How do efavirenz and nevirapine affect methadone levels?

Efavirenz and nevirapine are non-nucleoside reverse transcriptase inhibitors (NNRTIs) used primarily in the treatment of HIV. One significant aspect of their pharmacological profile is their interaction with the CYP450 enzyme system, particularly CYP3A4. Both efavirenz and nevirapine act as inducers of CYP3A4.

CYP3A4 is an enzyme involved in the metabolism of many drugs, including methadone. When efavirenz and nevirapine induce CYP3A4, they increase the enzyme's activity, which can enhance the metabolism of drugs that are metabolized by this pathway. As a result, when methadone is taken concurrently with efavirenz or nevirapine, the increased metabolism can lead to lower serum levels of methadone. This effect can ultimately result in a decreased therapeutic effect of methadone, potentially leading to withdrawal symptoms or reduced effectiveness in managing opioid dependence.

Understanding these interactions is critical for the effective management of patients who are on methadone treatment and require antiretroviral therapy for HIV. Adjusting the dosage of methadone may be necessary to counteract the effect of CYP3A4 induction by these NNRT