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Database of Antiretroviral Drug Interactions

Interactions with Methadone and Antiretrovirals

Antiretroviral (ARV)Dose of ARVDose of MethadoneEffect on ARV LevelsEffect on Methadone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Abacavir66
(ABC)(Ziagen)
600 mg BID40 mg QD; 90 mg QDNo significant changeMethadone clearance: increased 22%Decreased methadone effects (eg, withdrawal)-

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Amprenavir182
(APV)(Agenerase)
1200 mg BIDstable daily dose-R-methadone AUC: no significant change; Cmax: decreased 25%; Cmin: decreased 21%;S-methadone AUC: decreased 40%; Cmax: decreased 48%; Cmin: decreased 52%--

No dose adjustment necessary

Amprenavir189
(APV)(Agenerase)
1200 mg BID--Methadone concentration: decreased 35%Decreased methadone effects (eg, withdrawal)Possible induction of CYP450 3A4 by amprenavir

Monitor for signs and symptoms of methadone withdrawal; Some patients may need an increase in the methadone dose

Amprenavir60
(APV)(Agenerase)
1200 mg BID x 10 days44-100 mg QD for more than 30 days-R-methadone AUC: no significant change; Cmax: decreased 25%; Cmin: decreased 21%; S-methadone AUC: decreased 40%; Cmax: decreased 48%; Cmin: decreased 53%Decreased methadone effects (eg, withdrawal)Induction of CYP450 3A4 by amprenavir

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Amprenavir182
(APV)(Agenerase)
1200 mg BID x 10 daysstable dose-R-methadone AUC: no significant change; Cmax: decreased 25%; Cmin: decreased 21%; S-methadone AUC: decreased 40%; Cmax: decreased 48%; Cmin: decreased 52%Decreased methadone effects (eg, withdrawal)Possible induction of CYP450 3A4 by amprenavir

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Antiretroviral (ARV)Dose of ARVDose of MethadoneEffect on ARV LevelsEffect on Methadone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Atazanavir
(ATV)(Reyataz)
400 mg QD on d 2-15stable dose on d 1-15-Total methadone Cmax: decresed 15%--

No dose adjustment necessary

Darunavir543, 161, 181
(DRV)(Prezista)
600 mg BID with ritonavir 100 mg BID55-200 mg QD (stable dose)Not studiedR-methadone AUC: decreased 16%; Cmax: decreased 24%; S-methadone AUC: decreased 36%; Cmax: decreased 44%; Cmin: decreased 40%May decrease methadone effects (eg, withdrawal)-

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Delavirdine204
(DLV)(Rescriptor)
600 mg BID x 5 days40-120 mg QDNo significant changeNo significant change- -

No dose adjustment necessary

Didanosine203
(ddI)(Videx)
200 mg (buffered formulation) BID-Didanosine AUC: decreased 57%; Cmax: decreased 44%Not studiedDecreased didanosine effectsDecreased didanosine bioavailability by methadone

Dose adjustment not established

Didanosine84
(ddI)(Videx)
200 mg (buffered formulation) x 1 dosestableDidanosine AUC: decreased 41%; Cmax: decreased 59%Not studiedDecreased didanosine effectsDecreased didanosine bioavailability by methadone

Dose adjustment not established

Dolutegravir641
(Tivicay)
50 mg BID16-150 mg-No significant change --

No dose adjustment necessary

Antiretroviral (ARV)Dose of ARVDose of MethadoneEffect on ARV LevelsEffect on Methadone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Efavirenz184
(EFV)(Sustiva)
600 mg QD over period of 60 weeksstable dose over period of 60 weeks-Methadone AUC: decreased 39%; Cmax: decreased 33%; Cmin: decreased 44%EDDP (methadone metabolite) AUC: decreased 14.5%; Cmax: no significant change; Cmin: no significant changeDecreased methadone effects (eg, withdrawal)Induction of methadone metabolism by efavirenz

Study patients required mean dose increase of 30% over period of 60 weeks

Efavirenz205, 209
(EFV)(Sustiva)
600 mg QD x 14 days-Not studiedMethadone AUC: decreased 57%; Cmax: decreased 48%Decreased methadone effects (eg, withdrawal)Induction of CYP450 3A4 by efavirenz

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Efavirenz90
(EFV)(Sustiva)
600 mg x 14-21 days35-100 mg QD-Methadone AUC: decreased 52%; Cmax: decreased 45%Decreased methadone effects (eg, withdrawal)Induction of CYP450 3A4 by efavirenz

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Elvitegravir/cobicistat625
(Genvoya, Stribild)
150 mg/150 mg80-120 mgNo significant changeNo significant change--

No dose adjustment necessary

Elvitegravir/ritonavir-boosted protease inhibitor727
-- No effect expected Methadone AUC decreased 19-53% when co-administered with ritonavir-boosted protease inhibitors. Potential decreased methadone efficacy-

Monitor pain control and signs of opioid withdrawl. Dose adjust accordingly.

