Atazanavir, sold under the brand name Reyataz among others, is an

antiretroviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do n ...

used to treat

HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...

. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a

needlestick injury A needlestick injury is the penetration of the skin by a hypodermic needle or other sharp object that has been in contact with blood, tissue or other body fluids before the exposure. Even though the acute physiological effects of a needlestick i ...

or other potential exposure (postexposure prophylaxis (PEP)). It is taken by mouth once a day. Common side effects include

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, yellowish skin,

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...

trouble sleeping Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, and

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

. Severe side effects include rashes such as

erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...

and

high blood sugar Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

. Atazanavir appears to be safe to use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

. It is of the protease inhibitor (PI) class and works by blocking

HIV protease HIV-1 protease (PR) is a retroviral aspartyl protease (retropepsin), an enzyme involved with peptide bond hydrolysis in retroviruses, that is essential for the life-cycle of HIV, the retrovirus that causes AIDS. HIV protease cleaves newly synthesi ...

. Atazanavir was approved for medical use in the United States in 2003. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. 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 Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue. The medical condition is characterized by abnormal or degenerative conditions of the body's adipose tissue. ...

. There may be some cross-resistant with other protease inhibitors. When boosted with

ritonavir Ritonavir, sold under the brand name Norvir, is an antiretroviral drug used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor a ...

it is equivalent in potency to

lopinavir Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir (lopinavir/ritonavir). It was patented in 1995 and approved for medical ...

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,

, or toxic skin eruptions). Additionally, atazanavir should not be given with

alfuzosin Alfuzosin, sold under the brand names Alfosoft and Uroxatral, among others, is a medication of the α1 blocker class. It is used to treat benign prostatic hyperplasia (BPH). As an antagonist of the α1 adrenergic receptor, it works by relax ...

rifampin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used tog ...

irinotecan Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cispl ...

lurasidone Lurasidone, sold under the trade name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth. Common side effects include sleepiness, movement disorders, nausea, and diarrhea. ...

pimozide Pimozide (sold under the brand name Orap) is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis i ...

triazolam Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties ...

, orally administered

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of a ...

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 Cisapride is a gastroprokinetic agent, a drug that increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors incr ...

St. John's wort ''Hypericum perforatum'', known as St. John's wort, is a flowering plant in the family Hypericaceae and the type species of the genus ''Hypericum''. Possibly a hybrid between '' H. maculatum'' and '' H. attenuatum'', the species can be found a ...

lovastatin Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat hypercholesterolemia, high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It ...

simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart ...

sildenafil Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...

indinavir Indinavir (IDV; trade name Crixivan, made by Merck) is a protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS. It is soluble white powder administered orally in combination with other antiviral drugs. Th ...

, or

nevirapine Nevirapine (NVP), sold under the brand name Viramune among others, is a medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medications. It may be used to prevent mothe ...

Adverse effects

Common side effects include:

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 A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, peripheral neurologic symptoms,

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

muscle pain Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

, depression and

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

pill burden Polypharmacy (polypragmasia) is the simultaneous use of multiple medicines by a patient for their conditions. Most commonly it is defined as regularly taking five or more medicines but definitions vary in where they draw the line for the minimum ...

, as one 300 mg capsule may replace two 150 mg capsules. Nanoformulation of atazanavir is being tested in primates together with PI-booster

and NtRTI

tenofovir Tenofovir disoproxil, sold under the trade name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for preven ...

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