Brand name: Agenerase

Common name: amprenavir

Class: HIV protease inhibitor (PI)

Standard dose: Eight 150 mg (1200 mg) soft gelatin capsules twice a day, no food restrictions. Take a missed dose as soon as possible, but do not double the next dose. Approved for children ages 4 and older. Grape, bubblegum, peppermint flavored liquid. Adults should not use liquid if possible.

Wholesale cost: $7,994/yr., $666/month

Patient assistance number: 1 (800) 722–9294, www.agenerase.com

AIDS Treatment Information Service: 1 (800) HIV–0440 (448–0440)

Potential side effects:

Nausea, vomiting, abdominal pain, taste disorders, fatigue, headache, rash, anemia, colitis, bruising easily, prolonged bleeding, depressive or mood disorders, circumoral paresthesia (tingling or numbing around the mouth) and peripheral paresthesia. Gaseous symptoms are common and may be severe. Taking with food may help, but check for pancreatitis when there is severe stomach pain. Seen with all the other protease inhibitors are high blood levels of cholesterol and triglycerides (fats) and perhaps associated heart disease, 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), worsening or new cases of diabetes (symptoms include increased thirst and hunger, frequent urination, unexplained weight loss, fatigue, and dry itchy skin; see your doctor promptly) and increased bleeding in hemophiliacs.

Potential drug interactions:

Do not use Zocor or Mevacor; suggested alternatives are Lipitor, Lescol, Baycol, and Pravachol (looks best on paper for protease inhibitors). Alternatives should still be used with caution because of potential for liver toxicity. Rescriptor and Viracept greatly increase Agenerase blood levels (and usually stomach discomfort) and prescriber may need to adjust dose accordingly. Sustiva has been shown to significantly reduce blood levels of Agenerase unless also taken with Norvir mini-dose. Interacts with several antihistamines, sedatives, and anti-fungal drugs. Do not use with rifampin. Dose reduction of Mycobutin is necessary. Increased blood levels and drug activity are seen with dapsone, erythromycin, Sporonox, Xanax, Tranxene, Valium, flurazepam, Cardene, Procardia or Adalat CC and Nimotop. Each capsule contains vitamin E, so avoid taking with other blood thinners, such as Coumadin (warfarin), clotting factor, vitamin K, and low-dose daily aspirin, as well as herbs such as ginger, garlic, feverfew, ginseng and gingko biloba. Ibuprofren (Advil) can also be problematic. Do not take extra vitamin E. Protease inhibitors increase blood levels of Viagra (sidenafil citrate), and Viagra dose should be started at 12.5 mg and increased as needed and tolerated. It’s recommended that people do not exceed 25 mg in a 48 hour period because of potential for fatal reaction.

HIV Drug Guide Correction: Agenerase Warning
Editor's Note: An important class warning for the HIV protease inhibitors is left out of the printed version of the Agenerase page. This warning, under "Potential Drug Interactions," states, "Do not take with rifampin, Versed, Halcion, D.H.E. 45, Migranal, St. John's Wort, or ergot derivatives (such as Cafetrate, Cafergot, Wigraine and Methergine, in any form—serious interactions seen with dilation during gynecological exams)." In addition, Orap (pimozide) should not be taken with Agenerase.

Tips:

The huge number of horse pills is a major drawback. However, it can be reduced with Norvir (four Agenerase capsules [600 mg] with one capsule of Norvir [100 mg] twice a day equals the full Agenerase dose). Norvir significantly increased cholesterol and triglycerides. However, little data are available with Agenerase and Norvir. May also penetrate the lymph nodes, where virus can hide out. Severe rash can be life-threatening (grade 3 or 4, see Viramune). Avoid taking with food high in fat. Warning issued on Agenerase liquid solution. Should not be used by pregnant women, because the larger amount of propylene glycol in this formluation may be harmful to the fetus.

Manufacturer

Agenerase (amprenavir), approved April 1999, is an HIV protease inhibitor that, in clinical studies, has appeared to have significant antiviral activity when used in a variety of two-, three-, and four-drug combination regimens. Agenerase has been studied clinically in combination with numerous approved and investigational antiretroviral therapies, including nucleoside analogue reverse transcriptase inhibitors, non-nucleoside RTI’s and protease inhibitors. In clinical trials to date, Agenerase appears to have an acceptable safety profile with few treatment-limiting adverse events. The most commonly reported adverse events in clinical studies have included nausea, diarrhea, headache, fatigue, vomiting, rash and perioral parasthesia. Please refer to the full prescribing information for additional important safety information.

—GlaxoSmithKline

Doctor

FDA approved 4/15/99 to treat HIV-1 infected adults and children. Amprenavir is usually well tolerated. Side effects: rash (20%), diarrhea, nausea. No serious adverse events or laboratory tests abnormalities are usually found. It is recommended as an alternative for initial treatment of established HIV infection. Usual dose: eight 150 mg (1,200 mg) capsules twice a day (pill burden). Ritonavir increases amprenavir levels significantly (once-daily dosing with ritonavir is being evaluated). Ritonavir/amprenavir based regimen has been of value in salvage therapy. It has been shown that amprenavir is little cross-resistant with other PIs in less-than-2 PI-experienced patients. Amprenavir plasma concentrations are dramatically decreased by the association with Kaletra. Amprenavir pro-drug shows promise in early clinical trials.

—Carlos H. Zambrano, M.D.

Activist

Increasing their AIDS portfolio, in 1999 GlaxoSmithKline developed Agenerase, a protease inhibitor to go along with their nucleosides. There was a considerable delay for Agenerase to become available, as the last PI to be approved was in 1997. By this time people were in need of a new protease inhibitor since mutations from older PIs were showing up. But only one Agenerase mutation is not cross resistant to other PIs and clinical trial data shows only a modest benefit for those who are salvage patients. So, Agenerase would fall into the “me too” class of drugs offering not much evidence that it is useful in initial or third-line regimens. Short-term studies have shown no evidence for facial and limb wasting or signs of diabetes, yet showed a 90% increase in triglyceride levels. Now if Glaxo would develop a NNRTI they will corner the market. Then we’ll wait for a HAART combination pill.

—Matt Sharp