SEPTEMBER 1998

NUMBER ONE

HIV-Recreational Drug Interactions

This table analyzes potential drug interactions based on case reports and pharmacologic analyses by experts of the Cytochrome p450 liver metabolic pathways. See "p450 Metabolism".

Explanation of Table:
P450 substrate (S) is any drug that uses the Cytochrome p450 enzyme pathway.
P450 inhibitors (INH) generally increase concentrations of other drugs.
P450 inducers (IND) generally decrease concentrations of other drugs.
Some HIV drugs are both inducers and inhibitors.

		PCP: Uses p450 2C11 pathway. Ketamine/Special K (a derivative of PCP): A p450 inhibitor: possibly 3A4. In studies, 4 percent excreted in urine. Opium: Metabolized in liver.< Morphine: Uses p450 3A4 pathway. LSD/acid: Unknown. Barbituates: Strong p450 3A4 inducer; very slowly metabolized in liver. Alcohol: Metabolized by alcohol dehydrogenase, aldehype hydrogenase; may induce p450 3A and 2E1 (minor). Avoid or use moderately. Causes dehydration; drink a lot of water. Detox drugs used to help heroin/methadone withdrawal: Two antagonist clonidine: 30 percent of drug excreted unchanged in urine; liver metabolism to four non-p450 metabolites. Naltrexone: metabolized in liver; may uses p450 system Buprenorphine (Buproprion): Uses p450 liver pathway: a 2D6 inhibitor. IV Midzolam Sedation: Uses p450 3A4 liver pathway.
Marijuana/Marinol: Uses p450 3A4, 2C9, 2C6 liver pathways. Specific interactions unknown. Heroin: Uses p450 3A4 liver pathway. Reports suggest HIV drugs may cause heroin to be metabolized more quickly. A potential 50 percent or less decrease in heroin levels with ritonavir (a strong p450 2D6 inducer). Cocaine: Uses p450 liver pathways: Minor 2D6 inhibitor, 3A4 inducer, 2B1, 1A2. Unlikely interaction with protease inhibitors. In one reported test-tube study, cocaine made HIV reproduce 20 times faster than normal. Methadone: Uses p450 liver pathways: 2D6 inhibitor, 3A4 inhibitor. Reported twofold methadone level increase with ritonavir. An increase of 30 percent with indinavir. Not likely to interact with saquinavir. Unknown interaction with other HIV drugs. Likely increase with nelfinavir, delavirdine; decrease with nevirapine. Methadone has been found to increase AZT levels twofold, so halving the dose of AZT may get same anti-HIV effect.	LAMM: Metabolized similarly to methadone: 2D6 inhibitor, 3A4 inhibitor. Likely to increase concentrations of other drugs in blood. Not recommended for pregnant or nursing women. Amphetamines (Speed): Uses p450 liver pathways: 2D6. Potential twofold to threefold increase with ritonavir. Metamphetamines: 2D6. See amphetamines. Ecstasy (MDMA): Uses p450 liver pathways: 2D6. HIV drugs may cause a potential threefold to tenfold increase of MDMA in blood. GHB (gamma-hydroxy-butyrate) "liquid Ecstasy": uses p450: 2D6. Little is known about interactions with GHB but avoid alcohol and drink plenty of water. Amyl Nitrate (poppers): Unknown. Amyl nitrate is an organic nitrate excreted by liver (by glutathione).

TIPS:

• If you're HIV positive and abusing recreational drugs, consider getting help from a trained professional. A drug-addiction treatment program is often a first step toward HIV prevention and care. Be honest with your doctor about your use of any drugs.

• Avoid using recreational drugs during your first six to eight weeks on HIV combination therapies

• To reduce the risk of drug interactions, don't take HIV drugs and recreational drugs at the same time.

• Drink lots of water to flush out your kidneys; avoid alcohol.

• Getting high increases your chance of forgetting to take HIV drugs on schedule. A drug buddy, friend, or social-service case manager can offer support to help you manage your treatment regimen. Many agencies offer case-management services, refrigerate your drugs, etc.