Atazanavir

Atazanavir is a prescription drug used for the treatment of HIV infection. HIV is the virus that causes AIDS. Atazanavir belongs to a family of antiviral drugs known as protease inhibitors. Other members of this family include nelfinavir (Viracept) and amprenavir (Agenerase). Unlike many other protease inhibitors, atazanavir can be taken once a day and does not affect cholesterol levels. The U.S. Food and Drug Administration approved atazanavir in June 2003.

Other Names

Bristol-Myers Squibb markets atazanavir under the name Reyataz.

Uses

Atazanavir is used to treat HIV-1 infection in combination with other antiretroviral drugs.

How Atazanavir is Taken

Atazanavir is supplied as 100 mg, 150 mg, 200 mg, and 300 mg tablets.

Dosing in previously untreated people

The recommended dose for people who are treatment-naive (who have not received treatment) is 400 mg once daily taken WITH FOOD. The dose is reduced to 300 mg daily if taken with other antivirals. The dose is 300 mg daily when taken with 100 mg ritonavir (Norvir) if combined with any of the following:

• tenofovir (Viread)
• efavirenz
• some drugs used to treat ulcers (H2-receptor blockers and proton pump inhibitors)

Dosing for previously-treated adults

For adults who have been previously treated for HIV infection, the dosage is typically once daily administration of 300 mg atazanavir in combination with 100 mg ritonavir.

Dosing in Children

The recommended dosage for children 6 years to 18 years old is based on body weight and should not exceed the recommended adult dosage.

How Atazanavir Works

Replication and formation of new HIV particles in cells is dependent on proteins. In the life cycle of the virus, several proteins are cleaved by enzymes called proteases. The new proteins are used to make virus particles. Atazanavir is an HIV protease inhibitor. The drug inhibits the cleaving of specific viral proteins (Gag and Gag-Pol) in HIV infected cells. This prevents formation of mature viral particles and the spread of the virus to uninfected cells.

How the Body Affects Atazanavir

Atazanavir is rapidly absorbed with peak circulating levels reached at approximately 2.5 hours. It is extensively metabolized in the liver by an enzyme called CYP3A4. Approximately 80% of atazanavir is excreted in feces and the remainder in the urine.

Side Effects

Below are the most common side effects of atazanavir:

• nausea
• jaundice (a yellowing of the skin caused by liver malfunction)
• rash

Risks and Precautions

Atazanavir has been shown to interfere with electrical conduction in the heart in some people. The risk for heart-related problems is highest in people with pre-existing heart disease.

Atazanavir does not prevent HIV transmission.

Drug Interactions

Atazanavir is metabolized by CYP3A4 and numerous drugs inhibit this enzyme. Drugs that are CYP3A4 inhibitors can increase the blood concentrations of atazanavir. Some CYP3A4 inhibitors include the following:

• antifungals (e.g., ketoconazole (Nizoral) and itraconazole (Sporanox))
• venzodiazepines (e.g., midazolam), these drugs are typically used as sedatives or sleep aids
• other protease inhibitors
• herbal products, especially St. John’s Wort

Atazanavir can also inhibit CYP3A4 and could decrease the metabolism of co-administered drugs. This could increase blood concentrations of the co-administered drug. Some drugs that are metabolized by CYP3A4 that could interact with atazanavir include HMG-CoA reductase inhibitors ("statins" like atorvastatin (Lipitor)), anticancer agents, and ergot derivatives, which are used for migraine.

Drugs that reduce the acidity of the stomach, like proton pump inhibitors, cimetidine (Tagamet), and antacids, reduce the absorption of atazanavir. This effect is also seen with drugs that increase gastrointestinal function.

Neuroleptics typically used to treat schizophrenia, such as haloperidol (Haldol) and trazodone, may cause heart problems, much like the risk with atazanavir. The combination increases this risk, and often co-administration is discouraged.

The following drugs have been demonstrated or are likely to produce significant drug interactions with atazanavir:

• many antiHIV drugs (e.g., didanosine (Videx), tenofovir (Viread), efavirenz (Sustiva, Stocrin), and nevirapine (Viramune)
• Antiarrhythmics, which are used to treat abnormal electrical conduction in the heart (e.g., amiodarone (Cordarone), lidocaine, and quinidine)
• Anticoagulants (e.g., warfarin)
• Antidepressants, especially those called tricyclics (e.g., imipramine, amitriptyline)

Research

One study, called the CASTLE study, showed that the effectiveness of 300 mg atazanavir taken with 100 mg ritonavir was similar to that of combination lopinavir (400 mg) and ritonavir (100 mg) in previously untreated adult HIV patients.^[1]

References

1. ↑ MedicalNewsToday. CASTLE Study Showed Similar Efficacy Between Once-Daily REYATAZ® (atazanavir Sulfate)/ritonavir And Twice-Daily Lopinavir/ritonavir

External Links

FDA: Patient Information Sheet