EVOTAZ
EVOTAZ- atazanavir sulfate and cobicistat tablet
E.R. Squibb & Sons, L.L.C.
1 INDICATIONS AND USAGE
1.1 Indications
EVOTAZ® is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in the following populations [see Dosage and Administration (2.2, 2.3)]:
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- Adult patients
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- Pediatric patients weighing at least 35 kg.
1.2 Limitations of Use
Use of EVOTAZ in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions [see Clinical Pharmacology (12.4)].
2 DOSAGE AND ADMINISTRATION
2.1 Laboratory Testing Prior to Initiation and During Treatment with EVOTAZ
Renal Testing
Renal laboratory testing should be performed in all patients prior to initiation of EVOTAZ and continued during treatment with EVOTAZ. Renal laboratory testing should include estimated creatinine clearance, serum creatinine, and urinalysis with microscopic examination [see Warnings and Precautions (5.5,5.6)]. Cobicistat decreases estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function [see Warnings and Precautions (5.3)].
When coadministering EVOTAZ with tenofovir disoproxil fumarate (tenofovir DF), assess estimated creatinine clearance, urine glucose, and urine protein at baseline and routinely monitor during treatment. In patients with chronic kidney disease, also monitor serum phosphorus [see Warnings and Precautions (5.4)].
Hepatic Testing
Hepatic laboratory testing should be performed in patients with underlying liver disease prior to initiation of EVOTAZ and continued during treatment with EVOTAZ [see Warnings and Precautions (5.7)].
2.2 Recommended Dosage
EVOTAZ is a fixed-dose tablet containing 300 mg of atazanavir and 150 mg of cobicistat. The recommended dosage of EVOTAZ is one tablet taken once daily orally with food [see Clinical Pharmacology (12.3)] in HIV-1-infected treatment-naïve and treatment-experienced:
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- Adult patients
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- Pediatric patients weighing at least 35 kg
Administer EVOTAZ in conjunction with other antiretroviral agents [see Drug Interactions (7)]. Dose separation may be required when taken with H2 -receptor antagonists or proton-pump inhibitors [see Drug Interactions (7.2, 7.3)].
2.3 Dosage in Patients with Renal Impairment
EVOTAZ 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 (8.6) and Clinical Pharmacology (12.3)].
EVOTAZ coadministered with tenofovir DF is not recommended in patients with estimated creatinine clearance below 70 mL/min. Coadministration of EVOTAZ and tenofovir DF in combination with concomitant or recent use of a nephrotoxic agent is not recommended [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].
2.4 Not Recommended in Patients with Any Degree of Hepatic Impairment
EVOTAZ is not recommended in patients with any degree of hepatic impairment [see Warnings and Precautions (5.7), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].
2.5 Not Recommended During Pregnancy
EVOTAZ is not recommended for use during pregnancy and should not be initiated in pregnant individuals due to substantially lower exposures of cobicistat and consequently, lower exposures of atazanavir, during the second and third trimesters. An alternative regimen is recommended for individuals who become pregnant during therapy with EVOTAZ [see Use in Specific Populations (8.1)].
3 DOSAGE FORMS AND STRENGTHS
EVOTAZ tablets contain 342 mg atazanavir sulfate, equivalent to 300 mg of atazanavir, and 150 mg of cobicistat and are oval, biconvex, pink, film-coated, and debossed with “3641” on one side and plain on the other side.
4 CONTRAINDICATIONS
The concomitant use of EVOTAZ and the following drugs in Table 1, are contraindicated due to the potential for serious and/or life-threatening events or loss of therapeutic effect [see Warnings and Precautions (5.8, 5.9), Drug Interactions (7), and Clinical Pharmacology (12.3)].
EVOTAZ is contraindicated:
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- in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product [see Warnings and Precautions (5.2)].
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- when coadministered with drugs that are highly dependent on CYP3A or UGT1A1 for clearance, and for which elevated plasma concentrations of the interacting drugs are associated with serious and/or life-threatening events (see Table 5).
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- when coadministered with drugs that strongly induce CYP3A and may lead to lower exposure and loss of efficacy of EVOTAZ (see Table 1).
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- For additional information, including clinical comments and potential impact on exposure levels associated with drugs that are contraindicated with EVOTAZ, refer to Table 5 [see Drug Interactions (7.3)].
Table 1: Drugs Contraindicated with EVOTAZ
Drug Class | Drugs within class that are contraindicated with EVOTAZ |
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a Refer to Table 5 for sildenafil when administered for erectile dysfunction [see Drug Interactions (7.3)]. | |
b Refer to Table 5 for parenterally administered midazolam [see Drug Interactions (7.3)]. | |
Alpha 1-adrenoreceptor antagonist | alfuzosin |
Antianginal | ranolazine |
Antiarrhythmics | dronedarone |
Anticonvulsants | carbamazepine, phenobarbital, phenytoin |
Antigout | colchicine (when used in patients with hepatic and/or renal impairment) |
Antimycobacterials | rifampin |
Antineoplastics | irinotecan |
Antipsychotics | lurasidone, pimozide |
Ergot Derivatives | dihydroergotamine, ergotamine, methylergonovine |
GI Motility Agent | cisapride |
Hepatitis C Direct-Acting Antivirals | elbasvir/grazoprevir; glecaprevir/pibrentasvir |
Herbal Products | St. John’s wort (Hypericum perforatum) |
Hormonal Contraceptives | drospirenone/ethinyl estradiol |
Lipid-modifying Agents | lomitapide, lovastatin, simvastatin |
Non-nucleoside Reverse Transcriptase Inhibitor | nevirapine |
Phosphodiesterase-5 (PDE-5) Inhibitor | sildenafila when administered for the treatment of pulmonary arterial hypertension |
Protease Inhibitors | indinavir |
Sedative/hypnotics | triazolam, orally administered midazolamb |
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