Reataz

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

Indications of the reatase

It is used for antiretroviral therapy in people with a positive HIV test.

Release form

The release is carried out in capsules, in an amount of 6 pieces inside the blister pack. In a pack - 10 blister plates.

Pharmacodynamics

The drug has a selective blocking effect on the virus-specific activity of viral proteins such as Gag-Pol within cells infected with HIV. This helps to prevent damage to neighboring cells, followed by the formation of mature virions.

Pharmacokinetics

During clinical trials, the pharmacokinetic characteristics of atazanavir were investigated in volunteers, as well as in persons with a positive HIV test. In these groups, there was no significant difference in pharmacokinetics.

Atazanavir has non-linear pharmacokinetic parameters and significant intra-, as well as intersubjective variability, which often almost completely disappears in the case of drugs with food.

After repeated use of Reyatase in a daily dose of 400 mg with food, the maximum equilibrium values are noted after 2-3 hours (with the equilibrium serum levels in most patients observed after 4-8 days of the course). Improving the bioavailability of the drug is observed when combined with a meal. However, the use of capsules after meals can help reduce the individual variability of the pharmacokinetics of drugs.

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

Atazanavir passes inside most of the biological fluids in the body (among them seminal and cerebrospinal fluid).

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

With a single use of labeled atazanavir in the amount of 400 mg with feces, up to 79% of the portion was excreted, and a further 13% through the kidneys. Unchanged form has 20% of the substance being excreted with feces, and 7%, which are excreted in the urine (in case of daily use of 400 mg of the drug).

In volunteers, as well as people with HIV +, the average half-life of the drug is approximately 7 hours (with 400 mg of the drug daily along with light meals).

Dosing and administration

You need to take capsules inside. Appointment of therapy and monitor its implementation should be an experienced specialist who previously treated people with a positive test for HIV.

For adults, often administered intake of 0.4 g of drug per day. The attending doctor can also prescribe a complex therapy, which usually uses a single dose per day (along with food) of atazanavir (0.3 g) and ritonavir (0.1 g).

If you want to prescribe medication for people taking didanosine, you should set a gap between using both drugs, which will be at least 2 hours.

People with renal insufficiency should be prescribed drugs carefully (because in this case it is possible to change the maximum values of the drug inside the serum, as well as the speed of its removal).

[1]

Use of the reatase during pregnancy

Reyataz can be used during pregnancy, but exclusively with the appointment of a doctor and only with a higher probability of a positive result for a woman than the possibility of a risk of complications for the fetus.

Women with HIV + should refrain from breastfeeding, because this is likely to lead to infection of the baby.

Contraindications

The main contraindications:

• the presence of hypersensitivity to atazanavir or additional elements of the drug;
• appointment to people with severe degree of liver failure, and in addition, with a moderate form of the disease;
• use in people with lactase intolerance;
• the use of drugs for patients in childhood.

Caution should be used when the patient has concomitant hepatitis type B or C, an infected character (due to the fact that this increases the likelihood of developing hepatic diseases that could potentially become fatal). For such patients appoint permanent monitoring of the liver. With a strong increase in the serum values of AST or ALT elements, the drug should be discarded.

Caution is also required when prescribing Reytaz to people with hemophilia (types A or B), because this increases the risk of bleeding after atazanavir.

Side effects of the reatase

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

Combined antiretroviral course during individual tests caused a change in the distribution of subcutaneous fat deposits (development of lipodystrophy). For example, loss of peripheral and, at the same time, subcutaneous fat deposits in the face, increased volumes of intraperitoneal and visceral fat, as well as fat deposits in the upper parts of the back, and, in addition, an increase in the mammary glands.

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

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

• Disorders of metabolic processes: development of lipodystrophy, deterioration of appetite, and also lability of weight;
• lesions affecting the central nervous system: headaches, nightmares, memory or sleep disorders, sensation of causeless anxiety or confusion, various neurological manifestations of a peripheral nature, and the development of a depressive episode;
• abnormalities in the work of the gastrointestinal tract: the emergence of abdominal pain, a disorder of taste buds, bloating, manifestations of dyspepsia, the development of gastritis, hepatitis, pancreatitis, jaundice or aphthous form of stomatitis, and in addition the occurrence of vomiting or stool 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 function of ODA: the development of myalgia, pain in the joints, as well as muscular atrophy;
• lesions of the urogenital system: acceleration of the urinary process, the development of gynecomastia or hematuria, and in addition urolithiasis;
• others: pain in the sternum, allergic symptoms, hyperthermia, asthenia, and a feeling of severe fatigue.

In the process of treatment with Reatase (especially when combined with one substance NRTI or more), patients may experience hyperbilirubinemia, increase the level of creatine kinase, AST or ALT, as well as CGTP. In addition, the level of leukocytes of the neutrophil type may decrease and the values of serum transaminases (oxaloacetic glutamine) and lipase may increase. The possibility of increasing the values of transaminases is higher in people who also suffer from hepatic infection (such as hepatitis type B or C). But there are no differences in the likelihood of hyperbilirubinemia development, and besides the incidence of hepatitis in people with concomitant hepatic pathologies and without them - no.

