Posology : מינונים

2           DOSAGE AND ADMINISTRATION
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 ritonavir when using this agent.
2.1         Testing Prior to Initiation and During Treatment with REYATAZ

Renal laboratory testing should be performed in all patients prior to initiation of REYATAZ and continued during treatment with REYATAZ. Renal laboratory testing should include serum creatinine, estimated creatinine clearance, and urinalysis with microscopic examination [see Warnings and Precautions (5.5, 5.6)].

Hepatic laboratory testing should be performed in patients with underlying liver disease prior to initiation of REYATAZ and continued during treatment with REYATAZ [see Warnings and Precautions (5.4)].


2.2         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:        REYATAZ 300 mg with ritonavir 100 mg once daily Tenofovir
H2-receptor antagonist
Proton-pump inhibitor
•   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.
Table 1:                        REYATAZ Dosing Regimens
• 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- REYATAZ 400 mg with ritonavir 100 mg once daily receptor antagonist
•   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).]

2.3               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 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 a
The REYATAZ and ritonavir dose should be taken together once daily with food.
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.
Pregnancy Dosing During 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 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).]