Interaction Checker
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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