The renal excretion of lamivudine may be inhibited by other drugs mainly eliminated by active renal secretion, for example trimethoprim. Usual prophylactic doses of trimethoprim are unlikely to necessitate reductions in lamivudine dosage unless the patient has renal impairment, but the co-administration of lamivudine with the high doses of trimethoprim (as co-trimoxazole) used in pneumocystis pneumonia and toxoplasmosis should be avoided. Although there is usually no clinically significant interaction with zidovudine, severe anaemia has occasionally been reported in patients given lamivudine with zidovudine.
Lamivudine may antagonize the antiviral action of zalcitabine and the two drugs should not be used together. Once daily triple nucleoside regimens of lamivudine and tenofovir with either abacavir or didanosine are associated with a high level of treatment failure and of emergence of resistance, and should be avoided.