|
|
Test Positive Aware Network
Invirase (Saquinavir, SQV)
January/February 2008
| |
|
|
Brand Name: Invirase
Common Name: saquinavir (SQV)
Class: HIV protease inhibitor (PI)
Standard Dose: Two 500 mg film-coated tablets + Norvir 100 mg 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: $789.70/month for 500 mg and $649.26/month for 200 mg
Manufacturer contact: Roche Pharmaceuticals,
www.rocheusa.com, 1 (800) 526–6367
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, there can be increased levels of cholesterol and triglycerides (except possibly unboosted Reyataz) 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: |
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, Wigraine, Methergine, and D.H.E. 45), 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.
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. 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. Rescriptor, Crixivan, Norvir, Viracept and Kaletra all significantly increase Invirase's concentrations. No dosage change when taken with Kaletra.
Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis per 72 hours, 2.5 mg Levitra per 24 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 |
| Saquinavir is a PI that has had many lives. It was the first approved PI in its Invirase form, but it quickly fell out of favor because it was barely absorbed. Then came Fortovase, a soft-gel capsule formulation of saquinavir that actually made it into the bloodstream. Fortovase was later the first PI to be combined with Norvir, and the combination was effective…but not much fun to take because of the high doses of Norvir that were used. We then found out that Invirase, which came close to being taken off the market, was absorbed well when combined with Norvir and had fewer side effects than Fortovase. Fortovase promptly disappeared, and Invirase made a modest come-back, especially with the development of a 500 mg tablet. When Invirase is used now, it must always be boosted with a low-dose of Norvir. It's generally well tolerated, and a recent study found that it was as effective as Kaletra. However, because you still have to take three pills twice a day at current dose and there's no clear advantage over other PIs, it's still not widely used. Ongoing studies, including studies of once-daily doses using less Norvir, may change that, but for now it's generally viewed as an alternative to the standard PIs. -- Joel Gallant, M.D. |
| Activist |
| Invirase was the first protease inhibitor approved by the FDA, in 1995. Only around 4% of the drug a person took would become active in the blood. As a consequence of this poor bioavailability, a large percentage of the people who used Invirase failed quickly on the drug. More importantly, because they were receiving the equivalent of only a partial and inadequate dose of the drug, it quickly selected for resistant mutations, thus knocking out the whole class of the new wonder drugs within a matter of months. Activists fought bitterly with the manufacturer, Hoffman La Roche, about this since the company steadfastly defended the drug and aggressively marketed it, despite the warnings by many researchers and physicians. Many people who were familiar with this early era of protease inhibitors still believe that a significant number of people lost the opportunity to benefit from protease inhibitors because of this and subsequently died. Over time, Roche quietly acknowledged the problem and worked hard to come up with a formulation (Fortovase) that overcame this problem. Roche was close to taking Invirase off the market, but instead they ended up discontinuing Fortovase, which they had worked so hard to create. In yet another irony, in one of the earliest publications about Invirase, a research group in Boston had combined Invirase with full dose Norvir in a simple 2-drug combination and showed results equal to or better than most 3-drug combinations which included protease inhibitors. This early study was a very advanced concept at its time and a harbinger of things to come. Today, Invirase with a low dose Norvir booster is enjoying a new popularity as a potent and relatively non-toxic treatment. When Invirase goes off patent in 2010 and generic versions become available, there is talk that some payers might even require the use of generic Invirase as the first choice among protease inhibitors as a cost-savings move. -- Martin Delaney |
 |
|
|
This article was provided by Test Positive Aware Network. It is a part of the publication Positively Aware.
|
|
