Atazanavir

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Atazanavir
Atazanavir structure.svg
Atazanavir ball-and-stick.png
Clinical data
Pronunciation /ˌæ.tə.ˈzæ.nə.vɪər/, A-tə-ZA-nə-vir[2]
Trade names Reyataz, Evotaz, others[1]
AHFS/Drugs.com Monograph
MedlinePlus a603019
Pregnancy
category
  • AU: B2
  • US: B (No risk in non-human studies)
Routes of
administration
By mouth
ATC code J05AE08 (WHO)
Legal status
Legal status
Pharmacokinetic data
Bioavailability 60-68%
Protein binding 86%
Metabolism Liver (CYP3A4-mediated)
Biological half-life 6.5 hours
Excretion Fecal and kidney
Identifiers
CAS Number 198904-31-3 YesY
PubChem (CID) 148192
DrugBank DB01072 YesY
ChemSpider 130642 YesY
UNII QZU4H47A3S YesY
KEGG D01276 N
ChEBI CHEBI:37924 YesY
ChEMBL CHEMBL1163 YesY
NIAID ChemDB 057755
Chemical and physical data
Formula C38H52N6O7
Molar mass 704.856 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Atazanavir, sold under the trade name Reyataz among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth once a day.[1]

Common side effects include headache, nausea, yellowish skin, abdominal pain, trouble sleeping, and fever. Severe side effects include rashes such as erythema multiforme and high blood sugar. Atazanavir appears to be safe to use during pregnancy. It is of the protease inhibitor (PI) class and works by blocking HIV protease.[1]

Atazanavir was approved for medical use in the United States in 2003.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] In the United States it is not available as a generic medication.[4] The wholesale cost in the developing world is about 15.72 USD per month.[5] As of 2015, the cost for a typical month of medication in the United States was more than 200 USD.[4]

Medical uses[edit]

Two Reyataz 200 mg capsules

Atazanavir is used in the treatment of HIV. The efficacy of atazanavir has been assessed in a number of well designed trials in ART-naive and ART-experienced adults.[6]

Atazanavir is distinguished from other PIs in that it has lesser effects on lipid profile and appears to be less likely to cause lipodystrophy. There may be some cross-resistant with other PIs.[1] When boosted with ritonavir it is equivalent in potency to lopinavir for use in salvage therapy in people with a degree of drug resistance, although boosting with ritonavir reduces the metabolic advantages of atazanavir.[citation needed]

Pregnancy[edit]

Atazanavir is pregnancy category B in the United States, meaning that no evidence of harm has been found among pregnant women taking this medication. It is one of the preferred HIV medication to use in pregnant women who have not taken an HIV medication before.[7] It was not associated with any birth defects among over 2,500 live births observed. Atazanavir resulted in a better cholesterol profile and confirmed that it is a safe option during pregnancy.[7]

Contraindications[edit]

Atazanavir is contraindicated in those with previous hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions). Additionally, atazanavir should not be given with alfuzosin, rifampin, irinotecan, lurasidone, pimozide, triazolam, orally administered midazolam, ergot derivatives, cisapride, St. John's wort, lovastatin, simvastatin, sildenafil, indinavir, or nevirapine.[8]

Adverse effects[edit]

Common side effects include: nausea, jaundice, rash, headache, abdominal pain, vomiting, insomnia, peripheral neurlogic symptoms, dizziness, muscle pain, diarrhea, depression and fever.[8] Bilirubin levels in the blood are normally asymptomatically raised with atazanavir, but can sometimes lead to jaundice.

Mechanism of action[edit]

Atazanavir binds to the active site HIV protease and prevents it from cleaving the pro-form of viral proteins into the working machinery of the virus.[9] If the HIV protease enzyme does not work, the virus is not infectious, and no mature virions are made.[10][11] The azapeptide drug was designed as an analog of the peptide chain substrate that HIV protease would cleave normally into active viral proteins. More specifically, atazanavir is a structural analog of the transition state during which the bond between a phenylalanine and proline is broken.[12][13] Humans do not have any enzymes that break bonds between phenylalanine and proline, so this drug will not target human enzymes.

Formulations[edit]

Atazanavir is available as a 150 mg capsule, 200 mg capsule, 300 mg capsule, and 50 mg oral powder packet.[8] The 300 mg capsule should reduce pill burden, as one 300 mg capsule may replace two 150 mg capsules.

References[edit]

  1. ^ a b c d e "Atazanavir Sulfate". The American Society of Health-System Pharmacists. Retrieved 28 November 2016. 
  2. ^ "Atazanavir". MedlinePlus. National Institutes of Health. October 15, 2012. Retrieved August 3, 2013. 
  3. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  4. ^ a b Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 67. ISBN 9781284057560. 
  5. ^ "Atazanavir". International Drug Price Indicator Guide. Retrieved 28 November 2016. 
  6. ^ Croom KF, Dhillon S, Keam SJ.[1].Drugs 2009;69(8):1107-1140. doi:10.2165/00003495-200969080-00009.
  7. ^ a b "What's New in the Guidelines? | Adult and Adolescent ARV Guidelines | AIDSinfo". AIDSinfo. Retrieved 2016-11-10. 
  8. ^ a b c "Reyataz Package Insert" (PDF). Drugs@FDA. Food and Drug Administration. September 2016. Retrieved November 10, 2016. 
  9. ^ "Atazanavir". DrugBank. 9 November 2016. 
  10. ^ Kohl, N E; Emini, E A; Schleif, W A; Davis, L J; Heimbach, J C; Dixon, R A; Scolnick, E M; Sigal, I S (1 July 1988). "Active human immunodeficiency virus protease is required for viral infectivity.". Proceedings of the National Academy of Sciences of the United States of America. 85 (13): 4686–4690. doi:10.1073/pnas.85.13.4686. ISSN 0027-8424. PMC 280500Freely accessible. PMID 3290901. 
  11. ^ Lv, Z; Chu, Y; Wang, Y (2015). "HIV protease inhibitors: a review of molecular selectivity and toxicity. ". HIV/AIDS (Auckland, NZ). 7: 95–104. doi:10.2147/HIV.S79956. 
  12. ^ Graziani, Amy L (June 17, 2014). "HIV protease inhibitors". UpToDate.
  13. ^ New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development Guido Bold,*, Alexander Fässler,Hans-Georg Capraro,Robert Cozens,Thomas Klimkait,Janis Lazdins,Jürgen Mestan,Bernard Poncioni,Johannes Rösel,David Stover,Marina Tintelnot-Blomley,Figan Acemoglu,Werner Beck,Eugen Boss,Martin Eschbach,Thomas Hürlimann,Elvira Masso,Serge Roussel,Katharina Ucci-Stoll,Dominique Wyss, and Marc Lang 1998 41 (18), 3387-3401 DOI: 10.1021/jm970873c