Azimite - instructions for use, doses, side effects, contraindications

Core: carboxymethyl starch sodium (primogel) 5.0 mg / 15.0 mg, pregelatinized starch 5.0 mg / 15.0 mg, silicon colloidal dioxide (aerosil grade A-300) 0.4 mg / 1.2 mg , magnesium stearate - 0.6 mg / 1.8 mg, microcrystalline cellulose - 86.0 mg / 258.0 mg.

Film Sheath: Finished water-soluble film shell - 3.0 mg, 9.0 mg. (Composition of the coating: hydroxypropylmethylcellulose (hypromellose) 25.0%, copolyvidone 22.5%, polyethylene glycol 6000 (Macrogol 6000) 9.5%, glyceryl caprylcaprate 3.0%, polydextrose 15.0%, titanium dioxide - 25.0%).

Description:

For dosage of 100 mg: film-coated tablets, round, biconvex white or almost white.

For the dosage of 300 mg: film-coated tablets, capsular, biconvex with a risk on one side, white or almost white.

On a cross-section a tablet of white or white with a yellowish shade of color.

Pharmacotherapeutic group:Antiviral [HIV] agent

ATX: & nbsp

J.05.A.F.01 Zidovudine

Pharmacodynamics:

Synthetic analogue of nucleosides. Inside the cage zidovudine sequentially phosphorylated to the active metabolite - zidovudine-5'-triphosphate. Zidovudine-triphosphate inhibits reverse transcriptase of HIV by interrupting the synthesis of the virus DNA afterinclusion in the nucleotide chain. Zidovudine-triphosphate weakly inhibits cellular DNA polymerase alpha and gamma.

In combination with other antiviral drugs, the amount of CD4 + cells.

Pharmacokinetics:

Adults

Pharmacokinetics for oral administration is dose-independent in the dose range from 2 mg / kg every 8 hours to 10 mg / kg every 4 hours.

Absorption - fast, reception with fatty food reduces the degree and speed of absorption. Bioavailability in adults is 54-74%. Time to reach the maximum concentration in the blood (TC_mOh) after oral administration - 0.5-1.5 hours. The volume of distribution is 1.0-2.2 l / kg.

The connection with plasma proteins is less than 38%.

Penetrates into most tissues and body fluids. It is found in cerebrospinal fluid at a concentration of 15-64% of that in plasma. Metabolised in the liver. The main metabolite of zidovudine is glucuronide, the area under the concentration-time curve (AUC) of which is 3 times greater than the zidovudine AUC. The mean half-life (T1 / 2) of cells is 3.3 hours; from blood serum in adults - about 1 hour (0.8-1.2 h). After ingestion, 14% of zidovudine and 74% of its metabolite are found in the urine.

Patients with impaired renal function

In patients with severe renal failure, the maximum concentration of zidovudine in plasma is increased by 50% compared to that in patients without impaired renal function. The system exposure of the drug (defined as the area under the concentration-time curve) is increased by 100%; the half-life does not change significantly. With renal failure, there is a significant cumulation of the main metabolite of zidovudine - glucuronide, with no signs of toxic effects. Hemodialysis and peritoneal dialysis do not affect the elimination of zidovudine, while the removal of glucuronide is enhanced.

Patients with impaired hepatic function

With hepatic insufficiency, zidovudine cumulation may be observed due to a decrease in glucuronization, which requires correction of the dose of the drug.

Elderly patients

The pharmacokinetics of zidovudine has not been studied in patients older than 65 years.

Pharmacokinetics in children

In children older than 5-6 months, pharmacokinetic parameters are similar to those in adults.

Pregnancy

Pharmacokinetics in pregnant women is similar to that of non-pregnant women.

The concentration of zidovudine in the plasma in children at birth is the same as that of their mothers during childbirth.

Indications:

Treatment of HIV infection caused by HIV-1 (as part of combined antiretroviral therapy).

Prevention of perinatal transmission of HIV from an infected mother to a child, since zidovudine reduces the risk of intrauterine infection of the fetus.

