ACRIA - Spring 2005Important note: Information in this article was accurate in 2005. The state of the art may have changed since the publication date.
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Drug Interactions: HIV Medications, Street Drugs and Methadone

AIDS Community Research Initiative of America (ACRIA) - Spring 2005

James Learned and Maia Szalavitz

A drug interaction is what happens when one drug that you take affects the way another drug you take works in your body. An interaction can affect your body's ability to break down one drug or both drugs. It can also affect the strength or effectiveness of one drug or both drugs. Drug interactions become more complicated - and more likely to happen - the more drugs you take. In many cases, interactions aren't a problem. There are lots of drugs that don't affect each other at all. But some medications should never be used together because they combine to create a toxic reaction. Such interactions are dangerous, even life threatening.

The liver breaks down and absorbs (metabolizes) antiretrovirals for HIV, methadone, alcohol, street drugs like cocaine and heroin, prescription and over-the-counter medications, herbs, vitamins - the works. The liver has primary responsibility for drug metabolism, but the kidneys also play a role, mostly by eliminating drugs. Specific pathways of enzymes in the liver metabolize different drugs, but many drugs are metabolized by the same pathways. This is where interactions can occur.

The liver can only do so much work at one time. If you take two or more drugs at once, they can compete for the same enzymes in the liver in order to be broken down. This competition can affect the way the drugs are metabolized. One drug might be metabolized faster than usual, reducing levels of the drug in your blood and making it less effective. This could be a problem with a number of drugs. If your methadone levels are too low, for example, you could experience serious withdrawal symptoms. And if your anti-HIV drug is at low levels, it won't work as well and could allow your virus to become resistant to that drug and, perhaps, others as well.

Another kind of interaction can cause one of the drugs you're taking to be metabolized more slowly than usual. You could end up with a dangerously high dose of the drug in your system because it isn't being broken down and absorbed properly. In essence, this could cause an overdose and, depending on the drug, could be fatal.

It might be useful to think of the liver as a funnel - or many funnels, some of them having funnels within them. If drug A and drug B compete with one another for the same funnel, for example, a number of possibilities could occur:

The more drugs you add to the mix, the more difficulty the funnels may have metabolizing them properly. There are many possible interactions - some of them may not cause a problem, but others certainly could.

The following describes known and potential drug interactions that involve medications to treat HIV or prevent and treat opportunistic infections. Some of this information is based on studies that have been conducted in test tubes, animals, or people; some of it is based on case reports - incidents that have actually happened to people; and some of the information is theoretical, based on what we know about how different drugs are metabolized - which pathways they use and how they use them.

There hasn't been much research on how illegal street drugs and HIV medications interact. Certainly, your best bet is not to use street drugs at all if you're taking HIV medications. But some interactions are known to be more dangerous than others.

HIV Medications and Street/Recreational Drugs

It's difficult to study interactions between illegal drugs and antiretrovirals. Some people have a higher tolerance to some drugs than other people do. Also, there are too many different kinds of cuts put on drugs, especially heroin and cocaine, which are hardly ever pure. So laboratory tests using pure heroin or cocaine, for example, wouldn't necessarily tell us what might happen in your body with drugs bought on the street.

We have more information about interactions with prescription drugs that are used recreationally, But even then, some drugs that are available by prescription, when bought on the street, may be cut with other substances that could cause unexpected interactions with other drugs.

Alcohol

Amphetamines (speed, methamphetamine, crystal meth [Tina, ice])

Cocaine (coke, blow, crack)

Ecstasy (MDMA, X)

GHB (gamma-hydroxy-butyrate, grievous bodily harm, liquid X, G)

GHB is potentially dangerous with protease inhibitors, especially Norvir (full dose or lower doses), as well as the non-nucleosides Rescriptor and, possibly, Sustiva. And never mix GHB with alcohol.

Heroin (dope, smack, brown, junk, China White)

Ketamine (Special K)

When combined with some anti-HIV medications, Special K can lead to "chemical hepatitis," inflammation of the liver that could require hospitalization. The inflammation usually goes away in several weeks, but anything that damages the liver can be a serious problem for people with HIV. Norvir, Kaletra, Viracept, Agenerase, Lexiva, Rescriptor, and Sustiva are the antiretrovirals with the greatest potential to cause ketamine toxicity.

