Lexiva

Common Name: fos-amprenavir calcium

Brand name: Lexiva

Class: HIV protease inhibitor (PI)

Standard dose: For people on a PI for the first time: two 700 mg tablets with either one 100 mg or two 100 mg Norvir, both once daily; or two 700 mg tablets (without Norvir), twice daily; or one 700 mg tablet with 100 mg Norvir, twice daily. For PI-experienced patients, one 700 mg tablet of Lexiva with 100 mg Norvir, twice daily. A grape/bubblegum/peppermint-flavored oral suspension is also available. Can be taken with or without food, with no food restrictions, at any dose. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $820.99 / month for 60 tablets and $125.78 for 225 ml oral suspension (50 mg/mL)

Manufacturer contact: ViiV Healthcare, 1 (877) 844-8872

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 monitoring. Patients with hepatitis B or C should be monitored closely for the possibility of elevated liver enzyme levels. Dose adjustment is recommended for people with liver impairment. 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 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; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a 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. 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. Do not use Advicor, Altoprev, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution. Calcium channel blockers (such as Norvasc, Procardia, and others) should be used with caution and careful monitoring. Lexiva can lower methadone concentrations. A dose adjustment of Mycobutin (rifabutin) will be needed when used in combination with Lexiva. Steroids, such as 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. Use caution with Paxil. Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). Drug levels of Paxil are lowered; titrate dose based on clinical response. The effectiveness of birth control pills may be decreased when taking Lexiva; alternative or additional contraception methods with barrier should be used.

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: Last year, as with Kaletra, U.S. HIV treatment guidelines dropped Lexiva/Norvir as "preferred" for first-time therapy and listed it as an alternative. According to the guidelines, the change was made because regimens consisting of once-daily dosing and no more than 100 mg of Norvir are now favored. Lexiva 1,400 mg with Norvir 100 mg once daily was shown, in one study, to have similar virological and CD4 T-cell benefit when compared to once-daily boosted Reyataz. However, this dose was precluded from the preferred list due to the small study size. It can be taken once daily in treatment-naive patients. The lower dose of Norvir may cause less of an increase in 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. Another analysis from a French cohort showed Lexiva was associated with an increased risk of heart attacks and heart disease.

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. A related drug called amprenavir (Agenerase) was approved by the FDA in 1997, but amprenavir was discontinued when Lexiva came to market, as it was a better version. In 2007, fos-amprenavir was approved for once-daily dosing (two tablets) with low-dose ritonavir. The DHHS Guidelines Panel previously listed ritonavir-boosted Lexiva as one of the four preferred PI options, but in the past year, this drug was listed instead as an alternative to other preferred options. Overall this drug has a very similar profile in terms of efficacy and safety to Kaletra, except it is not co-formulated as is the case for Kaletra. As it offers no particular advantage over Kaletra, it is unclear when someone should be on Lexiva versus Kaletra. -- Cal Cohen, M.D.

Activist

Replacing the original Agenerase with easier dosing, it provides the option of being unboosted in those without prior PI experience. Everyone else will need the Norvir boost. Side effects are similar to most other PIs -- diarrhea, increased blood lipids, lipodystrophy, etc. Add to that the possibility of rash -- especially for those with a sulfa allergy (like a Bactrim allergy), and it's no wonder this drug has fallen out of favor compared to the newer protease inhibitors. -- Jeff Taylor