Reyataz

General Dosing Recommendations:

REYATAZ Capsules must be taken with food. Do not open the capsules. The recommended oral dosage of REYATAZ depends on the treatment history of the patient and the use of other coadministered drugs. When coadministered with H2-receptor antagonists or proton-pump inhibitors, dose separation may be required [see Dosage and Administration (2.1)]. When coadministered with didanosine buffered or enteric-coated formulations, REYATAZ should be given (with food) 2 hours before or 1 hour after didanosine. REYATAZ without ritonavir is not recommended for treatment-experienced adult or pediatric patients with prior virologic failure [see Clinical Studies (14)]. Efficacy and safety of REYATAZ 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 NORVIR® (ritonavir) when using this agent. 2.1 Recommended Adult Dosage

Table 1 summarizes the recommended REYATAZ dosing regimen in adults. All REYATAZ dosing regimens are to be administered as a single dose with food.

Table 1: REYATAZ Dosing Regimens Treatment-Naive Patients REYATAZ 300 mg with ritonavir 100 mg once daily    If unable to tolerate ritonavir REYATAZ 400 mg once daily    When combined with any of the following:
   Tenofovir
   H2-receptor antagonist
   Proton-pump inhibitor REYATAZ 300 mg with ritonavir 100 mg once daily    • The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 40 mg twice daily.
     Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor
     antagonist.
   • If unable to tolerate ritonavir, administer REYATAZ 400 mg once daily at least 2 hours before and at least
     10 hours after 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.
   • The proton-pump inhibitor dose should not exceed a dose comparable to omeprazole 20 mg daily and must
     be taken approximately 12 hours prior to REYATAZ and ritonavir.    When combined with efavirenz REYATAZ 400 mg with ritonavir 100 mg once daily    • Efavirenz should be administered on an empty stomach, preferably at bedtime. Treatment-Experienced Patients REYATAZ 300 mg with ritonavir 100 mg once daily    Do not coadminister with proton-pump inhibitors or efavirenz in treatment-experienced patients.    When given with an H2-receptor antagonist REYATAZ 300 mg with ritonavir 100 mg once daily    • The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily.
     Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor
     antagonist.    When given with both tenofovirand an H2-receptor antagonist REYATAZ 400 mg with ritonavir 100 mg once daily    • The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily.
     Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor
     antagonist.

[For these drugs and other antiretroviral agents for which dosing modification may be appropriate, see Drug Interactions (7).]

2.2 Recommended Pediatric Dosage

The recommended daily dosage of REYATAZ for pediatric patients (6 to less than 18 years of age) is based on body weight and should not exceed the recommended adult dosage. REYATAZ Capsules must be taken with food. The data are insufficient to recommend dosing of REYATAZ for any of the following: (1) patients less than 6 years of age, (2) without ritonavir in any pediatric patient less than 13 years of age, and (3) patients less than 40 kg receiving concomitant tenofovir, H2-receptor antagonists, or proton-pump inhibitors.

The recommended dosage of REYATAZ with ritonavir in pediatric patients at least 6 years of age is shown in Table 2.

Table 2: Dosage for Pediatric Patients (6 to less than 18 years of age) for REYATAZ Capsules with ritonavira Body Weight REYATAZ dose ritonavir dose a The REYATAZ and ritonavir dose should be taken once daily with food. 15 kg to less than 20 kg 150 mg 100 mg 20 kg to less than 40 kg 200 mg 100 mg at least 40 kg 300 mg 100 mg

For treatment-naive patients at least 13 years of age and at least 40 kg, who are unable to tolerate ritonavir, the recommended dose is REYATAZ 400 mg (without ritonavir) once daily with food. For patients at least 13 years of age and at least 40 kg receiving concomitant tenofovir, H2-receptor antagonists, or proton-pump inhibitors, REYATAZ should not be administered without ritonavir.

2.3 Pregnancy

Dosing During Pregnancy and the Postpartum Period:

REYATAZ should not be administered without ritonavir. REYATAZ should only be administered to pregnant women with HIV-1 strains susceptible to atazanavir. For pregnant patients, no dose adjustment is required for REYATAZ with the following exceptions: For treatment-experienced pregnant women during the second or third trimester, when REYATAZ is
coadministered with either an H2-receptor antagonist or tenofovir, REYATAZ 400 mg with ritonavir
100 mg once daily is recommended. There are insufficient data to recommend a REYATAZ dose
for use with both an H2-receptor antagonist and tenofovir in treatment-experienced pregnant
women. No dose adjustment is required for postpartum patients. However, patients should be closely monitored for
adverse events because atazanavir exposures could be higher during the first 2 months after delivery. [See
Use in Specific Populations (8.1) and Clinical Pharmacology (12.3).] 2.4 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 REYATAZ. Treatment-naive patients with end stage renal disease managed with hemodialysis should receive REYATAZ 300 mg with ritonavir 100 mg. REYATAZ should not be administered to HIV-treatment-experienced patients with end stage renal disease managed with hemodialysis. [See Use in Specific Populations (8.7).]

