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

Excipients: maltitol - 640.0 mg; glycerol - 100.0 mg; sodium saccharinate - 2.0 mg; citric acid - 3.5 mg, sodium benzoate - 2.0 mg; strawberry flavoring - 0.5 mg; water - up to 1 ml.

Description:A clear, colorless or light yellow solution with a characteristic odor.

Pharmacotherapeutic group:Antiviral (HIV) agent

ATX: & nbsp

J.05.A.F.01 Zidovudine

Pharmacodynamics:

Mechanism of action

Zidovudine is an antiviral drug, an analog 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 thymidylate 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 cellular α-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 HIV reverse transcriptase. The viruses acquire phenotypic resistance to thymidine analogues as a result of combined mutations in codons 41 and 215 or accumulation, 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 kinds of mutations lead to the development of multiple drug resistance.

In one case, mutations occur in 62, 75, 77, 116, and 151 codons of HIV reverse transcriptase, and in the second case T69S mutations with the 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 these mutations significantly limit the therapeutic possibilities for HIV infection.

Decreased sensitivity to zidovudine in vitro HIV isolates were observed with long-term 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.

Research in vitro zidovudine in combination with lamivudine have shown that zidovudine-resistant isolates of the virus become susceptible to zidovudine while simultaneously acquiring resistance to lamivudine. Clinical studies have demonstrated the fact that the use of zidovudine in combination with lamivudine delayed the emergence of zidovudin-resistant strains of the virus in patients who had not previously received antiretroviral therapy (Apt). Zidovudine is widely used as a component of a combined Apt together with other antiretroviral drugs of the same class (NRTIs) or other classes (inhibitors HIV proteases (IP of HIV), non-nucleoside reverse transcriptase inhibitors (NNRTIs)).

Pharmacokinetics:

Suction

Zidovudine is well absorbed after oral administration, the bioavailability 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 intake of 5 mg / kg zidovudine every 4 hours were 7.1 and 0.4 μmol respectively (or 1.9 and 0.1 μg / ml).

Distribution

Binding to blood plasma proteins is relatively low, amounts to 34-38%, so it is unlikely that interactions with other drugs that affect binding to plasma proteins are unlikely.

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, pharmacokinetic parameters are similar to those in adults.

Zidovudine is well absorbed from the intestine, bioavailability is 60-74% with an average of 65%. After taking zidovudine in doses of 120 mg / m² and 180 mg / m² surface area of the body as a solution for oral administration, the maximum equilibrium concentration was 4.45 μM (1.19 μg / ml) and 7.7 μM (2.06 μg / ml), respectively. In children, the average ratio of zidovudine concentration in the cerebrospinal fluid and plasma varied from 0.52 to 0.85 after 0.5-4 hours after administration preparation inside.

Pharmacokinetic data suggest that zidovudine glucuronization in newborns and infants is reduced, leading to increased bioavailability. Reduced clearance and a longer half-life are recorded in newborns under 14 days, then the pharmacokinetic parameters become similar to those in adults.

Elderly patients

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

Patients with impaired renal function

In patients with progressive renal dysfunctionthe maximum concentration of zidovudine in the blood plasma is increased by 50% compared with that in patients with normal renal function. The area under the concentration-time curve of zidovudine (AUC) increases by 100%, the half-life does not change significantly. In case of renal dysfunction, substantial cumulation of the main metabolite of 5'-glucuronide of zidovudine is observed. However, signs of toxic effects are not 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 liver function is abnormal, zidovudine cumulation may be observed due to a reduction in glucuronization, which may require dose adjustment, but since only limited data are available, it is impossible to provide accurate recommendations.

Pregnancy

The pharmacokinetics of zidovudine has been studied in 8 women during the last 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 blood plasma of infants at birth were similar to those in mothers plasma, which is consistent with passive zidovudine through the placenta.

