Zidovudine-AZT - instructions for use, dose, side effects, contraindications

Active substance:
Zidovudine	300.0 mg
Excipients:
Microcrystalline cellulose	62.0 mg
Crospovidone	20.0 mg
Hypromellose	12.0 mg
Magnesium stearate	4.0 mg
Silica colloidal dioxide	2.0 mg
Film sheath:
Opapray II (white) 85F48105 [polyvinyl alcohol - 46.9%, macrogol 4000 - 23.6%, talc - 17.4%, titanium dioxide - 12.1%]	12.0 mg

Description:

Tablets are round, biconvex, covered with a film coat of white or almost white color. The core of the tablet is white or almost white.

Pharmacotherapeutic group:antiviral [HIV] agent

ATX: & nbsp

J.05.A.F.01 Zidovudine

Pharmacodynamics:

Mechanism of action. Zidovudine - an antiviral drug, an analogue of thymidine, in vitro Highly active against retroviruses, including the human immunodeficiency virus (HIV).

Zidovudine undergoes phosphorylation in both infected and intact cells with the formation of monophosphate by means of cellular thymidine kinase. Subsequent phosphorylation of zidovudine monophosphate to zidovudine diphosphate, and then to zidovudine triphosphate is catalyzed by cellular thymidine kinase and nonspecific kinases, respectively. Zidovudine triphosphate acts as an inhibitor and substrate for viral reverse transcriptase. The formation of proviral DNA is blocked by the incorporation of zidovudine triphosphate into its chain, which leads to chain termination.The competition of zidovudine triphosphate for reverse transcriptase of HIV is approximately 100 times stronger than for the cellular alpha-polymerase of human DNA.

Antagonism between zidovudine and other antiretroviral drugs (abacavir, didanosine, lamivudine and interferon alfa) in vitro was not observed.

The development of resistance to thymidine analogues (zidovudine - one of them) occurs as a result of gradual accumulation of specific mutations in 6 codons (41, 67, 70, 210, 215 and 219) of reverse transcriptase. The viruses acquire phenotypic resistance to thymidine analogues as a result of combined mutations in codons 41 and 215 or the accumulation of at least 4 of 6 mutations. These mutations do not cause cross-resistance to other nucleoside analogs, which allows further inhibitors of reverse transcriptase to be used in the treatment of HIV infection.

Two types of mutations lead to the development of multiple drug resistance. In one case, mutations occur in 62, 75, 77, 116, and 151-th codons of HIV reverse transcriptase, in the second case it is a T69S mutation with insertion of 6 pairs of nitrogenous bases in this position, which is accompanied by the appearance of phenotypic resistance to zidovudine,as well as to other nucleoside reverse transcriptase inhibitors (NRTIs). Both types of mutations significantly limit the therapeutic possibilities for HIV infection.

Reduced sensitivity to zidovudine HIV isolates in vitro was observed with prolonged treatment of HIV infection with zidovudine. Available data indicate that in the early stages of HIV infection, the frequency and degree of decrease in sensitivity in vitro significantly less than in the late stages of the disease.

Currently, the relationship between sensitivity to zidovudine in vitro and the clinical effect of therapy has not been studied. Determination of sensitivity in vitro It has not been standardized, and the results may vary depending on methodological factors.

Studies of zidovudine in combination with lamivudine in vitro It showed that zidovudine-resistant virus isolates are sensitive to zidovudine, while the acquisition of resistance to lamivudine. In clinical studies demonstrated that the use of zidovudine in combination with lamivudine delays the appearance of resistant strains of lamivudine in patients previously treated with antiretroviral therapy (ART).

Zidovudine is widely used as a component of combination ARVT with other antiretroviral drugs of the same class (NRTIs) or other classes (HIV protease inhibitors-HIV-IP, non-nucleoside reverse transcriptase inhibitors-NNRTIs).

