Reduces Methadone Levels
At Lisbon, Susan Clarke,
David Back and others reported pharmacokinetics (blood levels) and tolerability
from a study of 11 HIV+ individuals receiving methadone and efavirenz. EFV is
both an inducer and inhibitor of cytochrome P450, the principal pathway through
which methadone is metabolized. There had been anecdotal reports that EFV
reduced methadone effectiveness but this is the first definitive PK study. 11
patients receiving stable methadone maintenance therapy (dose range 35-100 mg)
enrolled in study and started HIV treatment with EFV + 2 nucleoside analogues.
Methadone PK was determined before and after 3 weeks after starting EFV 600 mg
daily. Blood samples were obtained at times 0, 1,
2, 3, 4, 5, 6, 7, 8 and 24 hours post dosing.
9 patients complained of symptoms consistent with methadone withdrawal,
requiring a mean increase in methadone dose of 21.65% (mean increase 16 mg,
range 15-30 mg). When EFV was combined with methadone, there was a marked
decrease in the mean maximum plasma concentration of methadone from 689 (range
212-1568) to 358 (205-706) ng/ml (p=0.007).The mean AUC 0-24h for methadone also
significantly reduced in the presence of EFV from 12341 (range 3682-34147) to
5309 (2430-10349) ng.h/ml (p=0.011).
Upon examination of
graph of the reduction in methadone in all 11 patients, I observed individual
variability. Remember the methadone doses for 11 people ranged from 35 to 100
mg. One patient had about 35000 methadone AUC 0-24h (ng/ml.n) prior to starting
EFV and about 5000 after starting EFV. At the other extreme, a second person had
about 3000 AUC 0-24 prior to starting EFV and the same level after EFV. A third
person had about 12000 prior to EFV and about 2500 after EFV was added. A fourth
person had similar numbers as the third person. Four individuals appeared to
experience about a 50% reduction in methadone after adding EFV. I think it might
be helpful to measure an individualís methadone levels at the appropriate time
after they start EFV to identify their response.