Reyataz Disease Interactions

Atazanavir may prolong the PR interval of the electrocardiogram in some patients. In one study, the mean maximum change in PR interval from baseline was 24 msec following a 400 mg oral dose of atazanavir versus 13 msec following placebo dosing. In studies of healthy volunteers and HIV patients, abnormalities in atrioventricular (AV) conduction were asymptomatic and limited to first-degree AV block. Rarely, second-degree AV block and other conduction abnormalities have occurred in overdose. Due to limited clinical experience, therapy with atazanavir should be administered cautiously in patients with preexisting conduction abnormalities (e.g., marked first-degree AV block or second- or third-degree AV block).

Cases of nephrolithiasis, some of which resulted in acute interstitial nephritis, renal failure, and/or hospitalization, have been reported during postmarketing surveillance in HIV-infected patients receiving atazanavir therapy. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made. The median time between atazanavir initiation and the onset of nephrolithiasis was 1.7 years, with a range of 5 weeks to 6 years. Therapy with atazanavir should be administered cautiously in patients with a current or past history of nephrolithiasis, as well as possible risk factors such as renal and/or hepatic insufficiency. Adequate hydration and/or urine acidification may help reduce the risk. However, urine acidification may be poorly tolerated and possibly harmful, particularly in patients receiving concomitant treatment with sulfonamide antibiotics. Patients who are dehydrated may also be at increased risk and should be encouraged to consume additional amounts of liquid or given intravenous fluids if necessary. Patients should be instructed to seek medical attention if they experience potential signs and symptoms of nephrolithiasis/urolithiasis such as flank pain, hematuria, dysuria, anuria, and urinary urgency. Temporary interruption or discontinuation of therapy may be required.

Atazanavir is not recommended for use in HIV- treatment experienced patients with end stage renal disease managed with hemodialysis.

Patients with underlying hepatitis B or C viral infections or marked elevations in transaminases prior to atazanavir treatment may be at increased risk for developing further transaminase elevations or hepatic decompensation during use of atazanavir. In addition, atazanavir is primarily metabolized by the liver and may accumulate in patients with moderate or severe hepatic impairment. Therapy with atazanavir should be administered cautiously in patients with preexisting liver disease, liver enzyme abnormalities, or hepatitis. Atazanavir is not recommended for use in patients with severe hepatic impairment, and the combination of atazanavir/ritonavir is not recommended for patients with any degree of hepatic impairment.

Atazanavir oral powder (Reyataz) contains phenylalanine (a component of aspartame) which can be harmful to patients with phenylketonuria (PKE). Each packet contains 35 mg of phenylalanine. Atazanavir in capsules (Reyataz) does not contain phenylalanine.

There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors; however, a causal relationship has not been established. In some patients, additional factor VIII was given. In more than half of the reported cases, protease inhibitor therapy was continued or reintroduced. Patients with hemophilia or other coagulation defects should be monitored closely for bleeding during protease inhibitor therapy.

New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, and some cases of diabetic ketoacidosis have been reported during postmarketing surveillance in HIV-infected patients treated with protease inhibitors. Some patients required either initiation or dosage adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, hyperglycemia persisted despite discontinuation of protease inhibitor therapy. A causal relationship has not been established between protease inhibitor therapy and these events. Monitoring patients for hyperglycemia, new onset diabetes mellitus, or exacerbation of diabetes mellitus should be considered during protease inhibitor therapy.

Treatment with ritonavir alone or in combination with other protease inhibitors (e.g., lopinavir, saquinavir, tipranavir, fosamprenavir) has resulted in substantial increases in the concentration of total cholesterol and triglycerides. These effects have also been reported with other protease inhibitors but may be the most dramatic with ritonavir. The clinical significance of these elevations is unclear. Marked elevation in triglyceride levels is a risk factor for development of pancreatitis. Triglyceride and cholesterol testing is recommended before starting ritonavir (with or without other protease inhibitors) and periodically during therapy. Lipid disorders should be managed as clinically appropriate.