Azimitem

General characteristics. Structure:

Active ingredient: 100 mg and 300 mg of a zidovudine.

Excipients: sodium carboxymethylstarch, starch prezhelatinizirovanny, silicon dioxide colloid, magnesium stearate, cellulose microcrystallic.

Structure of a film cover: ready water-soluble film cover (gipromelloza, кополивидон, polyethyleneglycol 6000, glyceryl каприлокапрат, polydextrosum, titanium dioxide).

The antiviral drug which is actively applied to treatment of HIV infections.

Pharmacological properties:

Indications to use:

— treatment of the HIV infection caused by VICh-1 (as a part of the combined aitiretrovirusny therapy);

— prevention of perinatal transfer of HIV from the infected mother to the child as the zidovudine reduces risk of pre-natal infection of a fruit.

Route of administration and doses:

Inside, irrespective of meal. To adult patients drug is appointed in a dose of 600 mg a day in stages. To children with body weight more than 30 kg - on 300 mg 2 times a day or 200 mg 3 times a day. When calculating appoint 160 or 240 mg/sq.m to the surface area of a body 3 or 2 times a day respectively (a daily dose of 480 mg/sq.m).

At decrease in a hemoglobin content to 75-90 g/l and/or reduction of quantity of neutrophils to 0,75-1.0×109/л the dose decline of drug or cancellation of therapy zidovudipy before hemopoiesis recovery can be required. When developing anemia drug withdrawal not always reduces the need for hemotransfusion. For more bystry recovery of function of marrow the alpha in the recommended doses can be appointed эпоэтин.

Patients of advanced age. The zidovudine pharmacokinetics at patients is aged more senior than 65 years was not studied. However, considering age depression of function of kidneys and possible changes of indicators of peripheral blood, at such patients it is necessary to observe extra care at use of a zidovudine and to carry out the corresponding observation before and during treatment by drug.

Renal failure. At a heavy renal failure the recommended daily dose makes 300-400 mg. Depending on reaction from peripheral blood and clinical effect further dose adjustment can be required. The hemodialysis and peritoneal dialysis do not exert significant impact on elimination of a zidovudine, but accelerate removal of its metabolite - a glucuronide. For the patients with an end-stage of a renal failure who are on a hemodialysis or peritoneal dialysis, the recommended dose of a zidovudine makes 100 mg each 6-8 hours.

Liver failure. At patients with a liver failure cumulation of a zidovudine owing to decrease in a glyukuronization can be observed that can demand drug dose adjustment. If monitoring of concentration of a zidovudine in plasma is impossible, then the doctor should pay special attention to clinical signs of intolerance of drug and, if necessary, to carry out dose adjustment and/or to increase an interval between introduction of doses.

Prevention of transfer of HIV infection from mother to a fruit. 2 schemes of prevention are effective:

1. Pregnant women, since 14 weeks of pregnancy, are recommended to appoint a zidovudine inside prior to childbirth in a dose of 500 mg a day (on 100 mg of 5 times a day).

2. Pregnant women, since 36 weeks of pregnancy, are recommended to appoint a zidovudine inside in a dose of 600 mg a day (on 300 mg of 2 times a day) prior to childbirth, and then in a dose of 300 mg each 3 hours before delivery.

Features of use:

Use at pregnancy and feeding by a breast. The zidovudine gets through a placenta. Drug can be used during pregnancy before 14 weeks only if the potential advantage for mother exceeds possible risk for a fruit. Use of a zidovudine after 14 weeks of pregnancy with the subsequent use for newborns leads it to decrease in transmission frequency of HIV infection from mother to a fruit. The remote effects of use of a zidovudine for the children who received it in the pre-natal or neonatal periods are not known. It is impossible to exclude a possibility of cancerogenic influence completely.

In case of use of a zidovudine in the period of a lactation it is necessary to stop breastfeeding.

Use at abnormal liver functions. At patients with a liver failure cumulation of a zidovudine owing to decrease in a glyukuronization can be observed that can demand drug dose adjustment. If monitoring of concentration of a zidovudine in plasma is impossible, then the doctor should pay special attention to clinical signs of intolerance of drug and, if necessary, to carry out dose adjustment and/or to increase an interval between introduction of doses.

