REATAZ

Active material: Atazanavir
When ATH: J05AE08
CCF: Viricide, active against HIV
ICD-10 codes (testimony): B24
When CSF: 09.01.04.02
Manufacturer: BRISTOL-MYERS SQUIBB Company (United States)

Pharmaceutical form, composition and packaging

Capsules hard gelatin, size №1, with opaque blue CAP and blue; with white lettering “BMS”, “150mg” and blue – “3624”; contents of capsules – the mixture of powder and granule from white to light yellow in colour.

Excipients: lactose monohydrate, krospovydon, magnesium stearate.

6 PC. – blisters (10) – packs cardboard.

Capsules hard gelatin, size №0, with opaque lid and housing blue; with white lettering “BMS”, “200mg” and “3631”; contents of capsules – the mixture of powder and granule from white to light yellow in colour.

Excipients: lactose monohydrate, krospovydon, magnesium stearate.

6 PC. – blisters (10) – packs cardboard.

Pharmacological action

Viricide, azapeptidnyj inhibitor of HIV-1 protease. Atazanavir selectively ingibiruet virus-specific processing of viral Gag-Pol proteins in HIV-1-infected cells, preventing the formation of mature virions and infection of other cells.

Pharmacokinetics

Pharmacokinetic properties of atazanavir were evaluated in healthy adult volunteers and HIV-infected patients. When this essential difference between the two groups was not observed.

Absorption

After repeated admission Reataza dose 400 mg 1 times/day simultaneously with the admission of light food (C)_max atazanavir plasma installed in approximately 2.7 h after administration. C_ss atazanavir is achieved between 4 and 8 24 hours reception.

Application of Reataza along with the food improves its bioavailability and decreases the pharmacokinetic variability.

Distribution

Linking plasma protein is atazanavir 86%. The degree of bonding with the squirrels are not dependent on the concentration of. In a similar degree of atazanavir is associated with alpha₁-glycoprotein and albumin.

Atazanavir is defined in the spinal and semen.

Metabolism

Mostly metabolized by CYP3A4 izofermentom atazanavir to oksimetabolitov. Metabolites are excreted in the bile, as a free form, and in the form of glukuronidov. A small portion of atazanavir is metabolized by N-dealkylation and hydrolysis.

Deduction

After a single application ¹⁴P-atazanavir dose 400 mg in the faeces and urine was determined accordingly 79% and 13% of the total radioactivity. The proportion of unchanged drug in urine and feces, respectively approximately 20% and 7%.

Average T_1/2 atazanavir in healthy volunteers and HIV-infected adults was about 7 h when applied at a dose of atazanavir 400 mg/day, together with light food.

Testimony

— treatment of HIV-1 infection in combination with other antiretroviral drugs (for patients, receiving antiretroviral therapy earlier and previously untreated).

Dosage regimen

The decision to start therapy physician, has experience in the treatment of HIV infections.

The preparation appoint adults inside the dose 400 mg 1 times per day with meals.

In combination with ritonavir (100 mg 1 time / day) REYATAZ appointed dose 300 mg 1 times per day with meals.

In appointing the drug Reyataz simultaneously with the admission of the drug didanosine, the latter should take over 2 h after administration of the drug Reyataz.

Patients with renal insufficiency dose adjustment is not required.

Patients with mild hepatic insufficiency REYATAZ should be administered with caution. Patients with moderate hepatic insufficiency, It is recommended that you reduce the dose to Reataza 300 mg 1 time / day.

Use Reataza in combination with ritonavir in patients with hepatic insufficiency have not studied. This combination should be used with caution in patients with moderate hepatic insufficiency.

Clinical studies of the drug did not include enough patients aged 65 and older. Based on pharmacokinetic data, dose adjustment based on age is not required.

Side effect

Frequently emerging side effects and have, least, possible link with reception modes, comprised of Reyataz and one or more non-nucleoside reverse transcriptase inhibitors (NNRTI): nausea (24%), jaundice (12%), headache (11%) and abdominal pain (11%), jaundice (There was both a few days later, and a few months later; Cancel therapy required at <1% patients); 5% – moderate or expressed lipodystrophy.

Determination of the frequency of adverse reactions: Often (≥1/10), often (≥1/100, <1/10), sometimes (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000) and the extremely rare (<1/10 000).

From the central and peripheral nervous system: often – headache, insomnia, peripheral neurologic symptoms; sometimes – disturbing dreams, memory loss, confusion, drowsiness, anxiety, depression, sleep disorders.

From the digestive system: very often-jaundice; often – abdominal pain, diarrhea, dyspepsia, nausea, vomiting; sometimes – dysgeusia, flatulence, gastritis, pancreatitis, thrush, dry mouth, hepatitis; rarely – hepatosplenomegaly.

Dermatological reactions: often – rash; sometimes – alopecia, itch, hives; rarely – vasodilation, vesiculobullous rash.

