Drug Interactions Associated with the Protease Inhibitors

Tips on how to avoid the possibility of drug interactions by thoroughly communicating with your care providers were covered in an article published in the April edition of

Positive Living. In this article, Glenn Gaylord looks at the various drug interactions associated with protease inhibitors, Crixivan (indinavir), Invirase/Fortovase (saquinavir mesylate and saquinavir respectively), Viracept (nelfinavir mesylate), and Norvir (ritonavir).

As a quick generalization, Norvir is the protease inhibitor most likely to either interfere with the metabolism of other drugs or to have drug interaction concerns, while Crixivan and Viracept have concerns to a lesser degree. Both Invirase and its soft-gel formulation, Fortovase, have less potential to cause drug interactions than the others.

All of the protease inhibitors, however, affect liver enzymes, which can determine the way other drugs are processed, thus leading to drug interactions.

It is important to note, however, that the term "drug interaction" does not always refer to harmful combinations. At times, a combination of drugs will enhance each other's bioavailability. Studies have shown, for example, that the combination of saquinavir and ritonavir can produce a beneficial drug interaction.

The chart on this page detail some of the major drugs that one should avoid taking with protease inhibitors:

Drugs to avoid if you use Crixivan (indinavir) Drug Class Generic Name Brand Name anticonvulsant phenobarbital Quadrinal, Mudrane   phenytoin Dilantin   carbamazepine Tegretol anti-nausea cisapride Propulsid anti-mycobacterial rifampin Rifadin cold and allergy (antihistamine) terfenadine Seldane (no longer available)   astemizole Hismanal psychotropic (sedative / hypnotic) midazolam Versed   triazolam Halcion   Drugs to avoid if you use Invirase / Fortovase (saquinavir) Drug Class Generic Name Brand Name anti-mycobacterial rifabutin Mycobutin   rifampin Rifadin anti-convulsants phenobarbital Quadrinal, Mudrane   phenytoin Dilantin   carbamazepine Tegretol anti-nausea cisapride Propulsid cold and allergy (antihistamine) astemizole Hismanal   terfenadine Seldane   Drugs to avoid if you use Viracept (nelfinavir) Drug Class Generic Name Brand Name anti-nausea cisapride Propulsid anti-mycobacterial rifampin Rifadin antiseizure phenobarbital Quadrinal   phenytoin Dilantin   carbamazepine Tegretol cardiovascular (antarrhythmic) amiodarone Cordarone   quinidine Quinidex, Quiniglute cold and allergy (antihistamine) astemizole Hismanal   terfenadine Seldane oral contraceptives ethinyl estradiol Estinyl, Ovcon-35   norethindrone Norlutin sedative midazolam Versed   triazolam Halcion   Drugs to avoid if you use Norvir (ritonavir) Drug Class Generic Name Brand Name analgesic meperidine Demerol   piroxicam Feldene   propoxyphene Darvon cardiovascular (antarrhythmic) amiodarone Cordarone   encainide Enkaid   flecainide Tambacor   propafenone Rhythmol   quinidine Quinidex, Quiniglute anti-alcohol addiction disulfiram Antabuse anti-mycobacterial rifabutin Mycobutin   rifampin Rifadin cardiovascular (calcium channel blocker) bepridil Vascor cold and allergy (antihistamine) astemizole Hismanal antimigraine dihydroergotamine D.H.E. 45   ergotamine various anti-nausea cisapride Propulsid anti-bacterial metronidazole Flagyl anti-depressant bupropion Wellbutrin, Zyban anti-psychotics pimozide Orap   clozapine Clozaril oral contraceptives ethinyl estradiol Estinyl, Ovcon-35 psychotropic (sedative / hypnotic) alprazolam Xanax   clorazepate Tranxene   diazepam Valium   estazolam Prosom   flurazepam Dalmane   midazolam Versed   triazolam Halcion   zolpidem Ambien

Let's look at the drugs that appear on all four lists:

• Rifadin (rifampin). This antibiotic is designed to treat mycobacterial infections such as tuberculosis and MAC (Mycobacterium Avium Complex), and is known to decrease the levels of all protease inhibitors. The sister drug to rifampin, Mycobutin (rifabutin), should not be taken with ritonavir as it may increase side effects and toxicity. In some cases, care providers have been known to treat MAC with Rifadin and/or Mycobutin while curtailing any protease inhibitor therapy and will only introduce protease once the MAC treatment has stopped.

• Hismanal (astemizole) and Seldane (terfenadine). Hismanal and Seldane are fairly new antihistamines that have the distinct characteristic of not causing as much drowsiness as their counterparts. Seldane has been used in the past in people with HIV to reduce such side effects as rashes, swelling and HIVes. Both drugs have shown, however, to increase side effects when taken with protease inhibitors, and Seldane has, in fact, been removed from the market.

• Halcion, Xanax, Valium and Demerol are fairly common sedatives and analgesics found on some of the lists. Halcion, typically prescribed to treat insomnia, has been shown to increase the risk of toxicity with all of the protease inhibitors except Invirase/Fortovase while Xanax and Valium, anti-anxiety medications, have similar concerns when taken with ritonavir. Demerol, an opium-derived pain killer, and often used as a morphine substitute, has shown to produce adverse side effects when administered with ritonavir. Finally, it has been determined that levels of oral contraceptives (birth control pills) can be reduced by as much as 40 percent when taken with Viracept and Norvir, which may result in either an increased dosage of the oral contraceptive or a different combination choice.

This article is by no means a complete listing of the drug interactions involving protease inhibitors. If you have an area of concern, check with your care provider, pharmacist and treatment advocate before taking any medications.

Glenn Gaylord is a treatment advocate at AIDS Project Los Angeles. He can be reached by e-mail at GGaylord@APLA.org or by phoning (213) 993-1509.

This article has been reprinted at The Body with the permission of AIDS Project Los Angeles (APLA).