Reataz

Reyataz is a drug that inhibits HIV protease. It contains the substance atazanavir.

Indications Reataza

It is used for antiretroviral therapy in individuals who test positive for HIV.

Release form

The product is released in capsules, in the amount of 6 pieces inside a blister pack. There are 10 blister plates in a pack.

Pharmacodynamics

The drug has a selective blocking effect on the virus-specific activity of viral proteins of the Gag-Pol type inside HIV-infected cells. This prevents damage to neighboring cells with the subsequent formation of mature virions.

Pharmacokinetics

During clinical trials, the pharmacokinetic characteristics of atazanavir were studied in volunteers and HIV-positive individuals. No significant differences in pharmacokinetics were found between these groups.

Atazanavir has nonlinear pharmacokinetic parameters and significant intra- and intersubjective variability, which often almost completely disappears when the drug is taken with food.

After repeated use of Reataz in a daily dose of 400 mg with food, maximum equilibrium values are noted after 2-3 hours (while equilibrium serum values in most patients are noted after 4-8 days of the course). Improvement in drug bioavailability is observed with combined use with food. At the same time, taking capsules after meals helps to reduce individual variability in drug pharmacokinetics.

About 86% of the substance is synthesized with whey protein (α-1-glycoproteins and albumins). This figure does not depend on the size of the portion taken.

Atazanavir passes into most of the body's biological fluids (including seminal and cerebrospinal fluid).

The substance is converted by the isoenzyme CYP3 A4. As a result of this process, oxidized derivatives are formed, which are excreted from the body with bile in the form of elements conjugated from glucuronic acid, or in free form. A small amount of the consumed portion is converted by N-dealkylation processes, as well as hydrolysis.

When a single dose of 400 mg of labeled atazanavir was administered, up to 79% of the dose was excreted in the feces, and a maximum of 13% was excreted via the kidneys. Unchanged drug accounted for 20% of the drug excreted in the feces and 7% in the urine (in the case of daily use of 400 mg of the drug).

In volunteers and people with HIV+, the average half-life of the drug is approximately 7 hours (with daily use of 400 mg of the drug with a light meal).

Dosing and administration

The capsules must be taken orally. Therapy should be prescribed and monitored by an experienced specialist who has previously treated people with a positive HIV test.

For adults, the usual oral dose is 0.4 g of the drug per day. The attending physician may also prescribe combination therapy, which usually involves a single dose per day (with food) of atazanavir (0.3 g) and ritonavir (0.1 g).

If it is necessary to prescribe the drug to people who are also taking didanosine, then an interval of at least 2 hours should be established between the use of both drugs.

People with renal insufficiency should be prescribed drugs with caution (because in this case the maximum values of the drug in the serum, as well as the rate of its excretion, may change).

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Use Reataza during pregnancy

Reyataz can be used during pregnancy, but only with a doctor's prescription and only if the likelihood of a positive result for the woman is higher than the risk of complications for the fetus.

Women with HIV+ should avoid breastfeeding, as this can lead to infection of the baby.

Contraindications

Main contraindications:

• presence of hypersensitivity to atazanavir or additional components of the drug;
• appointment to people with a severe degree of liver failure, as well as in moderate forms of this disease;
• use in people with lactose intolerance;
• use of medicine for patients in childhood.

The drug should be used with caution in patients with concomitant hepatitis B or C, infectious in nature (due to the fact that this increases the likelihood of developing liver diseases that can potentially become fatal). For such patients, constant monitoring of liver function is prescribed. If the serum values of AST or ALT elements increase significantly, the drug should be discontinued.

Caution is also required when prescribing Reyataz to people with hemophilia (types A or B) because it increases their risk of bleeding after taking atazanavir.

Side effects Reataza

Most often, as a result of taking the drug in therapeutic doses (or a combination of the drug with ritonavir), side effects such as nausea, headaches and jaundice develop. In these cases, the risk of developing jaundice as a result of combined use of the drug with ritonavir (in doses of 0.3 and 0.1 g, respectively) was higher than with monotherapy using Reyataz. Jaundice can develop at the initial stage of the course or after several months from the start of therapy.

