Prezista

Common Name: darunavir (formerly TMC114)

Brand Name: Prezista

Class: HIV protease inhibitor (PI)

Standard dose: 800 mg (two 400 mg tablets) once daily for first-time therapy or 600 mg (one 600 mg tablet) twice a day for treatment-experienced adults. All doses must be taken with 100 mg Norvir and food. 75 mg and 150 mg tablets available for children over six, dose based on weight. Take missed dose as soon as possible, but not if more than 12 hours late on the once-daily dose (or six hours late on the twice-daily dose). Do not double up on your next dose; take the next dose on schedule.

AWP: $1,102.20 / month

Manufacturer contact: Tibotec Therapeutics, www.prezista.com, 1 (877) REACH-TT (732-2488)

Potential side effects and toxicity: Prezista may cause mild to moderate rash, but the most common side effects may include diarrhea, nausea, headache, and abdominal pain. Laboratory testing for liver function should be done before starting therapy and patients should be monitored. Increased monitoring should be considered for people with underlying chronic hepatitis, cirrhosis, or elevated levels of AST/ALT (lab measures of liver function), especially during the first several months of therapy. No dose adjustment is necessary for those with mild to moderate liver disease, but Prezista/Norvir is not recommended for people with severe liver impairment. Severe rash, while very rare, can be life-threatening. Seek medical attention immediately. You may need to stop all medications. Prezista contains a sulfa component and should be used cautiously by people with sulfa allergies.

As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides, although cholesterol changes were similar to those seen with Reyataz in a study of uninfected participants, and better than those seen with Kaletra in two head-to-head studies. Increased cholesterol and triglycerides 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: Do not take with oral midazolam, triazolam (Halcion), ergot derivatives (D.H.E. 45, Migranal, Cafergot, Ergomar, ergonovine, methylergonovine), or the herb St. John's wort, Cisapride, pimozide (Orap), and rifampin. Prezista may cause decrease in the levels of phenytoin (Dilantin) and phenobarbital (seizure medications); blood levels of these anticonvulsants should be monitored. A similar recommendation applies to the anticonvulsant carbamazepine (Tegretol). A reduced dose of rifabutin is recommended. 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. The antifungal drugs such as itraconazole and ketoconazole may increase levels of Prezista, and Prezista may increase theirs, so caution must be exercised when used together (maximum dose is 200 mg a day for the antifungals). Blood levels of voriconazole (Vfend) may decrease. Voriconazole should not be administered unless benefit/risk justifies its use.

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. Prezista may increase levels of blood pressure medications called calcium channel blockers, such as Norvasc and others, and clinical monitoring of patients is recommended. A lower dose of trazodone and desimpramine is recommended. Monitoring may be required when using Coumadin (warfarin), or immunosuppressants. Increased levels of the inhaled and nasal sprays with fluticasone (found in Advair, Flonase, and Flovent) can occur and therefore alternatives should be considered, particularly for long-term use. Effectiveness of birth control pills may decrease. Alternative or additional methods contraception with barrier should be used. No dosing adjustment required with Subutex or Suboxone, but monitoring is recommended.

Tips: Prezista is one of two recommended PIs for initial therapy in treatment-naïve people in the U.S. DHHS HIV guidelines. Tibotec received community kudos for not pricing Prezista higher than other new PIs. Please see package insert for more complete potential side effects and interactions.

Doctor

Prezista (darunavir) co-administered with ritonavir was approved in 2006 for treatment of HIV infection in antiretroviral treatment-experienced adults whose HIV had developed resistance to the PI class. At that time, there was considerable importance to this property, as a large number of people were in care whose HIV could not be fully suppressed with the PIs that were available. When this new PI became available, a much larger number of people could re-establish virologic suppression -- particularly when it was taken with two other newer antivirals that became available soon after. The contribution of this drug to prolonging many people's lives was also notable in that, in general, people had few side effects on it. As a result of this safety profile, as well as high degree of activity, in 2008 Prezista was also approved for once-daily dosing in those individuals just starting HIV therapy. The 2009 DHHS Guidelines Panel elevated once-daily ritonavir-boosted darunavir to one of the four preferred PI combinations for treatment of HIV infection, which was done at the same time that lopinavir/ritonavir was listed instead as an alternative rather than preferred choice. This was justified in part by a study comparing Kaletra to Prezista which showed that while these two antivirals are similarly successful in patients who adhere to treatment, Kaletra was less successful than Prezista in maintaining suppression in those who miss doses over time. While it is ideal to take each dose each day, it is clear that this is not necessarily something everyone can do, and that has led to consider the use of Prezista given its better "forgiveness" for missed doses. It must be taken with food once daily, but as most people eat at least once daily, this is a small factor to consider. Overall, many people taking it feel well on it, and there are few expected lab toxicities noted. It is important to note, however, that a small number of people can have a severe rash when starting it, and a small number have been reported to have liver function test changes, making it important to monitor this drug soon after starting it. In all, Prezista has become an increasingly popular choice in people selecting their first PI. -- Cal Cohen, M.D.

Activist

Versatile Prezista is a preferred regimen for both treatment-naive patients as well as those who have PI resistance (albeit at different dosages). With fewer pills and less Norvir boosting than Aptivus, it is much better tolerated for those with PI resistance. For treatment-naïves, it is fast replacing Kaletra as a durable and well tolerated PI-based regimen. Its maker, Tibotec, has earned praise from the community for bucking the trend of pricing new protease inhibitors ever higher, and for its groundbreaking trial of Prezista called GRACE that included primarily women and people of color, setting the bar for other companies to follow. -- Jeff Taylor