2 DOSAGE AND ADMINISTRATION Pretreatment testing : Renal laboratory testing should be performed in all patients prior to initiation of atazanavir capsule and continued during treatment with atazanavir capsule. Hepatic testing should be performed in patients with underlying liver disease prior to initiation of atazanavir capsule and continued during treatment with atazanavir capsule. ( 2.2 ) Treatment-naive adults: Atazanavir capsule 300 mg with ritonavir 100 mg once daily with food or atazanavir 400 mg once daily with food. ( 2.3 ) Treatment-experienced adults: Atazanavir capsule 300 mg with ritonavir 100 mg once daily with food. ( 2.3 ) Pediatric patients: Atazanavir capsule dosage is based on body weight not to exceed the adult dose and must be taken with food. ( 2.4 ) Pregnancy: Atazanavir capsule 300 mg with ritonavir 100 mg once daily with food, with dosing modifications for some concomitant medications. ( 2.6 ) Dosing modifications: may be required for concomitant therapy ( 2.3 , 2.4 , 2.6 ), renal impairment ( 2.7 ), and hepatic impairment ( 2.8 ). 2.1 Overview Atazanavir capsules must be taken with food. Do not open the capsules. The recommended oral dosage of atazanavir capsule 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 ( 2.3 , 2.4 and 2.6 ) and Drug Interactions ( 7 )]. Atazanavir capsules without ritonavir are not recommended for treatment-experienced adult or pediatric patients with prior virologic failure [see Clinical Studies ( 14 )]. Efficacy and safety of atazanavir 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 Testing Prior to Initiation and During Treatment with Atazanavir Capsules Renal laboratory testing should be performed in all patients prior to initiation of atazanavir capsules and continued during treatment with atazanavir capsules. 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 atazanavir capsules and continued during treatment with atazanavir capsules [see Warnings and Precautions ( 5.4) ]. 2.3 Dosage of Atazanavir in Adult Patients Table 1 displays the recommended dosage of atazanavir capsules in treatment-naive and treatment-experienced adults. Table 1 also displays recommended dosage of atazanavir capsules and ritonavir when given concomitantly with other antiretroviral drugs and H 2 -receptor antagonists (H2RA). Ritonavir is required with several atazanavir dosage regimens (see the ritonavir complete prescribing information about the safe and effective use of ritonavir). The use of atazanavir in treatment-experienced adult patients without ritonavir is not recommended. Table 1: Recommended Atazanavir Capsules and Ritonavir Dosage in Adultsa Atazanavir Capsules Once Daily Dosage Ritonavir Once Daily Dosage 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 DF, and didanosine). 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 DF 400 mg 100 mg 2.4 Dosage of Atazanavir Capsules in Pediatric Patients The recommended daily dosage of atazanavir 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 Atazanavir Capsules and Ritonavir in Pediatric Patients (6 to less than 18 years of age) a,b a Administer atazanavir 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 DF, and didanosine). c In treatment-experienced patients, atazanavir capsules must be administered with ritonavir. Body weight Atazanavir Capsules Daily Dosage Ritonavir Daily Dosage Treatment-Naive and Treatment-Experienced c Less than 15 kg Capsules not recommended N/A At least 15 kg to less than 35 kg 200 mg 100 mg At least 35 kg 300 mg 100 mg Treatment-Naive, at least 13 years old and cannot tolerate ritonavir At least 40 kg 400 mg N/A When transitioning between formulations, a change in dose may be needed. Consult the dosing table for the specific formulation. 2.6 Dosage Adjustments in Pregnant Patients Table 4 includes the recommended dosage of atazanavir capsules and ritonavir in treatment-naive and treatment-experienced pregnant patients. In these patients, atazanavir must be administered with ritonavir. There are no dosage adjustments for postpartum patients (see Table 1 for the recommended atazanavir capsules dosage in adults) [see Use in Specific Populations ( 8.1 )] . Table 4: Recommended Dosage of Atazanavir Capsules and Ritonavir in Pregnant Patientsa Atazanavir Capsules Once Daily Dosage Ritonavir Once Daily Dosage b Atazanavir is not recommended for treatment-experienced pregnant patients during the second and third trimester taking atazanavir with BOTH tenofovir DF 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 Tenofovir DF b In combination with EITHER H2RA OR tenofovir DF 400 mg 100 mg a See Drug Interactions (7) for instructions concerning coadministration of acid reducing medications (eg, H2RA or PPIs), and other antiretroviral drugs (eg, efavirenz, tenofovir DF and didanosine). 2.7 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 atazanavir capsules. Treatment-naive patients with end-stage renal disease managed with hemodialysis should receive atazanavir capsules 300 mg with ritonavir 100 mg. Atazanavir capsule is not recommended in treatment-experienced patients with HIV-1 infection who have end-stage renal disease managed with hemodialysis [see Use in Specific Populations ( 8.7 )]. 2.8 Dosage Adjustments in Patients with Hepatic Impairment Table 5 displays the recommended atazanavir capsule dosage in treatment-naive patients with hepatic impairment. The use of atazanavir capsule in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. The coadministration of atazanavir with ritonavir in patients with any degree of hepatic impairment is not recommended. Table 5: Recommended Dosage of Atazanavir Capsules in Treatment-Naive Adults with Hepatic Impairment Atazanavir Capsules 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) Atazanavir with or without ritonavir is not recommended