March/April 2009
Common Name: fos-amprenavir calcium (FPV)
Brand name: Lexiva
Class: HIV protease inhibitor (PI)
Standard dose: Once a day -- two 700 mg tablets with either one 100 or two 100 mg Norvir. Twice daily: either two 700 mg tablets (without Norvir) or one 700 mg tablet with 100 mg Norvir. PI-experienced patients should use Lexiva twice daily with 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: $806.79 / month for tablets and $120.65 for oral suspension (50 mg/mL)
Manufacturer contact: GlaxoSmithKline,
www.lexiva.com, 1 (888) 825-5249
AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: Because Lexiva has a "sulfa" component, it should be used with caution in patients with allergies to sulfa drugs. The most common moderate to severe side effects may 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 (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: 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 insufficient 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, oral 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) and 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 (such as Norvasc, Procardia, and others). 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. Trazodone concentrations may increase; a lower dose of trazodone is recommended. 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 or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours.
Tips: Lexiva is one of the four protease inhibitors recommended by the U.S. HIV treatment guidelines for people on antiviral therapy for the first time, but is probably the least popular of the bunch. It can be taken once daily in treatment-naive patients. The lower dose of Norvir may cause 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 it 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.
Doctor
Lexiva (fos-amprenavir) was approved (two tablets twice daily) for use in combination with other antiretroviral drugs in the treatment of HIV infection in 2003. Fos-amprenavir becomes amprenavir once in the body. Amprenavir (Agenerase) was approved by the FDA in 1997. I took an amprenavir once and I had difficulty getting it down. How were my patients going to take a lot of these daily? The answer -- amprenavir was discontinued when Lexiva came to market. In 2007, fos-amprenavir was approved for once-daily dosing (two tablets) with low dose ritonavir. The DHHS Guidelines Panel has listed ritonavir-boosted Lexiva as one of the four preferred PI options. If you have a "sulfa allergy" (can't take Bactrim for instance) you should let your health care provider know. We have observed significant rash in such individuals using Lexiva. -- Frank M. Graziano, M.D., Ph.D.
Activist
Lexiva is the new and improved Agenerase (now defunct), which after it is absorbed turns into amprenavir. Lexiva is better formulated than its earlier version, requiring fewer pills, has better absorption, and does not require Norvir boosting, if it is one's first PI. But when boosted for the PI-experienced, it can have activity against some PI-resistant virus and as such, is a "preferred" PI-based regimen of the DHHS guidelines. Lexiva is generally well tolerated but, because it contains sulfur, it can cause a rash if you are allergic to sulfa-based drugs such as Bactrim/Septra. And, resistance to Lexiva can develop quickly, putting one at risk for developing cross-resistance across the entire PI class if strict adherence is not maintained. -- Morris Jackson