Indications:

- Treatment of HIV infection in combination therapy;

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

Contraindications:

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

- neutropenia (the number of neutrophils is less than 0.75 x 10⁹/ l);

- reduction in hemoglobin (less than 75 g / l or 4.65 mmol / l).

Carefully:

- Patients of advanced age;

- oppression of bone marrow hematopoiesis;

- Anemia (hemoglobin 75-90 g / l);

- liver failure;

- hepatomegaly, hepatitis, or any risk factors for liver disease;

- neutropenia / leukopenia (number of neutrophils 0.75-1.0 * 10⁹/ l or 750-1000 / μl);

- deficiency of cyanocobalamin or folic acid;

- obesity.

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

Prevention of HIV transmission from mother to fetus

The use of zidovudine after 14 weeks of gestation followed by its administration in neonates leads to 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 week 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, injected zidovudine in the form of an injection. In the study, zidovudine monotherapy for oral administration in pregnant women, from the 36th week of gestation to delivery, resulted in a significant reduction in the rate of HIV transmission from the mother to the fetus (19% of the infection in the placebo group compared with 9% in the zidovudine group). In this study, mothers were not breast-fed with their children.

The long-term effects of zidovudine in children who received it in the prenatal or neonatal periods are unknown. Based on data on carcinogenicity and mutagenicity in animals, the possibility of carcinogenic effects in humans can not be completely ruled out. The significance of these data for infected and uninfected infants exposed to zidovudine is unknown. However, pregnant women considering the use of zidovudine during pregnancy should consider these findings.

Breastfeeding period

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

Dosing and Administration:

Treatment with drug Zidovudine should be conducted by a physician with experience in the treatment of HIV-infected patients.

A drug Zidovudine is intended for oral administration.

Adults and adolescents with a body weight of at least 30 kg

The recommended dose is 500 or 600 mg per day, divided into two doses, as part of a combination therapy.

Special groups of patients.

Children with a body weight of at least 9 kg, but less than 30 kg

The recommended dose is 18 mg / kg per day, divided into two doses, as part of a combination therapy. The maximum daily dose should not exceed 600 mg (2 times per day).

Children with a body weight of at least 4 kg, but less than 9 kg

The recommended dose is 24 mg / kg per day, divided into two doses, as part of a combination therapy.

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 kidney function and possible changes in peripheral blood levels,In such patients, special care should be taken when prescribing the drug and performing appropriate monitoring before and during treatment.

Patients with impaired renal function

With a severe degree of renal dysfunction, the recommended dose of the drug is 300-400 mg per day. Depending on the response from the peripheral blood and the clinical effect, further dose adjustment may be required.

Hemodialysis and peritoneal dialysis do not have a significant effect on the excretion of zidovudine, but the excretion of 5'-glucuronide of zidovudine is accelerated.

For patients with terminal stage of renal failure who are on hemodialysis or peritoneal dialysis, the recommended dose of the drug is 100 mg every 6-8 hours.

Patients with impaired hepatic function

The data obtained in patients with cirrhosis of the liver indicate that in patients with impaired hepatic function zidovudine can be cumulated due to a reduction in glucuronization, which may require dose adjustment. If monitoring the concentration of zidovudine 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 of the drug.

Correction of dose for undesirable reactions from the hematopoietic system

Adequate correction of the dosing regimen - dose reduction or drug cancellation Zidovudine - may be required in patients with adverse reactions from the hemopoietic system (in the case of a decrease in the hemoglobin concentration to 75-90 g / l (4.65-5.59 mmol / L) or neutrophil count to 0.75-1.0 x 10⁹/ l).

Prevention of HIV transmission from mother to fetus

The effectiveness of the following 2 prophylactic regimens for pregnant women was demonstrated

- Pregnant women, starting from the gestational age of 14 weeks, are recommended to prescribe the drug Zidovudine inside before the onset of labor at a dose of 500 mg / day (100 mg 5 times a day). During childbirth zidovudine in a dosage form for intravenous administration is administered intravenously at a dose of 2 mg / kg for 1 hour followed by a continuous intravenous infusion at a dose of 1 mg / kg / h until the umbilical cord is compressed.

