Reyataz (atazanavir)

June 2007     View PDF     En español
Reprinted from www.aidsmeds.com, US

What is Reyataz?
Reyataz is an anti-HIV medication. It is in a category of HIV medicines called protease inhibitors (PIs). Reyataz prevents cells infected by HIV from producing new virus. This reduces the amount of virus in your body.

Reyataz, manufactured by Bristol-Myers Squibb, was approved for the treatment of HIV by the U.S. Food and Drug Administration (FDA) in 2003.

Reyataz must be used in combination with at least two other anti-HIV drugs.

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What is already known about Reyataz?
For HIV-positive people who have not taken anti-HIV drugs in the past—that is, people starting anti-HIV drug treatment for the first time—the FDA-approved dose of Reyataz is 400mg (two 200mg capsules) taken once a day. However, a frequently prescribed dose is one 300mg capsule (or two 150mg capsules) of Reyataz plus a single 100mg Norvir® (ritonavir) capsule, both taken once a day. Norvir is used in this situation to boost Reyataz levels in the bloodstream, potentially making it more effective against HIV. In fact, this combination of Reyataz and Norvir is necessary for people who are using either Viread® (tenofovir) or Sustiva® (efavirenz) in a drug regimen that involves Reyataz. This is because both Viread and Sustiva can decrease Reyataz levels in the bloodstream.

For HIV-positive people who have taken anti-HIV drugs in the past – for example, people who have experienced a rebound in viral load while taking other anti-HIV medications (especially protease inhibitors)—the FDA-approved dose of Reyataz is one 300mg capsule (or two 150mg capsules) plus a single 100mg Norvir® (ritonavir) capsule, both taken once a day.

Reyataz should be taken with food, preferably a complete nutritious meal, to ensure proper absorption of the drug into the bloodstream.

Reyataz is not approved for use in HIV-positive children.

Clinical trials have determined that Reyataz is safe and effective when combined with other drugs, most notably two nucleoside reverse transcriptase inhibitors (NRTIs). Clinical trials have also suggested that Reyataz, combined with Norvir, is an effective option for people who have failed a protease inhibitor-based drug regimen in the past. A number of clinical trials have also demonstrated that Reyataz is less likely to cause increased lipid levels (cholesterol and triglycerides) than other protease inhibitors.

For HIV-positive adults beginning anti-HIV drug therapy for the first time, Reyataz plus Norvir is listed as a “preferred” protease inhibitor option by the United States Department of Health and Human Services in its treatment guidelines. Reyataz used without Norvir is listed as an “alternative” treatment option (if Reyataz is to be combined with Atripla™, Truvada®, or Viread®, it must be combined with Norvir).

If your viral load becomes detectable while taking a drug regimen that contains Reyataz, your doctor can order a drug-resistance test to see which drugs your virus are becoming less sensitive to. If your doctor finds that your virus is becoming resistant to Reyataz, it might be possible to begin taking a low dose of Norvir to boost the amount of Reyataz in the bloodstream. This may help overcome low-level resistance to Reyataz and help push viral load back down to undetectable levels.

Many of the currently available protease inhibitors are affected by cross-resistance. This means that, if you’ve tried and failed a drug regimen in the past that contained a protease inhibitor, your virus might be resistant to Reyataz. Similarly, if you take an anti-HIV drug regimen that contains Reyataz and your virus becomes resistant to the drug, your virus might also be resistant to many of the other protease inhibitors available. This is why it is very important to use drug-resistance testing to determine which drugs your virus are no longer responding to if you experience a rebound in your viral load while taking an anti-HIV drug regimen. Drug-resistance testing can also help you figure out which protease inhibitors your virus is still sensitive to.

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What about drug interactions?
Reyataz is broken down (metabolized) by the liver, like many medications used to treat HIV and AIDS. This means that Reyataz can interact with other medications. Reyataz can lower or raise the levels of other medications in the body. Similarly, other medications can lower or raise the levels of Reyataz in the body. While many interactions are not a problem, some can cause your medications to be less effective or increase the risk of side effects.

Tell your doctors and pharmacists about all medicines you take. This includes those you buy over-the-counter and herbal or natural remedies, such as St. John’s Wort. Bring all your medicines when you see a doctor, or make a list of their names, how much you take, and how often you take them. Your doctor can then tell you if you need to change the dosages of any of your medications.

