Azimitem tablets, 300 mg 60 pcs

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Indications

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

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

Active ingredient

Composition

1 tablet contains:

The active ingredient:

Zidovudine 300 mg

Excipients:

Each film-coated tablet contains:

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

Water-soluble film coating: Ready-made water-soluble film coating – 9.0 mg. (Shell composition: hydroxypropyl methylcellulose (hypromellose) – 25.0%, copolyvidone – 22.5%, polyethylene glycol 6000 (Macrogol 6000) – 9.5%, glyceryl caprylocaprate – 3.0%, polydextrose – 15.0%, titanium dioxide – 25.0%).

How to take, the dosage

Ingestion, regardless of meals.

In adults, the drug is prescribed in a dose of 600 mg per day in several doses. In children with body weight over 30 kg – 300 mg 2 times a day or 200 mg 3 times a day. If the body surface area is considered, 160 or 240 mg/m2 3 or 2 times daily, respectively (daily dose 480 mg/m2).

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, in these patients special caution should be exercised when using zidovudine and appropriate monitoring before and during treatment with the drug.

Renal failure

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

Hepatic failure

In patients with hepatic failure, there may be cumulation of zidovudine due to decreased glucuronidation, which may require adjustment of the drug dose. If monitoring of plasma concentrations of zidovudine is not possible, the physician 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.

Preventing mother-to-fetus transmission of HIV

There are 2 prevention regimens that are effective:

Interaction

Zidovudine is used as part of combined 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 typical for drugs that require careful use with zidovudine.

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

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

Clarithromycin: reduces absorption of zidovudine. A break of at least 2 hours between doses of the drugs.

Valproic acid, fluconazole, methadone: decrease the clearance of zidovudine, which increases its systemic exposure.

Ribavirin: the nucleoside analogue ribavirin is an antagonist of zidovudine. Simultaneous use of zidovudine and ribavirin should be avoided.

Rifampicin: The combination of zidovudine with rifampicin results in a 48%±34% decrease in the AUC for zidovudine; however, the clinical significance of this change is unknown.

Stavudine: zidovudine can inhibit intracellular phosphorylation of stavudine.

Stavudine should not be used concomitantly with zidovudine.

Other: medications such as paracetamol, acetylsalicylic acid, codeine, methadone, morphine, indomethacin, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, dapsone, isoprinosine can impair zidovudine metabolism through competitive inhibition of glucuronidation or direct inhibition 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 for emergency therapy, with potentially nephrotoxic and myelotoxic drugs (e.g., pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine, doxorubicin) increases the risk of adverse reactions to zidovudine. Renal function and blood parameters should be monitored and the dose of drugs should be reduced if necessary.

Special Instructions

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

Emergency prophylaxis for probable HIV infection

In accordance with international recommendations, if infection is probable through the blood of an HIV-infected person (e.g., through an injection needle), a combination therapy of zidovudine and lamivudine should be administered promptly (within 1 to 2 hours of infection). If there is a high risk of infection, a drug from the protease inhibitor group should be included in the antiretroviral therapy regimen. Prophylactic treatment is recommended for four weeks. Despite rapid initiation of antiretroviral treatment, 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 other HIV medications. The relationship between the symptoms that develop and the effects of zidovudine is often very difficult to establish, especially when the clinical picture of HIV infection is more advanced. 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 the unfolding of the disease with suppression of immunity and the occurrence of opportunistic infections and malignant neoplasms. In HIV infection, zidovudine reduces the risk of opportunistic infections, but does not reduce the risk of lymphoma.

Adverse reactions from the hematopoietic organs

Radiation therapy increases the myelosuppressive effect of zidovudine.

Lactic acidosis and marked hepatomegaly with steatosis

These complications can be fatal with both zidovudine monotherapy and when zidovudine is used as part of combination 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), respiratory symptoms (rapid breathing or dyspnea). In case of clinical or laboratory signs of lactic acidosis or toxic liver damage zidovudine should be discontinued.

Distribution of subcutaneous fatty tissue

In some patients, combination antiretroviral therapy may be accompanied by redistribution/accumulation of subcutaneous fatty tissue, including decreased facial and limb fat, increased visceral fat, breast fat, and fatty deposits around the back of the neck and back (“buffalo hump”), and elevated serum lipid and blood glucose concentrations.

While one or more of the above adverse reactions associated with the common syndrome often referred to as lipodystrophy can be caused by all drugs in the protease inhibitor and nucleoside reverse transcriptase inhibitor classes, accumulating evidence suggests that there are differences between individual members of these drug classes in their ability to cause these adverse reactions.

