POSITIVELY AWARE MARCH/APRIL 2011
brand name: Prezista
common name: darunavir
class: Protease inhibitor (PI)
manufacturer: Tibotec Therapeutics | www.prezista.com, (877) REACH-TT (732-2488)
Standard dose: 800 mg (two 400 mg tablets) with 100 mg Norvir once daily with food for first-time therapy and treatment-experienced adults without Prezista-related HIV resistance, or 600 mg (one 600 mg tablet) with 100 mg Norvir twice daily with food for treatment-experienced adults with at least one Prezista-related HIV drug resistance mutation. 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: $1,156.21 / month
Potential side effects and toxicity
Prezista contains sulfa, and should be used cautiously by people with sulfa allergies. 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. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides. Increased cholesterol and triglycerides may be associated with an increased risk of heart disease. Other possible side effects 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 alfuzosin, Revatio, oral Versed (midazolam), triazolam (Halcion), ergot derivatives (D.H.E. 45, Migranal, Cafergot, Ergomar, ergonovine, methylergonovine), the herb St. John’s wort, cisapride, pimozide (Orap), and rifampin. Prezista may decrease levels of phenytoin (Dilantin), phenobarbital, and Tegretol; blood levels should be monitored. A reduced dose of rifabutin is recommended. Do not use Advicor, Altoprev, Livalo, Mevacor, Simcor, Vytorin, or Zocor 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 calcium channel blockers, such as Norvasc and others, and clinical monitoring is recommended. A lower dose of trazodone and disipramine is recommended. Monitoring may be required when using Coumadin (warfarin). 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 be decreased; consider the use of alternative or additional methods of contraception. No dosing adjustment required with Subutex or Suboxone, but monitoring is re-commended. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine.
More information
Prezista is one of two recommended PIs for initial therapy in treatment-naïve people in the U.S. DHHS HIV guidelines. FDA approval in late 2010 allows once-daily dosing for treatment-experienced adults who do not have Prezista-related drug mutations in their HIV, and both show it to be as effective as twice-daily dosing. This will also hopefully help adherence and decrease side effects. See package insert. In one major study, Prezista showed success even in people who missed doses; while it’s not ideal to skip doses, its “forgiveness” profile helped make it popular. Tibotec received community kudos for not pricing Prezista higher than other new PIs. See package insert for more complete information on potential side effects and interactions.
Doctor’s comments
Prezista started out as the best of the “second-generation” PIs, showing excellent activity in most people with PI-resistant virus. Then, it was shown to be more effective and more “resistant to resistance” than Kaletra in people who had taken PIs before but whose virus was susceptible to both drugs. A later study found that a once-daily dose of Prezista/Norvir had a number of advantages over Kaletra for first-line therapy, including less diarrhea, less lipid elevation, and better activity at higher viral loads. The latest development has been the approval of the once-daily dose for treatment-experienced patients who have no Prezista mutations. In short, you could say it’s the “PI for all seasons.” The main downside of Prezista is that it’s more likely than other PIs to cause an allergic rash, and, unlike the rash with Sustiva, a rash when you’re on Prezista usually requires a switch to a different drug. Prezista must always be taken with Norvir, and with food. —Joel Gallant, MD, MPH
Activist’s comments
Appropriate for either treatment-naïve or experienced patients, Prezista (along with Reyataz) has largely replaced Kaletra. It has fewer side effects than the older drugs—especially salvage drugs like Aptivus, and has been shown to be durable and well tolerated. It still needs to be taken with food, and has many of the drug interactions common to other PIs. Tibotec earned a gold star from the community when they introduced this drug by breaking the usual industry practice of pricing all new drugs higher than past drugs—helping keep costs down for patients and payers. —Jeff Taylor