Contraindications:

Hypersensitivity to zidovudine or any other component of the drug; neutropenia / leukopenia (the number of neutrophils is below 0.75 x 10⁹/ l); anemia (hemoglobin below 75 g / l); simultaneous reception with stavudine, doxorubicin, other drugs that reduce antiviral activity of zidovudine; Children's age (with a body weight of less than 30 kg).

Carefully:

Inhibition of bone marrow hematopoiesis, deficiency of cyanocobalamin or folic acid, hepatic insufficiency, advanced age, obesity, hepatomegaly, hepatitis or any risk factors for liver disease, neutropenia / leukopenia (neutrophil count 0.75-1.0 x 10⁹/ l); Anemia (hemoglobin 75-90 g / l).

Pregnancy and lactation:

Zidovudine slips through the placenta.The drug can be used during pregnancy before 14 weeks only if the potential benefit to the mother exceeds the possible risk to the fetus. The use of zidovudine after 14 weeks of pregnancy and its subsequent use in neonates leads to a decrease in the frequency of HIV transmission from mother to the fetus. The long-term effects of zidovudine in children who received it in the intrauterine or neonatal periods are not known. It is impossible to completely exclude the possibility of carcinogenic effects.

If zidovudine is used during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, regardless of food intake.

Adult patients the drug is administered at a dose of 600 mg per day in several doses. Children with a body weight of more than 30 kg - 300 mg 2 times a day or 200 mg 3 times a day. When calculating the surface area of the body, 160 or 240 mg / m² 3 or 2 times a day, respectively (daily dose of 480 mg / m²).

If the hemoglobin content is reduced to 75-90 g / l and / or the neutrophil count is reduced to 0.75-1.0 x 107 L, a dose reduction or withdrawal of zidovudine therapy may be required before hematopoiesis is restored. When anemia occurs, drug cancellation does not always reduce the need for blood transfusion.For a more rapid recovery of bone marrow function may be prescribed epoetin alfa in recommended doses.

Elderly patients

The pharmacokinetics of zidovudine in patients over the age of 65 years has not been studied. However, given the age-related decline in renal function and possible changes in peripheral blood parameters, such patients should be especially careful when using zidovudine and perform appropriate monitoring before and during treatment with the drug.

Renal insufficiency

In severe renal failure, the recommended daily dose is 300-400 mg. Depending on the response from the peripheral blood and the clinical effect, further dose adjustment may be required. Hemodialysis and peritoneal dialysis have no significant effect on the elimination of zidovudine, but accelerate the excretion of its metabolite - glucuronide. For patients with end-stage renal failure who are on hemodialysis or peritoneal dialysis, the recommended dose of zidovudine is 100 mg every 6-8 hours.

Liver failure

In patients with hepatic insufficiency cumulation of zidovudine may be observed due to a reduction in glucuronization, which may require correction of the dose of the drug. If monitoring of zidovudine concentrations in plasma is not possible, the physician should pay special attention to the clinical signs of drug intolerance and, if necessary, adjust the dose and / or increase the interval between doses.

Prevention of mother-to-child transmission of HIV

Effective 2 schemes of prevention:

1. Pregnant women, starting from the 14th week of pregnancy, are recommended to prescribe zidovudine Inside before the onset of labor at a dose of 500 mg per day (100 mg 5 times per day).

2. Pregnant women, starting from the 36th week of pregnancy, are recommended to prescribe zidovudine inside at a dose of 600 mg per day (300 mg twice a day) before the onset of labor, and then at a dose of 300 mg every 3 hours until delivery.

Side effects:

Undesirable reactions that occur with zidovudine treatment are the same in children and adults.

To estimate the incidence of undesired reactions, the following grades are used: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1 / 10000, <1/1000), very rarely (<1/10000).

From the hematopoiesis: often anemia (which may require blood transfusion), neutropenia, leukopenia, infrequently - thrombocytopenia, pancytopenia with bone marrow hypoplasia, rarely - erythrocyte aplasia, very rarely - aplastic anemia.

From the gastrointestinal tract: very often - nausea, often - vomiting, pain in the upper abdomen, diarrhea, infrequent - flatulence, rarely - dyspepsia, taste distortion, pigmentation of the oral mucosa, pancreatitis, anorexia.

