The Bay Area Reporter - August 14, 1996
Kate Krauss, ACT UP/Golden Gate Writers Pool

So far, three protease inhibitors have been approved for sale by the FDA, and several more are in the pipeline and may be available within a year. The FDA-approved drugs are Abbott's Ritonavir (Norvir), Merck's Crixivan (Indinavir), and Hoffman-La Roche's Saquinavir (Invirase).

Before beginning therapy, people with AIDS should read Project Inform's guide to protease inhibitors or the National AIDS Treatment Advocacy Project's HIV Protease Inhibitor Report (see below for contact information). Patients should learn about the drugs ahead of time, so they can avoid having to discontinue therapy because of side effects or drug interactions. This is especially important with protease inhibitors, because any drop in the drug level in the blood (either because of a missed dose, a "drug holiday," or discontinuation of the therapy altogether) may allow resistant strains of the virus to emerge in the body. These drug-resistant strains may be resistant to other protease inhibitors, as well.

Because there are many variables in taking protease inhibitors (severe drug interactions, resistance, the importance of complying to a dosage schedule) patients should try to work closely with a doctor in choosing a treatment strategy that involves these drugs.

People with AIDS should also consider their own general health in deciding whether to take a protease inhibitor. Patients in relatively good health may benefit by waiting a few months before beginning protease inhibitor therapy. There will be more drugs to choose from, and we will know more about effective combinations, drug interactions, and side effects. For example, a person in stable health with a viral load of 10,000 copies and a CD4 cell count of 500 might be a good candidate to wait.

The drug's effectiveness is also, of course, important. Saquinavir is thought to be the least potent of the three available proteases, (although it can still be helpful), but the best tolerated by most people. Crixivan and Ritonavir are roughly on par in terms of efficacy, but Ritonavir causes many side effects. In addition, protease inhibitors are much more effective in combination with other antivirals (AZT/3TC/Saquinavir, for example) than on their own. The most effective combinations are comprised of drugs the patient has not used before.

People with AIDS should seriously evaluate the possible side effects of the drug, because stopping therapy could invite viral resistance. Ritonavir produces a wide range of serious side effects, including nausea, vomiting, lack of energy, and tingling around the mouth and extremities. Crixivan seems to cause fewer side effects, (the chief one is microscopic kidney stones, which can be alleviated by insuring adequate water intake) and is better tolerated. Saquinavir is well tolerated by most people, and this may mean that patients can stay on the drug a long time.

Drug interactions are another important consideration in choosing a protease inhibitor. Ritonavir blocks a liver enzyme that helps people process other drugs, and this can lead to life-threatening overdoses of drugs that they are taking with Ritonavir. Some of these drugs include the anti-MAC drug Rifabutin, as well as a variety of painkillers, antidepressants, cold/sinus/allergy medicines, and antabuse. People considering Ritonavir should carefully review the list of known drug interactions with their doctor. There are, no doubt, many more drugs that could cause this problem but have not been identified yet, so patients should proceed carefully with other compounds, including traditional and alternative therapies, over-the-counter medicines, and recreational drugs and alcohol.

All three protease inhibitors must be taken on a strict schedule to avoid allowing drug levels in the blood to drop. Patients should consider whether they will be able to adhere to such a schedule when deciding whether to try one of these drugs. People may want to try a strict schedule with vitamins, to gauge whether they will be able to comply with taking protease inhibitors.

Crixivan must be taken on an empty stomach, while Saquinavir and Ritonavir must be taken along with fatty meals. In addition, people must coordinate the protease inhibitor with the other drugs they are taking: for example, ddI should be taken one hour from Crixivan.

Patients should think about their history with drug-related side effects when choosing a protease inhibitor, as this may predict how well they will tolerate the new drug. For example, people who have experienced drug-related gastrointestinal problems in the past may be poor candidates for Ritonavir, which often causes these side effects. However, Abbott Labs claims that Ritonavir side effects may pass after a few weeks.

Patients starting a protease inhibitor should set aside time to adjust to side effects and any drug interactions, and should discuss possible side effects, and their treatment, before beginning therapy. People should not combine protease inhibitors on their own, because of potentially very serious drug interactions. People should not take Seldane or Hismana with any of the three approved protease inhibitors.

Here are some additional tips regarding the three FDA-approved proteases:

Saquinavir:

Must be taken three times a day, with fatty meals (this can be cheese, chocolate or peanut butter, in a pinch). Only four percent of this drug reaches the bloodstream; a stronger, more effective formulation may be available in six months to a year. Some people with AIDS are stockpiling the drug and taking it at double or triple the dosage to get more into the bloodstream, increasing efficacy. However, this doubles or triples the cost and may increase side effects (diarrhea, generally). The bioavailability of the drug (the amount that gets in to the body) can be increased by up to 50 percent by drinking grapefruit juice during and one hour after the dose (under a doctor's supervision - this may affect other drugs, as well.) The resistance profile of Saquinavir may allow you to take other protease inhibitors in the future. Saquinavir should not be taken with rifampin.

Crixivan:

In clinical trials, the most common side effect was tiny kidney stones composed of undissolved drug. The risk of developing these can be reduced by drinking plenty of water. (These microscopic kidney stones did not cause patients to drop the drug, generally.) Can be taken with a light snack (crackers). More effective than saquinavir; fewer side effects than Ritonavir. Persons taking Crixivan must halve their dosage of Rifabutin to avoid interactions. Drug interactions have been noted with ketoconazole, as well. At about $5,000 per year (depending on your payment plan), the cheapest of the currently available protease inhibitors.

Ritonavir

Severe side effects that may lessen with time. Abbott is suggesting that persons gradually increase dosage over five days to limit side effects (no longer than five days, or resistance may emerge. Also, don't try this gradual approach with the other protease inhibitors without medical advice, because of resistance concerns.) May cause severe drug interactions with at least 23 commonly used drugs; many more are likely to be discovered. Check the list of known drug interactions before taking this drug; the dosage of some other drugs may have to be adjusted upward. Tobacco is shown to reduce blood levels of Ritonavir by eighteen percent, possibly leading to a drop in effectiveness. Very effective in suppressing viral load and raising CD4 counts. Ritonavir has also been shown in clinical trials to prolong patients' lives.

Project Inform, National AIDS Treatment Advocacy Project http://www.aidsnyc.org/natap (718) 624-8541 (do not call late at night) or (415) 554-0555.

960814
BR960802

Always watch for outdated information. This article first appeared in 1996. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1996. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .