Atazanavir

Oral
HIV-1 infection

Treatment-experienced patient on haemodialysis: Contraindicated.

W/ ritonavir: Mild to severe: Contraindicated. W/o ritonavir (treatment-naive patient): Moderate (Child-Pugh category B): 300 mg daily. Severe (Child-Pugh category C): Contraindicated.

Should be taken with food.

Hypersensitivity. Treatment-experienced patient on haemodialysis. Mild to moderate (w/ ritonavir) and severe (w/ or w/o ritonavir) hepatic impairment. Lactation. Concomitant use w/ statins (e.g. simvastatin, lovastatin), antiarrhythmics (e.g. amiodarone, bepridil, quinidine, systemic lidocaine), antihistamines (e.g. astemizole, terfenadine), antipsychotics (e.g. pimozide, quetiapine), ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergometrine), GI prokinetics (e.g. cisapride), sedative and hypnotics (e.g. triazolam, oral midazolam), α₁-adrenergic antagonists (e.g. alfuzosin), sildenafil (for treatment of pulmonary arterial HTN), irinotecan, and indinavir.

Patient w/ haemophilia A/B, pre-existing cardiac conduction disorder (e.g. 1st-3rd degree AV or complex bundle branch block), DM, bradycardia, long congenital QT, electrolyte imbalance. Hepatic impairment (including chronic hepatitis B or C). Pregnancy.

Jaundice, GI disturbance (e.g. abdominal pain, diarrhoea, nausea, vomiting, dyspepsia), headache, insomnia, peripheral neurological symptoms, ocular icterus, asthenia, fatigue; mild to moderate rash (e.g. maculopapular rash), cholelithiasis, nephrolithiasis; hyperbilirubinaemia, elevated amylase, lipase, and liver enzymes, low neutrophils; lipodystrophy (e.g. central obesity, dorsocervical fat enlargement, peripheral wasting, breast enlargement, cushingoid appearance); insulin resistance, hyperglycaemia, hyperlactataemia; elevated creatine phosphokinase, myalgia, myositis; osteonecrosis, Grave’s disease, immune reconstitution syndrome. Rarely, rhabdomyolysis.
Potentially Fatal: Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions, drug rash w/ eosinophilia and systemic symptoms (DRESS); PR interval prolongation. Rarely, QT prolongation, torsade de pointes.

PO: B

Perform LFTs before and during treatment. Monitor viral load, CD4, blood lipids and glucose, and bilirubin. Monitor ECG esp in patient w/ pre-existing prolonged PR interval.

Symptoms: Jaundice, hyperbilirubinaemia, asymptomatic bifascicular block, PR interval prolongation. Management: Supportive treatment. Induce emesis or employ gastric lavage; activated charcoal may also be given.

Decreased concentration w/ PPIs, efavirenz, nevirapine, and rifampicin. May increase serum concentration of inhaled fluticasone and salmeterol.
Potentially Fatal: Increased risk for myopathy (i.e. rhabdomyolysis) w/ simvastatin and lovastatin. Increased risk for cardiac arrhythmia w/ cisapride. May increase risk of hypotension w/ alfuzosin. May increase potential of serious AR of amiodarone, bepridil, quinidine, and systemic lidocaine. May increase serum concentration of astemizole, terfenadine, pimozide, quetiapine, dihydroergotamine, ergometrine, ergotamine, methylergometrine, triazolam, and oral midazolam. May increase risk for hypotension, visual changes, and priapism w/ sildenafil (when used for pulmonary arterial HTN). May inhibit UGT1A1 causing an increase toxicity of irinotecan. May cause indirect hyperbilirubinaemia w/ indinavir.

Enhanced absorption w/ food. Decreased concentration w/ St John’s wort.

Description:
Mechanism of Action: Atazanavir, a synthetic azapeptide, is a selective, competitive, and reversible HIV-1 protease inhibitor. It inhibits the cleavage of viral Gag and Gag-Pol polyprotein precursors into individual functional proteins, preventing the processing of the polyproteins into mature and infectious virions.
Pharmacokinetics:
Absorption: Rapidly absorbed from the GI tract. Enhanced absorption w/ food. Time to peak plasma concentration: Approx 2-2.5 hr.
Distribution: Distributed in the CSF and semen in low concentration. Plasma protein binding: 86%, w/ similar affinity to albumin and α₁-acid glycoprotein.
Metabolism: Extensively metabolised in the liver by CYP3A4 enzyme, mainly via mono-oxygenation and deoxygenation into inactive metabolites; also undergoes glucuronidation, N-dealkylation, hydrolysis, and oxygenation w/ dehydrogenation into 2 minor inactive metabolites.
Excretion: Via faeces (79%, 20% as unchanged drug) and urine (13%, 7% as unchanged drug). Terminal elimination half-life: Approx 7 hr.

Source: National Center for Biotechnology Information. PubChem Database. Atazanavir, CID=148192, https://pubchem.ncbi.nlm.nih.gov/compound/Atazanavir (accessed on Jan. 21, 2020)

Store between 15-30°C.

Antivirals

J05AE08 - atazanavir ; Belongs to the class of protease inhibitors. Used in the systemic treatment of viral infections.

Anon. Atazanavir. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 12/10/2016.

Buckingham R (ed). Atazanavir Sulfate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/10/2016.

Joint Formulary Committee. Atazanavir. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/10/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Atazanavir Sulfate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 12/10/2016.

Reyataz Capsule, Gelatin Coated (A-S Medication Solutions). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 12/10/2016.