Specific interaction studies have not been performed with efavirenz and NRTIs other than lamivudine, zidovudine, and tenofovir disoproxil fumarate. Clinically significant interactions are not expected since the NRTIs are metabolised via a different route than efavirenz and would be unlikely to compete for the same metabolic enzymes and elimination pathways. No dosage adjustment is necessary for either medicinal product. 

Coadministration of tenofovir-DF (300 mg once daily) and efavirenz (600 mg once daily for 14 days) to 29 subjects resulted in no change in Cmax, AUC or Cmin of either tenofovir or efavirenz. No dosage adjustment is recommended when SUSTIVA is given with emtricitabine or tenofovir disoproxil fumarate.

There were no clinically significant pharmacokinetic interactions when tenofovir disoproxil fumarate was coadministered with efavirenz.

No clinically significant drug interactions hace been observed between tenofovir-DF and efavirenz.

The interaction between tenofovir and efavirenz was assessed in TDM samples from groups of HIV+ patients receiving efavirenz (600 mg once daily) alone or with tenofovir (300 mg once daily). Samples were collected 0.5-23.9 h post dose in the control group (n=118) and the tenofovir group (n=126). There was no significant difference between the groups for the time post dose or efavirenz concentrations (2.34 µg/ml vs 2.22 µg/ml, control vs plus tenofovir).

Nine cases have been reported of patients stable on efavirenz therapy who developed neuropsychiatric disturbances following the introduction of tenofovir to their antiretroviral regimens. The patients had been stable on efavirenz-containing regimens for a median duration of 31 months (range 5-58) during which no efavirenz related CNS effects were reported. Moderate to severe neuropsychiatric events occurred within 48 h of starting tenofovir in 5 patients, with symptoms developing in the remaining 4 patients after 2 weeks to 24 months after initiation of tenofovir. Treatment was changed in 6/9 patients; 3 switched from tenofovir to nevirapine, 2 to from tenofovir to zidovudine and one discontinued treatment. All 6 patients exhibited marked improvement in CNS intolerance. Of the 3 patients who remained on efavirenz and tenofovir, one had spontaneous progressive improvement within 2 weeks, but two had chronic persistent sleeping disorders. Efavirenz plasma concentrations were available for 2 patients before tenofovir (1.35 and 2.09 µg/ml) and for 4 patients on tenofovir (1.30-1.95 µg/ml). The neuropsychiatric disorders could be either a consequence of an unexplained interaction between efavirenz and tenofovir, or an infrequent tenofovir-related side effect. Further studies are required to evaluate precisely the incidence of these symptoms, including the assessment of efavirenz binding sites or metabolites.