March/April 2009
Common Name: darunavir (DRV, formerly TMC-114)
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 patients. All doses must be taken with 100 mg Norvir and food. 75 mg tablet available for children over six (five to eight tablets twice a day based on weight). Take missed dose as soon as possible, but if more than 12 hours late on the once-daily (or six hours late on the twice-daily dose), do not double up on your next dose; take the next dose on schedule.
AWP: $1,027.65 / month
Manufacturer contact: Tibotec Therapeutics, www.prezista.com, 1 (877) REACH-TT (732-2488)
AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov
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. New warning last year: measure liver function before starting Prezista/Norvir. Also, 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. The rare risk of liver toxicity seems to be greater in people who: have advanced HIV disease and are taking many other medications; have hepatitis B or C; and/or develop IRIS (see below). 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. If you experience blistering, mouth sores, conjunctivitis (redness or inflammation of eye, or pink eye, which if untreated may result in permanent vision loss), swelling, muscle or joint aches, fever, or general malaise (general ill feeling), seek medical attention immediately. You may need to stop all medications. Prezista contains a "sulfa" component to it and should be used cautiously by people with "sulfa" allergies. Overall, the rate of adverse effects were similar between Prezista and the comparator group studied, with diarrhea being the most common side effect, seen less in the Prezista groups.
As seen with other protease inhibitors, there can be increased levels of cholesterol and triglycerides (except unboosted Reyataz), 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 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: 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 Zocor, Simcor, Vytorin, Mevacor, Altoprev, Advicor, or Pravachol; lipid-lowering alternatives such as Lipitor or Crestor can 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 methods of non-hormonal contraception are recommended.
Tips: Once-daily Prezista was approved last year for people taking HIV therapy for the first time (called "treatment naive"), in addition to its approval for those who are treatment experienced. The new approval is based on 48-week results of the ARTEMIS study. Prezista is one of the four recommended PIs for initial therapy in treatment-naive people in the U.S. DHHS and IAS-USA HIV guidelines. Tibotec received community kudos for not pricing Prezista higher than other new PIs. In one study it demonstrated superior viral load responses when compared to Kaletra. Please see package insert for more complete potential side effects and interactions.
Doctor
Prezista (darunavir, known to some as TMC 114) co-administered with ritonavir was approved in 2006 for treatment of HIV infection in antiretroviral treatment-experienced adults having resistance strains to more than one PI. In 2008, Prezista was approved for once-daily dosing in those individuals infected with HIV and naive to therapy. Prezista now has the best of both worlds. Multiple studies have shown the drug to be effective in PI-experienced individuals with fewer short-term adverse events and fewer lipid abnormalities with long-term use. The 2008 DHHS Guidelines Panel elevated ritonavir-boosted darunavir to one of the four preferred PI combinations for treatment of HIV infection. Tolerability, ease of administration, reduced adverse events, and favorable resistance patterns have made Prezista a popular PI choice with patients and health care workers. -- Frank M. Graziano, M.D., Ph.D.
Activist
Prezista, the most recent protease inhibitor, recently received FDA approval for 800 mg with 100 mg Norvir/ritonavir-boosted once daily dosing in newcomers to HIV therapy and can now be dosed for children based on body weight. For us old-timers of HIV treatment, Prezista's prescribed dosing is still 600 mg (300 mg, twice a day) with 100 mg Norvir/ritonavir-boosting. Prezista is a good option for those resistant to other protease inhibitors: it is very good at quickly reducing viral load and it is an easy drug, in terms of both dosing and side effects compared to other PIs. Prezista makes the DHHS guidelines "preferred" listing of PI-based regimens. And as an aside, Tibotec, the maker of Prezista, included it in a first of its kind study, the GRACE (Gender, Race, and Clinical Experience) study, which investigated gender differences in HIV drugs. To their credit, Tibotec took great pains to recruit and enroll more women than men in this study, even going so far as to limit men's enrollment to one man for every three women. -- Morris Jackson