Azimitem pills, 100mg 100pcs

Composition

1 tablet contains:

Active ingredient:

Zidovudine 100 mg,

Auxiliary substances:

Each film-coated tablet contains:

Core: sodium carboxymethyl starch (primogel) – 5.0 mg, pregelatinized starch-5.0 mg, colloidal silicon dioxide (aerosil brand A-300) – 0.4 mg, magnesium stearate-0.6 mg, microcrystalline cellulose-86.0 mg.

Film shell: Ready-made water-soluble film shell – 3.0 mg. (Shell composition: hydroxypropylmethylcellulose (hypromellose) – 25.0%, copolividone-22.5%, polyethylene glycol 6000 (Macrogol 6000) – 9.5%, glyceryl caprylocaprate-3.0%, polydextrose-15.0%, titanium dioxide-25.0%).

Pharmacological action

Pharmacotherapy group: Antiviral [HIV] agentath: J. 05. A. F. 01 Zidovudine Pharmacodynamics : Synthetic analog of nucleosides. Inside the cell, zidovudine is sequentially phosphorylated to the active metabolite, zidovudine-5′ – triphosphate. Zidovudine triphosphate inhibits HIV reverse transcriptase by interrupting viral DNA synthesis after incorporation into the nucleotide chain. Zidovudine triphosphate weakly inhibits cellular DNA polymerases alpha and gamma.

In combination with other antiviral drugs, it increases the number of CD4+cells.

Pharmacokinetics:

Adult

Oral pharmacokinetics are dose-independent in the dose range from 2 mg/kg every 8 hours to 10 mg/kg every 4 hours.

Absorption – fast, intake with fatty foods reduces the degree and speed of absorption. Bioavailability in adults is 54-74%. The time to reach the maximum concentration in the blood (TMAX) after oral use is 0.5-1.5 hours. The volume of distribution is 1.0-2.2 l/kg.

Plasma protein binding is less than 38%.

Penetrates most tissues and body fluids. It is found in the cerebrospinal fluid at a concentration of 15-64% of that in plasma. It is metabolized 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 AUC of zidovudine. The average half-life (T 1/2) from cells is 3.3 hours; from blood serum in adults-about 1 hour (0.8-1.2 hours). After oral use,14% of zidovudine and 74% of its metabolite are detected in the urine.

Patients with impaired renal function

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

Patients with impaired liver function

In hepatic insufficiency, accumulation of zidovudine may occur due to a decrease in glucuronidation, which requires dose adjustment of the drug.

Elderly patients

The pharmacokinetics of zidovudine have not been studied in patients over 65 years of age.

Pharmacokinetics in children

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

Pregnancy

Pharmacokinetics in pregnant women are similar to those in non-pregnant women.

The plasma concentration of zidovudine 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, as zidovudine reduces the risk of intrauterine infection of the fetus.

Contraindications

Hypersensitivity to zidovudine or any other component of the drug; neutropenia/leukopenia (neutrophil count below 0.75 x 109/l); anemia (hemoglobin below 75 g/l); concomitant use with stavudine, doxorubicin, other drugs that reduce the antiviral activity of zidovudine; childhood (with a body weight of less than 30 kg).

With caution:

Inhibition of bone marrow hematopoiesis, cyanocobalamin or folic acid deficiency, liver failure, old 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).

Side effects

Adverse reactions that occur during zidovudine treatment are the same in children and adults.

To assess the frequency of adverse reactions, the following gradations were used: very often (>1/10), often (>>1/100, >><1/10), infrequently (>1/1000, <1/10), infrequently (><1/100), rarely (>1/10000, <1/100), rarely (><1/1000), very rarely (

From the side of hematopoietic organs:  often-anemia (which may require blood transfusions), neutropenia, leukopenia, infrequently-thrombocytopenia, pancytopenia with bone marrow hypoplasia, rarely-erythrocytic aplasia, very rarely-aplastic anemia.

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

From the side of the hepatobiliary system: often-hyperbilirubinemia, increased activity of “liver” enzymes, rarely-severe hepatomegaly with steatosis.

Nervous system disorders:  very often – headache, often-dizziness, rarely-paresthesia, insomnia, drowsiness, decreased mental performance, seizures, anxiety, depression.

Respiratory system disorders:  infrequently-shortness of breath, rarely-cough.

From the cardiovascular system:  cardiomyopathy.

From the urinary system:  rarely-frequent urination.

Endocrine and metabolic disorders:  often-hyperlactatemia, rarely-lactate acidosis, gynecomastia.

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

From the side of the skin:  infrequently – skin rash, pruritus, rarely – pigmentation of the nails and skin, increased sweating, urticaria.

Other services:  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 using zidovudine to prevent transmission of HIV infection from mother to fetus.

Zidovudine is well tolerated in pregnant women at the recommended doses. In children, there is a decrease in the content of hemoglobin, which, however, does not require blood transfusions. Anemia disappears 6 weeks after the end of zidovudine therapy.

Interaction

Zidovudine is used in combination antiretroviral therapy with other nucleoside reverse transcriptase inhibitors and drugs 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 together with zidovudine.

