Brand name: Invirase
Generic name: indinavir sulfate (indinavir), or IDV
Class: Protease inhibitor (PI)
Manufacturer: Genentech, www.genentech.com, (800) 626-3553
AWP: $1,112.09/month for 500 mg tablets
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 for patients over 16 years old. Must be taken with Norvir. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.
Potential side effects and toxicity: Most common are diarrhea, abdominal discomfort, vomiting, and nausea. Drug label warning 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, who have heart rate or heart rhythm problems, or low potassium or magnesium levels, are at greater risk. Symptoms may include lightheadedness and fainting. A medication guide is now required with a prescription. See chart for potential drug class side effects.
Potential drug interactions: PIs interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. 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 (additive effect on QT and PR interval prolongation may occur). Rescriptor, Crixivan, Norvir, Viracept, and Kaletra all significantly increase Invirase concentrations. No dosage change when taken with Kaletra, but additive effect on QT and PR interval prolongation may occur. Do not take with alfuzosin, Revatio, Tambocor (flecainide), Rythmol (propafenone), Biaxin (clarithromycin), dexamethasone, Cordarone (amiodarone), oral Versed (midazolam), Halcion (triazolam), Orap (pimozide), Lanoxin (digoxin), quinidine, 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 cholesterol. Cholesterol-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution and started at the lowest dose possible; you should be monitored closely for increased side effects from these medications. Cannot be taken with rifampin. Rifabutin can be used as alternative, but its dose needs to be decreased. Methadone doses may need to be increased. Invirase increases levels of fluticasone (active component of Advair, Flonase, and Flovent); use only if the benefits outweigh the risks, and monitor for signs of Cushing's syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Alternatives should be considered, particularly for long-term use. 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) as these medications will decrease Invirase levels. 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. Prilosec, Prevacid, or any other PPI (medications used to treat acid reflux or heartburn) increase Invirase levels, therefore monitor for possible side effects from Invirase if taken together. Use with caution with bosentan, salmeterol, and immunosuppressants (including transplant drugs). Refer to the package insert for the complete guide to the drug interactions. Use of the hepatitis C drug Victrelis (boceprevir) along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs -- combined use is not recommended.
More information: Rarely used, 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 DHHS HIV treatment guidelines for what to take when starting HIV therapy. People with previous QT or PR prolongation issues, those who take medications that increase the risk for these heart problems, and those with low potassium or magnesium levels should be aware of this, as Invirase/Norvir taken under these circumstances may lead to an increased risk for heart problems. Must be taken with food and always with Norvir. Patent expired in May 2011, but no generic is available. There's buzz about the ability to create a bioequivalent formulation. See package insert for more complete information on potential side effects and interactions.
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 recently issued a 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, M.D., M.P.H.
I believe Invirase was the first protease inhibitor, so it will have a place in the history books. "Back in the day" it had a place, though a small one -- with all the meal restrictions and complications from side effects, it never really stood out in my book. All the formulations saquinavir went through just made it more difficult to keep track of where it stood in the rankings. Some folks believe it will make a comeback with the generic version, but I doubt it. However, it may get yet another life when it goes generic in developing countries, as they need to develop stronger regimens.
-- Joey Wynn