Overdose

As a result of consuming excessively large portions of atazanavir, heart rhythm disturbances can occur in patients (this includes prolongation of the PR-interval), and in addition an increase in the values of indirect bilirubin (but against the background of this disorder, there are no signs of a disorder in the liver activity).

When poisoning the drug should perform procedures that will help reduce the systemic absorption of atazanavir - induce vomiting and give the victim sorbents. In persons who have exceeded the allowed dosage of drugs, it is required to monitor the ECG values and the work of the respiratory system, and in addition their general condition. Because most of the atazanavir undergoes a metabolic process and is synthesized with whey protein, dialysis procedures to eliminate abnormalities associated with drug overdose will be ineffective.

Reyataz does not have a special antidote.

Interactions with other drugs

Reyataz processes metabolic processes, which are carried out with the system of isoenzymes P450 (among them the element CYP3 A4), and atazanavir in this case helps to slow the activity of this isoenzyme. It is forbidden to combine the drug with drugs whose metabolic processes are carried out with the participation of the component CYP3 A4, and which have a narrow spectrum of drug activity. Among them - astemizole and bepridil with quinidine, as well as cisapride and terfenadine with pimozide and drugs of the horns.

Astemizole is not allowed to combine with drugs that promote the induction of the CYP3 A4 element - such as St. John's Wort (a combination of these drugs can weaken the activity of the antiviral drug).

The combination with didanosine weakens the properties of astemizole (due to antacid effects). If the need for a comprehensive application of these drugs still exists, it is required to observe the interval between their use, which is at least 2 hours.

Nevirapine with tenofovir and efavirenz weakens the effect of atazanavir in the case of their simultaneous administration. Information on the clinical use of reatase with nevirapine is rather small, so these medications should not be combined.

There was an increased risk of hyperbilirubinemia due to combined use of the drug with indinavir (due to suppression of the UGT1A1 element). In this regard, the simultaneous use of these drugs is prohibited.

The combination with ritonavir halves the AUC, as well as the peak values of drugs (7 times) - compared with monotherapy Reataz with the intake of 0.4 grams per day. Therefore, it is forbidden to use these drugs together.

Combination with antacids can lead to a decrease in absorption of atazanavir. If you want to appoint an antacid to a patient, you should consider that you can take them at least 2 hours before using atazanavir.

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

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

Combined use of reatase and beprinil is prohibited.

The combined use of therapeutic dosages of atazanavir and diltiazem causes an increase in the latter within the serum (twice or thrice), without affecting the pharmacokinetics of atazanavir. This effect can cause prolongation of the PR-interval (in comparison with its values when using only Reatase). If these preparations need to be combined, it is required to reduce the initial portion of diltiazem by 50% and, when selecting dosages, closely monitor the ECG readings.

Combination with the drug may cause an increase in serum values of verapamil. It is necessary to combine these preparations with care.

Simultaneous admission with medication can lead to a rise in the serum level of statins. Therefore, do not combine the medicine with simvastatin, lovastatin, and atorvastatin (because this increases the likelihood of myopathy or rhabdomyolysis).

Drugs that slow down the action of the proton pump and drugs, blocking the activity of histamine (H2) conductors as a result of combination with Reyatase reduce the serum parameters 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 within the serum, which is why the combined administration of drugs with drugs that reduce the level of gastric pH is not recommended.

Combined use with Reyatase can lead to an increase in the indices of immunosuppressants inside the serum (here include tacrolimus with sirolimus, as well as cyclosporin). Therefore, these substances should not be combined.

With caution, it is necessary to appoint a simultaneous reception of drugs with clarithromycin, as well as other macrolides. During studies of the combined use of the drug with clarithromycin (average dosage levels), the latter doubled, and in addition, a 70% decrease in the parameters of the main derivat of clarithromycin and a 28% increase in the level of AUC of atazanavir.

Atazanavir increases serum oral contraceptive rates (ritonavir, on the contrary, decreases the level of these drugs inside the plasma). Tests regarding the simultaneous administration of oral contraception and a combination of atazanavir / ritonavir preparations have not been conducted. During the treatment with Reyataz, other methods of contraception are required.

Significant clinical changes in the pharmacokinetics of atazanavir with rifabutin were not found in their complex administration, but in the case of rifabutin with the combination of atazanavir / ritonavir, its dosage should be reduced by 75%.

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

Reyataz is capable of increasing the risk of developing side-effects characteristic of the substance sildenafil - because it increases its serum values. For example, with a combination of these drugs, the risk of developing visual disorders or priapism, as well as a decrease in pressure, is increased.

Combination with atazanavir and ritonavir leads to an increase in the values of drugs that slow HIV-protease (such as itraconazole or ketoconazole). It is necessary to carefully appoint a daily dose of the latter at a rate of more than 0.2 g, if the patient also takes a combination of drugs atazanavir with ritonavir.

Taking warfarin with Reyatase increases the risk of bleeding (they can be potentially fatal).

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Storage conditions

Reyataz is required to be kept in a place that is closed from children's access. The temperature should not rise above 25 ° C.

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Shelf life

Reyataz is allowed to be used for 2 years after the release of the drug.