Potential side effects and toxicity: Most common are stomach related: diarrhea, abdominal discomfort and nausea. As seen with all other protease inhibitors are increased levels of cholesterol and triglycerides, except possibly unboosted Reyataz (atazanavir) and these increased levels may be associated with heart disease. Other possible side effects are lipodystrophy (body fat changes, including thinning of the face, arms and legs, with or without fat accumulation in the stomach, breasts and sometimes the upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs.
Potential drug interactions: Do not take with Tambocor (flecainide), Rythmol (propafenone), Versed, Halcion, Hismanol, Seldane, rifampin, ergot derivatives (such as Cafergot, Wigraine and Methergine, D.H.E. 45, in any form—serious interactions seen with dilation during gynecological exams), garlic supplements, or the herb St. John’s wort. Do not use Zocor (simvastatin) or Mevacor (lovastatin); lipid-lowering alternatives are Lipitor (atorvastatin), Lescol, and Pravachol (parvastatin), but they should be used with caution due to potential for liver toxicity. Recent data show that when rifampin is given with saquinavir/ritonavir, there is significant liver toxicity in 40% of patients.
Viramune, Sustiva and Mycobutin (rifabutin) decrease Invirase levels. Invirase may increase dapsone levels. Antifungals Nizoral (ketoconazole) or Sporonox (itraconazole), used for treatment of candidiasis (thrush) increase the amount of Invirase in the body. Do not take with birth control pills; Invirase reduces level of ethinyl estradiol by 40%. Prescriber may need to adjust doses accordingly. Rescriptor, Crixivan, Norvir, Viracept and Kaletra all significantly increase Invirase’s concentrations. No dosage change when taken with Kaletra.
Protease inhibitors increase blood levels of Viagra (sidenafil citrate), Cialis (tadalafil) and Levitra (vardenafil). Use with caution. Initially the Viagra dose should be 12.5 mg (1/2 of 25 mg tablet) and increased as needed and tolerated. It’s recommended that people on PIs do not exceed 25 mg of Viagra in a 48-hour period because of potential for serious reaction. Use Cialis at reduced doses of 10 mg every 72 hours and Levitra at reduced doses of no more than 2.5 mg every 72 hours, with increased monitoring for adverse events.
Tips: Due to the discontinuation of Fortovase in early 2006, Invirase will be the only formulation of saquinavir available. Switching to its original formulation, Invirase, is matched milligram for milligram. For example, five 200 mg Fortovase (1,000 mg) equals two 500 mg Invirase (1,000 mg). Invirase, the first HIV protease inhibitor out on the market, made a comeback over the past two years, due to study results indicating strong efficacy with fewer side effects when taken with a mini-dose of Norvir, as compared to Fortovase/Norvir. It has the considerable advantage of less diarrhea, vomiting and abdominal distension compared with Fortovase plus Norvir. Invirase/Norvir has demonstrated A1 safety and efficacy (the highest category rating) according to U.S. HIV treatment guidelines. This oldie is a goodie. Must be taken with food. There is also some research supporting Invirase 1000 mg + Kaletra standard dose twice-a-day.
Doctor
Saquinavir (SQV) was the first protease inhibitor to be approved by the FDA in 1995. This was the first true beginning of the era of HAART (highly active antiretroviral therapy). In its original formulation, saquinavir was poorly absorbed and required large numbers of pills. However, reformulation into convenient 500 mg tablets and the advent of boosting with ritonavir have revived this agent. As with most protease inhibitors, its main side effects include gastrointestinal upset, diarrhea, and bloating. Longer term toxicity includes hyperlipidemia (high cholesterol levels, especially triglycerides). It is potent, but still primarily used in salvage settings in combination with another protease inhibitor.—Chad J. Zawitz, MD
Activist
Invirase is a protease that has been reformulated three times. I remember being in the first study in 1995 with high hopes. Unfortunately we found out later that very little of the drug got absorbed, so I developed PI resistance early. Roche reformulated it in capsules later for better absorption, but with greater pill burden and GI side effects. The latest formulation seems to be the friendliest of all, taken with Norvir boosting, with lower GI side effects and pill burden. Too bad Roche launched this last formulation with little exciting data for doctors to prescribe it, since the drug has been around for so long. I would love to see comparison data with Kaletra and Reyataz for efficacy and lipids. The new Invirase formulation could find its niche for those who have to stop Kaletra for GI and lipid side effects, or Reyataz for bilirubin. It is also important to see more solid data on double PI boosted combos for salvage patients.—Nelson Vergel
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