 2019.

There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and drugs that prolong the QTc interval of the electrocardiogram. In healthy subjects, 75 mg once daily and 300 mg once daily (3 times and 12 times the dose in Edurant) have been shown to prolong the QTc interval of the electrocardiogram. Consider alternatives to rilpivirine when coadministered with a drug that is known to have a risk of torsade de pointes.

Edurant US Prescribing Information, Janssen Therapeutics, May 2019.

No Interaction Expected

Lamivudine (3TC)

Paracetamol (Acetaminophen)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolized by glucuronidation (UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15), sulfation and, to a lesser extent, by oxidation.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Paracetamol (Acetaminophen)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolized by glucuronidation (UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15), sulfation and, to a lesser extent, by oxidation.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Insulin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Insulin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Lisinopril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Lisinopril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Pregabalin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Pregabalin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Dalteparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but a clinically significant pharmacokinetic interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys.

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Dalteparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but a clinically significant pharmacokinetic interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Bupropion (Amfebutamone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bupropion is primarily metabolized by CYP2B6.

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Bupropion (Amfebutamone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bupropion is primarily metabolized by CYP2B6.

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6.

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant drug-drug interaction is unlikely as rosuvastatin is largely excreted unchanged via the faeces.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant drug-drug interaction is unlikely as rosuvastatin is largely excreted unchanged via the faeces.

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Paracetamol (Acetaminophen)

Quality of Evidence: Moderate

Summary:

Coadministration of rilpivirine (150 mg once daily) and paracetamol (500 mg single dose) increased rilpivirine Cmax, AUC and Cmin by 9%, 16% and 26%. Paracetamol Cmax and AUC decreased by 3% and 8%. No dose adjustment is needed for either drug. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The dosing recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.]

Description:

Coadministration of paracetamol (500 mg single dose) and a higher than the recommended dose of rilpivirine had no effect on paracetamol AUC or Cmax. Rilpivirine AUC and Cmax were unchanged, but Cmin increased by 26%. No dose adjustment is required.

Edurant Summary of Product Characteristics, Janssen-Cilag Ltd, January 2019.

Coadministration of rilpivirine (150 mg once daily) and paracetamol (500 mg single dose) was studied in 16 subjects. Rilpivirine Cmax, AUC and Cmin increased by 9%, 16% and 26%, respectively. Paracetamol Cmax and AUC decreased by 3% and 8%, respectively. No dose adjustment is needed for either drug.

Edurant PUS Prescribing Information, Janssen Therapeutics, May 2019.

Coadministration of rilpivirine (150 mg once daily) and paracetamol (500 mg single dose) was studied in 16 HIV-negative subjects. Rilpivirine Cmax, AUC and Cmin increased by 9%, 16% and 26%, respectively. Paracetamol Cmax and AUC decreased by 3% and 8%, respectively.
van Heeswijk RPG, et al. The effects of TMC278, a next generation non-nucleoside reverse transcriptase inhibitor, on the pharmacokinetics of acetaminophen and CYP2E1 activity in HIV-negative volunteers. 8th International Workshop on Clinical Pharmacology of HIV Therapy, Budapest, April 2007, abstract 67.

No Interaction Expected

Rilpivirine (RPV)

Abacavir (ABC)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with abacavir.

Description:

Coadministration with abacavir has not been studied. No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

Edurant Summary of Product Characteristics, Janssen-Cilag Ltd, January 2019.

No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with abacavir.

Edurant US Prescribing Information, Janssen Therapeutics, May 2019.

No Interaction Expected

Rilpivirine (RPV)

Lamivudine (3TC)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with lamivudine.

Description:

Coadministration with lamivudine has not been studied. No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

Edurant Summary of Product Characteristics, Janssen-Cilag Ltd, January 2019.

No clinically relevant drug-drug interaction is expected when rilpivirine is co-administered with lamivudine.

Edurant US Prescribing Information, Janssen Therapeutics, May 2019.

No Interaction Expected

Rilpivirine (RPV)

Bupropion (Amfebutamone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bupropion is primarily metabolized by CYP2B6.

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on the metabolism and clearance a clinically significant drug-drug interaction is unlikely as rosuvastatin is largely excreted unchanged via the faeces.

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Pregabalin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Insulin

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Lisinopril

Quality of Evidence: Very Low

Summary:

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

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Senna

Quality of Evidence: Very Low

Summary:

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant drug interactions are known.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Senna

Quality of Evidence: Very Low

Summary:

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant drug interactions are known.

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Senna

Quality of Evidence: Very Low

Summary:

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant drug interactions are known.

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Hydromorphone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Hydromorphone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7.

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Hydromorphone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7.