Pharmacokinetics:

Adults

Suction. Zidovudine well absorbed in the intestine. For all studied dosages, the bioavailability of the drug is 60-70%. The mean values of the maximum concentration in the equilibrium state (C_ss_max) and the minimum concentration in the equilibrium state (C_ss _min) in blood plasma with the administration of zidovudine at a dose of 200 mg every 4 hours were 4.5 and 0.4 μM (or 1.2 and 0.1 μg / ml), respectively.

Distribution. Binding to blood plasma proteins is relatively low (34-38%), so it is unlikely that interaction with other drugs affecting binding to blood plasma proteins is improbable. Zidovudine penetrates into the cerebrospinal fluid, placenta, amniotic fluid, fetal blood, sperm and breast milk.

Metabolism. Zidovudine 5'-glucuronide is the main end metabolite of zidovudine, is determined in blood plasma and urine and is approximately 50-80% of the dose of the drug that is excreted by the kidneys.

Excretion. The renal clearance of zidovudine greatly exceeds the creatinine clearance, which indicates the predominant excretion of zidovudine by tubular secretion.

Special patient groups

Children. In children older than 5-6 months, the pharmacokinetic profile of zidovudine does not differ from that in adults. Zidovudine well absorbed in the intestine.

Pregnant. The pharmacokinetics of zidovudine has been studied in 8 women during the third trimester of pregnancy. As the gestation period increased, there were no signs of zidovudine accumulation. The pharmacokinetics of zidovudine was similar to that of non-pregnant adults. Zidovudine concentrations in the blood plasma of infants at birth were similar to those in mothers plasma, which is consistent with passive zidovudine through the placenta.

Elderly patients. Special data on the pharmacokinetics of zidovudine in elderly patients are lacking.

Patients with impaired renal function. In patients with progressive renal dysfunction, the maximum concentration of zidovudine in the blood plasma is increased by 50% compared with that in patients with normal renal function.AUC zidovudine increases by 100%, the half-life does not change significantly. In case of renal dysfunction, a significant cumulation of 5'-glucuronide, the main metabolite of zidovudine, is observed, but no signs of toxic effect are detected. Hemodialysis and peritoneal dialysis do not affect the excretion of zidovudine, while the excretion of 5'-glucuronide zidovudine is enhanced.

Patients with impaired hepatic function. If there is a violation of the liver function, cumulation of zidovudine may be observed due to a decrease in glucuronization. which may require correction of the dose, but since there are only limited data, it is impossible to provide accurate recommendations.

Indications:

- Treatment of HIV-1 infection in combination ARVT in adults and children weighing more than 30 kg.

- Treatment of HIV-1 infection in pregnant women to reduce the frequency of transplacental transmission of HIV from mother to fetus.

Contraindications:

- Hypersensitivity to zidovudine or any other component of the drug.

- Neutropenia / leukopenia (number of neutrophils <0.75 x 10⁹/ l or <750 / μl).

- Anemia (hemoglobin <75 g / l or <4.65 mmol / l).

- Body weight less than 30 kg (for this dosage form).

- Severe kidney failure.

- Severe renal insufficiency, patients with terminal stage of renal failure, on hemodialysis or peritoneal dialysis (for this dosage form).

Carefully:

Inhibition of bone marrow hemopoiesis, deficiency of cyanocobalamin or folic acid, elderly age (over 65 years), hepatic insufficiency, obesity, hepatomegaly, hepatitis or any risk factors for liver disease, neutropenia / leukopenia (neutrophil count 0.75-1.0 x 10⁹/ l, or 750-1000 / mkl), anemia (hemoglobin 75-90 g / l).

Pregnancy and lactation:

Fertility

There is no evidence of the effect of zidovudine on women's fertile function. In men, zidovudine intake does not affect sperm composition, morphology and sperm motility.

Pregnancy

Zidovudine penetrates the placenta. Zidovudine It is possible to apply earlier 14 weeks of pregnancy only if the potential benefit to the mother exceeds the risk to the fetus.

