Atazanavir is manufactured under royalty-free license from Bristol-Myers Squibb Patents and intellectual property rights belong to Bristol-Myers Squibb

Therapeutic Category:

Antiretroviral Protease Inhibitor


Composition:

ATAZOR
Each capsule contains Atazanavir sulphate
Equivalent to Atazanavir…150/200 mg

Indications:

For the treatment of Human Immunodeficiency Virus -1 (HIV-1) infection.


Contraindications:

Atazanavir should not be administered to paediatric patients below the age of 3 months due to the risk of kernicterus Atazanavir is contraindicated in patients hypersensitive to any component of Atazanavir, including Atazanavir. Co administration of Atazanavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events like benzodiazepines(midazolam, triazolam), ergot derivatives like ergotamine, methylergonovine, GI motility drugs e.g. cisapride, Neuroleptics like pimozide.


Adverse Reactions:

Headache, nausea, vomiting, abdominal pain, jaundice/ scleral icterus, dizziness, insomnia, peripheral neuropathic symptoms, rash, fever, depression, myalgia.


Precautions:

Transient jaundice may develop in patients on Atazanavir. Caution should be exercised while giving Atazanavir to patients with impaired liver function, as Atazanavir is metabolised by liver. Liver functions need to be monitored in patients co-infected with Hepatitis B and Hepatitis C. Mild to moderate maculopapular skin eruptions may be seen. Few cases of erythema multiforme and Steven Johnson’s syndrome have been reported with use of Atazanavir. Few cases of increased bleeding have been reported when Atazanavir was administered in patients with haemophilia. Redistribution of body fat with peripheral wasting and central obesity may be seen, though the incidence is less with Atazanavir. Immune Reconstitution syndrome has been seen in patients receiving combination antiretroviral therapy including Atazanavir. P-R interval may be prolonged in patients on Atazanavir.


Pregnancy and lactation:

Category B drug . To be used in pregnancy only if potential benefit outweighs the risk. It is not known whether Atazanavir is secreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving Atazanavir.


Warnings:

Atazanavir is metabolised through CYP3A (CYP3A4 isomer), CYP2C9, CYP1A2 and UGT1A1. Co administration of Atazanavir with drugs metabolised by CYP3A (calcium channel blockers, HMG CoA reductase inhibitors, Phosphodiesterase inhibitors, immunosuppressants), CYP2C9, CYP1A2 and UGT1A1 (irinotecan) may result in increased plasma concentrations of the other drug which could result in excessive or prolonged therapeutic and adverse effects. Concomitant use of Atazanavir with ritonavir and fluticasone propionate is expected to reduce serum cortisol levels. Concomitant use of Atazanavir and St. John's wort (Hypericum perforatum), or products containing St. John's wort, is not recommended. Atazanavir should be used with caution in patients with pre existing conduction system disease (eg, marked first-degree AV block or second- or third-degree AV block)., Worsening of pre existing diabetes mellitus , hyperglycemias, new onset diabetes mellitus have been reported. Transient jaundice may develop in patients on Atazanavir. Caution should be exercised while giving Atazanavir to patients with impaired liver function, as Atazanavir is metabolised by liver. Liver functions need to be monitored in patients co-infected with Hepatitis B and Hepatitis C. Few cases of increased bleeding have been reported when Atazanavir was administered in patients with haemophilia.


Drug Interactions:

Atazanavir is an inhibitor of CYP3A, CYP2C9, CYP1A2, and UGT1A1. Co administration of Atazanavir and drugs primarily metabolized by CYP3A (eg, calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressants, and PDE5 inhibitors), CYP2C9, CYP1A2, or UGT1A1 (eg, irinotecan) may result in increased plasma concentrations of the other drug that could increase or prolong both its therapeutic and adverse effects. Atazanavir is metabolized in the liver by the cytochrome P450 enzyme system. Co administration of Atazanavir and drugs that induce CYP3A, such as rifampin, may decrease Atazanavir plasma concentrations and reduce its therapeutic effect. Co administration of Atazanavir and drugs that inhibit CYP3A may increase Atazanavir plasma concentrations. The potential for drug interactions with Atazanavir changes when Atazanavir is co administered with the potent CYP3A inhibitor ritonavir. The magnitude of CYP3A-mediated drug interactions (effect on Atazanavir or effect on co administered drug) may change when Atazanavir is co administered with ritonavir. Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of Atazanavir are expected if proton-pump inhibitors antacids, buffered medications, or H2-receptor antagonists are administered with Atazanavir. Atazanavir has the potential to prolong the PR interval of the electrocardiogram in some patients. Caution should be used when co administering Atazanavir with medicinal products known to induce PR interval prolongation (eg, atenolol, diltiazem) especially those that are metabolized by CYP3A (eg, verapamil). Based on known metabolic profiles, clinically significant drug interactions are not expected between Atazanavir and fluvastatin, pravastatin, dapsone, trimethoprim/sulfamethoxazole, azithromycin, erythromycin, or fluconazole. Atazanavir does not interact with substrates of CYP2D6 (eg, nortriptyline, desipramine, metoprolol). Additionally, no clinically significant drug interaction was observed when Atazanavir was co administered with methadone. Co administration of Atazanavir with hormonal contraceptives has not been studied. Because levels of contraceptive steroids from pills or contraceptive patches may be altered while patient is on Atazanavir or Atazanavir/ritonavir, a non hormonal method of contraception is recommended.


Dosage and administration:

  • Adults:
    Atazanavir Capsules must be taken with food.
  • The recommended oral dose of Atazanavir is as follows:
    • Therapy-Naive Patients
      Atazanavir 400 mg (two 200-mg capsules) once daily taken with food. There is no data regarding the use of Atazanavir/ritonavir in therapy-naive patients.
    • Therapy-Experienced Patients
      Atazanavir 300 mg (two 150-mg capsules) once daily plus ritonavir 100 mg once daily taken with food. Atazanavir without ritonavir is not recommended for treatment-experienced patients with prior virologic failure.
    • Efavirenz- In treatment-naive patients who receive efavirenz and Atazanavir, the recommended dose is Atazanavir 300 mg with ritonavir 100 mg and efavirenz 600 mg (all once daily). Dosing recommendations for efavirenz and Atazanavir in treatment-experienced patients have not been established.
    • Didanosine- When co administered with didanosine buffered formulations, Atazanavir should be given (with food) 2 hours before or 1 hour after didanosine. Tenofovir disoproxil fumarate. When co-administered with tenofovir, it is recommended that Atazanavir 300 mg be given with ritonavir 100 mg and tenofovir 300 mg (all as a single daily dose with food). Atazanavir without ritonavir should not be co administered with tenofovir.


Storage:

Atazanavir sulphate capsules to be stored at 25 °C (77°F). Excursions permitted to 15-30°C (59-86°F).