Atazanavir

Registered South African indications:

• HIV-1  infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Moderate hepatic impairment (boosted with ritonavir)
• Severe hepatic impairment  
• Porphyria
• Coadministration  with simvastatin or lovastatin
• Coadministration with  rifampicin
• Coadministration with sildenafil  when used for the treatment of pulmonary arterial hypertension
• Coadministration with medicinal products that are substrates of the CYP3A4 that have narrow therapeutic windows  
• Coadministration of ergot alkaloids
• Coadministration with grazoprevir-containing products
• Coadministration with glecaprevir/pibrentasivir fixed dose combination
• Coadministration with  St. John's wort

Cautions

• Pregnancy
• Breastfeeding
• Mild hepatic impairment
• Moderate hepatic impairment (unboosted)
• Chronic hepatitis B or C
• Haemodialysis
• PR interval prolongation
• Pre-existing conduction problems
• Second degree or higher atrioventricular or complex bundle-branch block
• Bradycardia
• Long congenital QT interval
• Electrolyte imbalances
• Haemophilia
• Diabetes mellitus
• Alcohol consumption
• Severe immunosuppression
• Higher body mass index
• Advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy
• Co-administration with ritonavir at doses > 100mg once daily
• Lactose allergy
• Lapp lactose deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: cap

First-line virological failure with dyslipidaemia or diarrhoea associated with lopinavir/ritonavir

• Oral (cap): 400mg, dly, or 300mg atazanavir with 100mg ritonavir, dly
  

Post-exposure prophylaxis

• Oral (cap): 400mg, dly or 300mg atazanavir with 100mg ritonavir, dly, in combination with tenofovir and emtricitabine or lamivudine; Treatment duration: 4 weeks
  

Paed. forms avail. in SA and covered in this monograph: cap

HIV infection

Younger than 6 years

• Not established for use

Between 6-18 years

• Oral (cap): 15-34.9kg: 200mg, dly plus ritonavir 100mg, dly
• Oral (cap): 35-39kg: 300mg, dly plus ritonavir 100mg, dly
• Oral (cap): >40kg: 300mg, dly plus ritonavir 100mg, dly

Older than 18 years

• See adult dosage

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Avoid atanzanvir capusles when < 15kg or < 6 years of age

Consult HIV/infectious disease specialists prior to any decisions related to ARV regimen termination/switch

Pregnancy 

• Caution
• A moderate amount of data in pregnant women (between 300-1000 pregnancy outcomes) indicate no malformative toxicity of atazanavir. Animal studies do not indicate reproductive toxicity. The use of atazanavir with ritonavir may be considered during pregnancy only if the potential benefit justifies the potential risk
• In clinical trial AI424-182 atazanavir/ritonavir (300/100 mg or 400/100 mg) in combination with zidovudine/lamivudine was administered to 41 pregnant women during the second or third trimester. Six of 20 (30%) women on atazanavir/ ritonavir 300/100 mg and 13 of 21 (62%) women on atazanavir/ritonavir 400/100 mg experienced grades 3 to 4 hyperbilirubinaemia. There were no cases of lactic acidosis observed in the clinical trial AI424-182
• The study assessed 40 infants who received antiretroviral prophylactic treatment (which did not include atazanavir) and were negative for HIV-1 DNA at the time of delivery and/or during the first 6 months postpartum. Three of 20 infants (15%) born to women treated with atazanavir/ ritonavir 300/100 mg and four of 20 infants (20%) born to women treated with atazanavir/ritonavir 400/100 mg experienced grade 3-4 bilirubin. There was no evidence of pathologic jaundice and six of 40 infants in this study received phototherapy for a maximum of 4 days. There were no reported cases of kernicterus in neonates
• It is not known whether atazanavir with ritonavir administered to the mother during pregnancy will exacerbate physiological hyperbilirubinaemia and lead to kernicterus in neonates and infants. In the prepartum period, additional monitoring should be considered

Breastfeeding

• Caution; not recommended
• Atazanavir has been detected in human milk. As a general rule, it is recommended that HIV infected women not breast-feed their infants in order to avoid transmission of HIV

Fertility

• In a nonclinical fertility and early embryonic development study in rats, atazanavir altered oestrus cycling with no effects on mating or fertility