There are reports of a slight, transient increase in serum lactate concentration,which may be due to mitochondrial dysfunction in newborns and infants exposed to the NRTI during the intrauterine or perinatal period. The clinical significance of the transient increase in serum lactate concentration is unknown. There are very few reports of cases of developmental delay, convulsive seizures and other neurological disorders (eg, muscle tone increase). Nevertheless, the cause-and-effect relationship between these phenomena and intrauterine or perinatal exposure of NRTIs is not established. These data do not affect these recommendations for use Apt during pregnancy to prevent vertical transmission of HIV.

Prevention of mother-to-child transmission of HIV

In the study ACTG 076 zidovudine after 14 weeks of gestation followed by administration to newborns resulted in a reduction in the vertical transmission rate of HIV (incidence of 23% in the placebo group compared to 8% in the zidovudine group). Therapy with zidovudine for oral administration began between the 14th and 34th weeks of pregnancy and continued until the onset of labor. During childbirth zidovudine was administered intravenously. Newborns were receiving zidovudine Inside up to 6-week-old age. Newborns unable to take the drug inside were injected zidovudine in the form of an injection. In the study of zidovudine monotherapy in pregnant women (from the 36th week of pregnancy to the birth), taking the drug inward led to a significant reduction in the frequency of HIV transmission from mother to the fetus (the incidence of infection was 19% in the placebo group compared to 9% in the zidovudine group) . In this study, mothers did not breastfeed their infants. The long-term consequences of zidovudine in children who received zidovudine in the prenatal or neonatal period, are unknown. Based on data on carcinogenicity and mutagenicity in animals, the possibility of carcinogenic effects of zidovudine in humans can not be completely ruled out. The significance of these data for infected and uninfected infants exposed to zidovudine is unknown. Pregnant women who are considering zidovudine during pregnancy should be informed of these findings.

Breastfeeding period

Specialists do not recommend breastfeeding to HIV-infected patients to avoid HIV transmission to the child. Because the zidovudine and HIV penetrate into breast milk, breastfeeding is contraindicated.

Dosing and Administration:

Inside, regardless of food intake.

Treatment with Zidovudine-AZT should be performed by a doctor with experience in the treatment of HIV-infected patients.

Adults and children weighing more than 30 kg

The drug is prescribed in a dose of 600 mg / day in 2 divided doses as part of a combination therapy.

Patients with impaired blood and lymphatic system

When the hemoglobin content is reduced to 75-90 g / l and / or the amount of neutrophils decreases to 0.75-1.0 x 10⁹/ l, it may be necessary to reduce the dose of the drug or cancel the therapy with zidovudine before hematopoiesis is restored.

Elderly patients

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

Patients with impaired renal function

The use of Zidovudine-AZT in patients with severe renal failure, as well as with terminal stage of renal failure, on hemodialysis or peritoneal dialysis (for this dosage form) is contraindicated.

Patients with impaired hepatic function

Data obtained from patients with cirrhosis of the liver indicate that in patients with hepatic insufficiency zidovudine cumulation may occur due to a reduction in glucuronization, which may require dose adjustment; However, the available data are limited and any recommendations are not possible. If monitoring of zidovudine concentration in the blood plasma is impossible, 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 of the drug.

Prevention of mother-to-child transmission of HIV

Pregnant women are recommended from the age of 36 weeks of pregnancy zidovudine inside at a dose of 600 mg / day (300 mg twice a day) before the onset of labor,and then in a dose of 300 mg every 3 hours before delivery.

Side effects:

Undesirable reactions that occur in the treatment of zidovudine in children and adults coincide.

Side effects noted in clinical trials and during the postgraduate experience of zidovudine use are given in accordance with the classification MedDRA: very often (≥1 / 10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10,000 and <1/1000), very rarely (<1/10 000) and the frequency is unknown (insufficient data to estimate the frequency of development).

