Atazanavir

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Atazanavir: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Atazanavir

ATX code: J05AE08

Active ingredient: atazanavir (Atazanavir)

Manufacturer: Nanopharma Development LLC (Russia); ZiO-Zdorovie CJSC (Russia); Pharmstandard-Leksredstva OJSC (Russia); Izvarino Pharma LLC (Russia)

Description and photo update: 2020-04-06

Prices in pharmacies: from 2776 rubles.

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Atazanavir is a protease inhibitor of the human immunodeficiency virus (HIV) with a high degree of antiretroviral (ARV) activity. Differs in the absence of a pronounced effect on carbohydrate metabolism and lipid profile, as well as significant safety. Recommended by the World Health Organization (WHO) as a component of combination ARV therapy.

Release form and composition

Atazanavir dosage form - capsules: gelatinous, solid, filled with a loose or compacted powdery mass from white to white with a yellowish tinge, or a granulate from white to light yellow in color with the presence of lumps and columns that disintegrate when lightly pressed with a glass rod:

dosage 150 mg - capsules No. 1; opaque, body and lid from white to white with a yellowish tinge / opaque, pink lid and white body / blue lid and blue body;
dosage 200 mg - capsules No. 0; opaque, white to white with a yellowish tint / opaque body and lid, orange lid and white body / lid and blue color;
dosage 300 mg - capsules No. 00; opaque, body and lid from white to white with a yellowish tinge / opaque, lid and body white / red lid and blue body.

10 pcs. in blisters, in a carton box 3 or 6 packages; 30 or 60 pcs. in cylindrical polyethylene cans with a screw cap equipped with a first opening control, in a cardboard box 1 can and instructions for the use of Atazanavir.

Composition for 1 capsule:

active substance: atazanavir - 150; 200 or 300 mg (in the form of atazanavir sulfate, respectively - 170.87; 227.83 or 341.74 mg);
auxiliary components: crospovidone, lactose monohydrate, magnesium stearate;
capsule shell: titanium dioxide, gelatin.

The composition of the capsule shell of colored capsules contains dyes, the color of which corresponds to the color of the capsules.

Pharmacological properties

Pharmacodynamics

Atazanavir, an azapeptide protease inhibitor (PI) of HIV-1, selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-infected cells, thus preventing the assembly of mature virions and damage to other cells.

Some patients may develop varying degrees of specific resistance during therapy - resistance to the action of atazanavir, or cross-resistance - resistance to the action of both atazanavir and other HIV PIs.

Specific resistance to atazanavir does not prevent sequential use of other HIV PIs.

Pharmacokinetics

Pharmacokinetic characteristics of atazanavir (assessed based on the results of studies on the use of the drug in healthy volunteers and HIV-infected patients):

absorption: C _ssmax (maximum equilibrium concentration) in plasma is established with long-term administration of atazanavir once a day at a dose of 400 mg (simultaneously with easily digestible food) approximately 2.7 hours after administration. C _ss (steady-state equilibrium concentration) is achieved between 4-8 days of therapy. Food intake improves bioavailability and reduces the variability of the pharmacokinetic properties of atazanavir;
distribution: binding to serum proteins (equally with albumin and α ₁ -acid glycoprotein) is 86% and does not depend on the concentration of atazanavir; the substance also penetrates into the cerebrospinal and seminal fluids;
metabolism: the main metabolizer of atazanavir is the CYP3A4 isoenzyme, as a result, oxidized metabolites are formed, which are excreted in free form or in the form of glucuronide conjugates into bile; to a small extent, atazanavir is metabolized by hydrolysis and N-dealkylation;
excretion: with a single injection of ¹⁴ C-isotopes of atazanavir (400 mg), the total radioactivity reached 79% in feces, and 13% in urine. Unchanged from the administered dose in feces was determined about 20%, in urine - 7%. The half-life (T _1/2) in healthy volunteers and adults with HIV was about 7 hours after taking 400 mg of atazanavir per day with an easily digestible food.