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Dalteparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but a clinically significant pharmacokinetic interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys.

Description:

(See Summary)

No Interaction Expected

Rilpivirine (RPV)

Vortioxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vortioxetine is mainly metabolized by CYP2D6 and to a lesser extent CYP2C9 and CYP3A4/5. Rilpivirine is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Vortioxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vortioxetine is mainly metabolized by CYP2D6 and to a lesser extent by CYP2C9 and CYP3A4/5. Abacavir does not interact with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Lamivudine (3TC)

Vortioxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vortioxetine is mainly metabolized by CYP2D6 and to a lesser extent by CYP2C9 and CYP3A4/5. Lamivudine does not interact with this metabolic pathway.

Description:

(See Summary)

No Interaction Expected

Abacavir (ABC)

Lamivudine (3TC)

Quality of Evidence: Moderate

Summary:

No significant pharmacokinetic interaction was observed in clinical studies. A high rate of virological failure and emergence of resistance reported when lamivudine was combined with tenofovir and abacavir as a once daily regimen. 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.

Description:

Clinical studies have shown that there are no clinically significant interactions between abacavir, zidovudine, and lamivudine. There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when abacavir was combined with tenofovir disoproxil fumarate and lamivudine as a once daily regimen.
Ziagen Summary of Product Characteristics, ViiV Healthcare UK Ltd, December 2018.

Fifteen HIV-infected patients were enrolled in a crossover-designed drug interaction trial evaluating single doses of abacavir (600 mg), lamivudine (150 mg), and zidovudine (300 mg) alone or in combination. Analysis showed no clinically relevant changes in the pharmacokinetics of abacavir with the addition of lamivudine or zidovudine or the combination of lamivudine and zidovudine. Lamivudine exposure (AUC decreased 15%) and zidovudine exposure (AUC increased 10%) did not show clinically relevant changes with concurrent abacavir.
Ziagen Prescribing Information, ViiV Healthcare, June 2019.

There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when lamivudine was combined with tenofovir disoproxil fumarate and abacavir as well as with tenofovir disoproxil fumarate and didanosine as a once daily regimen. Coadministration of sorbitol solution (3.2 g, 10.2 g, 13.4 g) with a single 300 mg dose of lamivudine oral solution resulted in dose-dependent decreases of 14%, 32%, and 36% in lamivudine exposure (AUC) and 28%, 52%, and 55% in the Cmax of lamivudine in adults. When possible, avoid chronic coadministration of Epivir with medicinal products containing sorbitol. Consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided.
Epivir Summary of Product Characteristics, ViiV Healthcare UK Ltd, February 2019.

Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine. Lamivudine and sorbitol solutions were coadministered to 16 healthy adult subjects in an open-label, randomized-sequence, 4-period, crossover trial. Each subject received a single 300-mg dose of lamivudine oral solution alone or coadministered with a single dose of 3.2 grams, 10.2 grams, or 13.4 grams of sorbitol in solution. Coadministration of lamivudine with sorbitol resulted in dose-dependent decreases of 20%, 39%, and 44% in the AUC(0-24), 14%, 32%, and 36% in the AUC(infinity), and 28%, 52%, and 55% in the Cmax; of lamivudine, respectively.
Epivir US Prescribing Information, ViiV Healthcare, May 2019.

The pharmacokinetics and safety of single doses of abacavir (600 mg), zidovudine (300 mg) and lamivudine (150 mg) were evaluated when given alone or with either or both of the other drugs to 13 HIV-infected subjects. Coadministration of abacavir with lamivudine (with or without zidovudine) decreased lamivudine AUC by ~15%, decreased Cmax by ~ 35% and delayed Tmax by ~1 h. While these changes are statistically significant, they are not considered to be clinically significant. There were no differences in the pharmacokinetics of abacavir when given alone, or with zidovudine or lamivudine, or with both zidovudine and lamivudine.
Single dose pharmacokinetics and safety of abacavir (1592U98), zidovudine, and lamivudine administered alone and in combination in adults with human immunodeficiency virus infection. Wang LH, et al. Antimicrob Agents Chemother, 1999, 43: 1708-1715.

The effect of sorbitol on the single dose pharmacokinetics of 3TC oral solution was evaluated in 16 HIV-negative subjects. Sorbitol had a dose-dependent effect on 3TC PK with decreases of 28%, 52%, and 55% in Cmax and decreases of 20%, 39%, and 44% in AUC when co-administered with 3.2 g, 10.2 g, and 13.4 g sorbitol, respectively.
Effect of sorbitol on 3TC PK after administration of lamivudine solution in adults. Adkinson KK, McCoig C, Wolstenholm A, et al. CROI 2017, Seattle USA, February 2017, abstract 428.

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