2.5 Hepatic Impairment

REYATAZ 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. REYATAZ should not be used in patients with severe hepatic impairment (Child-Pugh Class C). REYATAZ/ritonavir has not been studied in subjects with hepatic impairment and is not recommended. [See Warnings and Precautions (5.5) and Use in Specific Populations (8.8).]

General Dosing Recommendations:

REYATAZ Capsules must be taken with food. Do not open the capsules. The recommended oral dosage of REYATAZ depends on the treatment history of the patient and the use of other coadministered drugs. When coadministered with H2-receptor antagonists or proton-pump inhibitors, dose separation may be required [see Dosage and Administration (2.1)]. When coadministered with didanosine buffered or enteric-coated formulations, REYATAZ should be given (with food) 2 hours before or 1 hour after didanosine. REYATAZ without ritonavir is not recommended for treatment-experienced adult or pediatric patients with prior virologic failure [see Clinical Studies (14)]. Efficacy and safety of REYATAZ 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 NORVIR® (ritonavir) when using this agent.

 

Table 1 summarizes the recommended REYATAZ dosing regimen in adults. All REYATAZ dosing regimens are to be administered as a single dose with food.

Table 1: REYATAZ Dosing Regimens Treatment-Naive Patients REYATAZ 300 mg with ritonavir 100 mg once daily    If unable to tolerate ritonavir REYATAZ 400 mg once daily    When combined with any of the following:
   Tenofovir
   H2-receptor antagonist
   Proton-pump inhibitor REYATAZ 300 mg with ritonavir 100 mg once daily    • The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 40 mg twice daily.
     Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor
     antagonist.
   • If unable to tolerate ritonavir, administer REYATAZ 400 mg once daily at least 2 hours before and at least
     10 hours after 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.
   • The proton-pump inhibitor dose should not exceed a dose comparable to omeprazole 20 mg daily and must
     be taken approximately 12 hours prior to REYATAZ and ritonavir.    When combined with efavirenz REYATAZ 400 mg with ritonavir 100 mg once daily    • Efavirenz should be administered on an empty stomach, preferably at bedtime. Treatment-Experienced Patients REYATAZ 300 mg with ritonavir 100 mg once daily    Do not coadminister with proton-pump inhibitors or efavirenz in treatment-experienced patients.    When given with an H2-receptor antagonist REYATAZ 300 mg with ritonavir 100 mg once daily    • The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily.
     Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor
     antagonist.    When given with both tenofovir and an H2-receptor antagonist REYATAZ 400 mg with ritonavir 100 mg once daily    • The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily.
     Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor
     antagonist.

[For these drugs and other antiretroviral agents for which dosing modification may be appropriate, see Drug Interactions (7).]

 

The recommended daily dosage of REYATAZ for pediatric patients (6 to less than 18 years of age) is based on body weight and should not exceed the recommended adult dosage. REYATAZ Capsules must be taken with food. The data are insufficient to recommend dosing of REYATAZ for any of the following: (1) patients less than 6 years of age, (2) without ritonavir in any pediatric patient less than 13 years of age, and (3) patients less than 40 kg receiving concomitant tenofovir, H2-receptor antagonists, or proton-pump inhibitors.

The recommended dosage of REYATAZ with ritonavir in pediatric patients at least 6 years of age is shown in Table 2.

Table 2: Dosage for Pediatric Patients (6 to less than 18 years of age) for REYATAZ Capsules with ritonavira Body Weight REYATAZ dose ritonavir dose 15 kg to less than 20 kg 150 mg 100 mg 20 kg to less than 40 kg 200 mg 100 mg at least 40 kg 300 mg 100 mg

For treatment-naive patients at least 13 years of age and at least 40 kg, who are unable to tolerate ritonavir, the recommended dose is REYATAZ 400 mg (without ritonavir) once daily with food. For patients at least 13 years of age and at least 40 kg receiving concomitant tenofovir, H2-receptor antagonists, or proton-pump inhibitors, REYATAZ should not be administered without ritonavir.

 

Dosing During Pregnancy and the Postpartum Period:

REYATAZ should not be administered without ritonavir. REYATAZ should only be administered to pregnant women with HIV-1 strains susceptible to atazanavir. For pregnant patients, no dose adjustment is required for REYATAZ with the following exceptions: For treatment-experienced pregnant women during the second or third trimester, when REYATAZ is
coadministered with either an H2-receptor antagonist or tenofovir, REYATAZ 400 mg with ritonavir
100 mg once daily is recommended. There are insufficient data to recommend a REYATAZ dose
for use with both an H2-receptor antagonist and tenofovir in treatment-experienced pregnant
women. No dose adjustment is required for postpartum patients. However, patients should be closely monitored for
adverse events because atazanavir exposures could be higher during the first 2 months after delivery. [See
Use in Specific Populations (8.1) and Clinical Pharmacology (12.3).]