From the hepatobiliary system: often - hyperbilirubinemia, increased activity of "hepatic" enzymes, rarely expressed hepatomegaly with steatosis.

From the nervous system: very often - headache, often - dizziness, rarely - paresthesia, insomnia, drowsiness, decreased mental performance, convulsions, anxiety, depression.

From the respiratory system: infrequently - shortness of breath, rarely - cough.

From the cardiovascular system: cardiomyopathy.

From the urinary system: rarely - frequent urination.

From the endocrine system and metabolism: often - hyperlactatemia, rarely - lactate-acidosis, gynecomastia.

From the musculoskeletal system: often - myalgia, infrequently - myopathy.

From the skin: infrequent - skin rash, skin itch, rarely - pigmentation of nails and skin, increased sweating, urticaria.

Other: often - malaise, infrequently - fever, asthenia, generalized pain syndrome, rarely - flu-like syndrome, chills, chest pain, redistribution / accumulation of subcutaneous fat.

Adverse reactions that occur when zidovudine is used to prevent the transmission of HIV from mother to the fetus.

Pregnant women are well tolerated zidovudine in recommended doses. Children have a decrease in hemoglobin, which, however, does not require blood transfusions. Anemia disappears 6 weeks after the end of zidovudine therapy.

Overdose:

Symptoms: fatigue, headache, vomiting, violation of hematological parameters.

Treatment: symptomatic. Hemodialysis and peritoneal dialysis are not effective for removing zidovudine from the body, but accelerate the excretion of its metabolite - glucuronide.

Interaction:

Zidovudine is used in combinationantiretroviral therapy together with other nucleoside reverse transcriptase inhibitors and preparations from other groups (protease inhibitors, non-nucleoside reverse transcriptase inhibitors). The list of interactions listed below should not be considered exhaustive, but they are characteristic of drugs that require careful use with zidovudine.

Lamivudine: there is a moderate increase in the maximum concentration in the blood (28%) for zidovudine when given with lamivudine, however, the total exposure (AUC) is not impaired. Zidovudine does not affect the pharmacokinetics of lamivudine.

Phenytoin: zidovudine reduces the concentration of phenytoin in the blood, which requires monitoring the concentration of phenytoin in the blood with simultaneous administration with zidovudine.

Probenicides: reduces glucuronization and increases the average half-life and AUC of zidovudine. Renal excretion of glucuronide and zidovudine itself decreases in the presence of a probenicide.

Atovahon: zidovudine does not affect the pharmacokinetic parameters of the atovahona. Atovahon slows the glucuronization of zidovudine (zidovudine AUC in the equilibrium state increases by 33%, the maximum concentration of glucuronide decreases by 19%).It is unlikely that the safety profile of zidovudine given at doses of 500 or 600 mg per day will be altered, while simultaneous use with atavahone for three weeks.

If it is necessary to prolong the simultaneous use of these drugs, careful monitoring of the clinical condition of the patient is recommended.

Clarithromycin: reduces the absorption of zidovudine. The interval between doses should be at least 2 hours.

Valproic acid, fluconazole, methadone: reduce the clearance of zidovudine, resulting in increased its systemic exposure.

Ribavirin: a nucleoside analogue ribavirin is an antagonist of zidovudine. It should avoid the simultaneous use of zidovudine and ribavirin.

Rifampicin: combination of zidovudine with rifampicin leads to a decrease in AUC for zidovudine by 48% ± 34%, however, the clinical significance of this change is not known.

Stavudine: zidovudine can suppress intracellular phosphorylation becoming udine.

Do not use stavudine concurrent with zidovudine.

Other: such medicines as paracetamol, acetylsalicylic acid, codeine, methadone, morphine, indomethacin, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, dapsone, isoprinosine, can disrupt zidovudine metabolism by competitive inhibition of glucuronization or direct suppression of microsomal metabolism in the liver. The possibility of using these drugs in combination with zidovudine, especially for long-term therapy, should be approached with caution. The combination of zidovudine, especially with emergency therapy, with potentially nephrotoxic and myelotoxic drugs (eg, pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine, doxorubicin) increases the risk of adverse reactions to zidovudine. It is necessary to monitor the kidney function and blood counts and reduce the dose of drugs, if necessary.