Violations of the blood and lymphatic system: often - anemia (which may require blood transfusion), neutropenia and leukopenia (the incidence of neutropenia increases in patients who experienced a decrease in the number of neutrophils, hemoglobin and vitamin B₁₂ in the serum at the beginning of treatment). Anemia often occurs when taking high doses of the drug (1200-1500 mg / day) and in patients in the late stages of HIV infection, in particular at a concentration of CD4 lymphocytes of 100 cells / μl; infrequently - pancytopenia with bone marrow hypoplasia, thrombocytopenia; rarely - true erythrocyte aplasia; very rarely - aplastic anemia.

Disorders from the metabolism and nutrition: often - hyperlactatemia; rarely - lactic acidosis in the absence of hypoxemia, anorexia, redistribution / accumulation of subcutaneous fat; frequency is unknown - hypertriglyceridemia, hyperglycemia, lipodystrophy.

Disorders of the psyche: rarely - anxiety and depression.

Disturbances from the nervous system: very often - headache; often - dizziness; rarely - cramps, decreased cognitive function, insomnia, paresthesia, drowsiness.

Heart Disease: rarely - cardiomyopathy.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - shortness of breath; rarely - a cough.

Disorders from the gastrointestinal tract: very often - nausea; often - vomiting, diarrhea, abdominal pain; infrequently - flatulence; rarely - pigmentation of the oral mucosa, taste disorders, dyspepsia.

Disturbances from the liver and bile ducts: often - increased activity of hepatic transaminases and bilirubin in the blood serum; rarely - pancreatitis, liver disease, such as severe hepatomegaly in combination with steatosis.

Disturbances from the skin and subcutaneous tissues: infrequent - rash and itching; rarely - hives, skin and nails pigmentation, increased sweating.

Disturbances from musculoskeletal and connective tissue: often - myalgia; infrequently - myopathy; frequency unknown - osteonecrosis.

Disorders from the kidneys and urinary tract: rarely - frequent urination.

Violations of the genitals and mammary gland: rarely - gynecomastia.

Other undesirable phenomena: often - a feeling of indisposition; infrequently - asthenia, fever, generalized pain syndrome; rarely - pain in the chest, flu-like syndrome, chills; frequency unknown - asthenic syndrome, development of secondary infection, mitochondrial toxicity, mycobacterial infections. The frequency of common unwanted reactions is consistently reduced during the first few weeks of zidovudine therapy.

Undesirable reactions, The use of zidovudine to prevent the transmission of HIV from mother to 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.

When using nucleoside analogs, cases of lactate acidosis (sometimes with a lethal outcome), often accompanied by severe hepatomegaly and steatosis of the liver, were reported.

Possible development immunodeficiency syndrome, against which background the appearance of autoimmune diseases, the frequency of which varied, since these diseases could occur many months after initiation of therapy and have atypical manifestations.

Estimating the tolerability of the drug, it should be borne in mind that skin rashes, dizziness, weakness, headache, anorexia, diarrhea, myalgia, anemia, thrombocytopenia can be a manifestation of the HIV infection itself and secondary diseases associated with it, rather than the toxic effects of zidovudine.

The frequency of neutropenia development was higher in those patients in whom the amount of neutrophils, hemoglobin and vitamin content AT₁₂ in blood plasma were low at the beginning of zidovudine therapy.

The frequency of complications correlates with the dose and duration of the drug, so complications are more common in the late stages of the disease.In case of adverse reactions, it is advisable to continue treatment with zidovudine and prescribe other drugs to correct complications. With a pronounced toxic effect, zidovudine therapy is canceled until the affected systems are restored.

Overdose:

Symptoms. Specific symptoms of acute overdose of zidovudine are absent. There are known reactions listed as side effects: fatigue, headache, vomiting, in a number of cases, violations on the part of the blood system. There is one report of an overdose of an unknown amount of zidovudine; according to serum concentrations, the dose of the drug was more than 17 g. No clinical, biochemical or hematological short-term effects were observed.