 

For patients with renal impairment, including those with severe renal impairment who are not managed with hemodialysis, no dose adjustment is required for REYATAZ. Treatment-naive patients with end stage renal disease managed with hemodialysis should receive REYATAZ 300 mg with ritonavir 100 mg. REYATAZ should not be administered to HIV-treatment-experienced patients with end stage renal disease managed with hemodialysis. [See Use in Specific Populations (8.7).]

 

REYATAZ 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. REYATAZ should not be used in patients with severe hepatic impairment (Child-Pugh Class C). REYATAZ/ritonavir has not been studied in subjects with hepatic impairment and is not recommended. [See Warnings and Precautions (5.5) and Use in Specific Populations (8.8).]

 

General Dosing Recommendations:

• REYATAZ Capsules must be taken with food. • Do not open the capsules. • The recommended oral dosage of REYATAZ depends on the treatment history of the patient and the use of other coadministered drugs. When coadministered with H 2-receptor antagonists or proton-pump inhibitors, dose separation may be required [see Dosage and Administration (2.1)]. • When coadministered with didanosine buffered or enteric-coated formulations, REYATAZ should be given (with food) 2 hours before or 1 hour after didanosine. • REYATAZ without ritonavir is not recommended for treatment-experienced adult or pediatric patients with prior virologic failure [see Clinical Studies (14)]. • Efficacy and safety of REYATAZ 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 NORVIR ® (ritonavir) when using this agent. 2.1 Recommended Adult Dosage

Table 1 summarizes the recommended REYATAZ dosing regimen in adults. All REYATAZ dosing regimens are to be administered as a single dose with food.

Table 1: REYATAZ Dosing Regimens

Treatment-Naive Patients

REYATAZ 300 mg with ritonavir 100 mg once daily

   If unable to tolerate ritonavir

REYATAZ 400 mg once daily

   When combined with any of the following:
     Tenofovir
     H2-receptor antagonist
     Proton-pump inhibitor

REYATAZ 300 mg with ritonavir 100 mg once daily

• The H 2-receptor antagonist dose should not exceed a dose comparable to famotidine 40 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H 2-receptor antagonist. • If unable to tolerate ritonavir, administer REYATAZ 400 mg once daily at least 2 hours before and at least 10 hours after the H 2-receptor antagonist. 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. • The proton-pump inhibitor dose should not exceed a dose comparable to omeprazole 20 mg daily and must be taken approximately 12 hours prior to REYATAZ and ritonavir.

   When combined with efavirenz

REYATAZ 400 mg with ritonavir 100 mg once daily

• Efavirenz should be administered on an empty stomach, preferably at bedtime.

Treatment-Experienced Patients

REYATAZ 300 mg with ritonavir 100 mg once daily

   Do not coadminister with proton-pump inhibitors or efavirenz in treatment-experienced patients.

   When given with an H2-receptor antagonist

REYATAZ 300 mg with ritonavir 100 mg once daily

• The H 2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H 2-receptor antagonist.

   When given with both tenofovir and an H2-receptor antagonist

REYATAZ 400 mg with ritonavir 100 mg once daily

• The H 2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H 2-receptor antagonist.

[For these drugs and other antiretroviral agents for which dosing modification may be appropriate, see Drug Interactions (7).]

2.2 Recommended Pediatric Dosage

The recommended daily dosage of REYATAZ for pediatric patients (6 to less than 18 years of age) is based on body weight and should not exceed the recommended adult dosage. REYATAZ Capsules must be taken with food. The data are insufficient to recommend dosing of REYATAZ for any of the following: (1) patients less than 6 years of age, (2) without ritonavir in any pediatric patient less than 13 years of age, and (3) patients less than 40 kg receiving concomitant tenofovir, H2-receptor antagonists, or proton-pump inhibitors.

The recommended dosage of REYATAZ with ritonavir in pediatric patients at least 6 years of age is shown in Table 2.

Table 2: Dosage for Pediatric Patients (6 to less than 18 years of age) for REYATAZ Capsules with ritonavira Body Weight REYATAZ dose ritonavir dose a The REYATAZ and ritonavir dose should be taken together once daily with food.

15 kg to less than 20 kg

150 mg

100 mg

20 kg to less than 40 kg

200 mg

100 mg

at least 40 kg

300 mg

100 mg

For treatment-naive patients at least 13 years of age and at least 40 kg, who are unable to tolerate ritonavir, the recommended dose is REYATAZ 400 mg (without ritonavir) once daily with food. For patients at least 13 years of age and at least 40 kg receiving concomitant tenofovir, H2-receptor antagonists, or proton-pump inhibitors, REYATAZ should not be administered without ritonavir.