- Pregnant women, starting at 36 weeks of gestation, are recommended to prescribe the drug Zidovudine in a dose of 600 mg / day (300 mg twice a day) inside before the onset of labor. Then every 3 hours for 300 mg of the drug Zidovudine Inward from the onset of labor until delivery.

Next, the neonate shows the purpose of the drug Zidovudine solution for oral administration at a dose of 2 mg / kg body weight every 6 hours, starting no later than 12 hours after birth and continuing until the age of 6 weeks. Newborns who can not take the drug solution Zidovudine inside, you must enter zidovudine in a dosage form for intravenous administration at a dose of 1.5 mg / kg body weight for 30 minutes every 6 hours.

Instructions for using a dispensing syringe

The attached dispensing syringe and adapter are designed to accurately dispense the drug Zidovudine, solution for oral administration.

1. Remove the lid from the vial.

2. Insert the dispensing syringe into the neck of the vial.

3. Turn the vial over.

4. Pulling the plunger of the dispensing syringe, measure the exact amount of the first dose from the prescribed full dose of the drug.

5. Turn the bottle upside down, remove the syringe.

6. Carefully place the syringe in the mouth, on the cheek, swallow the drug, slowly pressing the plunger of the syringe.Do not press the plunger too much, the solution can get to the back of the pharynx and cause choking.

7. Repeat the procedures 3-7 until the complete dose is obtained.

8. Do not leave a syringe in the vial, after use, rinse the dosing syringe thoroughly with clean water.

9. Close the vial tightly.

Side effects:

The profile of adverse events with zidovudine is similar in adults and children. The adverse events presented below are listed according to anatomophysiological classification and frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥1/10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10,000 and <1/1000), rarely (<1/10000, including individual cases). Frequency categories were formed on the basis of clinical studies of zidovudine and post-registration surveillance.

From the side of hematopoiesis and lymphatic system: often - anemia (which may require blood transfusion), neutropenia and leukopenia. Anemia often occurs when taking high doses of zidovudine (1200-1500 mg / day) and in patients with advanced stages of HIV infection, particularly when the concentration of CH4-lymphocytes is less than 100 cells / μl. As a result, a dose reduction or discontinuation of therapy may be required.The incidence of neutropenia was higher in patients who had low neutrophil counts, hemoglobin and serum vitamin B12 concentrations before treatment; infrequently - thrombocytopenia and pancytopenia (with bone marrow hypoplasia); rarely - true erythrocytic aplasia; rarely aplastic anemia.

From the side of metabolism and nutrition: often - hyperlactatemia; rarely - lactic acidosis, anorexia.

From the central and peripheral nervous system: very often - headache; often - dizziness; rarely - Insomnia, paresthesia, drowsiness, decreased speed of thinking, convulsions.

From the psychic sphere: rarely - anxiety, depression.

From the cardiovascular system: rarely - cardiomyopathy.

From the respiratory system, the thoracic and mediastinal organs: infrequently - dyspnea; rarely - cough.

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

From the side of the liver, bile duct and pancreas: often - increased bilirubin concentration and liver enzyme activity; rarely - liver damage, such as severe hepatomegaly with steatosis; pancreatitis.

From the skin and subcutaneous fat: rarely - a rash, itchy skin; rarely - pigmentation of nails and skin, urticaria, increased sweating.

From the musculoskeletal system: often - myalgia; infrequently - Myopathy.

From the urinary system: rarely - frequent urination.

From the endocrine system: rarely - gynecomastia.

General and local reactions: often - malaise; infrequently - fever, generalized pain syndrome, asthenia; rarely - chills, chest pain, flu-like syndrome.

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 completion of zidovudine.