The following medications should not be taken while you are being treated with Reyataz:

HIV protease inhibitors: Crixivan® (indinavir)
Acid reflux/heartburn medications: Propulsid® (cisapride), Prevacid® (lansoprazole), Nexium® (esomeprazole), Prilosec® (omeprazole), Protonix® (pantoprazole), and all other proton-pump inhibitors.
Antibiotics: Rifadin® (rifampin)
Cancer chemotherapeutics: Camptosar® (irinotecan)
Antimigraine medications: Methergine®, Methylergometrine® (methylergonovine); Ergostat®, Cafergot®, Ercaf®, Wigraine® (ergotamine); Ergotrate®, Methergine® (ergonovine); or D.H.E. 45®, Migranal® (dihydroergotamine)
Antihistamines: Hismanal® (astemizole) or Seldane® (terfenadine)
Cholesterol-lowering drugs (statins): Zocor® (simvastatin) and Mevacor® (lovastatin)
Antipsychotics: Orap® (pimozide)
Sedatives: Versed® (midazolam) and Halcion® (triazolam)
Herbal medications: St. John’s wort

If Reyataz is combined with low-dose Norvir®, the following medications should also be avoided:

Antifungals: Vfend® (voriconazole)
Heart medications: Cordarone® (amiodarone), Tambocor® (flecainide), Vascor® (bepridil), Rythmol® (propafenone), or Quinaglute®/Quinidex® (quinidine)
Enlarged prostate: Uroxatral® (alfuzosin)

Anticonvulsants, such as Tegretol® (carbamazepine), Luminal® (phenobarbital), and Dilantin® (phenytoin), may decrease the amount of Reyataz in the bloodstream. It might be necessary to increase your dose of Reyataz if you are taking any of these drugs.

Anti-HIV protease inhibitors can interact with Reyataz. We know that Norvir® (ritonavir) increases the amount of Reyataz in the bloodstream. It is also likely that Kaletra® which contains lopinavir and ritonavir, will also increase Reyataz levels in the bloodstream. Reyataz increases Invirase® (saquinavir), Agenerase® (fosamprenavir), and Lexiva® (amprenavir) levels in the bloodstream. Crixivan® (indinavir) should not be combined with Reyataz, as both drugs can cause increases in bilirubin levels. Aside from the Reyataz and Norvir combination, no other formal dosing recommendations have been made.

Anti-HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs) can also interact with Reyataz. Sustiva® (efavirenz) can decrease Reyataz levels in the bloodstream (if these two drugs are used together, 100mg Norvir should be added to the regimen and the Reyataz dose should be dropped to 300mg). It is likely that Viramune® (nevirapine) will decrease Reyataz levels in the bloodstream. It is also likely that Rescriptor® (delavirdine), a third NNRTI, will increase Reyataz levels in the bloodstream.

It is also important to be careful when using the nucleotide reverse transcriptase inhibitor (NRTI) Viread® (tenofovir) with Reyataz. Viread can decrease Reyataz levels in the bloodstream and Reyataz can increase Viread levels in the bloodstream. If Viread is combined with Reyataz, then 300mg of Reyataz should be used with 100mg of Norvir (to increase Reyataz levels). To make sure that the increased Viread levels do not cause kidney damage (a possible side effect of Viread), blood tests to monitor kidney function should be performed regularly.

When taking Reyataz with Videx EC® (ddI), Reyataz should be taken with food two hours before or one hour after the Videx EC.

Reyataz can interact with some medications used to treat TB, MAC and other bacterial infections. Rifadin® (rifampin) should not be used with Reyataz. Reyataz can increase Mycobutin® (rifabutin) levels (the Mycobutin dose should be reduced to 150mg every other day or three times a week). Reyataz can increase Biaxin® (clarithromycin) levels in the bloodstream (the Biaxin dose should be reduced by half or an alternative antibiotic should be tried).

Reyataz can increase the blood levels of oral contraceptives/birth-control pills. No changes in dosing have been recommended.

Cholesterol-lowering drugs, also known as “statins,” can interact with Reyataz. There are two statins that should not be used with Reyataz: Zocor® (simvastatin) and Mevacor® (lovastatin). Levels of these two drugs can become significantly increased in the bloodstream if they are combined with Reyataz, which increases the risk of side effects. The two statins that are considered to be the safest in combination with Reyataz are Pravachol® (pravastatin) and Lescol® (fluvastatin). It is also possible to take Reyataz with Lipitor® (atorvastatin), although Reyataz can increase Lipitor levels in the bloodstream. If Lipitor is prescribed, it’s best to begin treatment with the lowest possible dose of the drug and then increase the dose if necessary. Little is known about the newest statin, Crestor® (rosuvastatin), although it is not expected to have any serious drug interactions with Reyataz or the other protease inhibitors.

