Atazanavir

Atazanavir, sold under the trade name Reyataz among others, is an antiretroviral medication used to treat and prevent HIV/AIDS.[2] It is generally recommended for use with other antiretrovirals.[2] It may be used for prevention after a needlestick injury or other potential exposure.[2] It is taken by mouth once a day.[2]

Atazanavir
Clinical data
Pronunciation/ˌætəˈzænəvɪər/ AT-ə-ZAN-ə-veer[1]
Trade namesReyataz, Evotaz, others[2]
AHFS/Drugs.comMonograph
MedlinePlusa603019
License data
Pregnancy
category
  • AU: B2
  • US: B (No risk in non-human studies)
    Routes of
    administration    		By mouth
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability60-68%
    Protein binding86%
    MetabolismLiver (CYP3A4-mediated)
    Elimination half-life6.5 hours
    ExcretionFecal and kidney
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    NIAID ChemDB
    CompTox Dashboard (EPA)
    ECHA InfoCard100.243.594
    Chemical and physical data
    FormulaC38H52N6O7
    Molar mass704.869 g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    Common side effects include headache, nausea, yellowish skin, abdominal pain, trouble sleeping, and fever.[2] Severe side effects include rashes such as erythema multiforme and high blood sugar.[2] Atazanavir appears to be safe to use during pregnancy.[2] It is of the protease inhibitor (PI) class and works by blocking HIV protease.[2]

    Atazanavir was approved for medical use in the United States in 2003.[2] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[3] In the United States it is not available as a generic medication.[4]

    Medical uses
    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.[5]

    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.[2] 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.

    Pregnancy

    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.[6] 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.[6]

    Contraindications

    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.[7]

    Adverse effects

    Common side effects include: nausea, jaundice, rash, headache, abdominal pain, vomiting, insomnia, peripheral neurologic symptoms, dizziness, muscle pain, diarrhea, depression and fever.[7] Bilirubin levels in the blood are normally asymptomatically raised with atazanavir, but can sometimes lead to jaundice.

    Mechanism of action

    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.[8] If the HIV protease enzyme does not work, the virus is not infectious, and no mature virions are made.[9][10] 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.[11][12] Humans do not have any enzymes that break bonds between phenylalanine and proline, so this drug will not target human enzymes.

    Formulations

    Atazanavir is available as a 150 mg capsule, 200 mg capsule, 300 mg capsule, and 50 mg oral powder packet.[7] The 300 mg capsule should reduce pill burden, as one 300 mg capsule may replace two 150 mg capsules.

    gollark: The worst thing about TJ09 is the utter lack of communication.
    gollark: - EATW was according to everyone taken down due to the viewbombing.- I used archived EATW data to prevent sickness/viewbombing in my hatchery.- TJ09 eventually noticed and IP-banned my hatchery so it stopped working and took all the eggs out automatically (that is a *slight* bug).- The email I got said *… did the same thing that got EATW banned from the API".- But presumably it just shut down due to viewbombing and not lack of API access…?
    gollark: Wow, that's quite TJ09…
    gollark: And for the NDfails which must have died to bring us this knowledge.
    gollark: Yes, about those.

    References
    1. "Atazanavir". MedlinePlus. National Institutes of Health. October 15, 2012. Archived from the original on August 2, 2013. Retrieved August 3, 2013.
    2. "Atazanavir Sulfate". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 28 November 2016.
    3. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    4. Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 67. ISBN 9781284057560.
    5. Croom, KF; Dhillon, S; Keam, SJ (2009). "Atazanavir: A Review of its Use in the Management of HIV-1 Infection". Drugs. 69 (8): 1107–1140. doi:10.2165/00003495-200969080-00009. PMID 19496633.
    6. "What's New in the Guidelines? | Adult and Adolescent ARV Guidelines | AIDSinfo". AIDSinfo. Archived from the original on 2016-11-15. Retrieved 2016-11-10.
    7. "Reyataz Package Insert" (PDF). Drugs@FDA. Food and Drug Administration. September 2016. Archived (PDF) from the original on November 11, 2016. Retrieved November 10, 2016.
    8. "Atazanavir". DrugBank. 9 November 2016. Archived from the original on 9 November 2016.
    9. Kohl, NE; Emini, EA; Schleif, WA; Davis, LJ; Heimbach, JC; Dixon, RA; Scolnick, EM; Sigal, IS (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. Bibcode:1988PNAS...85.4686K. doi:10.1073/pnas.85.13.4686. ISSN 0027-8424. PMC 280500. PMID 3290901.
    10. Lv, Z; Chu, Y; Wang, Y (2015). "HIV protease inhibitors: a review of molecular selectivity and toxicity. ". HIV/AIDS – Research and Palliative Care. 7: 95–104. doi:10.2147/HIV.S79956. PMC 4396582. PMID 25897264.
    11. Graziani, Amy L (June 17, 2014). "HIV protease inhibitors". UpToDate.
    12. Bold, G; Fässler, A; Capraro, HG; Cozens, R; Klimkait, T; Lazdins, J; Mestan, J; Poncioni, B; Rösel, J; Stover, D; Tintelnot-Blomley, M; Acemoglu, F; Beck, W; Boss, E; Eschbach, M; Hürlimann, T; Masso, E; Roussel, S; Ucci-Stoll, K; Wyss, D; Lang, M (August 1998). "New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors: Candidates for Clinical Development". Journal of Medicinal Chemistry. 41 (18): 3387–3401. doi:10.1021/jm970873c. PMID 9719591.
    • "Atazanavir". Drug Information Portal. U.S. National Library of Medicine.
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