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Important Updates to the Reyataz (Atazanvir) Label

August 21, 2008

The Reyataz (atazanavir) package insert has been updated to include important drug-drug interaction information regarding the administration of Reyataz with or without ritonavir and nevirapine, efavirenz, hormonal contraceptives, orally and parenterally administered midazolam, H2-receptor antagonists, and drugs that are substrates of cytochrome P450 2C8. Below is a summary of the changes.

Nevirapine:

Do not coadminister Reyataz with nevirapine because:

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  • nevirapine substantially decreases Reyataz exposures, and

  • potential risk exists for nevirapine associated toxicity due to increased nevirapine exposures

Efavirenz:

Efavirenz decreases Reyataz exposure:

  • For treatment-naïve patients the recommended dose is Reyataz 400 mg with ritonavir 100 mg and efavirenz 600 mg once daily. Efavirenz should be taken on an empty stomach preferably at bedtime

  • For treatment-experienced patients: Do not coadminister Reyataz with efavirenz because efavirenz decreases Reyataz exposure

Hormonal contraceptives:

Use with caution if co-administration of Reyataz or Reyataz/ritonavir with oral contraceptives is considered. If an oral contraceptive is administered with REYATAZ/ritonavir, it is recommended the oral contraceptive contain at least 35 mcg of ethinyl estradiol. If Reyataz is administered without ritonavir, the oral contraceptive should contain no more than 30 mcg of ethinyl estradiol.

Potential safety risk include substantial increases in progesterone exposure. The long-term effect of increases in concentration of the progestational agent are unknown and could include risk of insulin resistance, dyslipidemia and acne.

Coadministration of Reyataz or Reyataz/ritonavir with other hormonal contraceptives (e.g., contraceptive patch, contraceptive vaginal ring, or injectible contraceptives) or oral contraceptives containing progestagens other than norethindrone or norgestimate, or less than 25 mcg of ethinyl estradiol, has not been studied; therefore, alternative methods of non-hormonal contraception are recommended.

Midazolam:

Coadministration of oral midazolam with Reyataz is contraindicated. Concomitant use of parenteral midazolam with Reyataz may increase plasma concentrations of midazolam. Coadministration should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.

H2-receptor antagonists:

The packaged insert already contains the following dosing information for treatment naïve patients: Reyataz 300 mg with ritonavir 100 mg once daily with food should be administered simultaneously with, and/or at least 10 hours after, a dose of the H2-receptor antagonist. H2-receptor antagonist dose comparable to famotidine 40 mg twice daily can be used with Reyataz 300 mg with ritonavir 100 mg in treatment-naïve patients.

The label was updated to add the following:

For treatment-naïve patients unable to tolerate ritonavir, Reyataz 400 mg once daily with food should be administered at least 2 hours before and at least 10 hours after a dose of the H2-receptor antagonist. No single dose of the H2-receptor antagonist should exceed a dose comparable to famotidine 20 mg, and the total daily dose should not exceed a dose comparable to famotidine 40 mg.

Substrates of CYP2C8:

Atazanavir is a weak inhibitor of CY2C8. Caution should be used when Reyataz without ritonavir is coadministered with drugs highly dependent on CYP2C8 with narrow therapeutic indices (e.g., paclitaxel, repaglinide). When Reyataz with ritonavir is coadministered with substrates of CYP2C8, clinically significant interactions are not expected.

The complete, revised label will be available soon on the FDA website through Drugs@FDA, at www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.




This article was provided by U.S. Food and Drug Administration. Visit the FDA's website to find out more about their activities and publications.
 

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