Special instructions:

Patients should be informed of the danger of concomitant use of zidovudine with OTC drugs and that the use of zidovudine does not prevent the risk of HIV transmission to other people during sexual intercourse or blood transfusion.Therefore, patients should take appropriate precautions.

Emergency prevention in case of possible HIV infection

According to international recommendations, if a person infected with HIV is likely to be infected through the blood (for example, through an injection needle), a combination therapy of zidovudine and lamivudine should be prescribed urgently (within 1-2 hours after the infection). In the case of a high risk of infection, a drug from the protease inhibitor group should be included in the antiretroviral regimen. Preventive treatment is recommended for 4 weeks. Despite the rapid onset of treatment with antiretroviral drugs, seroconversion can not be ruled out.

Symptoms that are taken for adverse reactions to zidovudine, may be a manifestation of the underlying disease or a reaction to the intake of other drugs used to treat HIV infection. The relationship between evolved symptoms and the effects of zidovudine is often very difficult to establish, especially when the clinical picture of HIV infection is deployed. In such cases, it is possible to reduce the dose of the drug or to abolish it.

Zidovudine does not cure HIV infection, and patients remain at risk of developing a detailed picture of the disease with suppression of immunity and the emergence of opportunistic infections and malignant tumors. With HIV infection zidovudine reduces the risk of developing opportunistic infections, but does not reduce the risk of developing lymphomas.

Undesirable reactions from the organs of hematopoiesis

Anemia (usually observed 6 weeks after the start of zidovudine therapy, but sometimes it may develop earlier), neutropenia (usually occurs 4 weeks after the start of zidovudine therapy, but sometimes occurs earlier), leukopenia can occur in patients with a developed clinical picture of HIV infection, receiving zidovudine, especially in high doses (1200-1500 mg / day), with a reduced reserve of bone marrow before the start of therapy. When taking zidovudine in patients with a developed clinical picture of HIV infection, blood tests should be monitored at least once every 2 weeks during the first 3 months of therapy, and then monthly. In the early stage of HIV infection (when bone marrow hemopoiesis is still within the normal range), adverse reactions from the blood develop rarely,therefore, blood tests are performed less often - depending on the general condition of the patient once in 1-3 months.

If the hemoglobin content is reduced to 75-90 g / l and / or the neutrophil count is reduced to 0.75-1.0 x 109 / l, the daily dose of the drug should be reduced, or zidovudine is canceled for 2-4 weeks before the recovery of blood counts. Usually, the blood picture will be normalized after 2 weeks, after which zidovudine in a reduced dose can be re-assigned. When anemia occurs, drug cancellation does not always reduce the need for blood transfusion.

Radiation therapy enhances the myelosuppressive effect of zidovudine.

Lactic Acidosis and severe hepatomegaly with steatosis

These complications can have a fatal outcome, both with zidovudine monotherapy and with zidovudine in combination antiretroviral therapy.

The risk of these complications is higher in female patients. Signs of development of these complications can be general weakness, sudden unexplained weight loss, anorexia, symptoms of the digestive system (nausea, vomiting, pain in the abdominal area), symptoms from the respiratory system (rapid breathing or shortness of breath).In case of clinical or laboratory signs of lactic acidosis or toxic liver damage, zidovudine should be discontinued.

Redistribution of subcutaneous fat

In some patients, combined antiretroviral therapy may be accompanied by redistribution / accumulation of subcutaneous fat, incl. a reduction in the amount of adipose tissue in the face and limbs, an increase in visceral fat, an increase in mammary glands and fat deposition on the back of the neck and back ("buffalo buffalo"), and an increase in serum lipid concentrations and glucose concentrations in the blood.

Although one or more of the above unwanted reactions associated with a common syndrome, often called lipodystrophy, can cause all drugs from classes of protease inhibitors and nucleoside reverse transcriptase inhibitors, the accumulated evidence suggests that there are differences between individual representatives of these classes of drugs in the ability to induce these unwanted reactions.