Pharmacokinetics in special groups:

hepatic impairment: since atazanavir is metabolized and excreted mainly by the liver, hepatic dysfunction affects its concentration in blood plasma; the pharmacokinetics of atazanavir at doses up to 300 mg in patients with hepatic insufficiency has not been studied;
renal failure: in severe renal failure in hemodialysis patients taking 400 mg of atazanavir once a day, pharmacokinetic parameters were 30-50% lower than in patients with normal renal function. To date, the mechanism of such a decrease has not been clarified;
race and gender: there were no clinically significant differences in the pharmacokinetics of atazanavir depending on the race and gender of patients;
pregnancy and the postpartum period: C _ssmax and equilibrium area under the concentration-time curve (AUC _S) of atazanavir were 26-40% higher in women in the postpartum period (4 to 12 weeks) compared with non-pregnant HIV-infected patients. The minimum concentration (C _min) in the postpartum period in HIV-infected patients is approximately 2 times higher than that observed in them before pregnancy;
children: in children, the absorption of atazanavir is higher than in adults. When normalizing by body weight in young children, a slight tendency to increased clearance was revealed, and the variability of pharmacokinetic characteristics was also increased in children, compared with adults;
old age: an insufficient number of patients aged 65 years and older participated in clinical trials to determine the effect of older age on the kinetics of atazanavir.

Indications for use

Atazanavir is used for type 1 HIV infection in combination with other ARVs in patients who have or have not received ARV therapy.

Contraindications

Absolute:

severe hepatic dysfunction related to class C on the Child-Pugh scale (for any dosing regimens);
reception in combination with ritonavir for moderate and severe hepatic impairment, belonging to classes B and C on the Child-Pugh scale;
rare genetic lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
severe renal failure in patients on hemodialysis and in patients who have previously received ARV therapy;
taking in combination with the following drugs / substances: astemizole, bepridil, cisapride, terfenadine, pimozide, quinidine (including for the combination atazanavir + ritonavir), midazolam (for oral administration), triazolam, ergotamine derivatives (especially dihydroergotamine, ergometrine, ergotamine, methylergometrine), St. John's wort preparations, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase (lovastatin, simvastatin), quetiapine (including for the combination of atazanavir + rifonampinavir), alfuzosin, sildenafil (for the treatment of pulmonary arterial hypertension);
breast-feeding;
the child's weight is less than 35 kg (for capsules with a dosage of 300 mg);
the age of the child is under 6 years old;
hypersensitivity to atazanavir or other components of the drug.

The drug is used with caution in pregnancy, diabetes mellitus, hyperglycemia, dyslipidemia, hyperbilirubinemia, nephrolithiasis, viral hepatitis, chronic hepatitis in the active phase, mild to moderate liver dysfunctions (classes A and B on the Child-Pugh scale), in combination with ritonavir for mild liver dysfunctions (class A on the Child-Pugh scale), hemophilia A and B, syndrome of congenital lengthening of PR and PQ intervals, the need for combined use with drugs that prolong PR and PQ intervals (atenolol, diltiazem, verapamil), syndrome of congenital lengthening of the QT interval, low acidity (increased pH) of gastric juice.

Caution should also be exercised with the simultaneous use of Atazanavir with drugs / substances such as irinotecan, indinavir, nevirapine, efavirenz, glucocorticosteroids (GCS), voriconazole, clarithromycin, salmeterol, boceprevir, tenofovir, disoproxil, tacidine fumarate, fumarate sirolimus, cyclosporine, amiodarone, lidocaine (parenteral), fluticasone, tadalafil, sildenafil, vardenafil, atorvastatin, fluvastatin, pravastatin, buprenorphine, substrates of other cytochrome P ₄₅₀ (CYP) isoenzymes.

Atazanavir, instructions for use: method and dosage

Atazanavir capsules are intended for oral administration. They should be swallowed whole without chewing. The drug is recommended to be taken with meals.

Atazanavir is used as part of a combination ARV therapy, the decision to start which should be made by a doctor with experience in treating HIV infection. The efficacy and safety of atazanavir when used in combination with ritonavir at a dose greater than 100 mg / day has not been studied. It is known that ritonavir at a dose higher than 100 mg / day in combination with atazanavir can change the safety profile of the latter; this dosage should not be used.

