Description
Pharmacological action
Zidovudine-AZT – an antiviral drug, an analogue of thymidine, in vitro highly active against retroviruses, including human immunodeficiency virus (HIV). Zidovudine is widely used as a component of combination antiretroviral therapy (APT) together with other antiretroviral drugs of the same class (NRTIs) or drugs of other classes (HIV protease inhibitors – HIV HIV IP), non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Contraindications
hypersensitivity to zidovudine or any other component of the drug. neutropenia (neutrophil count less than 0.75-109 / l) decrease in hemoglobin content (less than 75 g / l or 4.65 mmol / l) breastfeeding period. With caution, elderly patients with liver failure with inhibition of bone marrow hematopoiesis.
Composition
Active ingredient: Zidovudine 300 mg Excipients: corn starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate
Dosage and Administration
Inside. Adults and children over 12 years old with a body weight of 30 kg or more. The recommended dose of zidovudine as part of combination therapy is 600 mg per day in several doses. Children aged 3 years to 12 years: Children weighing more than 21 kg but less than 30 kg. The recommended dose of zidovudine as part of combination therapy is 200 mg (two capsules of 100 mg) in the morning and 200 mg (two capsules of 100 mg) in the evening. Children weighing at least 14 kg and up to 21 kg The recommended dose of zidovudine as part of combination therapy is 100 mg (one capsule of 100 mg) in the morning and 200 mg (two capsules of 100 mg) in the evening. Children weighing at least 8 kg and up to 14 kg The recommended dose of zidovudine is 100 mg (one capsule of 100 mg) in the morning and 100 mg (one capsule of 100 mg) in the evening. Body weight (kg) Morning Evening Daily dose (mg) 8-13 one capsule 100 mg one capsule 100 mg 200 14-21 one capsule 100 mg two capsules 100 mg 300 22-30 two capsules 100 mg two capsules 100 mg per 400 Children with body weight less than 8 kg, as well as children unable to swallow capsules (regardless of body weight), it is recommended to use other dosage forms of zidovudine for oral use. Prevention of HIV transmission from mother to fetus Zidovudine is prescribed to pregnant women after 14 weeks of pregnancy at a dose of 500 mg / day (100 mg five times a day). The drug is taken before birth. During childbirth, with cesarean section, as well as newborns, for the prevention of vertical transmission of HIV, it is necessary to use other dosage forms of zidovudine in accordance with the recommended regimens. Dose adjustment for adverse reactions from the blood and lymphatic system With a pronounced decrease in hemoglobin (up to 75-90 g / l (4.65-5.59 mmol / l)) or the number of neutrophils (up to 0.75-1.0×109 / l ) may require correction of the dosage regimen – dose reduction or drug withdrawal. Elderly patients. In patients over 65 years of age, the pharmacokinetics of zidovudine has not been studied, and there are no corresponding data. However, taking into account age-related features – a decrease in renal function, a change in blood counts – elderly patients need special control. Before starting zidovudine and during therapy, the condition of such patients should be carefully monitored. Renal failure The recommended dose of zidovudine in severe renal failure (creatinine clearance <10 ml / min) and end-stage renal failure (patients on hemodialysis or peritoneal dialysis) is 100 mg every 6-8 hours (300-400 mg / day). Changes in blood counts and some clinical reactions may require dose adjustment. Hepatic insufficiency The data obtained in patients with cirrhosis suggest that hepatic failure may result in accumulation of zidovudine associated with suppression of glucuronidation. A dose adjustment may be required, however, the exposure of zidovudine in liver failure of varying degrees (from mild to severe) varies significantly. in connection with which it is difficult to provide specific recommendations on dose changes. If it is not possible to control the concentration of zidovudine in the plasma, it is necessary to be guided by the clinical signs of the drug intolerance (for example, severe adverse reactions from the blood system: anemia, leukopenia, neutropenia). If necessary, reduce the dose of zidovudine and / or increase the interval between doses of the drug. Side effects Mental disorders: rarely – anxiety, depression. From the nervous system: very often – headache often – dizziness rarely – insomnia, paresthesia, drowsiness, decreased speed of thought, convulsions. From the side of the heart: rarely – cardiomyopathy. From the respiratory system, chest and mediastinal organs: infrequently – shortness of breath rarely – cough. From the digestive tract: very often – nausea often – vomiting, pain in the upper abdomen, diarrhea infrequently – flatulence rarely – pigmentation of the oral mucosa, taste disturbance, dyspepsia pancreatitis. On the part of the liver and biliary tract: often – increased levels of bilirubin and activity of liver enzymes rarely – severe hepatomegaly with steatosis. On the part of the skin and subcutaneous tissues: infrequently – a skin rash (except for urticaria), itchy skin rarely – pigmentation of nails and skin, urticaria, increased sweating. From the musculoskeletal and connective tissue: often – myalgia infrequently – myopathy. On the part of the kidneys and urinary tract: rarely – frequent urination. From the genitals and mammary gland: rarely – gynecomastia. Other: often – malaise infrequently – fever, generalized pain syndrome, asthenia rarely – chills, chest