In addition, lipodystrophy syndrome has a multifactorial etiology; for example, the stage of HIV infection,the elderly age and duration of antiretroviral therapy play an important, potentially potentiating, role in the development of this complication. The long-term consequences of these undesirable reactions are not currently established. Clinical examination of patients should include an examination to identify signs of redistribution of adipose tissue. It should also monitor the concentration of lipids and glucose in the blood serum. Disorders of lipid metabolism should be adjusted in accordance with clinical indications.

Myopathy

It should be borne in mind that the development of myopathy symptoms (myalgia, weakness, increased activity of creatine phosphokinase) in HIV-infected patients may be associated with the underlying disease. When zidovudine is used in doses of 500 mg or 600 mg per day, myopathy associated with taking the drug is rarely observed. In the case of development of myopathy caused by zidovudine, the drug should be discontinued.

Immunodeficiency Syndrome

In HIV-infected patients with severe immunodeficiency during the onset of antiretroviral therapy, an inflammatory process may aggravate against a background of asymptomatic or sluggish opportunisticinfection, which can cause serious deterioration or worsening of symptoms. Usually, similar reactions were observed in the first weeks or months after the onset of antiretroviral therapy. The most significant examples are cytomegalovirus retinitis, generalized and / or focal mycobacterial infection and pneumocystis pneumonia. Any symptoms of inflammation should be immediately identified and start treatment in a timely manner. Autoimmune diseases (such as Graves' disease, polymyositis and Guillain-Barre syndrome) were observed against the background of restoration of immunity, but the time of primary manifestations varied, and the disease could occur many months after the initiation of therapy and have an atypical course.

Patients infected with both HIV and hepatitis C virus (HCV)

In vitro studies have shown that ribavirin can reduce the phosphorylation of analogues of pyrimidine nucleosides, incl. zidovudine. Although there is no obvious evidence of pharmacokinetic and pharmacodynamic interactions between ribavirin and zidovudine in patients with co-infection (HIV-1 / HCV).An exacerbation of ribavirin-induced anemia in HIV-infected patients receiving zidovudine therapy was reported. The mechanism of development of this effect is currently unknown. Therefore, simultaneous use of ribavirin and zidovudine is not recommended. Alternate antiretroviral therapy should be replaced zidovudine, especially in the presence of an anamnesis with anemia associated with zidovudine, in history.

Hepatic insufficiency (sometimes fatal) has been reported in patients infected with HIV-1 with concomitant hepatitis C receiving combination antiretroviral therapy for HIV-1 and interferon alfa with ribavirin or without ribavirin. When using zidovudine and interferon alfa with ribavirin or without ribavirin, careful monitoring of patients for signs of toxicity, especially liver failure, neutropenia, and anemia should be undertaken. With the increase in clinical manifestations of toxicity, especially liver failure (> 6 points on the Child-Pugh scale), doses should be reduced or canceled interferon alfa, ribavirin or both.In the case of myelosuppression, the possibility of interrupting or canceling zidovudine therapy should be considered.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions. When such undesirable phenomena as dizziness, drowsiness, inhibition, convulsions occur, one should refrain from performing these activities.

Form release / dosage:

The tablets covered with a film cover, on 100 and 300.

Packaging:

10 tablets are placed in a contour mesh box made of a polyvinylchloride film and aluminum foil printed lacquered.

For 20, 50, 60, 100, 200 or 500 tablets (for hospitals) are placed in a can of polymer and a lid of a pull-up with the control of the first opening. Free space is filled with cotton wool. On cans are labeled with paper label or from polymer materials, self-adhesive.

Secondary packaging of medicinal product.

By 1, 2, 3, 5, 6 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard for consumer containers.

Banks, together with an equal number of instructions for use, are placed in a group package - a box of corrugated cardboard.

Storage conditions:

Store in the original packaging of the manufacturer at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002134

Date of registration:11.07.2013 / 04.02.2016

Expiration Date:11.07.2018

The owner of the registration certificate:FARMSINTEZ, PAO FARMSINTEZ, PAO Russia

Manufacturer: & nbsp

FARMSINTEZ, JSC Russia

Information update date: & nbsp21.06.2017

Illustrated instructions

Instructions

Azimite (Azimitem)