Atazanavir (Adverse effects)

Atazanavir is an antiretroviral drug used in the treatment of HIV. This drug can inhibit the function of the UGT1A1 protein, causing jaundice as a side effect and being a reason for treatment interruption.

Atazanavir is a direct-acting antiviral drug that is often used together with other drugs, such as ritonavir or cobicistat, to treat human immunodeficiency virus (HIV) infection in adults and children who are at least 3 months old and weigh at least 10 kg. Atazanavir is in a class of drugs known as protease inhibitors. Atazanavir works by decreasing the amount of HIV in the blood. Although atazanavir does not cure HIV, it can reduce the chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medicines may decrease the risk of passing the HIV virus to other people.

Atazanavir is sometimes used to prevent infection in health care workers or other people who were accidentally exposed to HIV.

Currently, in 2020, it is being studied for the treatment of the SARS-CoV-2 coronavirus, but effectiveness studies are not yet conclusive.

MECHANISM OF ACTION

Atazanavir acts by inhibiting HIV protease, preventing the formation of mature virions in cells that are already infected and thus making it more difficult to infect other cells.

CONTRAINDICATIONS

Hypersensitivity to atazanavir.

Contraindicated in patients with severe hepatic insufficiency. Caution in patients with mild hepatic insufficiency.


Contraindicated in concomitance with: simvastatin, lovastatin, rifampicin, sildenafil for the treatment of pulmonary arterial hypertension, CYP3A4 substrates with narrow therapeutic margin (eg.quetiapine, alfuzosin, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, oral midazolam and ergot alkaloids, especially ergotamine, dihydroergotamine, ergonovine, methylergonovine), St. John's wort.

PHARMACOLOGICAL INTERACTIONS

Monitor possible adverse reactions if atazanavir is being administered together with: tenofovir, disoproxil, irinotecan.

Caution with: clarithromycin; ketoconazole and itraconazole (high doses greater than 200 mg/day not advisable); carbamazepine, lamotrigine, phenytoin and phenobarbital (monitor and adjust doses); pravastatin and fluvastatin; parenteral midazolam.

Monitor INR (or prothrombin time) if taking warfarin.

Azatanavir increases the concentration of: amiodarone and systemic lidocaine (caution and monitor concentration); immunosuppressants (cyclosporine, tacrolimus, sirolimus); rifabutin, buprenorphine and norbuprenorphine (monitor cognitive effects and sedation, consider reducing dose); diltiazem (reduce initial dose to 50%); verapamil.

SIDE EFFECTS

Headache, ocular jaundice, vomiting, diarrhea, abdominal pain, nausea, dyspepsia, jaundice; itching, fatigue; elevations of total bilirubin, elevations of liver enzymes CK, ALT, AST and lipase.

Decreased neutrophils.

Depression, fever, difficulty falling asleep, rash, pain or numbness in the hands or feet, muscle aches.

Other more serious side effects may include: irregular heartbeat, vision defects, pain or burning with urination, blood in the urine, swelling in the extremities, erections lasting more than 4 hours, blistering or peeling of the skin, red or inflamed eyes, canker sores in the mouth, swelling of the face or neck, very severe rashes.

BRAND NAMES

  • Reyataz® (contains Ataz®)
  • Evotaz® (contains Atazanavir, Cobicistat)

Genes analyzed

UGT1A1

Bibliography

Gammal RS, Court MH, Haidar CE, Iwuchukwu OF, Gaur AH, Alvarellos M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing. Clin Pharmacol Ther, 2016; 99(4):363–9

Vardhanabhuti S, Ribaudo HJ, Landovitz RJ, Ofotokun I, Lennox JL, Currier JS, et al. Screening for UGT1A1 Genotype in Study A5257 Would Have Markedly Reduced Premature Discontinuation of Atazanavir for Hyperbilirubinemia. Open forum Infect Dis, 2015;2(3):ofv08

Johnson DH, Venuto C, Ritchie MD, Morse GD, Daar ES, McLaren PJ, et al. Genomewide association study of atazanavir pharmacokinetics and hyperbilirubinemia in AIDS Clinical Trials Group protocol A5202. Pharmacogenet Genomics, 2014; 24(4):195–203

Rodríguez-Nóvoa S, Martín-Carbonero L, Barreiro P, González-Pardo G, Jiménez-Nácher I, González-Lahoz J, et al. Genetic factors influencing atazanavir plasma concentrations and the risk of severe hyperbilirubinemia. AIDS, 2007; 21(1):41–6

Rodríguez Nóvoa S, Barreiro P, Rendón A, Barrios A, Corral A, Jiménez-Nacher I, et al. Plasma levels of atazanavir and the risk of hyperbilirubinemia are predicted by the 3435C-->T polymorphism at the multidrug resistance gene 1. Clin Infect Dis, 2006; 42(2):291–5

Lankisch TO, Moebius U, Wehmeier M, Behrens G, Manns MP, Schmidt RE, et al. Gilbert’s disease and atazanavir: from phenotype to UDP-glucuronosyltransferase haplotype. Hepatology, 2006; 44(5):1324–32

Savic RM, Barrail-Tran A, Duval X, Nembot G, Panhard X, Descamps D, et al. Effect of adherence as measured by MEMS, ritonavir boosting, and CYP3A5 genotype on atazanavir pharmacokinetics in treatment-naive HIV-infected patients. Clin Pharmacol Ther, 2012; 92(5):575–83

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