3TC Drug Interactions





Zuellig Pharma
Full Prescribing Info
Drug Interactions
The likelihood of interactions is low due to limited metabolism and plasma protein binding and almost complete renal elimination of unchanged lamivudine.
Lamivudine is predominantly eliminated by active organic cationic secretion. The possibility of interactions with other medicinal products administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system e.g. trimethoprim. Other active substances (e.g. ranitidine, cimetidine) are eliminated only in part by this mechanism and were shown not to interact with lamivudine.
Active substances shown to be predominately excreted either via the active organic anionic pathway, or by glomerular filtration are unlikely to yield clinically significant interactions with lamivudine.
Effect of lamivudine on the pharmacokinetics of other agents: In vitro, lamivudine demonstrates no or weak inhibition of the drug transporters organic anion transporter 1B1 (OATP1B1), OATP1B3, breast cancer resistance protein (BCRP) or P-glycoprotein (Pgp), multidrug and toxin extrusion protein 1 (MATE1), MATE2-K or organic cation transporter 3 (OCT3). 3TC is therefore not expected to affect the plasma concentrations of drugs that are substrates of these drug transporters.
Lamivudine is an inhibitor of OCT1 and OCT2 in vitro with IC50 values of 17 and 33 uM, respectively, however lamivudine has low potential to affect the plasma concentrations of OCT1 and OCT2 substrates at therapeutic drug exposures (up to 300 mg).
Effect of other agents on the pharmacokinetics of lamivudine: Lamivudine is a substrate of MATE1, MATE2-K and OCT2 in vitro. Trimethoprim (an inhibitor of these drug transporters) has been shown to increase lamivudine plasma concentrations, however this interaction is not considered clinically significant as no dose adjustment of 3TC is needed.
Lamivudine is a substrate of the hepatic uptake transporter OCT1. As hepatic elimination plays a minor role in the clearance of lamivudine, drug interactions due to inhibition of OCT1 are unlikely to be of clinical significance.
Lamivudine is a substrate of Pgp and BCRP, however due to its high bioavailability it is unlikely that these transporters play a significant role in the absorption of lamivudine. Therefore co-administration of drugs that are inhibitors of these efflux transporters is unlikely to affect the disposition and elimination of lamivudine.
Interactions relevant to lamivudine: Sorbitol: 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 use of 3TC with sorbitol-containing medicines or consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided (see Precautions).
Zidovudine: A modest increase in Cmax (28%) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) was not significantly altered. Zidovudine had no effect on the pharmacokinetics of lamivudine (see Pharmacology: Pharmacokinetics under Actions).
Trimethoprim/sulphamethoxazole: Administration of trimethoprim/sulphamethoxazole 160 mg/800 mg (co-trimoxazole) causes a 40% increase in lamivudine exposure because of the trimethoprim component. However, unless the patient has renal impairment, no dosage adjustment of 3TC is necessary (see Dosage & Administration). Lamivudine has no effect on the pharmacokinetics of trimethoprim or sulphamethoxazole. The effect of co-administration of 3TC with higher doses of co-trimoxazole for the treatment of Pneumocystis jiroveci pneumonia and toxoplasmosis has not been studied.
Emtricitabine: 3TC may inhibit the intracellular phosphorylation of emtricitabine when the two medicinal products are used concurrently. Additionally, the mechanism of viral resistance for both 3TC and emtricitabine is mediated via mutation of the same viral reverse transcriptase gene (M184V) and therefore the therapeutic efficacy of these drugs in combination therapy may be limited. 3TC is not recommended for use in combination with emtricitabine or emtricitabine-containing fixed dose combinations.
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