and pediatric populations who have a history of seizures. Drug interactions Efavirenz is broken down in the liver by enzymes that belong to the cytochrome P450 system, which include both CYP2B6 and CYP3A4. Efavirenz is a substrate of these enzymes and can decrease the metabolism of other drugs that require the same enzymes. However, efavirenz also induces these enzymes, which means the enzyme activity is enhanced and the metabolism of other drugs broken down by CYP2B6 and CYP3A4 can be increased. People who are taking both efavirenz and other drugs metabolized by the same enzymes might need the dose of their drugs to be increased or decreased. One group of drugs that efavirenz affects is protease inhibitors, which are used for HIV/AIDS. Efavirenz will lower the blood levels of most protease inhibitors, including amprenavir, atazanavir, and indinavir. At lowered levels, protease inhibitors may not be effective in people taking both drugs, which means the virus that causes HIV/AIDS won't be stopped from replicating and may become resistant to the protease inhibitor. Efavirenz also affects antifungal drugs, which are used for fungal infections such as urinary tract infections. Similar to the effect seen with protease inhibitors, efavirenz lowers the blood levels of antifungal drugs like voriconazole, itraconazole, ketoconazole, and posaconazole. As a result of lowered levels, antifungal drugs may not be effective in people taking both drugs, which means that the fungi that cause the infection may become resistant to the antifungal. Mechanism of action Anti-HIV effects Efavirenz falls in the NNRTI class of antiretrovirals. Both nucleoside and non-nucleoside RTIs inhibit the same target, the reverse transcriptase enzyme, an essential viral enzyme which transcribes viral RNA into DNA. Unlike nucleoside RTIs, which bind at the enzyme's active site, NNRTIs act allosterically by binding to a distinct site away from the active site known as the NNRTI pocket. Efavirenz is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class. As most NNRTIs bind within the same pocket, viral strains which are resistant to efavirenz are usually also resistant to the other NNRTIs, nevirapine and delavirdine. The most common mutation observed after efavirenz treatment is K103N, which is also observed with other NNRTIs. Nucleoside reverse-transcriptase inhibitors (NRTIs) and efavirenz have different binding targets, so cross-resistance is unlikely; the same is true with regard to efavirenz and protease inhibitors.