For adults who have not previously received ARV therapy, it is recommended to take atazanavir at a dose of 400 mg or atazanavir - 300 mg + ritonavir - 100 mg once a day.

For adults who have previously received ARV therapy, it is recommended to take atazanavir - 300 mg + ritonavir - 100 mg once a day.

It is not recommended to use atazanavir without ritonavir in patients in whom previous ARV therapy led to an unfavorable virological outcome.

For children, Atazanavir is prescribed in combination with ritonavir (capsules or tablets); the drugs are taken simultaneously, once a day with meals.

Dosage for children 6 years of age and older:

body weight ≥ 15 but <35 kg: atazanavir - 200 mg + ritonavir - 100 mg;
body weight ≥ 35 kg: atazanavir - 300 mg + ritonavir - 100 mg.

The pediatric dose should not exceed the dose used for the treatment of adult patients.

Side effects

Most often (more than 10%) when using atazanavir with one or more nucleoside / nucleotide / non-nucleoside reverse transcriptase inhibitors, the following side reactions were observed: nausea - 20%, jaundice - 13%, diarrhea - 10%. In patients who received atazanavir - 300 mg + ritonavir - 100 mg, most often, in 19% of episodes, jaundice was observed, which in most cases developed several days or even months after the start of the course. The condition led to drug withdrawal in less than 1% of patients. Also, when using atazanavir with one or more nucleoside / nucleotide / non-nucleoside reverse transcriptase inhibitors, 5% of patients were diagnosed with moderate / severe lipodystrophy, possibly associated with therapy.

Moderate or severe side effects on the part of systems and organs, which were observed in adult patients [conventional classification: very often (≥ 0.1); often (≥ 0.01, but <0.1); infrequently (≥ 0.001, but <0.01); rarely (≥ 0.0001, but <0.001); extremely rare (<0.0001); with an unspecified frequency - based on the available data, it is impossible to establish the frequency of occurrence of adverse reactions]:

immune system: infrequently - hypersensitivity reactions;
central nervous system: often - headache; infrequently - dizziness, syncope, peripheral neuropathy, memory loss, depression, sleep disturbances, drowsiness / insomnia, changes in the nature of dreams, anxiety, disorientation;
digestive tract: often - diarrhea, dyspepsia, abdominal pain, nausea, vomiting; infrequently - taste perversion, dry mouth, gastritis, pancreatitis, flatulence, aphthous stomatitis;
skin and subcutaneous fat: often - rash; infrequently - itching, urticaria, alopecia, erythema multiforme, toxic skin rash, drug hypersensitivity syndrome (DRESS syndrome), angioedema *; rarely - vasodilation, eczema, vesicular-bullous dermatosis, Stevens-Johnson syndrome *;
musculoskeletal system and connective tissue: infrequently - muscle atrophy, arthralgia, myalgia; rarely, myopathy;
urinary system: infrequently - frequent urination, hematuria, proteinuria, nephrolithiasis *, interstitial nephritis; rarely - pain in the kidney area;
organ of vision: often - yellowness of the sclera;
metabolism: infrequently - increased appetite, anorexia, weight loss / increase; with an unknown frequency - diabetes mellitus *, hyperglycemia *, hyperlactatemia *;
reproductive system: infrequently - gynecomastia;
cardiovascular system: infrequently - an increase in blood pressure (blood pressure), ventricular tachycardia such as Torsades de Pointes *; rarely - rapid heartbeat, edema, lengthening of the QTc interval *; with an unknown frequency - AV (atrioventricular) block II and III degrees *;
respiratory system: infrequently - shortness of breath;
hepatobiliary system: often - jaundice; infrequently - hepatitis, cholelithiasis, cholestasis *; rarely - hepatosplenomegaly, cholecystitis *;
general disorders: often - fatigue; infrequently - fever, chest pain, weakness, malaise, redistribution of fatty tissue (lipodystrophy); rarely - gait disturbance; in some cases (when using PI in patients with hemophilia A and B) - bleeding, spontaneous skin reactions, hemarthrosis;
laboratory data: very often (when using atazanavir with one or more nucleoside / nucleotide / non-nucleoside reverse transcriptase inhibitors) - an increase in total serum bilirubin, mainly unbound (indirect) - 87%; often (≥ 2%) - an increase in the activity of creatine phosphokinase - 7%, alanine aminotransferase (ALT) - 5%, aspartate aminotransferase (AST) - 3%, lipase - 3%, a decrease in the number of neutrophilic leukocytes - 5%. Cancellation of therapy was required in 5% of patients, both receiving and not receiving ARV therapy. In 2% of cases, there was a competitive increase in the concentration of ALT / AST and total bilirubin grade 3-4.