Lamivudine: there is a moderate increase in the maximum blood concentration (28%) for zidovudine when administered together with lamivudine, however, the total exposure (AUC) is not affected. 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 when it is administered simultaneously with zidovudine.

Probenicide: reduces glucuronidation and increases the mean half-life and AUC of zidovudine. Renal excretion of glucuronide and zidovudine itself is reduced in the presence of probenicide.

Atovakhon:  zidovudine does not affect the pharmacokinetic parameters of atovahone. Atovahone slows down the glucuronidation of zidovudine (AUC of zidovudine at steady state increases by 33%, maximum concentrations of glucuronide decrease by 19%). It is unlikely that the safety profile of zidovudine, given at doses of 500 or 600 mg per day, will change when co-administered with atovahone for three weeks.

If a longer concomitant use of these drugs is necessary, careful monitoring of the patient’s clinical condition is recommended.

Clarithromycin: reduces the absorption of zidovudine. The break between taking medications should be at least 2 hours.

Valproic acid, fluconazole, methadone: reduce the clearance of zidovudine, which increases its systemic exposure. Ribavirin: The nucleoside analog of ribavirin is an antagonist of zidovudine. Concomitant use of zidovudine and ribavirin should be avoided.

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

Stavudin:  zidovudine can inhibit intracellular phosphorylation of stav udine. Stavudine should not be used simultaneously with zidovudine. Other: Medications such as paracetamol, acetylsalicylic acid, codeine, methadone, morphine, indomethacin, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, dapsone, and isoprinosine may interfere with zidovudine metabolism by competitively inhibiting glucuronidation or directly suppressing 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 in emergency therapy, with potentially nephrotoxic and myelotoxic drugs (for example, 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 kidney function and blood parameters and reduce the dose of drugs, if necessary.

How to take, course of use and dosage

Inside, regardless of food intake.

For adult patients, the drug is prescribed 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 body surface area,160 or 240 mg/m2 is prescribed 3 or 2 times a day, respectively (a daily dose of 480 mg/m2).

If the hemoglobin content decreases to 75-90 g / l and / or the neutrophil count decreases to 0.75-1.0 x 107 l, it may be necessary to reduce the dose of the drug or cancel zidovudine therapy until hematopoiesis is restored. If anemia occurs, discontinuing the drug does not always reduce the need for blood transfusions. To restore bone marrow function more quickly, epoetin alfa may be prescribed in the recommended doses.

Elderly patients

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

Kidney failure

In severe renal insufficiency, the recommended daily dose is 300-400 mg. Depending on the peripheral blood response and the clinical effect, further dose adjustment may be required. Hemodialysis and peritoneal dialysis do not significantly affect the elimination of zidovudine, but accelerate the elimination of its metabolite, glucuronide. For patients with end-stage renal failure undergoing hemodialysis or peritoneal dialysis, the recommended dose of zidovudine is 100 mg every 6-8 hours.

Liver failure

Patients with hepatic insufficiency may experience accumulation of zidovudine due to reduced glucuronidation, which may require dose adjustment. If monitoring of zidovudine plasma concentrations is not possible, the doctor should pay special attention to clinical signs of intolerance to the drug and, if necessary, adjust the dose and / or increase the interval between doses.

Prevention of mother-to-fetus transmission of HIV

2 prevention schemes are effective:

1. Pregnant women, starting from 14 weeks of pregnancy, are recommended to prescribe zidovudine orally before the start of labor at a dose of 500 mg per day (100 mg 5 times a day). 2. Pregnant women, starting from 36 weeks of pregnancy, are recommended to prescribe zidovudine orally at a dose of 600 mg per day (300 mg 2 times a day) before the start of labor, and then at a dose of 300 mg every 3 hours until delivery.

Overdose

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

Treatment: symptomatic. Hemodialysis and peritoneal dialysis are not very effective in removing zidovudine from the body, but they speed up the elimination of its metabolite, glucuronide.

Special instructions

Patients should be informed about the dangers of concomitant use of zidovudine with over-the-counter medications and that the use of zidovudine does not prevent the risk of HIV transmission to other people through sexual contact or blood transfusions. Therefore, patients should take appropriate precautions.

Emergency prevention in case of possible HIV infection

According to international recommendations, in case of probable infection through the blood of an HIV – infected person (for example, through an injection needle), it is necessary to urgently (within 1-2 hours from the moment of infection) prescribe a combination therapy with zidovudine and lamivudine. If there is a high risk of infection, a drug from the protease inhibitor group should be included in the antiretroviral therapy regimen. Preventive treatment is recommended for 4 weeks. Despite the rapid start of treatment with antiretroviral drugs, the possibility of seroconversion cannot be excluded.

