Invirase
Common Name: saquinavir
Brand Name: Invirase
Class: HIV protease inhibitor (PI)
Standard dose: Two 500 mg film-coated tablets with 100 mg Norvir two times a day with food, or within two hours after a meal. Must be taken with Norvir. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.
AWP: $996.44 / month for 500 mg tablets
Manufacturer contact: Roche Pharmaceuticals,
www.rocheusa.com, 1 (800) 526-6367
Potential side effects and toxicity: Most common are diarrhea, abdominal discomfort, vomiting, and nausea. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects seen with protease inhibitors are lipodystrophy (body fat changes, including thinning of the face, arms and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.
Potential drug interactions: Viramune, Sustiva, and Mycobutin (rifabutin) decrease Invirase levels. Not recommended to be used with Aptivus/Norvir or Prezista. Should be used with caution and may require dose adjustment with Reyataz. Rescriptor, Crixivan, Norvir, Viracept, and Kaletra all significantly increase Invirase’s concentrations. No dosage change when taken with Kaletra.
Do not take with Tambocor (flecainide), Rythmol (propafenone), Biaxin (clarithromycin), dexamethasone, Cordarone (amiodarone), Versed (midazolam), Halcion (triazolam), Rifadin (rifampin), Orap (pimozide), Lanoxin (digoxin), ergot derivatives (such as Cafergot, D.H.E. 45, Methergine, and Wigraine), quindine, garlic supplements, or the herb St. John’s wort. Do not use Advicor, Altoprev, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution. Data show that when rifampin is taken with Invirase/Norvir, there is significant liver toxicity in 40% of patients. The combination should be avoided. Methadone doses may need to be increased. Invirase increases levels of fluticasone (active component of Advair, Flonase, Flovent). Trazodone concentrations may increase; a lower dose of trazodone is recommended. Use calcium channel blockers with caution. Monitor digoxin levels; digoxin dose may need to be decreased. Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin).
Invirase may increase dapsone levels. Do not take with birth control pills; Invirase reduces level of ethinyl estradiol. Prescriber may need to adjust doses accordingly.
Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours.
Tips: The GEMINI study compared Invirase to Kaletra, both twice daily. Similar viral suppression and increase in CD4 count were seen. Invirase/Norvir has demonstrated safety, and is listed in the U.S. DHHS HIV treatment guidelines as an alternative choice when starting HIV therapy. The higher pill burden and increase in Norvir (greater than 100 mg per day) is the reason for its alternative listing. Must be taken with food. Please see package insert for more complete potential side effects and interactions.
Doctor
Invirase (saquinavir) was the first protease inhibitor approved (in 1995) for combination therapy in the treatment of HIV infection. The drug was initially taken unboosted, but studies in later years showed that its use was more reliable when taken twice daily with ritonavir. In addition, a few smaller studies showed reasonable activity when saquinavir was taken just once daily, also with ritonavir. This drug is usually well tolerated with few expected side effects. Larger studies were done in the past five years which did show that the twice-daily dose is similarly effective to lopinavir, and some international guidelines have included this PI in the choice of preferred options. However, current guidelines usually do not include saquinavir on the preferred list of PIs to start on, as there are other choices in the PI class that have enough advantages over saquinavir. This drug has minimal use at present. There is interest in what will happen when this PI becomes “generic,” which usually means it may be far less expensive versus the current “name brand.” As this drug did do fairly well compared to other choices, there may be times when financial circumstances lead to a reconsideration of the value of this drug. —Cal Cohen, MD
Activist
A drug that has come full circle—Invirase was one of the first protease inhibitors and was not well absorbed and had to be taken with a high fat meal. Even then, drug uptake was uneven, and the company switched to a gel capsule they called Fortovase. Fortovase caused lots of stomach upset and diarrhea, and quickly fell out of favor. Then studies showed that the original Invirase boosted with Norvir had fewer side effects and better absorption, so it’s back among the recommended alternative regimens. But its twice-daily dosing with food means that it’s losing ground to newer PIs such as Reyataz and Prezista. —Jeff Taylor