Treatment. Patients should be carefully monitored for signs of toxicity. If necessary, designate appropriate maintenance therapy.

The effectiveness of hemodialysis and peritoneal dialysis for the elimination of zidovudine is limited, but they are able to accelerate the excretion of 5'-glucuronide (zidovudine metabolite).

Interaction:

Zidovudine is mainly excreted as an inactive metabolite, which is a glucuronide conjugate formed in the liver. Drugs that have a similar elimination route can inhibit zidovudine metabolism. Zidovudine is used in combination Apt together with other NRTIs and drugs from other groups (HIV, NNRTIs).

The list of interactions listed below should not be considered exhaustive, but they are characteristic of drugs that require careful use with zidovudine.

Atovahon. Zidovudine does not affect the pharmacokinetic parameters of the atovahona. Atovahon slows the transformation of zidovudine into a glucuronide metabolite (zidovudine AUC in the equilibrium state is increased by 33%, and the maximum concentrations of glucuronide are reduced by 19%). It is unlikely that the safety profile of zidovudine changes at doses of 500 or 600 mg / day when combined with atavahone for 3 weeks. If a longer combined use of these drugs is necessary, careful monitoring of the patient's condition is recommended.

Clarithromycin reduces the absorption of zidovudine.The interval between the use of zidovudine and clarithromycin should be at least 2 hours.

Lamivudine. There is a moderate increase in C_maxzidovudine (by 28%) with simultaneous application with lamivudine, but the total exposure (AUC) does not change. Zidovudine does not affect the pharmacokinetics of lamivudine. Phenytoin. With the simultaneous use of zidovudine with phenytoin, the concentration of the latter in the blood plasma decreases, and in one case an increase in the concentration of phenytoin was noted; When this combination is used, the concentration of phenytoin in the blood plasma should be monitored.

Probenecid. Limited data showed that probenecid reduces glucuronization and increases the mean half-life and AUC of zidovudine.

Kidney excretion of glucuronide (and, possibly, zidovudine itself) in the presence of probenecid decreases.

Ribavirin. The nucleoside analogue ribavirin is an antagonist of zidovudine, and their combination should be avoided.

Rifampicin. Limited data showed that the combination of zidovudine with rifampicin leads to a decrease in AUC for zidovudine by 48 ± 34%, but the clinical significance of this change is unknown.

Stavudine. Zidovudine can suppress intracellular phosphorylation of stavudine in a joint application, therefore stavudine it is not recommended to be used simultaneously with zidovudine.

Doxorubicin. Joint use of zidovudine and doxorubicin should be avoided, since in vitro their incompatibility was demonstrated.

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

Other medicines, such as acetylsalicylic acid, codeine, methadone, morphine, indomethacin, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, dapsone, inosine pranobeks, 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 with prolonged therapy, should be approached with caution.

The combination of zidovudine with potentially nephrotoxic and myelotoxic drugs (for example, pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin B, flucytosine, ganciclovir, interferon alpha, vincristine, vinblastine, doxorubicin), especially with emergency therapy, may increase the risk of developing unwanted reactions to zidovudine. It is necessary to observe the function of the kidneys and the blood formula; if necessary, the doses of drugs are reduced.

Since some patients receiving zidovudine, opportunistic infections may develop, it may be necessary to consider the concomitant use of prophylactic antibacterial therapy. Such prophylaxis includes co-trimoxazole, pentamidine in aerosol form, pyrimethamine and acyclovir. Limited data from clinical studies of zidovudine do not indicate a significantly increased risk of developing adverse reactions to zidovudine with simultaneous use with these drugs.

Special instructions:

Patients should be informed of the danger of simultaneous use of Zidovudine-AZT with other drugs, and that zidovudine does not prevent HIV infection through sexual contact or through infected blood.Appropriate safety measures are required.