Note

* According to post-registration observations.

The safety profile of atazanavir in pediatric patients 6 years of age and older is comparable to that in adult patients.

Adverse reactions observed in children: very often (3-4 degree) - deviations of laboratory parameters [increase in total bilirubin by more than 2.6 times from the upper limit of normal (UHN) - 45%]; most often (2-4 degrees) - cough - 21%, increase in body temperature - 18%, jaundice or yellowing of the sclera - 15%, rash - 14%, vomiting - 12%, diarrhea - 9%, headache - 8%, peripheral edema - 7%, nasal congestion - 6%, pain in the limbs - 6%, pain when swallowing - 6%, nasal discharge - 6%, shortness of breath - 6%; rarely - asymptomatic AV-blockade of I and II degrees - less than 2%.

In the case of taking Atazanavir by patients with combined forms of viral hepatitis (hepatitis B and hepatitis C), the likelihood of an increase in the activity of hepatic transaminases increases in comparison with uninfected patients. At the same time, there is no difference in the frequency of an increase in bilirubin. The incidence of hepatitis or an increase in the activity of hepatic enzymes in combined forms of viral hepatitis (B and C) is comparable for the drug and comparison modes.

Patients with concomitant chronic hepatitis (B and C) have an increased risk of developing side effects from the liver, both severe and potentially fatal.

Overdose

In clinical studies, when healthy volunteers were taken atazanavir in doses up to 1200 mg once, no adverse reactions were recorded. A case of atazanavir overdose was described in HIV-infected patients who took 29,200 mg of the drug, which is 73 times more than the recommended dose of 400 mg. Intoxication caused asymptomatic blockade of both branches of the His bundle and prolongation of the PQ interval. Subsequently, according to the results of electrocardiography, it was determined that these signs disappeared spontaneously.

Expected symptoms of atazanavir overdose: jaundice without changes in liver test data (due to an increase in the concentration of unbound bilirubin) and a prolongation of the PQ interval (heart rhythm disturbance).

Therapy: the specific antidote is unknown; it is recommended to monitor the main physiological indicators, monitor the general condition of the patient, and control the electrocardiogram. To remove drug residues, the patient is advised to perform gastric lavage, induce vomiting and give activated charcoal.

Since atazanavir is characterized by intense metabolism in the liver and a high degree of binding to proteins, dialysis is ineffective for its excretion from the body.

special instructions

Atazanavir is inappropriate to prescribe to patients with multiple resistance to HIV PIs with four or more mutations. The choice of drug for the treatment of previously treated ARV patients should be based on evidence of individual resistance and the results of previous treatment.

Despite the fact that effective inhibition of viral replication by ARV therapy significantly reduces the risk of HIV transmission through sexual contact, the possibility of infection cannot be completely ruled out. Therefore, it is important to take precautions when using barrier methods of contraception.

Directions for using the drug in special cases:

diabetes mellitus and hyperglycemia: while taking HIV PIs, some HIV-infected patients were noted to have hyperglycemia, the development or exacerbation of already diagnosed diabetes mellitus, and diabetic ketoacidosis. A causal relationship between these cases and HIV PI therapy has not been established;
hemophilia: in hemophilia types A and B, during the use of HIV PIs, bleeding occurred, including spontaneous cutaneous punctate hemorrhages and hemarthrosis. In some cases, coagulation factor VIII was needed. After a break in therapy, HIV PIs were most often continued or resumed. A causal relationship between hemorrhagic diseases and HIV PI therapy has not been established. Patients with hemophilia type A or B should be advised of the potential for increased bleeding;
lipodystrophy: in isolated cases, patients showed a redistribution of adipose tissue, manifested by central obesity, accumulation of fatty tissue, lipohypertrophy in the dorsocervical region ("buffalo hump"), weight loss of the face and limbs, breast augmentation, cushingoid appearance. It was not possible to establish a causal relationship between HIV PI therapy and the redistribution of adipose tissue. In the presence of risk factors for the development of lipodystrophy, such as long-term use of antiviral drugs, old age, metabolic disorders, patients need a clinical examination, including a visual assessment of the redistribution of adipose tissue;
metabolic characteristics: ARV therapy may increase body weight and blood lipid / glucose ratio / content. These changes may be due to both the therapy of the underlying disease and the lifestyle. According to the recommendations for the treatment of HIV-infected patients, control of fats and carbohydrates in the blood is ensured; lipid metabolism disorders are controlled according to clinical practice. With combined ARV therapy, including together with oral contraceptives, cases of dyslipidemia have been reported;
immune reconstitution syndrome: the development of the immune reconstitution syndrome was observed in patients receiving ARV therapy, including atazanavir. At the beginning of combination ARV therapy, the immune system may develop in HIV-infected patients in response to asymptomatic or residual opportunistic infections (tuberculosis, Mycobacterium avium-induced generalized / local mycobacterial infections, cytomegalovirus retinitis, caused by Pneumocystis jirovecii pneumonia). As a result, signs of inflammation are likely to appear, which can lead to serious clinical consequences or worsening of the patient's condition. As a rule, such reactions develop at the beginning of the course of therapy, in the first few weeks or months. It is necessary to examine the patient and prescribe the appropriate treatment. During the restoration of immunity, cases of autoimmune disorders (Graves' disease) were noted, but the onset of their development in different patients varied in a wide range and could occur many months after the first intake of atazanavir;
hyperbilirubinemia: with atazanavir therapy, some patients had a reversible increase in the concentration of unbound (free) bilirubin caused by inhibition of uridine-5-diphosphate glucuronyltransferase (UDP-HT). It should be borne in mind that the increase in the activity of transaminases, noted with an increased level of bilirubin, may be due to other diseases accompanied by hyperbilirubinemia. When jaundice or yellowing of the sclera is unacceptable for the patient, an alternative to atazanavir ARV therapy may be considered. The dose of the drug should not be reduced, because this may contribute to the development of resistance, weaken the therapeutic effect or lead to its loss. There is insufficient data on the safety of the drug with a long-term concentration of bilirubin exceeding the ULN by more than 5 times. Since indinavir also inhibits UDP-HT, causing an increase in unbound bilirubin levels, its use with atazanavir is not recommended;
Prolongation of the PQ interval: Atazanavir may cause prolongation of the PQ and PR intervals in some patients. The drug should be used with caution in case of cardiac conduction disorders, for example, II and III degree AV blockade, as well as simultaneously with drugs that prolong the PQ interval, such as atenolol, verapamil, diltiazem;
QT interval prolongation: Episodes of QT interval prolongation in some patients, depending on the dose of atazanavir, have been described. Use the drug in case of cardiac conduction disorders (AV-blockade of II and III degree or blockade of the bundle of His bundle) in conjunction with QT-prolonging agents (clarithromycin, salmeterol), as well as in the presence of risk factors (congenital prolongation of the QT interval, bradycardia, electrolyte imbalance) should be used with caution only when the potential benefit of therapy outweighs the potential risk from taking atazanavir;
skin rashes: during the first 3 weeks from the start of the course, there may be a maculopapular rash, usually of mild to moderate severity. In some cases, the development of erythema multiforme, Stevens-Johnson syndrome, toxic skin rash and DRESS syndrome was noted. Patients should be warned of signs and symptoms of possible skin reactions that need to be closely monitored. If severe rash develops, the drug is discontinued. Careful monitoring of the condition of the skin allows early diagnosis and timely interruption of treatment. Patients who have been previously diagnosed with Stevens-Johnson syndrome and DRESS syndrome associated with atazanavir should not use the drug after stopping treatment;
nephrolithiasis and cholelithiasis: in the course of post-registration studies on the safety of using atazanavir in HIV-infected patients, cases of kidney and / or cholelithiasis have been reported. Some of them required hospitalization to carry out the necessary therapy, and some patients had complications. Sometimes nephrolithiasis was accompanied by the development of acute renal failure and impaired renal function. The presence of symptoms of nephrolithiasis / cholelithiasis requires interruption of therapy for a while or complete cessation of treatment;
decreased gastric acidity: with an increase in the pH value of gastric juice, regardless of the causes that caused it, the concentration of atazanavir in the blood plasma may decrease;
osteonecrosis: with prolonged use of combined ARV therapy, the likelihood of developing osteonecrosis increases, especially in patients with risk factors such as immunosuppression, high body mass index, concomitant use of GCS, alcohol consumption. The appearance of pain in the joints or difficulty in movement in a patient may indicate the development of osteonecrosis.