2.3 Pregnancy

Dosing During Pregnancy and the Postpartum Period:

• REYATAZ should not be administered without ritonavir. • REYATAZ should only be administered to pregnant women with HIV-1 strains susceptible to atazanavir. • For pregnant patients, no dose adjustment is required for REYATAZ with the following exceptions: o For treatment-experienced pregnant women during the second or third trimester, when REYATAZ is coadministered with either an H 2-receptor antagonist or tenofovir, REYATAZ 400 mg with ritonavir 100 mg once daily is recommended. There are insufficient data to recommend a REYATAZ dose for use with both an H 2-receptor antagonist and tenofovir in treatment-experienced pregnant women. • No dose adjustment is required for postpartum patients. However, patients should be closely monitored for adverse events because atazanavir exposures could be higher during the first 2 months after delivery. [See Use in Specific Populations (8.1) and Clinical Pharmacology (12.3).] 2.4 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 REYATAZ. Treatment-naive patients with end stage renal disease managed with hemodialysis should receive REYATAZ 300 mg with ritonavir 100 mg. REYATAZ should not be administered to HIV-treatment-experienced patients with end stage renal disease managed with hemodialysis. [See Use in Specific Populations (8.7).]

2.5 Hepatic Impairment

REYATAZ 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. REYATAZ should not be used in patients with severe hepatic impairment (Child-Pugh Class C). REYATAZ/ritonavir has not been studied in subjects with hepatic impairment and is not recommended. [See Warnings and Precautions (5.5) and Use in Specific Populations (8.8).]

2.1 Recommended Adult Dosage

Table 1 summarizes the recommended REYATAZ dosing regimen in adults. All REYATAZ dosing regimens are to be administered as a single dose with food.

Table 1: REYATAZ Dosing Regimens

Treatment-Naive Patients

REYATAZ 300 mg with ritonavir 100 mg once daily

   If unable to tolerate ritonavir

REYATAZ 400 mg once daily

   When combined with any of the following:
     Tenofovir
     H2-receptor antagonist
     Proton-pump inhibitor

REYATAZ 300 mg with ritonavir 100 mg once daily

• The H 2-receptor antagonist dose should not exceed a dose comparable to famotidine 40 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H 2-receptor antagonist. • If unable to tolerate ritonavir, administer REYATAZ 400 mg once daily at least 2 hours before and at least 10 hours after the H 2-receptor antagonist. 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. • The proton-pump inhibitor dose should not exceed a dose comparable to omeprazole 20 mg daily and must be taken approximately 12 hours prior to REYATAZ and ritonavir.

   When combined with efavirenz

REYATAZ 400 mg with ritonavir 100 mg once daily

• Efavirenz should be administered on an empty stomach, preferably at bedtime.

Treatment-Experienced Patients

REYATAZ 300 mg with ritonavir 100 mg once daily

   Do not coadminister with proton-pump inhibitors or efavirenz in treatment-experienced patients.

   When given with an H2-receptor antagonist

REYATAZ 300 mg with ritonavir 100 mg once daily

• The H 2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H 2-receptor antagonist.

   When given with both tenofovir and an H2-receptor antagonist

REYATAZ 400 mg with ritonavir 100 mg once daily

• The H 2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H 2-receptor antagonist.

[For these drugs and other antiretroviral agents for which dosing modification may be appropriate, see Drug Interactions (7).]

2.2 Recommended Pediatric Dosage

The recommended daily dosage of REYATAZ for pediatric patients (6 to less than 18 years of age) is based on body weight and should not exceed the recommended adult dosage. REYATAZ Capsules must be taken with food. The data are insufficient to recommend dosing of REYATAZ for any of the following: (1) patients less than 6 years of age, (2) without ritonavir in any pediatric patient less than 13 years of age, and (3) patients less than 40 kg receiving concomitant tenofovir, H2-receptor antagonists, or proton-pump inhibitors.

The recommended dosage of REYATAZ with ritonavir in pediatric patients at least 6 years of age is shown in Table 2.

Table 2: Dosage for Pediatric Patients (6 to less than 18 years of age) for REYATAZ Capsules with ritonavira Body Weight REYATAZ dose ritonavir dose a The REYATAZ and ritonavir dose should be taken together once daily with food.

15 kg to less than 20 kg

150 mg

100 mg

20 kg to less than 40 kg

200 mg

100 mg

at least 40 kg

300 mg

100 mg

For treatment-naive patients at least 13 years of age and at least 40 kg, who are unable to tolerate ritonavir, the recommended dose is REYATAZ 400 mg (without ritonavir) once daily with food. For patients at least 13 years of age and at least 40 kg receiving concomitant tenofovir, H2-receptor antagonists, or proton-pump inhibitors, REYATAZ should not be administered without ritonavir.

