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Risky Cocktails

Interactions Between Street Drugs and HIV Medications

By Guy Pujol
 From AIDS Survival Project

April 2003

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Recreational/Street Drug/Abused Prescription HIV/Prescription Medication Interaction Comments
Alcohol ABC/Ziagen/Abacavir Increases ABC levels in blood. One study observed a 41% increase in ABC.1 ABC is metabolized by alcohol dehydrogenase, therefore increasing ABC levels.
Alcohol APV/Agenerase/Amprenavir Increases APV levels in blood. Alcohol may decrease metabolism of propylene glycol in APV solution.
Alcohol SQV-hgc/Invirase/Saquinavir-hard gel cap Increases metabolism, Decreases SQV-hgc plasma levels.  
Alcohol Protease Inhibitors (PI) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) Acute ingestion of alcohol leads to enzyme (CYP2E1 and 3A4) inhibition. Chronic ingestion leads to enzyme induction which may result in subtherapeutic levels of PIs and NNRTIs.
Amphetamines Protease Inhibitors (PI) 2x-3x amphedamine build-up in blood. Inhibits CYP2D6 metabolism.2 Increased likelihood of overdose: hypertension, hyperthermia, seizures, arrhythmias, tachycardia, and tachypnea may be seen as a result.
Amphetamines and Cocaine Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants Combination may increase serotonin release, resulting in Serotonin Syndrome.3 Both metabolize through CYP2D6.
Anabolic Steroids RTV/Norvir/Ritonavir 2x-3x build-up of anabolics in blood.  
Antidepressants (tricyclic) RTV/Norvir/Ritonavir Inhibits metabolism of antidepressants, increases plasma concentrations.  
Barbituates Protease Inhibitors (PI) Increases blood levels of barbituates.  
Ecstasy/X/E/MDMA MAOI Antidepressants (Nardil, Marplan, or Parnate) Increases levels of both MAOIs and MDMA. Decreases CYP2D6 metabolism.
Ecstasy/X/E/MDMA RTV/Norvir/Ritonavir 3x-10x build-up of MDMA in blood. Interferes with (decreases) CYP2D6 metabolism. Toxicities include hyponatremia, hyperthermia, arrhythmias, tremor, hyperreflexia, sweating, seizures, and tachycardia. At least one reported death from MDMA/RTV interaction.4
Gamma Htdroxybutyrate/GHB/ Liquid X ("Date Rape Drug") Protease Inhibitors (PI) 5x-10x increase of GHB. One case of GHB toxicity with RTV/SQV.5 Overdose symptoms include myoclonic or seizure activity, bradycardia, respiratory depression, or loss of consciousness.
Heroin RTV/Norvir/Ritonavir Decreases heroin levels by 50%. Heroine rapidly converts to morphine by plasma and liver esterases. Expect interactions once converted to morphine. Watch for opiate withdrawal.
Ketamine/K/Special K Protease Inhibitors (PI) Build-up of K in blood with antiretrovirals, especially RTV, NFV, and EFV. CYP2B6 is main metabolic enzyme. 3A and 2C9 are utilized to a lesser extent.6
Ketamine/K/Special K RTV/Norvir/Ritonavir Build-up of Ketamine likely. Overdose symptoms include respiratory depression, loss of consciousness, and hallucinations.
Lysergic Acid Diethylmide/LSD Protease Inhibitors (PI) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) PI and NNRTI CYP450 inhibitors may cause build-up of LSD. Overdose symptoms include hallucinations, agitation, psychosis, and "flashbacks."
Marijuana Protease Inhibitors (PI) Increases THC (active compound in marijuana) levels. Slowed metabolism of THC by Protease Inhibitors, therefore, smaller amounts required for medicinal purposes.
Marijuana Protease Inhibitors (PI) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) Smoked marijuana may lower PI and NNRTI levels. Smoked THC in one study decreased NFV by 17% and IDV by 21%.7 THC interferes with CYP3A4, 2C9, and 2D6. Increases in THC if using medications that inhibit CYP450; decreases in THC if using medications that induce CYP450.
Phencyclidine/PCP Protease Inhibitors (PI) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) Possible increased levels of PCP in blood. Overdose symptoms include seizures, hypertension, rhabdonyolysis, and hyperthermia. Metabolism by CYP3A and CYP2C11; and inhibits CYP2B1.8
Poppers/Amyl Nitrate Viagra Decreases blood pressure, can be fatal.  
Rohypnol ("Date Rape Drug") RTV/Norvir/Ritonavir 2x-3x build-up of Rohypnol in blood.  
Sedatives Protease Inhibitors (PI) Inhibits metabolism of sedatives, increases plasma concentrations.  
Speed/Crystal Meth/Tina RTV/Norvir/Ritonavir 2x-3x build-up of Crystal Meth in blood.  
Temazepam (Jellies) RTV/Norvir/Ritonavir Temazepam metabolized more quickly.  
Valium (Diazepam) RTV/Norvir/Ritonavir Huge increase in blood levels of Diazepam.  
Viagra RTV/Norvir/Ritonavir 4x build-up of Viagra in blood.  
Poppers/Amyl Nitrate HIV (itself, not the medications) Increases disease progression.  
Methadone HIV (itself, not the medications) Methadone can increase the infectivity of R5 strains of HIV -- those that use the CCR5 coreceptor. Findings: (1) Methadone upregulates (increases) CCR5 expression on cell surfaces. (2) Methadone inhibits the production of beta chemokines that decrease infectivity. (3) Methadone increases Cortisol levels, temporarily driving CD4+ cells out of the blood and into lymph nodes and tissues. CD4+ cells return when cortisol levels decrease. (4) Methadone also enhances the activation and replication of latently infected cells.
Alcohol HIV (itself, not the medications) 4x less likely to achieve a low viral load. This study compared heavy drinkers compared to non-heavy drinkers.
Cocaine HIV (itself, not the medications) Increases viral replication (200x).9 May increase the number of CCR5 and CXCR4 receptors on CD4+ cells that HIV uses to infect the cells.
Ecstasy/X/E/MDMA HIV (itself, not the medications) One dose of MDMA (100 mg) decreased CD4+ cells by 30% within hours after a single dose. Two doses of MDMA, four hours apart, decreased CD4+ cells by 40%.10 Additional finding: decreased ability of CD4+ cells to fight infection.10
GHB/Liquid X HIV (itself, not the medications) Suppresses the immune system.  
Methadone AZT/Retrovir/Zidovudine (NRTI) Increases AZT levels by 50% in blood.  
Methadone d4T/Zerit/Stavudine (NRTI) Decreases d4T levels by 13% in blood.  
Methadone ddI/Videx/Didanosine Methadone may decrease ddI levels by about 50% below normal.  
Methadone ddI/Videx/Didanosine (NRTI) Decreases ddI levels by 52% in blood.  
Methadone EFV/Sustiva/Efavirenz (NNRTI) Decreases Methadone levels by 60% in blood. Recommendation: Increase methadone dose by 5 mg to 50 mg (avg. 22 mg).
Methadone IDV/Crixivan/Indinavir and SQV-sgc/Fortovase/Saquinavir-Soft Gel Does not decrease Methadone levels in blood. May increase Methadone levels slightly (studies pending).
Methadone LPV-r/Kaletra/Lopinavir+Ritonavir Decreases Methadone levels by 53% in blood.  
Methadone NFV/Viracept/Nelfinavir Decreases Methadone (-)enantiomer by 47% and (+)enantiomer by 39% in blood.  
Methadone NVP/Viramune/Nevirapine Decreases Methadone levels by 60% in blood. Recommendation: Increase methadone dose by as much as 150 mg to avoid symptoms of withdrawal.
Methadone RTV/Norvir/Ritonavir Effect unpredictable; either increase or decrease methadone levels. One study showed a decrease of Methadone levels by 40% in blood.
Methadone RTV/Norvir/Ritonavir Decreases Methadone levels by 40% in blood.  
Methadone RTV/Norvir/Ritonavir and NFV/Viracept/Nelfinavir. Decrease Methadone levels by 30%-40% in blood.  


