Invirase

Protease Inhibitor

Common Name: saquinavir (SQV)

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 a missed dose as soon as possible, but do not double up on your next dose. The 200 mg hard-gel capsules are still available.

AWP: $952.26 / month for 500 mg and $931.83 / month for 200 mg

Manufacturer contact: Roche Pharmaceuticals,
www.rocheusa.com, 1 (800) 562-6367

AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov

Potential side effects and toxicity: Most common are stomach-related -- diarrhea, abdominal discomfort, 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 sometimes the 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; report symptoms of illness, such as shingles and TB, to health care provider.

Potential drug interactions: Viramune, Sustiva and Mycobutin (rifabutin) decrease Invirase levels. Not recommended to be used with Aptivus/Norvir. 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), oral 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 Crestor (rosuvastatin), Zocor (simvastatin), Vytorin, or Mevacor (lovastatin); lipid-lowering alternatives are Lipitor (atorvastatin), Lescol (fluvastatin), and Pravachol (pravastatin), but they should be used with caution due to potential for liver toxicity. Data show that when rifampin is given with saquinavir/ritonavir, there is significant liver toxicity in 40% of patients. The combination should be avoided. Methadone doses may need to be increased. Increases levels of fluticasone (active component of Advair, Flonase, Flovent) and trazodone. Trazodone concentrations may increase; a lower dose of trazodone is recommended. Use calcium channel blockers with caution.

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: 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 (a different formulation of saquinavir, now discontinued) plus Norvir. Invirase/Norvir has demonstrated safety, but the efficacy according to U.S. HIV treatment guidelines is inferior to Kaletra in patients new to HIV treatment. Must be taken with food. There is also some research supporting Invirase 1,000 mg + Kaletra standard dose twice a day in people with limited treatment options. 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. It is difficult to convey the anticipation and excitement this new class of antiretrovirals brought for our patients sick with AIDS or untreatable because of HIV resistance to their current antiretrovirals. Unfortunately, for some with resistance mutations, Invirase was monotherapy. We had no other active drugs to combine with it. The history of Invirase in the treatment of HIV infection, however, appears to me to be a lesson in "pressure to get a drug to market." Dosing of this drug was three hard-gel capsules taken three times daily in combination with two other antiretrovirals. Invirase was relatively well tolerated but very poorly absorbed in the gut. To improve absorption a full and/or high-fat meal was required each time it was taken. I remember this being difficult for many patients to do. Those who did, gained weight (not a bad thing for those who were very thin) and often a lot of weight (for some a problem). Because of the difficulty obtaining adequate blood levels of Invirase, failure of HAART therapy with this drug was observed. In 1997, a soft gel saquinavir capsule (Fortovase) was approved. With Fortovase, better blood levels were obtained, but gastrointestinal side effects meant tolerability was decreased. The number of pills, dietary needs (still needed the full meal), and tolerability issues led to poor adherence for some and, eventually, failure to control the virus. Things came full circle in 2005 when Fortovase was taken off the market and Invirase (now 500 mg capsules dosed two capsules twice daily with a meal) boosted with low-dose ritonavir (one 100 mg capsule, twice daily) showed efficacy. Now, blood levels are consistent and tolerability is not as much an issue. However, with the newer protease inhibitors now available, use of Invirase has not measurably increased. Invirase is a drug to consider (with testing for genotype and phenotype) for those new to HAART therapy. -- Frank M. Graziano, M.D., Ph.D.

Activist

Invirase is the newer version of Fortovase which went bye-bye three years ago. Invirase was the first FDA-approved PI compound marketed back in 1995, but because it wasn't absorbed well, it was basically useless. Its low bioavailability also allowed for drug resistance to develop quickly, wiping out the entire PI class for many before most of them were even developed. Invirase, reformulated as a 500 mg tablet about a year ago, is the third attempt to make it a more useful drug, and boosted with Norvir twice a day, it seems to be doing a better job. -- Morris Jackson

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