SUBSTANCE USE

Appendix A: Drug-Drug Interactions Between ARVs and Recreational Drugs

February 2009

Drug Route of Elimination Effect When Combined with ARVs
Alcohol Metabolized by alcohol dehydrogenase
  • ↑ ABC AUC 41%
  • Clinical significance likely minimal
Amphetamines Metabolized by CYP2D6 Toxicity may be potentiated by ritonavir (low- or full-dose)
Barbituates Several are metabolized by CYP3A4 and induce CYP3A4
  • May ↓ PIs, NNRTIs, MVC, and RAL.
  • Avoid co-administration or use with close monitoring.
Benzodiazepines Several are metabolized by CYP3A4 (midazolam, triazolam)
  • Oral midazolam and triazolam are contraindicated with PIs, EFV, and DLV.  
  • IV midazolam may be co-administered with very close monitoring.
  • Consider alternative benzodiazepines (lorazepam, oxazepam, or temazepamMinor metabolism by CYP3A4 to hepatotoxic metabolite) with ARV therapy co-administration.
Cocaine Minor metabolism by CYP3A4 to hepatotoxic metabolite None known
Gamma hydroxybutyrate (GHB) Metabolized by CYP2D6; eliminated via first pass metabolism RTV and other boosted PIs may precipitate life-threatening toxicity when GHB used concurrently
Heroin Metabolized to morphine, then to morphine-6-glucuronide via glucuronidation None known
Ketamine Metabolized via CYP2B6, 3A4, and 2C9 PIs, DLV, and ETR may significantly ↑ ketamine serum concentrations
Marijuana Metabolized via hydroxylation, some involvement of CYP3A4, 2C9, and 2C6 Effect of smoked marijuana and oral tablets on IDV or NFV concentrations not clinically significant
Meperidine Metabolized via hydroxylation and CYP450, CYP2D6, and CYP1A2
  • Ritonavir associated with ↓ meperidine AUC by 67% and ↑ normeperidine AUC by 47%.
  • Avoid co-administration with any boosted PI.
Methylenedioxy-methamphetamine (MDMA) Metabolized via CYP2D6
  • RTV and other boosted PIs may precipitate life-threatening toxicity when MDMA used concurrently

 

Morphine Metabolism via glucuronidation None known
Oxycodone Metabolized via CYP2D6 to oxymorphone CYP3A4 to noroxycodone ketoreductase None known
PCP  Metabolized via CYP3A, 2C11; inhibits CYP2B1 Metabolized via CYP3A, 2C11; inhibits CYP2B1
Abbreviation key: Abacavir (ABC); delavirdine (DLV); efavirenz (EFV); etravirine (ETR); indinavir (IDV); maraviroc (MVC); nelfinavir (NFV); non-nucleoside reverse transcriptase inhibitor (NNRTI); protease inhibitor (PI); raltegravir (RAL); ritonavir (RTV)

Appendix B: ARVs for Patients with Hepatic Impairment: Drug Interactions and Dosing

The links listed below are to sources that provide information on drug-drug interactions between HIV-related medications and psychotropic and opioid medications and to ARV dosing recommendations for patients with hepatic impairment.

AIDSinfo: Guidelines for the Use of Antiretroviral (ARV) Agents in HIV-1-Infected Adults and Adolescents

Drug Interaction Databases: Look up interactions between HIV drugs and other specific drugs or classes of drugs.

New York & New Jersey AETC: Psychiatric Medications and ARVS: A Drug Interaction Guide for Clinicians