Appendix XI: Opioid Medication Interactions

Updated December 2011

Table 1: Interactions Between HIV-Related Medications and Medications Used in the Treatment of Opioid (Heroin and Prescription Opioid) Addiction
	Methadone		Buprenorphine
Medication	Effect on Methadone	Effect on Medication	Effect on Buprenorphine	Effect on Medication
NRTI
Abacavir (ABC)	22% ↑ Methadone clearance, but dose adjustment not needed	↑ Time to peak concentration, 34% ↓ Peak concentration	Unknown, but interaction unlikely	Unknown, but interaction unlikely
Didanosine (ddI)	None reported	↓ ddI AUC by 57% (with buffered formulation). Use ddI EC with methadone co-administration.	No significant change	No significant change
Emtricitabine (FTC)	Not studied, but interaction unlikely	Not studied, but interaction unlikely	Unknown, but interaction unlikely	Unknown, but interaction unlikely
Lamivudine (3TC)	None	None	Unknown, but interaction unlikely	Unknown, but interaction unlikely
Stavudine (d4T)	None	↓ d4T AUC by 23%. Unlikely to be significant; use standard dose.	Unknown, but interaction unlikely	Unknown, but interaction unlikely
Tenofovir (TDF)	None reported	None	Unknown, but interaction unlikely	Unknown, but interaction unlikely
Zidovudine (ZDV)	None	ZDV AUC ↑ 29-43%. Monitor for ZDV adverse reactions.	No significant change	No significant change
NNRTI
Efavirenz (EFV)	↓ Methadone levels by 52%; may need to ↑ methadone dose to prevent heroin relapse	Not reported, but unlikely to affect EFV	↓ Buprenorphine AUC 50%; monitor for withdrawal	Not affected
Etravirine (ETR)	No significant change in active R-methadone	ETR PK parameters comparable to historical control	No data. May ↓ buprenorphine serum concentration. Use standard dose with monitoring	No data; ETR unlikely to be affected
Nevirapine (NVP)	↓ Methadone AUC by 41%; may need to ↑ methadone dose to prevent heroin relapse	No significant change	No significant change	No significant change
Rilpivirine (RPV)	Methadone AUC ↓ by 26%. Monitor for withdrawal symptoms	No data	No data; interaction unlikely	No data; RPV unlikely to be affected
PI
Atazanavir (ATV)	Not affected with unboosted ATV. With ATV/r, ↓ R-methadone levels 16-18%. Monitor for withdrawal with ATV/r.	Not measured	With ATV and ATV/r co-administration, buprenorphine AUC ↑ 92% and 67%. Some patients experienced ↑ sedation.	Not affected; Do not co-administer buprenorphine with unboosted ATV
Darunavir/ritonavir (DRV/r)	↓ AUC 24h 16%, symptoms associated with opiate withdrawal observed in some patients. May need to ↑ dose	None	Potential ↑ buprenorphine activity	No data, but change in DRV not expected
Fosamprenavir (FPV)	With APV, R-methadone Cmin ↓ 21%; no significant change in AUC (18%). No change in unbound methadone. No withdrawal symptoms observed. Monitor and titrate methadone as indicated	Not measured	Potential ↑ buprenorphine activity	No data, but change in FPV not expected
Indinavir (IDV)	No change	No change	Potential ↑ buprenorphine activity	No data, but change in IDV not expected
Lopinavir/ritonavir (LPV/r)	↓ Methadone AUC 26-53%. Conflicting data on withdrawal symptoms – monitor for need to ↑ methadone dose	Not reported	No significant change	No significant change
Nelfinavir (NFV)	↓ Methadone AUC 40%; may require ↑ in methadone dose	None	No significant change	No significant change
Ritonavir (RTV)	No significant change	None reported	Potential ↑ buprenorphine activity	No data, but change in RTV not expected
Saquinavir/ritonavir (SQV/r)	↓ Methadone R-isomer AUC 19% (studied with SQV/r 1000/1000 mg BID); No withdrawal symptoms observed. Monitor for need to ↑ methadone dose	None reported	Potential ↑ buprenorphine activity	No data, but change in SQV not expected
Tipranavir/ritonavir (TPV/r)	↓ Methadone AUC 48%; may require ↑ in methadone dose	None	Buprenorphine AUC not affected, but ↓ norbuprenorphine (active metabolite) AUC ~80%. No withdrawal symptoms observed.	Compared to historical control, TPV AUC ↓ 26%; monitor for antiviral efficacy
FI
Enfuvirtide (T-20)	Not studied; interaction unlikely	Not studied; interaction unlikely	No data; interaction unlikely	No data; interaction unlikely
CCR5 Co-receptor Antagonist
Maraviroc (MVC)	Not studied; interaction unlikely	Not studied; interaction unlikely	No data; interaction unlikely	No data; interaction unlikely
Integrase Inhibitor
Raltegravir (RAL)	Not studied; interaction unlikely	Not studied; interaction unlikely	No data; interaction unlikely	No data; interaction unlikely
Other common medications used in the treatment of HIV-infected persons
Carbamazepine	↓ Methadone concentrations; consider using valproic acid or levetiracetam as an alternative	None reported	May ↓ buprenorphine activity	No data but change of carbamazepine unlikely
Fluconazole	↑ Methadone concentrations by ~30%; monitor for symptoms of opioid toxicity	None reported	May ↑ buprenorphine activity	No data but change of fluconazole unlikely
Phenobarbital	↓ Methadone concentrations, often sharply; consider using valproic acid or levetiracetam as an alternative	None reported	May ↓ buprenorphine activity	No data but change of phenobarbital unlikely
Phenytoin	↓ Methadone concentrations, often sharply; consider using valproic acid or levetiracetam as an alternative	None reported	May ↓ buprenorphine activity	No data but change of phenytoin unlikely
Rifabutin	No effect on methadone	None reported	May ↓ buprenorphine activity	No data but change of rifabutin unlikely
Rifampin	↓ Methadone concentrations 33-68%; ↑ methadone dose	None reported	May ↓ buprenorphine activity	No data but change of rifampin unlikely