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Atavir

Atazanavir Sulfate Capsules

COMPOSITION

AtaviR
Each capsule contains:
Atazanavir sulfate ….. 300 mg

INDICATIONS

ATAVIR Capsules are indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection.

The following points should be considered when initiating therapy with ATAVIR Capsules :

In Study AI424-045, atazanavir/ritonavir and lopinavir/ritonavir were similar for the primary efficacy outcome measure of time-averaged difference in change from baseline in the HIV RNA level. This study was not large enough to reach a definitive conclusion that atazanavir/ritonavir and lopinavir/ritonavir are equivalent on the secondary efficacy outcome measure of proportions below the HIV RNA lower limit of detection.
The number of baseline primary protease inhibitor mutations affects the virologic response to atazanavir/ritonavir.

DOSAGE AND ADMINISTRATION

General Dosing Recommendations

ATAVIR Capsules must be taken with food.
The recommended oral dosage of ATAVIR Capsules depends on the treatment history of the patient and the use of other co-administered drugs. When co-administered with H 2 -receptor antagonists, or proton-pump inhibitors, dose separation may be required (see dose recommendations below).
When co-administered with didanosine buffered or enteric-coated formulations, ATAVIR Capsules should be given (with food) 2 hours before or 1 hour after didanosine.
ATAVIR Capsules without ritonavir are not recommended for treatment-experienced patients with prior virologic failure.
Efficacy and safety of atazanavir with ritonavir in doses greater than 100 mg once daily have not been established. The use of higher ritonavir doses might alter the safety profile of atazanavir (cardiac effects, hyperbilirubinemia) and, therefore, is not recommended. Prescribers should consult the complete prescribing information for ritonavir when using this agent.

Dose Recommendations for Therapy-Naive Adult Patients
For treatment-naive patients, the recommended dosage is ATAVIR Capsules 300 mg with ritonavir 100 mg once daily (all as a single dose with food).

For treatment-naive patients who are unable to tolerate ritonavir, the recommended dosage is atazanavir 400 mg (without ritonavir) once daily taken with food.

Concomitant Therapy

ATAVIR Capsules 300 mg should be administered with ritonavir 100 mg once daily (all as a single dose with food) if combined with any of the following:

Tenofovir
H 2 - Receptor a ntagonist: The H 2 -receptor antagonist dose should not exceed a dose comparable to famotidine 40 mg twice daily. ATAVIR Capsules 300 mg and ritonavir 100 mg should be administered simultaneously with, and/or at least 10 hours after, the dose of the H 2 -receptor antagonist. For patients unable to tolerate ritonavir, atazanavir 400 mg once daily with food should be administered at least 2 hours before and at least 10 hours after the H 2 receptor antagonist. For these patients, no single dose of the H 2 -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.
Proton- Pump i nhibitors: The proton-pump inhibitor dose should not exceed a dose comparable to omeprazole 20 mg and must be taken approximately 12 hours prior to the ATAVIR Capsules 300 mg and ritonavir 100 mg dose.
If atazanavir is combined with efavirenz, atazanavir 400 mg (two 200 mg capsules) with ritonavir 100 mg should be administered once daily (all as a single dose with food), and efavirenz should be administered on an empty stomach, preferably at bedtime.

Dose Recommendations for Therapy-Experienced Adult Patients

ATAVIR Capsules 300 mg with ritonavir 100 mg once daily (all as a single dose with food).

Concomitant Therapy

Whenever an H 2 -receptor antagonist is given to a patient receiving atazanavir with ritonavir, the H 2 -receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily, and the atazanavir and ritonavir doses should be administered simultaneously with, and/or at least 10 hours after, the dose of the H 2 -receptor antagonist.

ATAVIR Capsules 300 mg with ritonavir 100 mg once daily (all as a single dose with food) if taken with an H 2 -receptor antagonist.
Atazanavir 400 mg with ritonavir 100 mg once daily (all as a single dose with food) if taken with both tenofovir and an H 2 -receptor antagonist.

Proton-pump inhibitors should not be used in treatment-experienced patients receiving atazanavir.
Efavirenz: Do not co-administer ATAVIR Capsules with efavirenz in treatment-experienced patients due to decreased atazanavir exposure.

[For these drugs and other antiretroviral agents for which dosing modification may be appropriate, see Drug Interactions].

Patients with Renal Impairment
For patients with renal impairment, including those with severe renal impairment who are not managed with hemodialysis, no dose adjustment is required for ATAVIR Capsules . Treatment-naive patients with end-stage renal disease managed with hemodialysis should receive ATAVIR Capsules 300 mg with ritonavir 100 mg. ATAVIR Capsules should not be administered to HIV-treatment-experienced patients with end-stage renal disease managed with hemodialysis (see PHARMACOLOGY, Special Populations , Renal Impairment ).

Patients with Hepatic Impairment
ATAVIR Capsules should be used with caution in patients with mild to moderate hepatic impairment. For patients with moderate hepatic impairment (Child-Pugh Class B) who have not experienced prior virologic failure, a dose reduction to 300 mg once daily should be considered. ATAVIR Capsules should not be used in patients with severe hepatic impairment (Child-Pugh Class C). Atazanavir/ritonavir have not been studied in subjects with hepatic impairment and are not recommended (see WARNINGS AND PRECAUTIONS ).

CONTRAINDICATIONS

ATAVIR Capsules are contraindicated in the following cases:

In patients with previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of its ingredients, including atazanavir.
When co-administered with drugs that are highly dependent on CYP3A or UGTIA1 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. These drugs are listed in Table 2.

Table 2: Drugs that are contraindicated with ATAVIR Capsules

Drug c lass	Drugs Within Class That Are Contraindicated with Atazanavir	Clinical Comment
Antimycobacterials	Rifampin	Rifampin substantially decreases plasma concentrations of atazanavir, which may result in loss of therapeutic effect and development of resistance.
Antineoplastics	Irinotecan	Atazanavir inibits UGT1Al and may interfere with the metabolism of irinotecan, resulting in increased irinotecan toxicities.
Benzodiazepines	Triazolam, orally administered midazolam a	Triazolam and orally administered midazolam are extensively metabolized by CYP3A4. Co-administration of triazolam or orally administered midazolam with ATAVIR Capsules may cause large increases in the concentration of these benzodiazepines. Potential for serious and/or life-threatening events such as prolonged or increased sedation or respiratory depression.
Ergot Derivatives	Dihydroergotamine, ergotamine, ergonovine, methylergonovine	Potential for serious and/or life-threatening events such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues.
Gastrointestinal Motility Agent	Cisapride	Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Herbal Products	St. John`s wort (Hypericum perforatum )	Patients taking ATAVIR Capsules should not use products containing St. John`s wort because co-administration may be expected to reduce plasma concentrations of atazanavir. This may result in loss of therapeutic effect and development of resistance.
HMG-CoA Reductase Inhibitors	Lovastatin, simvastatin	Potential for serious reactions such as myopathy, including rhabdomyolysis.
Neuroleptic	Pimozide	Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Protease Inhibitors	Indinavir	Both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia.

a See WARNINGS AND PRECAUTIONS, Drug Interactions, Table 3 , for parenterally administered midazolam.

PACKAGING INFORMATION

ATAVIR Capsules -----------------------Container of 30 capsules

For full prescribing information, click here

Last Updated: January 2010

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