The combined antiretroviral course during individual tests caused a change in the volume of distribution of subcutaneous fat deposits (development of lipodystrophy). For example, there was a loss of peripheral, and at the same time subcutaneous fat deposits in the facial area, an increase in the volume of intraperitoneal and visceral fat, as well as fat deposits in the upper back, and in addition, an increase in the mammary glands.

Combination antiretroviral therapy can cause metabolic disorders. Among the problems noted in people undergoing such a course of treatment were insulin resistance, hypertriglyceridemia, hyperlactatemia, as well as hyperglycemia and hypercholesterolemia. During tests, it was found that the risk of developing metabolic disorders increases with the combined use of several drugs that have an antiretroviral effect.

In addition, the use of drugs can lead to the appearance of such negative reactions:

• metabolic disorders: development of lipodystrophy, loss of appetite, and also weight instability;
• lesions affecting the central nervous system: headaches, nightmares, memory or sleep disorders, a feeling of causeless anxiety or confusion, various neurological manifestations of a peripheral nature, as well as the development of a depressive episode;
• gastrointestinal disorders: occurrence of abdominal pain, taste bud disorders, bloating, manifestations of dyspepsia, development of gastritis, hepatitis, pancreatitis, jaundice or aphthous stomatitis, as well as the appearance of vomiting or bowel disorders;
• manifestations on the surface of the skin and in the subcutaneous layer: the appearance of itching, rashes, urticaria, and the development of alopecia;
• disorders of the musculoskeletal system: development of myalgia, pain in the joints, and muscle atrophy;
• lesions of the urogenital system: acceleration of the process of urination, development of gynecomastia or hematuria, and also urolithiasis;
• others: pain in the sternum, allergic symptoms, hyperthermia, asthenia, and a feeling of severe fatigue.

During treatment with Reyataz (especially when combined with one or more NRTIs), patients may experience hyperbilirubinemia, increased creatine kinase, AST or ALT, and SGPT. In addition, the level of neutrophilic leukocytes may decrease and the values of serum transaminases (oxaloacetic glutamic) and lipase may increase. The possibility of an increase in transaminase values is higher in people who also suffer from a liver infection (such as hepatitis type B or C). However, there are no differences in the likelihood of developing hyperbilirubinemia, or in the incidence of hepatitis in people with and without concomitant liver pathologies.

Overdose

As a result of using excessively large doses of atazanavir, patients may experience disturbances in heart rhythm (this includes prolongation of the PR interval), as well as an increase in indirect bilirubin levels (but against the background of this disturbance, no pronounced signs of liver dysfunction develop).

In case of poisoning with the drug, procedures should be performed that will help reduce the systemic absorption of atazanavir - induce vomiting and give the victim sorbents. In individuals who have exceeded the permitted dosage of the drug, it is necessary to monitor the ECG values and the work of the respiratory system, as well as their general condition. Since most of the atazanavir undergoes the process of metabolism and is synthesized with serum protein, dialysis procedures to eliminate disorders associated with an overdose of drugs will be ineffective.

Reyataz has no specific antidote.

Interactions with other drugs

Reyataz undergoes metabolism processes that are carried out with the help of the P450 isoenzyme system (including the CYP3 A4 element), and atazanavir in this case helps to slow down the activity of this isoenzyme. It is prohibited to combine the drug with drugs whose metabolic processes are carried out with the participation of the CYP3 A4 component and which have a narrow spectrum of drug activity. Among these are astemizole and bepridil with quinidine, as well as cisapride and terfenadine with pimozide and oral medications.

Astemizole should not be combined with drugs that promote the induction of the CYP3 A4 element, such as St. John's wort (the combination of these drugs may lead to a weakening of the activity of the antiviral drug).

Combination with didanosine weakens the properties of astemizole (due to antacid effect). If there is still a need for complex use of these drugs, it is necessary to observe an interval between their use of at least 2 hours.