pain, flu-like syndrome. There is experience in prescribing a solution of zidovudine for iv administration over 2 weeks up to 12 weeks. The most common adverse effects were anemia, leukopenia, and neutropenia infrequent – local reactions. Adverse reactions that occur with the use of zidovudine to prevent transmission of HIV infection from mother to fetus: pregnant women tolerate zidovudine in recommended doses. In children, there is a decrease in the hemoglobin content, which, however, does not require blood transfusions. Anemia disappears after 6 weeks after completion of zidovudine therapy. Drug Interactions Available data suggest that co-administration of zidovudine and rifampicin leads to a decrease in AUC of zidovudine (area under the pharmacokinetic curve) by 48% В± 34%. This can lead to a partial or complete loss of the effectiveness of the drug. The combined use of zidovudine and rifampicin should be avoided. With ribavirin, stavudine, doxorubicin, antagonism was established in the manifestation of the antiviral effect of zidovudine. The combined use of zidovudine and stavudine, ribavirin, or doxorubicin should be avoided. Probenecid increases the AUC of zidovudine by 106% (100-170%). Patients receiving both drugs need careful monitoring of blood counts. The combined use of zidovudine and lamivudine leads to a slight increase in Cmax (28%), however, the total exposure (AUC) varies slightly. Zidovudine has no effect on the pharmacokinetics of lamivudine. In a number of patients taking zidovudine, there was a decrease in the concentration of phenytoin in the blood, while in one patient, on the contrary, an increase in phenytoin concentration was observed. With the joint use of these drugs, the concentration of phenytoin in the blood should be monitored. Atovachone: zidovudine does not affect the pharmacokinetics of atovachone. However, pharmacokinetic data demonstrate that atovaquone decreases the rate of transformation of zidovudine into glucuronide (AUC of zidovudine in equilibrium increases by 33%, peak plasma concentration of glucuronide decreases by 19%). It is unlikely that a three-week intake of atovaquone together with zidovudine (at a dose of 500-600 mg / day) can increase the frequency of adverse reactions associated with an increase in the plasma concentration of the latter. Nevertheless, it is necessary to monitor the condition of patients receiving atovachone together with zidovudine. Concomitant use with other drugs containing zidovudine. Zidovudine should not be prescribed with other medicines containing zidovudine. The combined use of zidovudine and valproic acid, fluconazole or methadone leads to an increase in the AUC of zidovudine and a corresponding decrease in its clearance. When taking zidovudine and valproic acid, fluconazole or methadone in combination, patients should be carefully monitored to avoid toxic effects associated with zidovudine. Taking zidovudine as part of combination therapy for HIV can aggravate the anemia associated with taking ribavirin, however, the mechanisms of this phenomenon are not clear. Due to the increased risk of anemia, concomitant use of ribavirin and zidovudine is not recommended. If the patient is already receiving zidovudine as part of HAART, consider replacing it with another drug. This is especially important if you have a history of anemia caused by taking zidovudine. Concomitant therapy (especially emergency) with potentially nephrotoxic or myelosuppressive drugs (for example, systemic pentamidine, dapsone, pyrimethamine, cotrimoxazole, amphotericin B, flucytosine, ganciclovir, interferon alfa, vincristine, vinblastine and doxorubicin-associated reactions may increase the risk of taking unwanted reactions) zidovudine. If concomitant therapy with any of the listed drugs is necessary, you should carefully monitor the patient’s condition (especially renal function and blood counts) and, if necessary, reduce the dosage of one or more drugs. There is no significant increase in the risk of adverse reactions associated with taking zidovudine if co-trimoxazole, pentamidine (in the form of an aerosol), pyrimethamine and acyclovir are used in prophylactic dosages. Clarithromycin (tablet form) reduces the absorption of zidovudine. A two-hour or longer interval between doses of zidovudine and clarithromycin avoids this reaction. Others: acetylsalicylic acid, codeine, methadone, morphine, indomethacin, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, dapsone, inosine pranobex can interfere with zidovudine metabolism by competitively inhibiting glucuronization or direct suppression of microsomal metabolism. The possibility of using these drugs in combination with zidovudine, especially with prolonged therapy, should be approached with caution. Overdose Symptoms There are no specific symptoms or signs of an acute overdose of zidovudine. Known reactions are observed, listed as side effects: fatigue, headache, vomiting, in some cases, disorders of the blood system develop. There is one report of an overdose of an unknown amount of zidovudine according to serum concentrations, the dose was more than 17 g. However, no clinical, biochemical or hematological short-term effects were observed. Treatment Patients should be carefully monitored for toxic symptoms. If necessary, appropriate maintenance therapy is prescribed. The effectiveness of hemodialysis and peritoneal dialysis to eliminate zidovudine is limited, but they can accelerate the excretion of glucuronide (a metabolite of zidovudine). active substance Zidovudine Terms of delivery from pharmacies Prescription tablet dosage form of tablets