2.3 Pregnancy

Dosing During Pregnancy and the Postpartum Period:

• REYATAZ should not be administered without ritonavir. • REYATAZ should only be administered to pregnant women with HIV-1 strains susceptible to atazanavir. • For pregnant patients, no dose adjustment is required for REYATAZ with the following exceptions: o For treatment-experienced pregnant women during the second or third trimester, when REYATAZ is coadministered with either an H 2-receptor antagonist or tenofovir, REYATAZ 400 mg with ritonavir 100 mg once daily is recommended. There are insufficient data to recommend a REYATAZ dose for use with both an H 2-receptor antagonist and tenofovir in treatment-experienced pregnant women. • No dose adjustment is required for postpartum patients. However, patients should be closely monitored for adverse events because atazanavir exposures could be higher during the first 2 months after delivery. [See Use in Specific Populations (8.1) and Clinical Pharmacology (12.3).] 2.4 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 REYATAZ. Treatment-naive patients with end stage renal disease managed with hemodialysis should receive REYATAZ 300 mg with ritonavir 100 mg. REYATAZ should not be administered to HIV-treatment-experienced patients with end stage renal disease managed with hemodialysis. [See Use in Specific Populations (8.7).]

2.5 Hepatic Impairment

REYATAZ 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. REYATAZ should not be used in patients with severe hepatic impairment (Child-Pugh Class C). REYATAZ/ritonavir has not been studied in subjects with hepatic impairment and is not recommended. [See Warnings and Precautions (5.5) and Use in Specific Populations (8.8).]

2.1 Overview • REYATAZ capsules and oral powder must be taken with food. • Do not open the capsules. • The recommended oral dosage of REYATAZ depends on the treatment history of the patient and the use of other coadministered drugs. When coadministered with H 2-receptor antagonists or proton-pump inhibitors, dose separation may be required [see Dosage and Administration (2.2, 2.3, 2.4, 2.5) and Drug Interactions (7)]. • REYATAZ capsules without ritonavir are not recommended for treatment-experienced adult or pediatric patients with prior virologic failure [see Clinical Studies (14)]. • REYATAZ oral powder must be taken with ritonavir and is not recommended for use in children who weigh less than 5 kg [see Dosage and Administration (2.4) ]. • Efficacy and safety of REYATAZ with ritonavir when ritonavir is administered in doses greater than 100 mg once daily have not been established. The use of higher ritonavir doses may 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 ritonavir. 2.2 Dosage of REYATAZ in Adult Patients

Table 1 displays the recommended dosage of REYATAZ capsules in treatment-naive and treatment-experienced adults. Table 1 also displays recommended dosage of REYATAZ and ritonavir when given concomitantly with other antiretroviral drugs and H2-receptor antagonists (H2RA). Ritonavir is required with several REYATAZ dosage regimens (see the ritonavir complete prescribing information about the safe and effective use of ritonavir). The use of REYATAZ in treatment-experienced adult patients without ritonavir is not recommended.

Table 1: Recommended REYATAZ and Ritonavir Dosage in Adultsa,b a See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or proton pump inhibitors [PPIs]), and other antiretroviral drugs (eg, efavirenz, tenofovir, and didanosine). b For adult patients who cannot swallow the capsules, REYATAZ oral powder is taken once daily with food at the same recommended adult dosage as the capsules along with ritonavir.

REYATAZ Once Daily

Dosage

Ritonavir Once Daily

Dosage

Treatment-Naive Adult Patients

  recommended regimen

300 mg

100 mg

  unable to tolerate ritonavir

400 mg

N/A

  in combination with efavirenz

400 mg

100 mg

Treatment-Experienced Adult Patients

  recommended regimen

300 mg

100 mg

  in combination with both H2RA and tenofovir

400 mg

100 mg

2.3 Dosage of REYATAZ Capsules in Pediatric Patients

The recommended daily dosage of REYATAZ capsules and ritonavir in pediatric patients (6 years of age to less than 18 years of age) is based on body weight (see Table 2).

Table 2: Recommended Dosage of REYATAZ Capsules and Ritonavir in Pediatric Patients (6 to less than 18 years of age)a,b Body weight REYATAZ Daily Dosage Ritonavir Daily Dosage

Treatment-Naive and Treatment-Experiencedc

Less than 15 kg

Capsules not recommended

N/A

15 kg to less than 20 kg

150 mg

100 mg

20 kg to less than 40 kg

200 mg

100 mg

At least 40 kg

300 mg

100 mg

Treatment-Naive, at least 13 years old and cannot tolerate ritonavirc

At least 40 kg

400 mg

N/A

a Administer REYATAZ capsules and ritonavir simultaneously with food.
b The same recommendations regarding the timing and maximum doses of concomitant PPIs and H2RAs in adults also apply to pediatric patients. See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or PPIs), and other antiretroviral drugs (eg, efavirenz, tenofovir, and didanosine).
c In treatment-experienced patients, REYATAZ capsules must be administered with ritonavir.

2.4 Dosage and Administration of REYATAZ Oral Powder in Pediatric Patients

REYATAZ oral powder is for use in treatment-naive or treatment-experienced pediatric patients who are at least 3 months of age and weighing at least 5 kg. REYATAZ oral powder must be mixed with food or beverage for administration and ritonavir must be given immediately afterwards. Table 3 displays the recommended dosage of REYATAZ oral powder and ritonavir.