Nevirapine with tenofovir and efavirenz reduce the effect of atazanavir when taken concomitantly. There is little information on the clinical use of Reyataz with nevirapine, so combining these drugs is not recommended.

An increased risk of hyperbilirubinemia has been identified due to the combined use of the drug with indinavir (due to the suppression of the UGT1A1 element). In this regard, the simultaneous use of these drugs is prohibited.

Combination with ritonavir reduces AUC values by half, as well as peak values of the drug (by 7 times) - compared to monotherapy with Reyataz with a daily intake of 0.4 g of the drug. Therefore, using these drugs together is prohibited.

Combination with antacids may lead to decreased absorption of atazanavir. If antacids are required, they should be taken at least 2 hours before using atazanavir.

When the drug is combined with quinidine, lidocaine, and amiodarone, their serum values increase. In addition, the likelihood of developing side effects of these drugs may increase.

The drug may potentiate the toxic properties of irinotecan when combined (due to the slowing down of the activity of the UGT1A1 component).

The combined use of Reataz and bepridil is prohibited.

Concomitant use of therapeutic doses of atazanavir and diltiazem causes an increase in the serum levels of the latter (twofold or threefold), without affecting the pharmacokinetics of atazanavir. This effect may cause prolongation of the PR interval (compared to its values when using Reyataz alone). If these drugs need to be combined, it is necessary to reduce the initial dose of diltiazem by 50% and carefully monitor ECG readings when selecting dosages.

Combination with the drug may cause an increase in serum verapamil values. It is necessary to combine these drugs with caution.

Concomitant use with the drug may lead to an increase in serum levels of statins. Therefore, the drug should not be combined with simvastatin, lovastatin, and atorvastatin (because this increases the likelihood of myopathy or rhabdomyolysis).

Proton pump inhibitors and drugs that block the activity of histamine (H2) conductors when combined with Reyataz reduce the serum levels of the latter and weaken its medicinal properties. There is also a risk of developing resistance to atazanavir due to a decrease in its values in the serum, which is why combined use of the drug with agents that reduce gastric pH is not recommended.

Combined use with Reyataz may lead to an increase in serum levels of immunosuppressants (including tacrolimus with sirolimus, as well as cyclosporine). Therefore, these substances should not be combined.

Concomitant use of the drug with clarithromycin and other macrolides should be prescribed with caution. During studies of the combined use of the drug with clarithromycin (average drug dosages), a twofold increase in the latter's values was noted, as well as a 70% decrease in the main derivative of clarithromycin and a 28% increase in the AUC level of atazanavir.

Atazanavir increases serum levels of oral contraceptives (while ritonavir, on the contrary, decreases the level of these drugs in plasma). No tests have been conducted regarding the simultaneous use of oral contraceptives and the combination of atazanavir/ritonavir. During treatment with Reyataz, other methods of contraception must be used.

No clinically significant changes in the pharmacokinetics of atazanavir with rifabutin were detected when they were taken in combination, but when rifabutin is used with a combination of atazanavir/ritonavir, its dosage should be reduced by 75%.

It is prohibited to use the drug in combination with rifampicin (because this leads to a significant reduction (up to 90%) in the effect of drugs that slow down the activity of HIV protease).

Reyataz can increase the risk of developing side effects characteristic of the substance sildenafil - because it increases its serum values. For example, when combining these drugs, the risk of developing visual disturbances or priapism increases, as well as a decrease in pressure.

The combination with atazanavir and ritonavir increases the levels of HIV protease inhibitors (such as itraconazole or ketoconazole). Caution is required when prescribing the latter daily dose in excess of 0.2 g if the patient is also taking the combination of atazanavir and ritonavir.

Taking warfarin with Reyataz increases the risk of bleeding (which can be potentially fatal).

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Storage conditions

Reyataz should be kept in a place out of reach of children. The temperature should not rise above 25°C.

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Shelf life

Reyataz can be used for 2 years from the date of release of the drug.