Zidovudine-AZT does not cure HIV, and patients are at risk for developing opportunistic infections and malignant tumors, which is due to immunosuppression. Although zidovudine reduces the risk of developing opportunistic infections, data on the risk of developing neoplasms, including lymphomas, against the background of the use of the drug are limited. The available data on patients who received treatment for HIV infection in advanced stages indicate that the risk of developing lymphoma corresponds to that of patients who have not received treatment. In patients with an early stage of HIV infection receiving long-term treatment, the risk of developing lymphoma is unknown.

Pregnant women considering the possibility of using zidovudine during pregnancy to prevent the transmission of HIV to their children should be informed that in some cases transmission can occur even despite treatment.

Emergency prophylaxis for possible contamination

According to international recommendations, if there is a probable contact with HIV-infected blood, for example, when a needle is pricked, it is necessary to prescribe combination therapy with zidovudine and lamivudine within 1-2 hours from the moment of infection.In the case of a high risk of infection, a drug from the HIV group of HIV should be included in the treatment regimen. Preventive treatment is recommended for 4 weeks. Data on the effectiveness of preventive treatment after accidental HIV infection have not been accumulated enough, no controlled studies have been conducted. Despite the rapid onset of treatment with antiretroviral drugs, seroconversion can not be ruled out.

Undesirable reactions from the hematopoiesis system

Anemia (usually observed 6 weeks after starting the use of Zidovudine-AZT, but sometimes it may develop earlier), neutropenia (usually occurs 4 weeks after initiation of ZD treatment, but sometimes occurs earlier), leukopenia (usually of a secondary nature due to neutropenia ) may occur in patients receiving zidovudine and having reduced bone marrow hematopoiesis before the start of treatment, especially in the advanced stage of HIV infection.

During the administration of Zidovudine-AZT in patients with a developed clinical picture of HIV infection, hematological parameters should be monitored at least once every 2 weeks during the first 3 months of therapy, and then monthly.In the early stages of HIV infection (with unexhausted reserves of bone marrow hematopoiesis), undesirable reactions from the hematopoiesis system are rare. General blood tests can be performed less often, depending on the general condition of the patient (for example, 1 time in 1-3 months). If the hemoglobin content decreases to 75-90 g / l (4.65-5.59 mmol / l) or the amount of neutrophils decreases to 0.75-1.0 x 10⁹/ l (750 / μl), the daily dose of Zidovudine-AZT should be reduced to restore blood counts or the drug is withdrawn for 2-4 week before the recovery of blood. Usually, the blood picture will be normalized after 2 weeks, after which zidovudine in a reduced dose can be reassigned. Despite a reduction in the dose of the drug, severe anemia may require blood transfusion.

Lactate acidosis and severe hepatomegaly with steatosis

These complications can be fatal, both with monotherapy with zidovudine, and with Zidovudine-AZT as part of combination therapy. The risk of these complications increases in women. Clinical signs of these complications can be symptoms from the gastrointestinal tract (nausea, vomiting and abdominal pain), general weakness, anorexia, lack of appetite,rapid unexplained weight loss, respiratory symptoms (dyspnea and tachypnea), or neurological symptoms (including motor weakness). The use of nucleoside analogues should be discontinued if symptomatic hyperlactatemia and metabolic acidosis / lactate acidosis, progressive hepatomegaly, or a rapid increase in aminotransferase activity occur.

Caution should be exercised when prescribing Zidovudine-AZT to patients (especially overweight women) with hepatomegaly, hepatitis, or other known risk factors for liver damage and steatosis of the liver (including the use of certain drugs and alcohol use).

Patients with co-infection with hepatitis C and patients who are treated with interferon alfa and ribavirin may be at a particular risk group.

Patients with an increased risk require special attention. Zidovudine-AZT should be withdrawn in all cases of clinical or laboratory signs of lactic acidosis with or without hepatitis, which may include hepatomegaly with steatosis even in the absence of an increase in transaminase activity.