Etravirine405
(ETR)(Intelence)
-60-130 mg QD-R-methadone: no significant effect; S-methadone: no significant effect--

No dose adjustment necessary

Antiretroviral (ARV)Dose of ARVDose of MethadoneEffect on ARV LevelsEffect on Methadone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Fosamprenavir403
(FPV)(Lexiva)
700 mg BID with 100 mg ritonavir BID x 14 days70-120 mg QDNo significant changeR-methadone AUC: decreased 18%; Cmax: decreased 21% S-methadone AUC: decreased 43%; Cmax: decreased 43%; Cmin: decreased 41%-Possible displacement of methadone of plasma binding proteins

No dose adjustment typically necessary. Consider monitoring for opioid withdrawal and adjust methadone dose as clinically indicated.

Indinavir193, 16
(IDV)(Crixivan)
800 mg Q8H x 1 week20-60 mg QD x 1 weekNo significant changeNo significant change- -

No dose adjustment necessary

Lamivudine202
(3TC)(Epivir)
150 mg lamivudine/300 mg zidovudine (combination tablet)-Not studiedNo significant effect--

No dose adjustment necessary

Lopinavir/ritonavir78
(LPV/r)(Kaletra)
400 mg/100 mg BID x 10 days5 mg x 1 dose-Methadone AUC: decreased 53%; Cmax: decreased 45%Decreased methadone effects (eg, withdrawal)Possible induction of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust methadone as indicated

Lopinavir/ritonavir192
(LPV/r)(Kaletra)
400/100 mg BID x 14 days-Not studiedMethadone AUC: decreased 36%; Cmax: decreased 44%Decreased methadone effects (eg, withdrawal)-

Monitor and adjust methadone as indicated

Lopinavir/ritonavir187
(LPV/r)(Kaletra)
400/100 mg BID x 7 daysStable methadone dose-Methadone AUC: decreased 26%; Cmax: decreased 28%; Cmin: decreased 28%Decreased methadone effects (eg, withdrawal)Possible induction of methadone metabolism by lopinavir/ritonavir

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Antiretroviral (ARV)Dose of ARVDose of MethadoneEffect on ARV LevelsEffect on Methadone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Nelfinavir201
(NFV)(Viracept)
1250 mg BID x 5 days40-120 mg QD x 4 weeksCmin: increased 300%- Not clinically significantInhibition of nelfinavir metabolism by methadone

No dose adjustment necessary

Nelfinavir199, 200
(NFV)(Viracept)
1250 mg BID x 8 days10 to 40 mg QD x 1 month- Decreased methadone and methadone metabolite exposureWithdrawal symptoms not observedInduction of CYP450 3A4 by nelfinavir

Monitor and adjust methadone as indicated

Nevirapine210
(NVP)(Viramune)
200 mg QD x 14 daysStable methadone doseNot studiedMethadone AUC: decreased 51%; Cmax: decreased 36%Decreased methadone effects (eg, methadone withdrawal)Induction of CYP450 3A4 by nevirapine

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Nevirapine183
(NVP)(Viramune)
200 mg QD x 14 days, then 200 mg BID thereafterstable dose: racemic methadone 35-220 mg daily; (R)-methadone 45-115 mg daily-racemic methadone AUC: decreased 37%; (R)-methadone AUC: decreased 44%Decreased methadone effects (eg, withdrawal)Possible induction of CYP450 2B6 by nevirapine

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Nevirapine207, 208, 209, 95
(NVP)(Viramune)
200-400 mg QDStable methadone maintenanceNot studiedMethadone AUC: decreased 46%Decreased methadone effects (eg, methadone withdrawal; interaction observed one week into therapyInduction of CYP450 3A4 by nevirapine

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Nevirapine186
(NVP)(Viramune)
unknownstable doseNevirapine AUC: decreased 40%Not reportedDecreased methadone effectsInduction of CYP450 3A4 by nevirapine