While Reyataz should not be combined with proton-pump inhibitors (used to treat heartburn and acid reflux), it can be combined with medications known as H2-receptor antagonists. Examples of H2-receptor antagonists include: Tagamet® (cimetidine), Pepcid® (famotidine), Axid® (nizatidine), and Zantac® (ranitidine). However, these medications must be used very carefully with Reyataz because they can decrease the amount of Reyataz absorbed into the bloodstream.

For HIV-positive people new to anti-HIV treatment using the 400mg dose of Reyataz (without Norvir), an H2-receptor antagonist should be taken at least ten hours before or two hours after Reyataz. For example, if you usually take your Reyataz at 8:00am, you shouldn’t take an H2-receptor antagonist any later than 10:00pm the night before or any early that 10:00am that morning.

For HIV-positive people new to anti-HIV treatment using 300mg Reyataz combined with 100mg Norvir, the H2-receptor antagonist can be taken at the same time as the Reyataz/Norvir.

For HIV-positive people who have tried and failed other treatments in the past, if an H2-receptor antagonist is to be used, Reyataz (300mg) must be combined with Norvir (100mg). What’s more, the H2-receptor antagonist should only be taken at least ten hours before or two hours after the daily Reyataz/Norvir dose.

Viagra® (sildenafil), Levitra® (vardenafil) and Cialis® (tadalafil) levels in the bloodstream likely increase when combined with Reyataz. In turn, it is best to use a lower dose of these drugs in order to reduce the risk of side effects.

H erbal products can also interact with Reyataz. St. John’s wort should not be used with Reyataz, since it can greatly reduce the amount of Reyataz in the bloodstream. HIV-positive people should also be cautious about using garlic supplements or milk thistle with Reyataz—test tube studies suggest that both herbal products can interact with the same liver enzyme system (cytochrome P450 3A4) responsible for metabolizing Reyataz. This may alter the amount of Reyataz in the bloodstream. These and other herbal products should be used with caution, until further studies are conducted.

A number of other negative drug interactions are possible if Reyataz is combined with Norvir® (ritonavir).

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What is known about side effects?
Reyataz can increase levels of bilirubin, a pigment found in the liver. Increased bilirubin can cause the skin, nails, and the whites of the eyes to appear yellowish-brown. Increased bilirubin can also be a sign of liver damage. However, in people who have taken Reyataz in clinical trials, an increase in bilirubin has not been associated with any other signs of liver damage. Reyataz should not be combined with Crixivan® (indinavir), another protease inhibitor that can cause increased bilirubin levels.

There have been reports of patients developing painful kidney stones while on HIV drug regimens containing Reyataz. While little is known about the frequency of the kidney stones, or if certain risk factors are involved, consuming eight glasses of water a day while taking Reyataz may help decrease the risk of this possible side effect.

Changes in the way your heart beats may occur when taking Reyataz. If you get dizzy or lightheaded these could be symptoms of a heart problem.

Other possible side effects of Reyataz include headaches, pain/tingling in the arms and legs, nausea, diarrhea, abdominal discomfort, and rash.

Reyataz may not increase fat levels in the blood—a symptom of lipodystrophy—like other protease inhibitors. In a few studies comparing Reyataz to other protease inhibitors, those receiving Reyataz had no increases in triglycerides (which can cause pancreatitis) or “bad” LDL cholesterol, which can increase the risk of heart disease or stroke. There were, however, significant increases in HDL (“good”) cholesterol, which can help reduce the risk of heart disease.

It is still not known if Reyataz can cause lipodystrophy’s body-shape changes, such as an increase in fat around the gut or a loss of fat in the arms, legs, or face. It is also not known if HIV-positive people who continue taking Reyataz for a long period of time (e.g., longer than one year) will be able to keep their cholesterol and triglyceride levels low.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

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Who should not take Reyataz?
Reyataz is classified by the FDA as a pregnancy category B drug. Pregnancy category B means that animal studies have failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women. HIV-positive women who become pregnant should discuss the benefits and possible side effects of anti-HIV treatment to help protect their babies from HIV.

It is not known whether Reyataz passes into breast milk and what effect it may have on a nursing baby. To prevent transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.

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Where can I learn more about clinical trials of Reyataz?
If you would like to find out if you are eligible for any clinical trials that include Reyataz, there is an interactive web site run by ACRIA, the AIDS Community Research Initiative of America.

Another useful service for finding clinical trials is AIDSinfo.nih.gov, a site run by the U.S. National Institutes of Health. They have “health information specialists” you can talk to at their toll-free number at 1-800-HIV-0440 (1-800-448-0440).

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