Nevirapine + Methadone = Precautionary

Effect on Concentration

Nevirapine
No change
Applies within class?
No
Methadone
Decrease
Applies within class?
No

Pharmacologic Effects

Nevirapine
Effect
N/A
Applies within class?
No
Methadone
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 05-Jul-2018

Summary

Sources

Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone. ^

Study Design

The results of an interaction between nevirapine and methadone are based on effects seen with other NNRTIs. Eleven patients on stable methadone maintenance therapy, due to commence antiretroviral therapy (ART), participated in this study. Steady state methadone kinetic profiles were obtained on two occasions 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h post dosing. Following centrifugation, separated plasma was heated at 58 °C for 30 min to inactivate HIV and stored at −80 °C until methadone analysis by high performance liquid chromatography. Case studies of the clinical effect of nevirapine on methadone therapeutics have also been described.

Study Results

When combined with efavirenz there was a marked decrease in the maximum plasma concentration (Cmax) of methadone from 689 (range 212–1568) to 358 (range 205–706) ng ml−1, P = 0.007 : 95% confidence interval (CI) 112–549. The mean area under the methadone concentration curve 0–24 h (AUC(0,24 h)) was also significantly reduced from 12341 (range 3682–34147) to 5309 (range 2430–10349) ng ml−1 h in the presence of efavirenz, P = 0.012 : 95% CI 1921–12143. Nine patients described symptoms of methadone withdrawal and received a dose increase. Although methadone AUC(0,24 h) was reduced by over 50% following efavirenz the mean increase in methadone dose required was 22% (range 15–30 mg). In Altice’s case review, all seven patients, due to the lack of prior information regarding a significant pharmacokinetic interaction between these agents, the possibility of opiate withdrawal was not anticipated. Three patients, for whom methadone levels were available at the time of development of opiate withdrawal symptoms, had subtherapeutic methadone levels. In each case, a marked escalation in methadone dose was required to counteract the development of withdrawal symptoms and allow continuation of antiretroviral therapy. Three patients continued nevirapine with methadone administered at an increased dose; however, four chose to discontinue nevirapine.

Study Conclusions

The inclusion of the NNRTI efavirenz in once daily ART for HIV patients with a history of IDU receiving methadone maintenance results in a significant reduction in methadone plasma concentrations mediated by enzyme induction. It is important to distinguish efavirenz neurological effects which were observed between days 1–5 of therapy from symptoms of methadone withdrawal which occurred from day 8 onwards. The dose of methadone was adjusted by increments of 10 mg to counteract the efavirenz inducing effect.

References

Altice FL, Friedland GH, Cooney EL. Nevirapine induced opiate withdrawal among injection drug users with hiv infection receiving methadone. Aids. 1999; 8: 957-962.