Symptoms that are mistaken for adverse reactions to zidovudine may be a manifestation of the underlying disease or a reaction to taking other medications used to treat HIV infection. The relationship between the developed symptoms and the effect of zidovudine is often very difficult to establish, especially with a detailed clinical picture of HIV infection. In such cases, it is possible to reduce the dose of the drug or cancel it. Zidovudine does not cure HIV infection, and patients remain at risk of developing a detailed picture of the disease with immune suppression and the emergence of opportunistic infections and malignancies. In HIV infection, zidovudine reduces the risk of developing opportunistic infections, but does not reduce the risk of developing lymphomas.

Adverse reactions from the hematopoietic system

Anemia (usually observed 6 weeks after the start of zidovudine therapy, but sometimes may develop earlier), neutropenia (usually develops 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 bone marrow reserve 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 hematopoiesis is still within the normal range), side effects from the blood rarely develop, so blood tests are performed less often-depending on the general condition of the patient once every 1-3 months. If the hemoglobin content decreases to 75-90 g / l and/or the neutrophil count decreases to 0.75-1.0 x 109 / L, the daily dose of the drug should be reduced, or zidovudine should be discontinued for 2-4 weeks until blood parameters are restored. Usually, the blood picture returns to normal after 2 weeks, after which zidovudine in a reduced dose can be prescribed again. If anemia occurs, discontinuing the drug does not always reduce the need for blood transfusions.

Radiation therapy enhances the myelosuppressive effect of zidovudine.

Lactic acidosis and severe hepatomegaly with steatosis

These complications can be fatal both with zidovudine monotherapy and with zidovudine as part of combined antiretroviral therapy.

The risk of these complications is higher in female patients. Signs of these complications may include general weakness, sudden unexplained weight loss, anorexia, digestive symptoms (nausea, vomiting, abdominal pain), and respiratory symptoms (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 a redistribution/accumulation of subcutaneous adipose tissue, including a decrease in the amount of adipose tissue in the face and limbs, an increase in visceral fat, an increase in mammary glands and fat deposition along the back of the neck and back (“buffalo hump”), as well as an increase in serum lipids and blood glucose concentrations.

Although one or more of the above-mentioned adverse reactions associated with the common syndrome, often referred to as lipodystrophy, can be caused by all drugs from the classes of protease inhibitors and nucleoside reverse transcriptase inhibitors, accumulated data indicate that there are differences between individual representatives of these drug classes in the ability to cause these adverse reactions.

In addition, lipodystrophy syndrome has a multi-factorial etiology; for example, the stage of HIV infection, advanced age, and duration of antiretroviral therapy play an important, possibly potentiating, role in the development of this complication. The long-term consequences of these adverse reactions are currently unknown. Clinical examination of patients should include an examination for signs of adipose tissue redistribution. Serum lipid and glucose concentrations should also be monitored. Lipid metabolism disorders should be corrected according to clinical indications.

Myopathy

It should be taken into account that the development of symptoms of myopathy (myalgia, weakness, increased creatine phosphokinase activity) in HIV-infected patients may be associated with the underlying disease. When using zidovudine in doses of 500 mg or 600 mg per day, myopathy associated with taking the drug is rarely observed. If zidovudine-induced myopathy develops, the drug should be discontinued.

Immune recovery syndrome

In HIV-infected patients with severe immunodeficiency during the initiation of antiretroviral therapy, an exacerbation of the inflammatory process may occur against the background of an asymptomatic or slow-moving opportunistic infection, which may cause a serious deterioration of the condition or aggravation of symptoms. Usually, such reactions were observed in the first weeks or months after the start 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 identified immediately and treatment should be started in a timely manner. Autoimmune diseases (such as Graves ‘ disease, polymyositis, and Guillain-Barre syndrome) were observed during immune recovery, but the time of initial manifestations varied, and the disease could occur many months after the start of therapy and have an atypical course.

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

In vitro studies have shown that ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues, including zidovudine. Although there is no clear evidence of a pharmacokinetic or pharmacodynamic interaction between ribavirin and zidovudine in patients with co-infection (HIV-1/HCV). Exacerbation of ribavirin-induced anemia has been reported in HIV-infected patients receiving concomitant zidovudine therapy. The mechanism of development of this effect is currently unknown. Therefore, the concomitant use of ribavirin and zidovudine is not recommended. The antiretroviral therapy regimen should be replaced with an alternative that does not contain zidovudine, especially if there is a history of zidovudine-related anemia in the anamnesis. 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 alpha with or without ribavirin. When zidovudine and interferon alfa are co-administered with or without ribavirin, patients should be closely monitored for signs of toxicity, especially hepatic insufficiency, neutropenia and anemia. If clinical signs of toxicity increase, especially hepatic insufficiency (> 6 points on the Child-Pugh scale), the dose of interferon alpha, ribavirin, or both drugs should be reduced or discontinued. If myelosuppression develops, discontinuation or discontinuation of zidovudine therapy should be considered. Influence on the ability to drive vehicles and mechanisms:

During the treatment period, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. If you experience such undesirable phenomena as dizziness, drowsiness, lethargy, convulsions, you should refrain from performing these types of activities.

Storage conditions

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

Shelf

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

Active ingredient

Zidovudine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Adults as prescribed by a doctor

Indications

HIV infection