Table 3: Recommended Dosage of REYATAZ Oral Powder and Ritonavir in Pediatric Patients (at least 3 months of age and weighing at least 5 kg)a,b Body Weight Daily Dosage of REYATAZ
Oral Powder Daily Dosage of Ritonavir a The same recommendations regarding the timing and maximum doses of concomitant PPIs and H2RAs in adults also apply to pediatric patients. See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or PPIs), and other antiretroviral drugs (eg, efavirenz, tenofovir, and didanosine).
b For pediatric patients at least 25 kg who cannot swallow REYATAZ capsules, 300 mg (6 packets) REYATAZ oral powder is taken once daily with food along with 100 mg ritonavir.
c Only patients weighing 5 to less than 10 kg who do not tolerate the 200 mg (4 packets) dose of REYATAZ oral powder and have not previously taken an HIV protease inhibitor, may take 150 mg (3 packets) REYATAZ oral powder with close HIV viral load monitoring.
d Each packet contains 50 mg of REYATAZ.

5 kg to less than 15 kg

200 mg (4 packets)c,d

80 mgc

15 kg to less than 25 kg

250 mg (5 packets)d

80 mgc

Instructions for Mixing REYATAZ Oral Powder [see FDA-approved Instructions for Use]

• Determine the number of packets (3, 4, 5 or 6 packets) that are needed. • Prior to mixing, tap the packet to settle the powder. • It is preferable to mix REYATAZ oral powder with food such as applesauce or yogurt. Mixing REYATAZ oral powder with a beverage (milk, infant formula, or water) may be used for infants who can drink from a cup. For young infants (less than 6 months) who cannot eat solid food or drink from a cup, REYATAZ oral powder should be mixed with infant formula and given using an oral dosing syringe. Administration of REYATAZ and infant formula using an infant bottle is not recommended because full dose may not be delivered. • Use a clean pair of scissors to cut each packet along the dotted line. • Mixing with food: Using a spoon, mix the recommended number of REYATAZ oral powder packets with a minimum of one tablespoon of food (such as applesauce or yogurt). Feed the mixture to the infant or young child. Add an additional one tablespoon of food to the small container, mix, and feed the child the residual mixture. • Mixing with a beverage such as milk or water in a small drinking cup: Using a spoon, mix the recommended number of REYATAZ oral powder packets with a minimum of 30 mL of the beverage. Have the child drink the mixture. Add an additional 15 mL more of beverage to the drinking cup, mix, and have the child drink the residual mixture. If water is used, food should also be taken at the same time. • Mixing with liquid infant formula using an oral dosing syringe and a small medicine cup: Using a spoon, mix the recommended number of REYATAZ oral powder packets with 10 mL of prepared liquid infant formula. Draw up the full amount of the mixture into an oral syringe and administer into either right or left inner cheek of infant. Pour another 10 mL of formula into the medicine cup to rinse off remaining REYATAZ oral powder in cup. Draw up residual mixture into the syringe and administer into either right or left inner cheek of infant. • Administer ritonavir immediately following REYATAZ powder administration. • Administer the entire dosage of REYATAZ oral powder (mixed in the food or beverage) within one hour of preparation (may leave the mixture at room temperature during this one hour period). Ensure that the patient eats or drinks all the food or beverage that contains the powder. Additional food may be given after consumption of the entire mixture. 2.5 Dosage Adjustments in Pregnant Patients

Table 4 includes the recommended dosage of REYATAZ capsules and ritonavir in treatment-naive and treatment-experienced pregnant patients. In these patients, REYATAZ must be administered with ritonavir. There are no dosage adjustments for postpartum patients (see Table 1 for the recommended REYATAZ dosage in adults). [See Use in Specific Populations (8.1).]

Table 4: Recommended Dosage of REYATAZ and Ritonavir in Pregnant Patientsa REYATAZ
Once Daily
Dosage Ritonavir
Once Daily
Dosage a See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or PPIs), and other antiretroviral drugs (eg, efavirenz, tenofovir, and didanosine).
b REYATAZ is not recommended for treatment-experienced pregnant patients during the second and third trimester taking REYATAZ with both tenofovir and H2RA.

Treatment-Naive and Treatment-Experienced

Recommended Regimen

300 mg

100 mg

Treatment-Experienced During the Second or Third Trimester When Coadministered with either H2RA or Tenofovirb

In combination with either H2RA or tenofovir

400 mg

100 mg

2.6 Dosage in 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 REYATAZ. Treatment-naive patients with end stage renal disease managed with hemodialysis should receive REYATAZ 300 mg with ritonavir 100 mg. REYATAZ is not recommended in HIV-treatment-experienced patients with end stage renal disease managed with hemodialysis. [See Use in Specific Populations (8.7).]