On the part of the musculoskeletal system: sometimes – arthralgia; muscular atrophy, myalgia; rarely – myopathy.

From the urinary system: sometimes – hematuria, frequent urination, proteinuria; rarely – pain in kidneys, urolithiasis disease.

Metabolism: often – lipodystrophy; sometimes – anorexia, increased appetite, weight loss, weight gain.

From the laboratory parameters: common – increase in total bilirubin, with the increasing prevalence of indirect (unbound) bilirubin), increase the level of amylase, CPK, GOLD, IS, low neutrophil leukocytes, increased levels of lipase.

Other: often – ikterichnost sclera, generalized weakness; sometimes – allergic reactions, chest pain, fatigue, fever, general malaise, gynecomastia.

Contraindications

-hereditary metabolic disturbances – galactose intolerance, deficiency of lactase and glucose and galactose malabsorption;

- Up to 18 years;

-simultaneous intake of rifampicin;

- Hypersensitivity to the drug.

Not recommended to appoint Reyataz in combination with ritonavir to patients with severe hepatic insufficiency.

Not recommended to appoint Reyataz simultaneously with CYP3A4 inducers (St. John's wort preparations), preparations, izofermenta CYP3A4 substrates are with narrow therapeutic range (incl. astemizol, terfenadine, cisapride, pimozid, quinidine, bepridil and ergot alkaloids, especially ergotamine, digidroergotamin, jergonovin, metiljergonovin).

Pregnancy and lactation

Adequate and well-controlled studies of the safety of drugs in pregnancy did not take place. Application of pregnancy is possible in cases, when the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

If necessary, use during lactation should stop breastfeeding.

Cautions

Treatment with protease inhibitors, some HIV-infected patients marked hyperglycemia, the occurrence of diabetes or decompensation diabetes available. In some cases, the celebrated Diabetic Ketoacidosis.

Atazanavir is metabolized, mainly, liver, Therefore, to apply the drug in patients, suffering from liver failure, It should be treated with caution due to possible increase in its concentration. In patients suffering from viral hepatitis b or c or observed prior to treatment increase in transaminaz liver, increased risk of further increases in transaminases.

In patients with hemophilia type a and b in the face of treatment protease inhibitors described bleeding, incl. spontaneous bleeding and skin hemarthrosises. Some of these patients required infusion of factor VIII. More than half of the patients treated with protease inhibitors was continued or resumed after the break,. A causal relationship between protease inhibitor therapy and these cases has not been established. Patients with hemophilia must be advised of the possibility of such complications.

Patients should be warned about, that antiretroviral therapy will not prevent the risk of HIV transmission through blood or during sexual intercourse. Patients should be careful.

Patients, receiving Reyataz, There were cases of reversible increase in indirect (free) bilirubin, associated with inhibition of uridindifosfat-gljukuroniltransferazy (UGT). There is no long-term data on the safety of patients, with the constant raising cium more, than 5 times compared to the norm. Can be considered the possibility of appointing an alternative antiretroviral therapy Reatazu, If jaundice or ikterichnost skler pose to patients cosmetic problems. Reataza dose reduction is not recommended because. long-term effectiveness of low doses was not installed.

The rash is usually mild to moderate rash papuleznah makulo-observed during the first 3 weeks from the beginning of therapy Reatazom. The majority of patients, the rash disappear within 2 weeks with continued therapy. Application of Reataza should be discontinued if severe rash development.

Overdose

Symptoms: possible jaundice due to rising indirect bilirubin levels (without other signs of liver) and abnormal heart rhythm (PR interval extension).

Treatment: gastric lavage, artificial vomiting to remove nevsosavshegosja in blood preparation, administration of activated charcoal, control the basic physiological indicators and ECG, monitor the general condition of the patient. Because atazanavir intensively metabolised in the liver and binds to proteins, dialysis is not effective for removing the drug from the body. A specific antidote to overdose of atazanavir no.

Drug Interactions

Atazanavir is metabolized in the liver, with the participation of zitohroma p 450 isoenzymes and is inhibitor of CYP3A4. Combined use of Reataza and other drugs, metaboliziruthan, mainly, CYP3A4 (eg, Calcium channel blockers, inhibitors g-KoA-reduktaza, immunosuppressants and FDJe5 inhibitors) may lead to increased plasma concentrations of one of them and cause increased or prolongation of its therapeutic and side effects.

Combined use of Reataza and drugs, inducing CYP3A4, such as rifampin, can lead to a decrease in the concentration of atazanavir plasma and reduce its therapeutic effect. Combined use of Reataza and drugs, ингибирующих CYP3A4, can lead to an increase in the concentration of atazanavir plasma.