Redistribution of subcutaneous fat

Redistribution and / or accumulation of subcutaneous fat, including a central type of obesity, an increase in the fat layer on the posterior surface of the neck ("buffalo buffalo"), a reduction in the subcutaneous fat layer on the face and limbs, an increase in the mammary glands, an increase in serum lipids and glucose in the blood was noted both in the complex and separately in some patients who received a combined Apt. Until now, all drugs from the class of HIV AI and NRTI have been associated with one or more specific undesirable phenomena associated with a common syndrome, often called lipodystrophy. However, clinical data show differences in the risk of developing this syndrome between specific representatives of therapeutic classes. In addition, lipodystrophy syndrome has a multifactorial etiology, for example, factors such as the stage of HIV infection, elderly age and duration Apt, play an important, perhaps synergistic role. The long-term consequences of this phenomenon are currently unknown. Clinical examination should include a physical examination to assess the presence of redistribution of subcutaneous fat.It should be recommended to study the concentration of serum lipids and glucose in the blood. Lipid disorders should be treated according to clinical indications.

Immunodeficiency Syndrome

In HIV-infected patients with severe immunodeficiency during the onset of APT, inflammation may aggravate against an asymptomatic or residual opportunistic infection, which can lead to serious worsening or worsening of the symptoms. Typically, such reactions have been described in the first weeks or months of APT. The most significant examples are cytomegalovirus retinitis, generalized and / or focal mycobacterial infection and pneumonia caused by Pneumocystis jirovecii (R. carinii). Any symptoms of inflammation should be immediately identified and if necessary begin treatment.

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.

Concomitant viral hepatitis C

A rise in ribavirin-induced anemia in HIV-infected patients receiving zidovudine at the same time has been reported, but the exact mechanism of this phenomenon is unknown. Therefore, the combined use of ribavirin and zidovudine is not recommended. You must change the mode Apt, applying a scheme that does not contain zidovudine, especially in patients with a history of zidovudine-induced anemia. In patients infected with HIV and hepatitis C virus and receiving a combination Apt about HIV and interferon alfa in combination with ribavirin or without it, hepatic insufficiency (sometimes with lethal outcome) was observed. It is necessary to ensure that patients receiving interferon alfa with or without ribavirin, and zidovudine, in order to identify the toxic effects associated with treatment, especially the development of hepatic insufficiency, neutropenia and anemia. In such cases, consideration should be given to discontinuing the use of Zidovudine-AZT. Also, consideration should be given to reducing the dose or stopping the use of interferon alfa, ribavirin, or both drugs in the event of increased clinical toxicity, including the development of liver failure (eg, more than 6 on the Child-Pugh scale).instructions for use for interferon alfa and ribavirin).

Myopathy and myositis

Myopathy and myositis with pathological changes characteristic of the course of HIV infection were associated with prolonged use of Zidovudine-AZT.

Joint use with zidovudine-containing drugs

Zidovudine-AZT should not be taken with drugs containing zidovudine as one of the components (for example, combinations lamivudine and zidovudine or abacavir, lamivudine and zidovudine).

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

Studies to study the effect of zidovudine on the ability to drive a car or work with mechanisms have not been conducted. Pharmacodynamic properties of the drug do not allow to assume the presence of a similar effect. Nevertheless, when evaluating the ability to drive or work with machinery, the general condition of the patient and the nature of the adverse reactions should be taken into account.

Form release / dosage:

Film-coated tablets, 300 mg.

Packaging:

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

For 60 tablets in a jar (bottle) polymer for medicines or a jar (bottle) for medicines made of plastic.

Free space in the jar (bottle) is filled with cotton absorbent medical cotton.

Each jar (bottle), 6 contour mesh packages together with instructions for use are placed in a pack of cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003977

Date of registration:22.11.2016

Expiration Date:22.11.2021

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

TECHNOLOGY OF DRUGS, LTD. Russia

Information update date: & nbsp14.12.2016

Illustrated instructions

Instructions

Zidovudine-AZT (Zidovudine-AZT)