Overdose:

Symptoms

There may be a feeling of fatigue, headache, vomiting; very rarely: changes from the blood indicators.There is one report of an overdose of an unknown amount of zidovudine when the zidovudine concentration in the blood exceeded the usual therapeutic concentration 16-fold, however, there were no clinical, biochemical or hematologic symptoms.

Treatment

Symptomatic therapy and maintenance therapy. Hemodialysis and peritoneal dialysis do not have a high efficiency for the removal of zidovudine from the body, but increase the excretion of its metabolite - 5'-glucuronide of zidovudine.

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 potentially inhibit zidovudine metabolism.

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

Atovahon: zidovudine does not affect the pharmacokinetic parameters of the atovahona. Atovahon slows the transformation of zidovudine into a glucuronide metabolite (AUC zidovudine 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 will change at doses of 500 or 600 mg / day when combined with atavahone for three weeks to treat PCP. If a longer combined use of these drugs is necessary, careful monitoring of the clinical condition of the patient is recommended.

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

Lamivudine: a moderate increase in the maximum concentration of zidovudine (FROMmOh) by 28% with simultaneous application with lamivudine, but the total exposure (AUC) this does not change. Zidovudine does not affect the pharmacokinetics of lamivudine.

Phenytoin: while the simultaneous use of zidovudine with phenytoin reduces the concentration of the latter in blood plasma,it is necessary to monitor the concentration of phenytoin in the blood plasma when using this combination.

Probenecid: reduces glucuronization and increases the average half-life and AUC zidovudine. Kidney excretion of glucuronide and zidovudine itself decreases in the presence of probenecid.

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

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

Stavudine: zidovudine can suppress intracellular phosphorylation of stavudine. Thus, it is not recommended to apply stavudine concurrent with zidovudine.

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

Valproic acid, fluconazole, methadone reduce the clearance of zidovudine, which is why its systemic exposure is increased.

Others: acetylsalicylic acid, codeine, morphine, methadone, indomethacin, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, dapsone, inosine pranobex 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 B, flucytosine, ganciclovir, interferon alpha, vincristine, vinblastine, doxorubicin) may increase the risk of unwanted reactions to zidovudine. It is necessary to monitor the function of the kidneys and the blood formula, if necessary, reduce the dose of drugs.

Since in some patients, even despite the treatment with zidovudine, opportunistic infections can develop, it is necessary to consider the possibility of prescribing prophylactic antimicrobial therapy. Such prophylaxis includes co-trimoxazole, pentamidine in aerosol, pyrimethamine and acyclovir. Limited data from clinical trials did not reveal a significant increase in the risk of developing adverse reactions in the joint use of zidovudine with these drugs.

Special instructions:

Treatment with drug Zidovudine should be conducted by a physician with experience in the treatment of HIV-infected patients.

Patients should be warned that the prevention of the risk of transmission of HIV to others through sexual contact or exposure to infected blood with zidovudine has not been proven, so patients should continue to take appropriate precautions.

A drug Zidovudine does not cure of HIV infection, and patients have a risk of developing opportunistic infections and malignant tumors, which is due to immunosuppression. Although the drug 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 infection.

According to international recommendations, if there is a probable contact with HIV-infected material (blood, other fluids), it is necessary to prescribe combination therapy with zidovudine and lamivudine within T-2 hours from the time of infection. In the case of a high risk of infection, a drug from the HIV protease inhibitor group (HIV-1I) should be included in the treatment regimen.

Preventive treatment is recommended for 4 weeks. 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 the start of the drug Zidovudine, but it can sometimes develop earlier), neutropenia (usually occurs 4 weeks after the start of treatment with the drug Zidovudine, but sometimes occurs earlier), leukopenia (usually of a secondary nature due to neutropenia) can occur in patients with a developed clinical picture of HIV infection receiving Zidovudine, especially in high doses (1200-1500 mg / day), and having reduced bone marrow hematopoiesis before treatment, especially at a late stage of HIV infection.