2.7 Dosage Adjustments in Patients with Hepatic Impairment

Table 5 displays the recommended REYATAZ dosage in treatment-naive patients with hepatic impairment. The use of REYATAZ in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. The coadministration of REYATAZ with ritonavir in patients with any degree of hepatic impairment is not recommended.

Table 5: Recommended Dosage of REYATAZ Capsules in Treatment-Naive Adults with Hepatic Impairment

REYATAZ Once Daily Dosage

Mild hepatic impairment (Child-Pugh Class A)

400 mg

Moderate hepatic impairment (Child-Pugh Class B)

300 mg

Severe hepatic impairment (Child-Pugh Class C)

REYATAZ with or without ritonavir is not recommended

2.1 Overview • REYATAZ capsules and oral powder must be taken with food. • Do not open the capsules. • The recommended oral dosage of REYATAZ depends on the treatment history of the patient and the use of other coadministered drugs. When coadministered with H 2-receptor antagonists or proton-pump inhibitors, dose separation may be required [see Dosage and Administration (2.2, 2.3, 2.4, 2.5) and Drug Interactions (7)]. • REYATAZ capsules without ritonavir are not recommended for treatment-experienced adult or pediatric patients with prior virologic failure [see Clinical Studies (14)]. • REYATAZ oral powder must be taken with ritonavir and is not recommended for use in children who weigh less than 5 kg [see Dosage and Administration (2.4) ]. • Efficacy and safety of REYATAZ with ritonavir when ritonavir is administered in doses greater than 100 mg once daily have not been established. The use of higher ritonavir doses may 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 ritonavir. 2.2 Dosage of REYATAZ in Adult Patients

Table 1 displays the recommended dosage of REYATAZ capsules in treatment-naive and treatment-experienced adults. Table 1 also displays recommended dosage of REYATAZ and ritonavir when given concomitantly with other antiretroviral drugs and H2-receptor antagonists (H2RA). Ritonavir is required with several REYATAZ dosage regimens (see the ritonavir complete prescribing information about the safe and effective use of ritonavir). The use of REYATAZ in treatment-experienced adult patients without ritonavir is not recommended.

Table 1: Recommended REYATAZ and Ritonavir Dosage in Adultsa,b a See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or proton pump inhibitors [PPIs]), and other antiretroviral drugs (eg, efavirenz, tenofovir, and didanosine). b For adult patients who cannot swallow the capsules, REYATAZ oral powder is taken once daily with food at the same recommended adult dosage as the capsules along with ritonavir.

REYATAZ Once Daily

Dosage

Ritonavir Once Daily

Dosage

Treatment-Naive Adult Patients

  recommended regimen

300 mg

100 mg

  unable to tolerate ritonavir

400 mg

N/A

  in combination with efavirenz

400 mg

100 mg

Treatment-Experienced Adult Patients

  recommended regimen

300 mg

100 mg

  in combination with both H2RA and tenofovir

400 mg

100 mg

2.3 Dosage of REYATAZ Capsules in Pediatric Patients

The recommended daily dosage of REYATAZ capsules and ritonavir in pediatric patients (6 years of age to less than 18 years of age) is based on body weight (see Table 2).

Table 2: Recommended Dosage of REYATAZ Capsules and Ritonavir in Pediatric Patients (6 to less than 18 years of age)a,b Body weight REYATAZ Daily Dosage Ritonavir Daily Dosage

Treatment-Naive and Treatment-Experiencedc

Less than 15 kg

Capsules not recommended

N/A

15 kg to less than 20 kg

150 mg

100 mg

20 kg to less than 40 kg

200 mg

100 mg

At least 40 kg

300 mg

100 mg

Treatment-Naive, at least 13 years old and cannot tolerate ritonavirc

At least 40 kg

400 mg

N/A

a Administer REYATAZ capsules and ritonavir simultaneously with food.
b The same recommendations regarding the timing and maximum doses of concomitant PPIs and H2RAs in adults also apply to pediatric patients. See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or PPIs), and other antiretroviral drugs (eg, efavirenz, tenofovir, and didanosine).
c In treatment-experienced patients, REYATAZ capsules must be administered with ritonavir.

2.4 Dosage and Administration of REYATAZ Oral Powder in Pediatric Patients

REYATAZ oral powder is for use in treatment-naive or treatment-experienced pediatric patients who are at least 3 months of age and weighing at least 5 kg. REYATAZ oral powder must be mixed with food or beverage for administration and ritonavir must be given immediately afterwards. Table 3 displays the recommended dosage of REYATAZ oral powder and ritonavir.

Table 3: Recommended Dosage of REYATAZ Oral Powder and Ritonavir in Pediatric Patients (at least 3 months of age and weighing at least 5 kg)a,b Body Weight Daily Dosage of REYATAZ
Oral Powder Daily Dosage of Ritonavir a The same recommendations regarding the timing and maximum doses of concomitant PPIs and H2RAs in adults also apply to pediatric patients. See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or PPIs), and other antiretroviral drugs (eg, efavirenz, tenofovir, and didanosine).
b For pediatric patients at least 25 kg who cannot swallow REYATAZ capsules, 300 mg (6 packets) REYATAZ oral powder is taken once daily with food along with 100 mg ritonavir.
c Only patients weighing 5 to less than 10 kg who do not tolerate the 200 mg (4 packets) dose of REYATAZ oral powder and have not previously taken an HIV protease inhibitor, may take 150 mg (3 packets) REYATAZ oral powder with close HIV viral load monitoring.
d Each packet contains 50 mg of REYATAZ.

