Atazanavir, sold under the brand name Reyataz among others, is an antiretroviral medication used to treat 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 (postexposure prophylaxis (PEP)). It is taken by mouth once a day. Common side effects include

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, nausea, yellowish skin, abdominal pain,

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, 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. Atazanavir was approved for medical use in the United States in 2003. It is on the World Health Organization's List of Essential Medicines. As of 2017 there is a generic version available in the United States manufactured by

Teva Pharmaceuticals Teva Pharmaceutical Industries Ltd. (also known as Teva Pharmaceuticals) is an Israeli multinational pharmaceutical company with headquarters in Tel Aviv, Israel. It specializes primarily in generic drugs, but other business interests include ...

Medical uses

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. Atazanavir is distinguished from other protease inhibitors 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 protease inhibitors. 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

No evidence of harm has been found among pregnant women taking atazanavir. It is one of the preferred HIV medications to use in pregnant women who have not taken an HIV medication before. 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.

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

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, rifampin, irinotecan, lurasidone, pimozide, triazolam, orally administered midazolam,

ergot Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''. The most prominent member of this group is ''Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that ca ...

derivatives, cisapride, St. John's wort, lovastatin, simvastatin,

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, indinavir, or nevirapine.

Adverse effects

Common side effects include: nausea,

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

, rash,

, abdominal pain, vomiting, insomnia, peripheral neurologic symptoms, dizziness, muscle pain, diarrhea, depression and fever.

Bilirubin Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

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. If the HIV protease enzyme does not work, the virus is not infectious, and no mature virions are made. The azapeptide drug was

designed A design is a plan or specification for the construction of an object or system or for the implementation of an activity or process or the result of that plan or specification in the form of a prototype, product, or process. The verb ''to design'' ...

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 Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

and

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

is broken. 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. The 300 mg capsule should reduce

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, as one 300 mg capsule may replace two 150 mg capsules. Nanoformulation of atazanavir is being tested in primates together with PI-booster ritonavir and NtRTI tenofovir for a long-acting therapy.

References

External links

* {{Portal bar , Medicine , Viruses Bristol Myers Squibb CYP3A4 inhibitors HIV protease inhibitors 2-Pyridyl compounds Wikipedia medicine articles ready to translate World Health Organization essential medicines