Reyataz

Common Name: atazanavir sulfate

Brand Name: Reyataz

Class: HIV protease inhibitor (PI)

Standard dose: One 300 mg capsule plus 100 mg Norvir, once daily (this dose must be used if taking Viread or Truvada), or two 200 mg capsules, once daily; take with food. Also available in 100 mg and 150 mg capsules. 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: $1,077.22 / month for 300 mg capsules

Manufacturer contact: Bristol-Myers Squibb, www.reyataz.com, 1 (800) 321-1335

Potential side effects and toxicity: Dizziness and lightheadedness. Elevated levels of unconjugated bilirubin (produced by the liver) may result in cases of jaundice (yellowing of the skin or eyes), reported in 4-9% of individuals. However, no evidence of liver problems was reported. Nevertheless, report jaundice to your health care provider right away. Other side effects may include rash, kidney stones, and elevated liver function enzymes, a sign of liver damage; this may be more common in people with hepatitis B or C. Reyataz is the only PI not associated with increased levels of cholesterol and triglycerides, which are in turn associated with increased risk of heart disease, but greater lipid levels may be seen if Reyataz is boosted with Norvir. 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: Treatment-experienced people cannot take with proton pump inhibitors (PPIs -- long-acting medicine for acid reflux). Treatment-naive people can take a PPI with a dose comparable to Prilosec OTC 12 hours before their Reyataz/Norvir. H2-receptor antagonists like Pepcid may be taken (no more than 20 mg twice a day if treatment-experienced or 40 mg twice a day if treatment-naive, or equivalent doses) at the same time as Reyataz/Norvir (before the antacid has started to work) or at least 10 hours later. If taking with Viread or Truvada and an H2-receptor antagonist, you must take them with the 400 mg Reyataz/100 mg Norvir dose for treatment-experienced people. When taking Reyataz without Norvir, dose can be taken at least two hours before and at least 10 hours after Pepcid, Zantac, or Axid. Reyataz should be taken two hours before or one hour after antacids (Rolaids, Tums, and Mylanta). Do not take with rifampin, Camptosar (irinotecan), Versed (midazolam), Halcion, ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), pimozide, Crixivan, or 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.

Must be taken two hours apart from Videx, due to Videx's buffer, and must be taken 2 hours before or 1 hour after Videx EC (unless taking Videx EC with Viread). Treatment-naive people should take 400 mg Reyataz and boost with Norvir (100 mg) when taking in combination with Sustiva, but HIV treatment-experienced people should not use Reyataz with Sustiva. Viread decreases the concentration levels of Reyataz. In addition, Reyataz increases Viread concentrations, which could increase Viread-associated adverse events, including kidney disorders. Those taking Reyataz and Viread should be monitored for Viread-associated adverse events. The heart medications bepridil, Cordarone, quinidine, and lidocaine should be used cautiously. Monitoring may be required when used with Coumadin or immunosuppressants. Increased levels of the inhaled and nasal sprays with fluticasone (found in Advair, Flonase, and Flovent) can occur and should be used with caution. Effectiveness of birth control pills may be decreased, alternative or additional contraception with barrier should be used. Oral contraception should contain no more than 30 mcg of ethinyl estradiol if taking Reyataz without Norvir and and at least 30 mcg if taken with Norvir. Use caution when using itraconazole or ketoconazole. Vfend is not recommended. Reducing dose and frequency of rifabutin to 150 mg every other day or three times a week is recommended. Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). 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. Calcium channel blockers should be monitored. A lower dose of trazodone is recommended.

Tips: Boosted Reyataz is one of two protease inhibitors recommended by the U.S. HIV treatment guidelines for people on antiviral therapy for the first time. Please see package insert for more complete potential side effects and interactions.

Doctor

Reyataz (atazanavir) was approved for use in combination with other antiretrovirals in 2003, and was the first protease inhibitor to be approved for once-daily dosing. While it could be taken without the ritonavir boost, atazanavir boosted and unboosted were compared head to head in a study done a few years ago, and it was observed that boosted atazanavir had enough advantages both in terms of an increased likelihood of suppression, as well as minimizing the risk of resistance in those whose viral load was not fully suppressed. Since then, studies have pursued ways in which treatment could be started with boosted atazanavir and, after achieving virologic suppression, the ritonavir could be removed and the people would remain on unboosted atazanavir instead. This approach is still undergoing exploration. However, the combination of boosted atazanavir plus Truvada once daily is among the more commonly selected first regimens in the U.S. Atazanavir is often well tolerated with low rates of GI side effects such as diarrhea, but there are two issues of note: one is that yellow discoloration of the skin and eyes can occur in perhaps one out of 10 who take the drug. It is important to note that this coloration is a "cosmetic" concern, since the reason it occurs is an increase in the blood levels of a normal substance called indirect bilirubin and such increases are not known to be harmful. Second, this drug requires stomach acid for absorption and there are dosing recommendations for those who require the use of acid-reducing medications to minimize their impact on atazanavir levels. There are advantages to this PI versus most of the others in having less of an impact on lipid (cholesterol) levels, and it has several favorable attributes which contribute to why it is now considered by the 2009 DHHS guidelines to be one of the two preferred PIs to consider for initial use. -- Cal Cohen, M.D.

Activist

The first once-a-day protease inhibitor, Reyataz remains -- with Prezista -- one of the two most popular PIs. It can also be taken without a Norvir boost -- though it should be taken with food if unboosted. This can help avoid many of the Norvir-associated problems -- diarrhea, raised cholesterol and triglyceride levels, and fat accumulation (aka PI belly). The yellowing of the skin and/or eyes can be disconcerting, but isn't dangerous, and will go away when you stop the drug, if it doesn't improve over time on therapy. Another drawback for some is that it can't be taken with the proton-pump inhibitors popular for controlling acid reflux, although there are options, like Pepcid, to which you can switch. -- Jeff Taylor