Influence on the ability to drive vehicles and complex mechanisms

The effect of atazanavir on human psychomotor functions has not been studied. Cases of dizziness and drowsiness have been reported during treatment. Given these adverse reactions, care must be taken when driving and operating complex machinery.

Application during pregnancy and lactation

Atazanavir is prescribed to pregnant women only when the potential benefit of treatment to the mother outweighs the possible risk of impaired growth and development of the fetus. The use of the drug during the gestation period requires regular medical monitoring of the patient's condition.

Analysis of a moderate amount of data (from 300 to 1000 pregnancy outcomes) revealed the absence of fetal malformations due to the toxic effect of atazanavir. In experiments on animals, no signs of toxicity of the drug in relation to the reproductive system were found.

In the II and III trimesters of pregnancy, the combination of atazanavir - 300 mg + ritonavir - 100 mg, taken 1 time / day, may not be enough to achieve a therapeutic response, especially with drug resistance. A decrease in atazanavir levels is expected when used together with tenofovir disoproxil fumarate or H ₂ -histamine receptor blockers. To ensure an adequate response to therapy, atazanavir at a dose of 400 mg is recommended to be taken with ritonavir - 100 mg once a day. There is insufficient information on the use of this combination in pregnant women who received ARV therapy before.

In the postpartum period (within 2 months), medical monitoring of the woman's health is important, since the content of atazanavir may increase, increasing the likelihood of developing adverse reactions. During this period, atazanavir is prescribed in doses as before pregnancy, including when used together with drugs that reduce its concentration in the blood.

Newborns whose mothers took atazanavir need to be monitored during the first days of life, since they are more likely to develop severe hyperbilirubinemia and kernicterus. In the prenatal period, additional monitoring of the fetus is also required.

According to studies conducted in rats, atazanavir passes into breast milk. There is no data on its effect on the secretion of breast milk. Since it is possible to transmit HIV to a child through mother's milk, and because of the risk of developing serious side effects in infants, breastfeeding is contraindicated during therapy with Atazanavir.

Preclinical studies of the effect of atazanavir on fertility and embryonic development in animals showed the absence of its effect on reproductive function, despite the change in the estrous cycle.

Pediatric use

Contraindications to the use of Atazanavir in pediatric practice:

child's weight less than 35 kg (for capsules with a dosage of 300 mg);
child's age up to 6 years.

There are no recommendations for the use of 300 mg capsules in children weighing less than 35 kg.

The safety profile of the drug in children weighing 35 kg and above is comparable to that in adult patients.

In children, asymptomatic lengthening of the PR interval (more often than in adult patients) and asymptomatic II and III degree AV block were observed. In this regard, the use of Atazanavir capsules with drugs that contribute to the lengthening of the PR interval, as well as for cardiac conduction disorders (AV block II and III degree, bundle branch block) should be used with caution only when the potential benefit of therapy outweighs the possible risk of complications … In case of manifestation of clinical symptoms (for example, bradycardia), it is necessary to ensure monitoring of the function of the cardiovascular system.

With impaired renal function

No dose adjustment is required in patients with renal insufficiency who are not on hemodialysis.

For hemodialysis patients who have not received ARV therapy before, atazanavir at a dose of 300 mg is prescribed only in combination with ritonavir - 100 mg, 1 time / day.