LSD (acid, blotter)

No known interactions. But it's possible that some anti-HIV medications, especially Norvir, could lead to a longer or more intense trip than planned or desired.

Marijuana

According to one study, smoked marijuana slightly lowers levels of the protease inhibitors Crixivan and Viracept, although the decreased levels weren't enough to affect the antiretrovirals' activity. Protease inhibitors may also increase THC levels, the active ingredient in marijuana - so smaller doses may make you more stoned. The same is true of the synthetic version, Marinol (dronabinol), which contains THC and is used to treat nausea and increase appetite. This interaction doesn't seem to be dangerous - although you should consider it if you're planning on being coherent!

Sustiva makes many people feel at least somewhat disoriented. Using marijuana might heighten these feelings - and not necessarily in a good way.

PCP (angel dust, rocket fuel)

Levels of PCP may increase due to interactions with protease inhibitors or the non-nucleosides, Rescriptor and, possibly, Sustiva. These interactions could cause PCP toxicity. If you're on anti-HIV medications and using PCP, think about using less PCP than you might otherwise to avoid a possible interaction.

Poppers (amyl nitrate or butyl nitrate

Be sure not to use poppers if you take Viagra, Levitra, or Cialis. Poppers increase levels of these drugs, lowering your blood pressure enough to cause serious, even lethal, reactions (see below for more detail).

Ritalin (methylphenidate)

There are no known interactions between Ritalin and any medications specific to HIV.

Sedatives & Tranquilizers:

Interactions between barbiturates, benzodiazepines and antiretrovirals, especially the protease inhibitors and non-nucleosides, are tricky. There are many possible variables that could affect the interactions listed below, including other drugs that you might be taking.

Barbiturates (barbs, downers)

Barbiturates are rarely used on the street since they don't provide much of an attractive high or down. But if you are taking barbiturates, there are some things that could be helpful to know:

Benzodiazepines (bennies, benzos, downers)

Bottom line: Mixing downs can be very dangerous. Mixing depressant drugs - alcohol and opioids; alcohol and barbiturates; alcohol and benzodiazepines; or a combination of depressant drugs - is the cause of most overdose deaths.

Viagra (sildenafil), Levitra (vardenafil), and Cialis (tadalafil)

HIV Medications and Methadone

The same liver enzymes that metabolize methadone break down many medications for HIV and drugs that prevent and treat opportunistic infections. So these drugs can cause changes in the way you respond to your methadone dose. Some can increase the effects of methadone; others can decrease it. Methadone can have an effect on the strength of some anti-HIV drugs, too.

It's best to tell both your HIV healthcare provider and the provider at your methadone clinic about all the medications you're taking. But if you don't share the information, at least know the drugs that you're on. Most of the important methadone-medication interactions decrease the effect of the methadone. If your dose isn't comfortable for you, it isn't "addictive behavior" to want one that is.

People considering detoxing from methadone should be aware that this might not be a good idea for some people with HIV, particularly if your CD4 count is low. Methadone-maintained people have fewer hospitalizations and are more likely to receive anti-HIV medications than many heroin users who aren't on methadone. When lowering your methadone dose it may be safest to go slowly and wait until you've adjusted to each decrease before moving on to the next one.

The following are some of the known drug interactions with methadone. There may be others. This area, like most involving drug users, hasn't been thoroughly studied - although, because methadone is legal, the information about possible drug interactions is more complete and there's more of it compared to that for illegal drugs. If you start a new medication and find that your methadone dose isn't "holding" you or that it makes you feel drowsy or over-medicated, talk to the provider at your clinic. If they refuse to adjust your methadone to meet your needs, ask your HIV care provider to discuss it with them. You shouldn't have to suffer because of ignorance about drug interactions from some clinic staff.

DRUGS THAT MAY MAKE METHADONE STRONGER (MORE POTENT)

DRUGS WITH MIXED OR CONTRADICTORY EFFECTS

DRUGS THAT MAKE METHADONE WEAKER (LESS POTENT)

DRUGS THAT METHADONE MAKES WEAKER

DRUGS THAT METHADONE MAKES STRONGER

James Learned is Director of Treatment Education at ACRIA and Editor of ACRIA Update.

Maia Szalavitz is the co-author of Recovery Options: The Complete Guide: How You and Your Loved Ones Can Understand and Treat Alcohol and Other Drug Problems (Wiley, 2000).

Thanks to Carlos Santiago and Constance T. Chang for their research assistance.

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