Guy Pujol is Executive Director of AIDS Treatment Initiatives (ATI).


References

  1. McDowell J.A., Chittick G.E., Pilati-Stevens C., Edwards K.D., Stein D.S. Pharmacokinetic Interaction of Abacavir (1592U89) and Ethanol in Human Immunodeficiency Virus-Infected Adults. Antimicrob Agents Chemother 2000;44:1686-90.

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  2. Lin L.Y., Di Stefano E.W., Schmitz D.A., Hsu L., Ellis S.W., Lennard M.S., et. al. Oxidation of Methamphetamine and Methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos 1997;25:1059-64.

  3. Nolan S. and Scoggin J.A. Serotonin Syndrome: Recognition and Management. US Pharmacist, February 1998;23:2.

  4. Henry J.A., Hill I.R. Fatal Interaction between Ritonavir and MDMA. Lancet 1988;352:1751-52.

  5. Harrington R.D., Woodward J.A., Hooton T.M., Horn J.R. Life-Threatening Interactions between HIV-1 Protease Inhibitors and the Illicit Drugs MDMA and Gamma-hydroxybutyrate. Arch Intern Med 1999; 159:2221-24.

  6. White P.F., Way W.L., Trevor A.J. Ketamine-Its Pharmacology and Therapeutic Uses. Anesthesiology 1982;56:119-36.

  7. Kosel B.W., Aweeka F.T., Benowitz, Shade S.B., Hilton J.F., Lizak P.S., et. al. The Effects of Cannabinoids on the Pharmacokinetics of Indinavir and Nelfinavir. AIDS 2002;16:543-50.

  8. Laurenzana E.M., Owens S.M. Metabolism of Phencyclidine by Human Liver Microsomes. Drug Metab Dispos 1997;25:557-63.

  9. Roth M.D., Tashkin D.P., et. al. Cocaine Enhances Human Immunodeficiency Virus Replication in a Model of Severe Combined Immunodeficient Mice Implanted with Human Peripheral Blood Leukocytes. J Infect Dis 2002 Mar 1;185(5):701-05.

  10. Pacifici R., Zuccaro P., et. al. Effects of Repeated Doses of MDMA ("Ecstacy") on Cell-Mediated Immune Response in Humans. Life Sciences 2001; 69:2931-2941.

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!




  
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This article was provided by AIDS Survival Project. It is a part of the publication Survival News.
 
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