Tenvir-L Drug Interactions

Interaction studies have only been performed in adults.
Based on the results of in vitro experiments and the known elimination pathways of lamivudine and tenofovir, the potential for CYP450-mediated interactions with other medicinal products is low.
Interactions relevant to lamivudine: Co-administration with trimethoprim/sulfamethoxazole 160 mg/800 mg results in a 40% increase in lamivudine exposure, because of the trimethoprim component; the sulfamethoxazole component did not interact. However, unless the patient has renal impairment, no dose adjustment of lamivudine/tenofovir disoproxil fumarate is necessary. Lamivudine has no effect on the pharmacokinetics of trimethoprim or sulfamethoxazole. When concomitant administration is warranted, patients should be monitored clinically. Co-administration of lamivudine with high doses of co-trimoxazole for the treatment of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis should be avoided.
The possibility of interactions with other medicinal products administered concurrently should be considered, particularly when the main route of elimination is active renal secretion via the organic cationic transport system e.g. trimethoprim. Other medicinal products (e.g. ranitidine, cimetidine) are eliminated only in part by this mechanism and were shown not to interact with lamivudine. The nucleoside analogues (e.g. didanosine) like zidovudine, are not eliminated by this mechanism and are unlikely to interact with lamivudine.
A modest increase in Cmax (28 %) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) is not significantly altered. Zidovudine has no effect on the pharmacokinetics of lamivudine (see Pharmacology: Pharmacokinetics under Actions).
Due to similarities, Lamivudine/Tenofovir Disoproxil Fumarate 300 mg/300 mg Tablets should not be administered concomitantly with other cytidine analogues, such as emtricitabine. Moreover, Lamivudine/Tenofovir Disoproxil Fumarate 300 mg/300 mg Tablets should not be taken with any other medicinal products containing lamivudine (see Precautions).
In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting. Some clinical findings also support a possible interaction between lamivudine and cladribine. Therefore, the concomitant use of lamivudine with cladribine is not recommended (see Precautions).
Interactions relevant to tenofovir: Didanosine: Co-administration of tenofovir disoproxil and didanosine is not recommended (see Precautions and Table 2).
Renally eliminated medicinal products: Since tenofovir is primarily eliminated by the kidneys, coadministration of tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion via transport proteins hOAT 1, hOAT 3 or MRP 4 (e.g. cidofovir) may increase serum concentrations of tenofovir, or the co-administered medicinal products, or both.
Tenofovir disoproxil should be avoided with concurrent use of a nephrotoxic medicinal product. Some examples include, but are not limited to, aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2 (see Precautions).
Given that tacrolimus can affect renal function, close monitoring is recommended when it is coadministered with tenofovir disoproxil.
Tenofovir disoproxil should not be administered concomitantly with adefovir dipivoxil.
Other interactions: Interactions between Lamivudine/Tenofovir Disoproxil Fumarate 300 mg/300 mg Tablets and HIV protease inhibitors, as well as antiviral agents other than protease inhibitors, are listed as follows (increased exposure is indicated as "↑", decreased exposure as "↓", no change as "↔"). (See Table 2.)

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Other medicinal products: There were no clinically significant pharmacokinetic interactions when Lamivudine/Tenofovir Disoproxil Fumarate 300 mg/300 mg Tablets is co-administered with indinavir, efavirenz, saquinavir (ritonavir-boosted), methadone, ribavirin, rifampicin, tacrolimus, or the hormonal contraceptive norgestimate/ethinylestradiol.
Food effect: Food has no influence on the absorption of lamivudine and enhances the bioavailability of tenofovir disoproxil (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).