At the time of taking the drug Zidovudine 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 undeveloped reserves of bone marrow hematopoiesis), unwanted reactions from the hematopoiesis system are rare, so general blood tests can be performed less often, depending on the patient's general condition (for example, once every 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, the daily dose of the drug Zidovudine should be reduced until recovery of blood counts or drug 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 the drug Zidovudine in a reduced dose can be reassigned. Despite a reduction in the dose of the drug Zidovudine with severe anemia, blood transfusions may be required.

Lactic Acidosis and severe hepatomegaly with steatosis

These complications can have a fatal outcome both with monotherapy with the drug Zidovudine, and when using the drug Zidovudine in the 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 neurologic symptoms (including motor weakness). The use of nucleoside analogues should be discontinued when symptomatic hyperlactatemia occurs andmetabolic acidosis / lactic acidosis, progressive hepatomegaly, or with a rapid increase in aminotransferase activity.

Care should be taken when prescribing the drug to patients (especially women with excessive body weight), 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. A drug Zidovudine should be eliminated 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 the activity of transaminases.

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 back of the neck ("buffalo buffalo"), a reduction in the subcutaneous fat layer on the face and extremities,an increase in mammary glands, an increase in serum lipids and glucose in the blood was noted both in the complex and individually in some patients who received combination antiretroviral therapy.

To date, all preparations from the class of HIV protease inhibitors (IP) and nucleoside reverse transcriptase inhibitors (NRTIs) have been associated with one or more specific adverse events 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, the elderly age and the duration of antiretroviral therapy play an important, possibly synergistic role.

The long-term consequences of this phenomenon are currently unknown. Clinical The examination should include a physical examination to assess the availability 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 treat according to clinical indications.

Immunodeficiency Syndrome

In HIV-infected patients with severe immune deficiency at the time of initiation of antiretroviral therapy may increase the inflammatory process in the background asymptomatic or residual opportunistic infections that can cause serious deterioration or worsening of symptoms. Typically, such reactions have been described in the first weeks or months of onset of antiretroviral therapy. The most significant examples are cytomegalovirus retinitis, generalized and / or focal mycobacterial infection, and pneumonia caused by Pneumocystis jiroveci (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.

Co-infection of HIV and 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. It is necessary to change the regimen of antiretroviral therapy, using 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 combined antiretroviral therapy for HIV and interferon alfa in combination with or without ribavirin, hepatic insufficiency (sometimes fatal) was observed.

It is necessary to ensure that patients receiving interferon alfa with or without ribavirin and the drug 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 the drug Zidovudine. Also, consideration should be given to reducing the dose or stopping the use of interferon alfa, ribavirin, or both in the case of increased clinical toxicity, including the development of hepatic impairment (for example, more than 6 on the Child-Pugh scale) (cf.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.

Joint use with zidovudine-containing drugs

A drug Zidovudine Do not use with drugs containing zidovudine, as one of the components.

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

Effect of the drug Zidovudine the ability to drive a car or machinery has not been studied. However, an adverse effect on these abilities is unlikely, based on the pharmacokinetics of the drug. Nevertheless, when deciding whether to control a car or moving machinery, one should keep in mind the patient's condition and the possibility of developing adverse reactions (dizziness, drowsiness, blocking, convulsions).

Form release / dosage:

Solution for oral administration 10 mg / ml.

Packaging:

For 200 ml of solution in a bottle of orange glass glass or a polymer bottle for medicines, equipped with a plastic dissector / adapter,Sealed with a polymeric screw cap with a first opening control or a polymeric cover with a "push-turn" system.

One bottle together with the instructions for use, as well as a syringe-dispenser is placed in a cardboard package (bundle).

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 the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004317

Date of registration:01.06.2017

Expiration Date:01.06.2022

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp22.06.2017

Illustrated instructions

Instructions

Zidovudine (Zidovudine)