POSITIVELY AWARE MARCH/APRIL 2011
brand name: Invirase
common name: saquinavir
class: Protease inhibitor (PI)
manufacturer: Genentech | www.genentech.com, (800) 626-3553
Standard dose: Two 500 mg film-coated tablets with 100 mg Norvir two times a day with food, or within two hours of 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: $1,057.13 / month for 500 mg tablets
Potential side effects and toxicity
Most common are diarrhea, abdominal discomfort, vomiting, and nausea. New warning added to the drug label last year states that Invirase/Norvir may change the electrical activity of the heart, which may lead to abnormal heart rhythms called prolonged QT or PR intervals. People with underlying heart conditions, or who have heart rate or heart rhythm problems, are at greater risk. Symptoms may include lightheadedness and fainting. A medication guide is now required with a prescription. 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 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 alfuzosin, Revatio, Tambocor (flecainide), Rythmol (propafenone), Biaxin (clarithromycin), dexamethasone, Cordarone (amiodarone), oral Versed (midazolam), Halcion (triazolam), Orap (pimozide), Lanoxin (digoxin), ergot derivatives (such as Cafergot, D.H.E. 45, Methergine, and Wigraine), quindine, trazodone, Tykosyn (dofetilide), lidocaine (systemic), garlic supplements, or the herb St. John’s wort. Colchicine levels may be increased and dose reduction is necessary. Do not use Advicor, Altoprev, Livalo, 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, and Flovent); use with caution. 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. Invirase may alter Coumadin levels; additional monitoring may be required. Do not take with birth control pills as Invirase reduces the level of the hormone ethinyl estradiol. 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. Use with caution with bosentan, salmeterol, and immunosuppressants (including transplant drugs).
More information
Invirase has efficacy similar to Kaletra with less hyperlipidemia (elevated cholesterol and triglycerides). Invirase/Norvir was downgraded from “alternative choice” to the list of “regimens that are acceptable but should be used with caution” in the U.S. DHHS HIV treatment guidelines for what to take when starting HIV therapy due to the new warning on heart activity (see Potential Side Effects). Must be taken with food. See package insert for more complete information on potential side effects and interactions.
Doctor’s comments
Saquinavir has a long and confusing history. In the form of Invirase, it was the first approved PI, but it had limited appeal because of poor absorption and low drug levels. Then came Fortovase, which was better absorbed but had more gastrointestinal side effects. The combination of Fortovase plus Norvir (initially using high doses of both drugs) was highly effective but not easy to take. Since the boosting effect of Norvir eliminated the absorption concerns with Invirase, Fortovase was eventually retired and Invirase made a small comeback, combined with lower, better tolerated doses of Norvir. In fact, it would still be a reasonable combination if it weren’t for the availability of once-daily boosted PIs (Prezista and Reyataz) that use half the daily dose of Norvir. The FDA also issued a recent warning about potentially serious EKG changes with Invirase. Saquinavir will be the first PI to go generic, though it seems unlikely that this will increase its use much, at least in the United States. —Joel Gallant, MD, MPH
Activist’s comments
A drug with many names and many lives—as one of the first PIs, it required many pills taken twice a day with a high fat meal, and it still had uneven absorption. A new version dubbed Fortovase came in a gel cap with better absorption, but also caused more GI problems like gas and diarrhea, and it quickly fell out of favor as better-tolerated PIs were introduced. Then it was discovered that with Norvir boosting you could just take two of the old pills twice a day (still with food) but with far fewer side effects. It’s still one of the better tolerated twice-daily PIs, and it may get yet another life when it goes generic and payers require patients to sacrifice the convenience of once-daily dosing to save money. —Jeff Taylor
