fos-amprenavir calcium (FPV)
Class: HIV protease inhibitor (PI)
Standard dose: Once-a-day: two 700 mg tablets with either one 100 or two 100 mg Norvir.
Twice-a-day: Either two 700 mg tablets (without Norvir) or one 700 mg tablet with 100 mg Norvir.
A grape-bubblegum-peppermint-flavored oral suspension is also available. No food restrictions (may be taken with or without food) with any dosing. Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $734.56 / month for tablets and $112.55 for oral suspension (50 mg/mL)
Manufacturer contact: GlaxoSmithKline,
www.lexiva.com, 1 (888) 825–5249
1 (800) HIV–0440 (448–0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: Because Lexiva has a “sulfa” part, it should be used with caution in patients with allergies to sulfa drugs. The most common moderate to severe side effects include nausea, rash, diarrhea, headache, vomiting, fatigue, and abdominal pain. Rash occurred in about 19% of patients, but severe rashes were uncommon. If you experience a rash, notify your doctor. For mild or moderate rashes, your doctor may choose to continue Lexiva, with close follow-up and monitoring. Side effects and laboratory abnormalities were similar when Lexiva was taken once or twice daily, with or without Norvir.
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: Not recommended to be taken with Kaletra. When taken with Sustiva, boost a once-daily dose of Lexiva with 300 mg of Norvir. There is insufficent information on combining Lexiva and Kaletra, or the two of them with Sustiva—consider monitoring drug blood concentrations if used. Do not take with Tambocor, Rythmol, Versed (midazolam), Halcion (triazolam), rifampin, Orap (pimozide), ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), or the herb St. John’s wort (hypericum perforatum). Do not use Zocor (simvastatin), Vytorin, or Mevacor (lovastatin). Lexiva can raise levels of Lipitor (atorvastatin) Crestor (rosuvastatin); if used in combination, the lowest possible dose of Lipitor or Crestor should be used. Lipid-lowering alternatives are Lescol (fluvastatin) and Pravachol (pravastatin), but they should be used with caution due to potential for liver toxicity. Also avoid certain calcium channel blockers, used for heart disease. Lexiva can lower methadone concentrations. A dose adjustment of Mycobutin (rifabutin) will be needed when used in combination with Lexiva. Steroids, especially Decadron, may decrease levels of Lexiva. Increased levels of the inhaled and nasal sprays with fluticasone, a steroid for asthma or allergies (found in Advair, Flonase, and Flovent) can occur with Lexiva and therefore should be used with caution. The effectiveness of birth control pills may be decreased when taking Lexiva; women and their male partners should consider the use of alternative contraception methods with barrier.
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: L exiva is one of the three protease inhibitors recommended for people on antiviral therapy for the first time by the U.S. HIV treatment guidelines. It can be taken once daily in treatment naïve patients. The lower dose of Norvir may have less increase of cholesterol and triglycerides, but there is limited clinical data with this dose. Studies have demonstrated that protease inhibitor-experienced patients should take Lexiva 700 mg with Norvir 100 mg, both twice daily. The once daily dosing is not recommended for treatment-experienced patients for whom a PI therapy has previously failed. It is important to take Lexiva exactly as your doctor instructs, and not to change dosing without discussing with your doctor. The FDA points out that the study comparing Lexiva/Norvir against Kaletra in protease inhibitor experienced patients was not large enough to show that the combination was clinically equivalent to Kaletra.
A liquid formula of Lexiva is available. Please see package insert for more complete potential side effects and interactions.
Lexiva turns into amprenavir after it gets absorbed. Amprenavir used to be available as Agenerase, which came in big, suppository-sized capsules. You had to take a lot of them, and they caused nausea, diarrhea, and other unpleasantness. The switch to Lexiva was a big improvement. With or without Norvir, the dose has been four pills per day, which can be taken with or without food either once a day (with Norvir) or twice a day (with or without Norvir). The FDA also just approved a once-daily dose of Lexiva with a lower dose of Norvir, which may lower the effect on lipids and decrease GI side effects. However, if you have PI resistance, you should take Norvir-boosted Lexiva twice a day. Failure of unboosted Lexiva could lead to mutations that can cause cross-resistance to Prezista, but that’s not a problem if you boost Lexiva with Norvir.—Joel Gallant, M.D.
Lexiva (fos-amprenavir) is an improved version of an earlier protease inhibitor from GlaxoSmithKline called Agenerase. Agenerase was poorly absorbed and required a large number of pills taken daily. Lexiva solved that problem and can be used with and without a Norvir booster. Generally speaking, Lexiva doesn’t require boosting when used as one’s first protease inhibitor but does require the booster if a patient has had prior experience with protease inhibitors. When boosted, Lexiva can work against some forms of protease resistant virus and is generally well tolerated. Given its high potency, relative ease of use and low toxicity, it is a mystery why it is not more widely used. It deserves to play a larger role in treatment-experienced patients. —Martin Delaney