In addition, lipodystrophy syndrome has a multifactorial etiology; for example, the stage of HIV infection, older age, and duration of antiretroviral therapy play an important, possibly potentiating, role in the development of this complication. The long-term effects of these adverse reactions are currently unknown. The clinical evaluation of patients should include 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 at 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 taking zidovudine, the drug should be discontinued.

Immune reconstitution syndrome

In HIV-infected patients with severe immunodeficiency during initiation of antiretroviral therapy, inflammation may worsen with asymptomatic or sluggish opportunistic infection, which may cause serious deterioration or exacerbation of symptoms. Usually such reactions have been 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 started promptly. Autoimmune diseases (such as Graves’ disease, polymyositis and Guillain-Barré syndrome) were observed against the background of immune recovery, but the timing of the primary manifestations varied, and the disease could occur many months after the start of therapy and have an atypical course.

Patients co-infected with HIV and hepatitis C virus (HCV)

In vitro studies have shown that ribavirin can reduce phosphorylation of pyrimidine nucleoside analogs, including zidovudine. Although no clear evidence of pharmacokinetic and pharmacodynamic interaction between ribavirin and zidovudine in patients with co-infection (HIV-1/HCV) has been found. An exacerbation of ribavirin-induced anemia has been reported in HIV-infected patients receiving concomitant therapy with zidovudine. The mechanism of this effect is currently unknown. Therefore, concomitant use of ribavirin and zidovudine is not recommended. The antiretroviral therapy regimen should be changed to an alternative regimen that does not contain zidovudine, especially if there is a history of anemia associated with taking zidovudine.

Cases of hepatic failure (sometimes fatal) have been reported in patients infected with HIV-1 with concomitant hepatitis C receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin. If zidovudine and interferon alfa with or without ribavirin are used concomitantly, patients should be closely monitored for signs of toxicity, particularly liver failure, neutropenia, and anemia. If clinical signs of toxicity increase, especially hepatic failure (> 6 points on the Child-Pugh scale), doses should be reduced or interferon alfa, ribavirin or both should be withdrawn. In case of development of myelosuppression, discontinuation or withdrawal of therapy with zidovudine should be considered.

Effect on the ability to drive motor vehicles:

During treatment, caution should be exercised when driving motor vehicles and engaging in other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions. If such adverse events as dizziness, somnolence, lethargy and seizures occur, the following activities should be avoided.

Contraindications

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

Inhibition of medullary hematopoiesis, cyanocobalamin or folic acid deficiency, liver failure, older age, obesity, hepatomegaly, hepatitis or any liver disease risk factors, neutropenia/leukopenia (neutrophil count 0.75-1.0 x 109/L); anemia (hemoglobin 75-90 g/L).

Side effects

The adverse reactions that occur when treated with zidovudine are the same in children and adults.

The following gradations are used to estimate the incidence of adverse reactions: very common (>1/10), common (>1/100, < 1/10), infrequent (>1/1000, < 1/100), rare (>1/10000, < 1/1000), very rare (< 1/10000).

Hematopoietic organs: often – anemia (which may require hemotransfusions), neutropenia, leukopenia, infrequent – thrombocytopenia, pancytopenia with bone marrow hypoplasia, rare – red cell aplasia, very rare – aplastic anemia.

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

Hepatobiliary system: often – hyperbilirubinemia, increased activity of “liver” enzymes, rarely – marked hepatomegaly with steatosis.

Nervous system: very common – headache, common – dizziness, rare – paresthesia, insomnia, somnolence, decreased mental performance, seizures, anxiety, depression.

Respiratory system: infrequent – shortness of breath, rare – cough.

Cardiovascular system: cardiomyopathy.

Urinary system disorders: rarely – frequent urination.

Endocrine system and metabolism: frequently – hyperlactatemia, rarely – lactate acidosis, gynecomastia.

Musculoskeletal system: often – myalgia, rarely – myopathy.

Skin disorders: infrequent – skin rash, itching, rarely – pigmentation of nails and skin, increased sweating, urticaria.

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

Some adverse reactions occurring when using zidovudine to prevent mother-to-fetus transmission of HIV.

Pregnant women tolerate zidovudine in recommended doses well. In children there is a decrease in hemoglobin, which, however, does not require hemotransfusions. Anemia disappears 6 weeks after completion of therapy with zidovudine.

Overdose

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

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

Pregnancy use

Zidovudine passes through the placenta. The drug can be used during pregnancy earlier than 14 weeks only if the potential benefit to the mother exceeds the possible risk to the fetus. Use of zidovudine after 14 weeks of pregnancy with its subsequent use in newborns leads to a decrease in the frequency of HIV transmission from mother to fetus. Long-term effects of zidovudine in children who received it in the intrauterine or neonatal periods are not known. The possibility of carcinogenic effects cannot be completely excluded.

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