Interactions with Methadone

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Database of Antiretroviral Drug Interactions

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
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
Darunavir^{543, 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
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
Efavirenz^{205, 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
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.
Indinavir^{193, 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
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
Nelfinavir^{199, 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
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
Nevirapine^{207, 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
Ritonavir^{196, 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
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
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 fumarate^{96, 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
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 Q4H	30 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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