Renal Impairment

• No dose adjustment recommended
  Atazanavir with ritovavir is not recommended in patients undergoing haemodialysis

Hepatic Impairment

• Mild: With/ without ritonavir: Caution; no dose adjustment recommended
• Moderate: Unboosted: Caution; dose adjustment recommended
  300mg, dly
• Moderate to Severe: With Ritonavir: Contraindicated
• Severe: Unboosted: Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Disorientation
• Anxiety
• Insomnia
• Abnormal dreams
• Headache
• Peripheral neuropathy
• Syncope
• Amnesia
• Dizziness
• Somnolence
• Asthenia
• Malaise

Cardiovascular Disorders

• Torsades de pointes
• QTc prolongation
• Oedema
• Palpitation
• Hypertension

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Dyspepsia
• Pancreatitis
• Gastritis
• Abdominal distension
• Stomatitis aphthous
• Flatulence
• Dry mouth

Hepatobiliary Disorders

• Jaundice
• Hepatitis
• Cholelithiasis
• Cholestasis
• Hepatosplenomegaly
• Cholecystitis

Genitourinary Disorders

• Nephrolithiasis
• Hematuria
• Proteinuria
• Pollakiuria
• Interstitial nephritis
• Kidney pain
• Chronic kidney disease
• Gynaecomastia

Endocrine and Metabolic Disorders

• Decreased weight
• Increased weight
• Anorexia
• Appetite increased

Musculoskeletal Disorders

• Muscle atrophy
• Arthralgia
• Myalgia
• Myopathy
• Osteonecrosis

Skin and Subcutaneous Tissue Disorders

• Rash
• Erythemia multiforme
• Toxic skin eruptions
• Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome
• Angioedema
• Urticaria
• Alopecia
• Pruritus
• Stevens-Johnson syndrome
• Vesiculobullous rash
• Eczema
• Vasodilatation

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity

Sensory Disorders

• Ocular icterus
• Dysgeusia

Others

• Fever
• Gait disturbance
• Chest pain

• CYP3A4 substrates with narrow therapeutic windows
• Quetiapine
• Lurasidone
• Alfuzosin
• Astemizole
• Terfenadine
• Cisapride
• Pimozide
• Quinidine
• Bepridil
• Triazolam
• Midazolam
• Grazoprevir-containing agents
• Glecaprevir/pibrentasvir fixed dose combination
• Voxilaprevir
• Agents which prolong PR interval  
• Agents which prolong QT interval
• Didanosine
• Protease inhibitors
• Boceprevir
• Indinavir
• Tenofovir
• Efavirenz  
• Nevirapine
• Clarithromycin
• Ketoconazole
• Itraconazole
• Voriconazole
• Rifabutin  
• Rifampicin
• Famotidine
• Warfarin
• Carbamazepine
• Phenytoin
• Phenobarbital
• Lamotrigine
• Irinotecan
• Immunosuppressants
• Cyclosporin
• Tacrolimus
• Sirolimus
• Antiarrhythmics
• Amiodarone
• Systemic lidocaine
• Calcium channel blockers
• Diltiazem
• Verapamil
• Fluticasone propionate
• PDE5 inhibitors
• Sildenafil
• Tadalafil
• Vardenafil
• St. John's wort  
• Oral contraceptives
• HMG CoA reductase inhibitors
• Atorvastatin
• Lovastatin
• Simvastatin
• Pravastatin
• Fluvastatin
• Salmeterol
• Buprenorphine
• Benzodiazepines
• Ergot derivatives
• Ergotamine
• Dihydroergotamine
• Ergonovine
• Methylergonovine
• Proton pump inhibitors
• Omeprazole
• Antacids
• Tricyclic antidepressants
• Trazodone
• H2-receptor antagonists

• Skin reactions
• Viral load
• CD4 count
• Hepatic function
• Kidney function

Specific cases may require

• Electrocardiogram
• Blood glucose

Atazanavir is an azapeptide HIV-1 protease inhibitor (PI). It selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells.

Capsule 150mg

• Aspen Atazanavir (Pharmacare)
• Atazor-150 (Emcure)
• Reyataz (Bristol-Myers) originator

Capsule 200mg

• Aspen Atazanavir (Pharmacare)
• Atazor-200 (Emcure)
• Reyataz (Bristol-Myers) originator

Capsule 300mg

• Atazor-300 (Emcure)