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Antiretroviral (ARV)Dose of ARVDose of MethadoneEffect on ARV LevelsEffect on Methadone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Rilpivirine567
(RPV)(Edurant)
25 mg QD60-100 mg QDNo significant effectR-methadone AUC: decreased 16%; Cmin: decreased 22%; S-methadone AUC: decreased 16%; Cmin: decreased 21%;Potentially decreased methadone effects (eg, withdrawal)-

Monitor for signs and symptoms of methadone withdrawal; Some patients may need an increase in the methadone dose

Ritonavir187
(RTV)(Norvir)
100 mg BID x 7 daysStable methadone dose-No significant effect--

Monitor and adjust methadone as indicated

Ritonavir198
(RTV)(Norvir)
400 mg BID combined with 400 mg BID saquinavir--S-methadone AUC: decreased 25%; R-methadone AUC: decreased 20%Not clinically significantInduction of CYP450 by ritonavir and saquinavir

Monitor and adjust methadone as indicated

Ritonavir196, 197
(RTV)(Norvir)
400 mg BID x 7 days90 mg QD x 2 years- Methadone AUC: decreasedDecreased methadone effects (eg, methadone withdrawal)Possible induction of CYP450 2C9, 3A4 and 2D6 by ritonavir

Monitor and adjust methadone as indicated

Saquinavir75
(SQV)(Fortovase, Invirase)
1000 mg BID with 100 mg ritonavir BID x 14 days60-120 mg QDSaquinavir AUC: decreased 19%Decreased methadone levels- -

Methadone dosage may need to be increased when coadministered with saquinavir/ritonavir

Saquinavir463
(SQV)(Fortovase, Invirase)
1000mg BID with ritonavir 100 mg BID60-120 mg QDNo significant changeR-methadone AUC: decreased 19%; S-methadone AUC: decreased 21%Decreased methadone effects (e.g. withdrawal)-

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Antiretroviral (ARV)Dose of ARVDose of MethadoneEffect on ARV LevelsEffect on Methadone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Saquinavir195
(SQV)(Fortovase, Invirase)
1600 mg (soft gel caps) QD with ritonavir 100 mg QD x 14 days35-100 mg QD x 14 daysNo significant changeUnbound R-methadone GMR: decreased 8%; alpha-1-acid glycoprotein GMR: increased 14%-Reduction in unbound R-methadone mediated by increased alpha1-acid glycoprotein

No dose adjustment necessary

Saquinavir198
(SQV)(Fortovase, Invirase)
400 mg BID combined with 400 mg BID ritonavir-Not studiedS-methadone AUC: decreased 25%; R-methadone AUC: decreased 20%Not clinically significantInduction of CYP450 by saquinavir/ritonavir

Monitor and adjust methadone as indicated

Stavudine203
(d4T)(Zerit)
40 mg BID-Stavudine AUC: decreased 23%; Cmax: decreased 44%--Decreased stavudine bioavailability

No dose adjustment necessary

Tenofovir disoproxil fumarate185
(TDF)(Viread)
300 mg QD40-110 mg/dayNot reportedNo significant change--

No dose adjustment necessary

Tenofovir disoproxil fumarate96, 188
(TDF)(Viread)
300 mg QD on days 2-15stable dose (range 45-130 mg) QDNot studiedR-methadone: no significant change;S-methadone: no significant change;total methadone: no significant change--

No dose adjustment necessary

Tipranavir154
(TPV)(Aptivus)
500 mg BID with 200 mg ritonavir BID5 mg x 1-Methadone AUC: decreased 53%; Cmax: decreased 55%; Cmin: decreased 50%; R-methadone AUC: decreased 48%; Cmax: decreased 46%; S-methadone AUC: decreased 63%; Cmax: decreased 62%Decreased methadone effects (eg, withdrawal)Induction of CYP450 by tipranavir/ritonavir

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Zidovudine202
(AZT, ZDV)(Retrovir)
150 mg lamivudine/300 mg zidovudine (combination tablet)- - No significant effect- -

No dose adjustment necessary

Zidovudine81
(AZT, ZDV)(Retrovir)
200 mg Q4H30 to 90 mg QD- No significant change- -

No dose adjustment necessary

Zidovudine191
(AZT, ZDV)(Retrovir)
oral and IV-Zidovudine AUC: increased 29% (oral zidovudine); AUC: increased 41% (IV zidovudine); clearance: decreased 26%No significant effect--

No dose adjustment necessary

"-" indicates that there are no data available
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