In severe renal failure, atazanavir is contraindicated in hemodialysis patients and patients who have received ARV therapy earlier.

For violations of liver function

Atazanavir is metabolized mainly in the liver, therefore, with hepatic insufficiency, its concentration in plasma may increase. Patients with impaired hepatic function should take the drug with caution.

With combined ARV therapy in patients with liver dysfunction, including active chronic hepatitis, the incidence of liver dysfunction increases, which requires careful monitoring of the patient's condition. If the condition worsens, the doctor may decide to interrupt or end the course of therapy.

The likelihood of a further increase in the activity of hepatic transaminases and decompensation of hepatic function is present in viral hepatitis B or C, as well as in the observed increased activity of transaminases before treatment. Patients should be provided with laboratory monitoring of hepatic function before starting atazanavir and during therapy.

In moderate and severe hepatic insufficiency, the content of atazanavir, both when taken together with ritonavir, and without, may increase.

It is contraindicated to use the drug: for patients with severe hepatic dysfunction (class C on the Child-Pugh scale) - with any dosage regimens patients with moderate and severe liver dysfunction (classes B and C on the Child-Pugh scale) - in combination with ritonavir.

Atazanavir should be used with caution: with mild and moderate liver dysfunction (classes A and B on the Child-Pugh scale); for mild liver dysfunctions (class A on the Child-Pugh scale) - in combination with ritonavir.

For patients with moderate hepatic dysfunction (class B on the Child-Pugh scale) who have not received ARV therapy earlier, it is recommended to reduce the dose to 300 mg 1 time / day.

Use in the elderly

Based on the results of pharmacokinetic studies, it was found that elderly patients do not require dose adjustment of Atazanavir.

Drug interactions

Atazanavir metabolism occurs in the liver with the participation of the cytochrome P _{450 system}; atazanavir inhibits the isoenzyme CYP3A4, which is part of this system. The combined use of other drugs with the same metabolic pathways, such as BMCC (slow calcium channel blockers), immunosuppressants, some HMG-CoA reductase inhibitors, phosphodiesterase inhibitors, can increase their plasma concentration with an increase in the severity or prolongation of therapeutic and side effects.

The use of atazanavir in combination with inducers of the isoenzyme CYP3A4 (rifampicin) can cause a significant decrease in the plasma concentration of atazanavir and, accordingly, its therapeutic activity. Inhibitors of the isoenzyme CYP3A4 can increase the plasma concentration of atazanavir. The severity of these interactions may change in the case of taking atazanavir with ritonavir, which is a potent inhibitor of the CYP3A4 isoenzyme. Complete information on drug interactions with ritonavir should be obtained by reading the instructions for use.

Drugs that are contraindicated for use with atazanavir:

quinidine: increased risk of serious and life-threatening arrhythmias (for the combination atazanavir + ritonavir);
rifampicin: significantly reduces the concentration of atazanavir in blood plasma, thereby decreasing the therapeutic efficacy and promoting the development of resistance to atazanavir;
bepridil: significantly increases the risk of life-threatening side effects;
Ergotamine derivatives (dihydroergotamine, ergometrine, ergotamine, methylergometrine): significantly increase the risk of life-threatening side effects; acute toxicity of ergotamine derivatives is manifested by peripheral vasospasm, ischemia of the extremities and other zones;
cisapride, pimozide: increase the risk of developing life-threatening arrhythmias;
lovastatin, simvastatin: the risk of developing myopathy increases, up to its extreme degree - rhabdomyolysis;
midazolam (parenteral), triazolam: their concentration increases, the likelihood of prolongation of sedation and respiratory depression increases;
drugs Hypericum perforatum (St. John's wort): can reduce the level of atazanavir in plasma, leading to a loss of therapeutic effect and the development of drug resistance;
astemizole, terfenadine: the risk of developing serious life-threatening adverse reactions increases (for the combination of atazanavir + ritonavir);
alfuzosin: an increase in its concentration is possible, as a result of which hypotension may develop (for a combination of atazanavir + ritonavir);
sildenafil: as a drug for the treatment of pulmonary hypertension, it is contraindicated to use with atazanavir;
quetiapine: atazanavir increases the risk of quetiapine-related adverse reactions; an increase in the content of quetiapine in the blood plasma can lead to the development of coma.