5 kg to less than 15 kg

200 mg (4 packets)c,d

80 mgc

15 kg to less than 25 kg

250 mg (5 packets)d

80 mgc

Instructions for Mixing REYATAZ Oral Powder [see FDA-approved Instructions for Use]

• Determine the number of packets (3, 4, 5 or 6 packets) that are needed. • Prior to mixing, tap the packet to settle the powder. • It is preferable to mix REYATAZ oral powder with food such as applesauce or yogurt. Mixing REYATAZ oral powder with a beverage (milk, infant formula, or water) may be used for infants who can drink from a cup. For young infants (less than 6 months) who cannot eat solid food or drink from a cup, REYATAZ oral powder should be mixed with infant formula and given using an oral dosing syringe. Administration of REYATAZ and infant formula using an infant bottle is not recommended because full dose may not be delivered. • Use a clean pair of scissors to cut each packet along the dotted line. • Mixing with food: Using a spoon, mix the recommended number of REYATAZ oral powder packets with a minimum of one tablespoon of food (such as applesauce or yogurt). Feed the mixture to the infant or young child. Add an additional one tablespoon of food to the small container, mix, and feed the child the residual mixture. • Mixing with a beverage such as milk or water in a small drinking cup: Using a spoon, mix the recommended number of REYATAZ oral powder packets with a minimum of 30 mL of the beverage. Have the child drink the mixture. Add an additional 15 mL more of beverage to the drinking cup, mix, and have the child drink the residual mixture. If water is used, food should also be taken at the same time. • Mixing with liquid infant formula using an oral dosing syringe and a small medicine cup: Using a spoon, mix the recommended number of REYATAZ oral powder packets with 10 mL of prepared liquid infant formula. Draw up the full amount of the mixture into an oral syringe and administer into either right or left inner cheek of infant. Pour another 10 mL of formula into the medicine cup to rinse off remaining REYATAZ oral powder in cup. Draw up residual mixture into the syringe and administer into either right or left inner cheek of infant. • Administer ritonavir immediately following REYATAZ powder administration. • Administer the entire dosage of REYATAZ oral powder (mixed in the food or beverage) within one hour of preparation (may leave the mixture at room temperature during this one hour period). Ensure that the patient eats or drinks all the food or beverage that contains the powder. Additional food may be given after consumption of the entire mixture. 2.5 Dosage Adjustments in Pregnant Patients

Table 4 includes the recommended dosage of REYATAZ capsules and ritonavir in treatment-naive and treatment-experienced pregnant patients. In these patients, REYATAZ must be administered with ritonavir. There are no dosage adjustments for postpartum patients (see Table 1 for the recommended REYATAZ dosage in adults). [See Use in Specific Populations (8.1).]

Table 4: Recommended Dosage of REYATAZ and Ritonavir in Pregnant Patientsa REYATAZ
Once Daily
Dosage Ritonavir
Once Daily
Dosage a See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or PPIs), and other antiretroviral drugs (eg, efavirenz, tenofovir, and didanosine).
b REYATAZ is not recommended for treatment-experienced pregnant patients during the second and third trimester taking REYATAZ with both tenofovir and H2RA.

Treatment-Naive and Treatment-Experienced

Recommended Regimen

300 mg

100 mg

Treatment-Experienced During the Second or Third Trimester When Coadministered with either H2RA or Tenofovirb

In combination with either H2RA or tenofovir

400 mg

100 mg

2.6 Dosage in 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 REYATAZ. Treatment-naive patients with end stage renal disease managed with hemodialysis should receive REYATAZ 300 mg with ritonavir 100 mg. REYATAZ is not recommended in HIV-treatment-experienced patients with end stage renal disease managed with hemodialysis. [See Use in Specific Populations (8.7).]

2.7 Dosage Adjustments in Patients with Hepatic Impairment

Table 5 displays the recommended REYATAZ dosage in treatment-naive patients with hepatic impairment. The use of REYATAZ in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. The coadministration of REYATAZ with ritonavir in patients with any degree of hepatic impairment is not recommended.

Table 5: Recommended Dosage of REYATAZ Capsules in Treatment-Naive Adults with Hepatic Impairment

REYATAZ Once Daily Dosage

Mild hepatic impairment (Child-Pugh Class A)

400 mg

Moderate hepatic impairment (Child-Pugh Class B)

300 mg

Severe hepatic impairment (Child-Pugh Class C)

REYATAZ with or without ritonavir is not recommended