Antiretroviral medications for the treatment of HIV

Nucleoside reverse transcriptase inhibitors

Didanosine tablets noticeably reduces the effect of atazanavir, as contained in tablets of didanosine antatsida reduce acidity gastric juice. REYATAZ does not affect the effectiveness of didanosine. Therefore, preparations of didanosine should be taken through 2 hours after taking the drug Reyataz.

Nucleotide reverse transcriptase inhibitors

Tenofovir decreases the effect of atazanavir while applying.

Non-nucleoside reverse transcriptase inhibitors

Jefavirenz reduces the effect of atazanavir while applying.

Study of combination Reataza + ritonavir and Nevirapine were launched. Expected, Chto nevirapine, CYP3A4 inducer how, capable of reducing the effect of atazanavir. Due to the lack of data sharing application with Reatazom and ritonavir is not recommended.

Protease inhibitors

Indinavir can cause giperbilirubinemiju (increased indirect bilirubin concentration) by inhibiting the UGT. Therefore, the simultaneous application of the drug, Reyataz is not recommended.

Effect of saquinavir (in the form of soft gelatin capsules) When coupled with the Reatazom. No data, enable you to make appropriate recommendations for dosing the combination.

When ritonavir with atazanavir increases concentration Reatazom.

The simultaneous use of combinations of Reyataz + ritonavir with other protease inhibitors are not recommended.

Other drugs

Antacids and medications, containing antacids, reduce the acidity of gastric contents and reduce absorption of atazanavir. REYATAZ should be appointed for 2 hours before or after 1 hours after taking these drugs.

Together with the admission Reatazom may increase plasma concentrations of amiodarone, lidocaine (when administered systemically), xinidina. When applying the data combinations required special care, It is recommended that monitoring of therapeutic concentrations of these drugs. Quinidine is contraindicated for use with Reataza ritonavir.

Atazanavir ingibiruet UGT and can affect the metabolism of irinotekana, increasing its toxicity.

Not recommended simultaneous application with lovastatinom and simvastatinom atazanavir.

If you are applying with diltiazem Reatazom leads to increased diltiazema actions and metabolite-dezacetildiltiazema. It is recommended to reduce the dose of diltiazem on 50% and monitoring of the ECG.

Bepridil can potenzirovti development difficult and/or life-threatening reactions. Is not suitable for the application of Reataza in combination with ritonavir.

Together with other blokatorami calcium channels, such as release ad.felodipin, nifedipine, nikardeepin and verapamil shows their doses titration, ECG monitoring.

When inhibitors of HMG-CoA reductase inhibitors with Reatazom effect of atorvastatin and tseriwastatina may increase. The risk of myopathy, including rhabdomyolysis, can increase. When data combinations required special care.

Histamine H₂-protone pump receptor and reduce the concentration of atazanavir plasma, that can lead to a reduction in the therapeutic activity of the drug or to the development of resistance. Taking these drugs should be separately. To avoid undesirable interaction, We recommend taking the drug Reyataz at night before going to bed.

When coupled with immunodepressantami (cyclosporine, tacrolimus, sirolimusa) and Reataza may increase in the blood concentration of immunosuppressive agents, therapeutic concentration monitoring is recommended.

Clarithromycin concentration increases when coupled with the use of Reatazom, that can cause QTc interval extension, Therefore, when coupled with Reatazom ==, antibiotic dose must be reduced by 50%.

Oral contraceptives (ethinylestradiol, norethindrone) It is not recommended to take simultaneously with medication Reyataz. In the presence of oral contraceptives increases the concentration of atazanavir. Lowering HDL or an increase in insulin resistance may be due to increased concentrations of norethindrone, especially in women, diabetes. Each component of the oral contraceptive is recommended for use in the smallest effective dose. It is advisable to use other reliable methods of contraception.

Activity of rifabutin when coupled with the use of Reatazom increases. While receiving these drugs recommended reducing the dose of rifabutin to 75% (ie. 150 mg a day or 3 times/week.).

Rifampin should not be applied simultaneously with Reatazom. Rifampicin reduces the activity of most protease inhibitors about 90%.

When coupled with FDJe5 inhibitors for protease inhibitors (sildenafil, tadalafil, Vardenafil) the increase in the concentration of inhibitors of FDJe5 and their side effects.

When you apply ketoconazole and itraconazole with Reatazom without ritonavir atazanavir concentration increases slightly. In combination with drugs Reyataz and ritonavir, ketoconazole and itraconazole can improve their concentration. Caution must be exercised in the appointment of ketoconazole and itraconazole in a daily dose above 200 mg together with a combination of drugs Reyataz and ritonavir.

Together with the use of warfarin with Reatazom possibly clinically significant and/or life threatening bleeding, due to increased activity of warfarin. With this combination, we recommend that you monitor the INR.

Atazanavir is metabolized primarily by CYP3A4 izofermentom, Therefore, it is not recommended to appoint Reyataz together with drugs, are inducers or substrates izofermenta CYP3A4.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 2 year.