Drugs for which it may be necessary to change the dosage regimen if used together with atazanavir:

ARVs for HIV therapy: nucleoside reverse transcriptase inhibitors - didanosine, tenofovir disoproxil fumarate, efavirenz; non-nucleoside reverse transcriptase inhibitors - nevirapine; protease inhibitors - boceprevir, saquinavir, ritonavir; other inhibitors of HIV proteases; antacids and buffers;
antiarrhythmic drugs: amiodarone, lidocaine (parenteral), quinidine;
β-blockers: atenolol;
BMCC: diltiazem, felodipine, nifedipine, nicardipine, and verapamil;
non-selective endothelin receptor antagonists: bosentan;
HMG-CoA reductase inhibitors: atorvastatin, rosuvastatin, pravastatin, fluvastatin;
proton pump inhibitors: omeprazole, etc.;
blockers of H ₂ -histamine receptors: famotidine;
immunosuppressants: cyclosporine, tacrolimus, sirolimus;
antidepressants: tricyclic antidepressants - amitriptyline, desipramine, imipramine, nortriptyline; trazodone; benzodiazepines - midazolam;
antiepileptic drugs: carbamazepine, phenytoin, phenobarbital, lamotrigine;
antibiotics macrolides: clarithromycin;
oral contraceptives: ethinyl estradiol, norethisterone, norgestimate;
drugs for the treatment of gout: colchicine;
antimycobacterial drugs: rifabutin;
PDE (phosphodiesterase) -5 inhibitors for the treatment of erectile dysfunction: vardenafil, sildenafil, tadalafil;
antimycotic drugs: voriconazole, itraconazole, ketoconazole;
anticoagulants: warfarin;
corticosteroids (inhaled / nasal): fluticasone propionate, budesonide;
narcotic analgesics: buprenorphine;
inhaled beta ₂ -adrenomimetics: salmeterol;
other drugs: irinotecan, indinavir.

The following drugs are not expected to have clinically significant pharmacological interactions with atazanavir: lamivudine, zidovudine, abacavir, raltegravir, fluconazole, methadone, dapsone, trimethoprim / sulfamethoxazole, azithromycin, erythromycin. Subject to the dosing regimen, dose adjustment is not required.

Analogs

Atazanavir analogs are Atazanavir Canon, Atazanavir-Nanolek, Atazanavir-TL, Atazor, Reataz, Simanod.

Terms and conditions of storage

Store in original packaging at temperatures up to 25 ° С in a place protected from light. Keep out of the reach of children.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Atazanavir

The drug is used as part of a complex treatment, therefore, there are practically no reviews about Atazanavir, which allow us to evaluate its therapeutic effect separately. Some patients complain about the unavailability of the product in pharmacies.

Experts note the absence of a detrimental effect of atazanavir on carbohydrate metabolism and the patient's lipid profile. This makes it possible to predict a decrease in the risk of the appearance and development of cardiovascular pathologies in patients with HIV infection when using this drug in ARV therapy regimens. However, confirmation of this hypothesis requires long-term clinical studies.

Today, due to its unique characteristics, atazanavir is one of the most promising PIs for use as part of combined ARV therapy regimens in patients with HIV infection.

The price of Atazanavir in pharmacies

The maximum selling prices for Atazanavir registered in the List of Essential and Essential Medicines (VED):

capsules 150 mg: 30 pcs. - from 495 rubles; 60 pcs. - from 990 to 3505 rubles;
capsules 200 mg: 30 pcs. - from 660 to 2323 rubles; 60 pcs. - from 1320 to 4660 rubles;
capsules 300 mg: 30 pcs. - from 990 to 3505 rubles; 60 pcs. - from 1980 rubles.

Atazanavir: prices in online pharmacies

Drug name

Price

Pharmacy

Atazanavir canon capsules 150mg 30 pcs

RUB 2776

Buy

Atazanavir canon capsules 200mg 30 pcs

3612 RUB

Buy

Atazanavir canon 300mg capsules 30 pcs

5552 RUB

Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!