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Interactions with Methadone and Antiretrovirals
Antiretroviral (ARV) | Dose of ARV | Dose of Methadone | Effect on ARV Levels | Effect on Methadone Levels | Potential Clinical Effects | Mechanism of Interaction | Management |
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Abacavir66 (ABC)(Ziagen) | 600 mg BID | 40 mg QD; 90 mg QD | No significant change | Methadone 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 BID | stable 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 days | 44-100 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 days | stable 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 ARV | Dose of Methadone | Effect on ARV Levels | Effect on Methadone Levels | Potential Clinical Effects | Mechanism of Interaction | Management |
Atazanavir (ATV)(Reyataz) | 400 mg QD on d 2-15 | stable 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 BID | 55-200 mg QD (stable dose) | Not studied | R-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 days | 40-120 mg QD | No significant change | No significant change | - | - | No dose adjustment necessary
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Didanosine203 (ddI)(Videx) | 200 mg (buffered formulation) BID | - | Didanosine AUC: decreased 57%; Cmax: decreased 44% | Not studied | Decreased didanosine effects | Decreased didanosine bioavailability by methadone | Dose adjustment not established |
Didanosine84 (ddI)(Videx) | 200 mg (buffered formulation) x 1 dose | stable | Didanosine AUC: decreased 41%; Cmax: decreased 59% | Not studied | Decreased didanosine effects | Decreased didanosine bioavailability by methadone | Dose adjustment not established |
Dolutegravir641 (Tivicay) | 50 mg BID | 16-150 mg | - | No significant change | - | - | No dose adjustment necessary |
Antiretroviral (ARV) | Dose of ARV | Dose of Methadone | Effect on ARV Levels | Effect on Methadone Levels | Potential Clinical Effects | Mechanism of Interaction | Management |
Efavirenz184 (EFV)(Sustiva) | 600 mg QD over period of 60 weeks | stable 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 change | Decreased 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 studied | Methadone 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 days | 35-100 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 mg | 80-120 mg | No significant change | No 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
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Antiretroviral (ARV) | Dose of ARV | Dose of Methadone | Effect on ARV Levels | Effect on Methadone Levels | Potential Clinical Effects | Mechanism of Interaction | Management |
Fosamprenavir403 (FPV)(Lexiva) | 700 mg BID with 100 mg ritonavir BID x 14 days | 70-120 mg QD | No significant change | R-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 week | 20-60 mg QD x 1 week | No significant change | No significant change | - | - | No dose adjustment necessary
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Lamivudine202 (3TC)(Epivir) | 150 mg lamivudine/300 mg zidovudine (combination tablet) | - | Not studied | No significant effect | - | - | No dose adjustment necessary |
Lopinavir/ritonavir78 (LPV/r)(Kaletra) | 400 mg/100 mg BID x 10 days | 5 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 studied | Methadone 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 days | Stable 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 ARV | Dose of Methadone | Effect on ARV Levels | Effect on Methadone Levels | Potential Clinical Effects | Mechanism of Interaction | Management |
Nelfinavir201 (NFV)(Viracept) | 1250 mg BID x 5 days | 40-120 mg QD x 4 weeks | Cmin: increased 300% | - | Not clinically significant | Inhibition of nelfinavir metabolism by methadone | No dose adjustment necessary
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Nelfinavir199, 200 (NFV)(Viracept) | 1250 mg BID x 8 days | 10 to 40 mg QD x 1 month | - | Decreased methadone and methadone metabolite exposure | Withdrawal symptoms not observed | Induction of CYP450 3A4 by nelfinavir | Monitor and adjust methadone as indicated
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Nevirapine210 (NVP)(Viramune) | 200 mg QD x 14 days | Stable methadone dose | Not studied | Methadone 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 thereafter | stable 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 QD | Stable methadone maintenance | Not studied | Methadone AUC: decreased 46% | Decreased methadone effects (eg, methadone withdrawal; interaction observed one week into therapy | Induction 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) | unknown | stable dose | Nevirapine AUC: decreased 40% | Not reported | Decreased methadone effects | Induction 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 ARV | Dose of Methadone | Effect on ARV Levels | Effect on Methadone Levels | Potential Clinical Effects | Mechanism of Interaction | Management |
Rilpivirine567 (RPV)(Edurant) | 25 mg QD | 60-100 mg QD | No significant effect | R-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 days | Stable 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 significant | Induction of CYP450 by ritonavir and saquinavir | Monitor and adjust methadone as indicated |
Ritonavir196, 197 (RTV)(Norvir) | 400 mg BID x 7 days | 90 mg QD x 2 years | - | Methadone AUC: decreased | Decreased methadone effects (eg, methadone withdrawal) | Possible induction of CYP450 2C9, 3A4 and 2D6 by ritonavir | Monitor and adjust methadone as indicated
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Saquinavir75 (SQV)(Fortovase, Invirase) | 1000 mg BID with 100 mg ritonavir BID x 14 days | 60-120 mg QD | Saquinavir AUC: decreased 19% | Decreased methadone levels | - | - | Methadone dosage may need to be increased when coadministered with saquinavir/ritonavir
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Saquinavir463 (SQV)(Fortovase, Invirase) | 1000mg BID with ritonavir 100 mg BID | 60-120 mg QD | No significant change | R-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 ARV | Dose of Methadone | Effect on ARV Levels | Effect on Methadone Levels | Potential Clinical Effects | Mechanism of Interaction | Management |
Saquinavir195 (SQV)(Fortovase, Invirase) | 1600 mg (soft gel caps) QD with ritonavir 100 mg QD x 14 days | 35-100 mg QD x 14 days | No significant change | Unbound 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 studied | S-methadone AUC: decreased 25%; R-methadone AUC: decreased 20% | Not clinically significant | Induction 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 QD | 40-110 mg/day | Not reported | No significant change | - | - | No dose adjustment necessary |
Tenofovir disoproxil fumarate96, 188 (TDF)(Viread) | 300 mg QD on days 2-15 | stable dose (range 45-130 mg) QD | Not studied | R-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 BID | 5 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
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Zidovudine202 (AZT, ZDV)(Retrovir) | 150 mg lamivudine/300 mg zidovudine (combination tablet) | - | - | No significant effect | - | - | No dose adjustment necessary
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Zidovudine81 (AZT, ZDV)(Retrovir) | 200 mg Q4H | 30 to 90 mg QD | - | No significant change | - | - | No dose adjustment necessary
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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 |