Use at renal failures. At a heavy renal failure the recommended daily dose makes 300-400 mg. Depending on reaction from peripheral blood and clinical effect further dose adjustment can be required. The hemodialysis and peritoneal dialysis do not exert significant impact on elimination of a zidovudine, but accelerate removal of its metabolite - a glucuronide. For the patients with an end-stage of a renal failure who are on a hemodialysis or peritoneal dialysis, the recommended dose of a zidovudine makes 100 mg each 6-8 hours.

Use for children. Drug is contraindicated to children with body weight less than 30 kg.

Use for elderly patients. The zidovudine pharmacokinetics at patients is aged more senior than 65 years was not studied. However, considering age depression of function of kidneys and possible changes of indicators of peripheral blood, at such patients it is necessary to observe extra care at use of a zidovudine and to carry out the corresponding observation before and during treatment by drug.

Patients have to be informed on danger of simultaneous use of a zidovudine with drugs of non-prescription dispensing and that use of a zidovudine does not prevent risk of transfer of HIV to other people at sexual contacts or hemotransfusion. Therefore patients have to observe the appropriate measures of precaution.

The emergency prevention at probable infection of HIV. According to the international recommendations, at probable infection through blood of the HIV-positive person (for example, through a syringe needle), it is necessary urgently (within 1-2 hours from the infection moment) to appoint a combination therapy a zidovudine and lamivudiny. In case of high risk of infection the scheme of aptiretrovirusny therapy has to include drug from group of inhibitors of protease. Preventive treatment is recommended to be carried out within 4 weeks. Despite treatment quick start anti-retrovirus drugs, it is impossible to exclude a possibility of seroconversion.

Symptoms which take for side reactions on a zidovudine can be manifestation of a basic disease or reaction to reception of other drugs used for treatment of HIV infection. It is often very difficult to establish interrelation between the developed symptoms and action of a zidovudine, especially at the developed clinical picture of HIV infection. In such cases the dose decline of drug or its cancellation is possible.

The zidovudine does not cure of HIV infection, and at patients the risk of development of the developed disease picture with suppression of immunity and developing of opportunistic infections and malignant new growths remains. At HIV infection the zidovudine reduces risk of development of opportunistic infections, but does not reduce risk of development of lymphoma.

Undesirable reactions from bodies of a hemopoiesis. Anemia (it is usually observed in 6 weeks from the beginning of therapy by a zidovudine, but sometimes can develop earlier), a neutropenia (usually develops in 4 weeks from the beginning of therapy by a zidovudine. but sometimes arises earlier), a leukopenia it is mighty - to occur at the patients with the developed clinical picture of HIV infection receiving a zidovudine. especially in high doses (1200-1500 mg/days), at a reduced reserve of marrow prior to therapy. During reception of a zidovudine at patients with the developed clinical picture of HIV infection it is necessary to control blood tests at least once in 2 weeks within the first 3 months of therapy, and then monthly. In an early stage of HIV infection (when a marrowy hemopoiesis within norm) side reactions from blood develop seldom therefore blood tests are made less often - depending on the general condition of the patient once in 1-3 months.

At decrease in a hemoglobin content to 75-90 g/l and/or reduction of quantity of iyeytrofil to 0.75-1.0×109/л the daily dose of drug has to be reduced, or the zidovudine is cancelled for 2-4 weeks before recovery of indicators of blood. Usually the picture of blood is normalized in 2 weeks then the zidovudine in a reduced dose can be appointed repeatedly. When developing anemia drug withdrawal not always reduces the need for hemotransfusion.

Radiation therapy strengthens myelosuppressive action of a zidovudine.

Lactic acidosis and the expressed hepatomegalia with a steatosis. These complications can have a fatal outcome both at monotherapy by a zidovudine, and at use of a zidovudine as a part of the combined anti-retrovirus therapy. The risk of development of these complications is higher at female patients. The general weakness, sudden inexplicable decrease in body weight, anorexia, symptoms from the alimentary system (nausea, vomiting, pains in abdominal area), symptoms from respiratory system (hurried breathing or an asthma) can be signs of development of these complications. In case of clinical or laboratory signs of lactic acidosis or toxic damage of a liver reception of a zidovudine should be stopped.

Redistribution of a hypodermic fatty tissue. At some patients the combined anti-retrovirus therapy can be followed by redistribution/accumulation of a hypodermic fatty tissue, including reduction of amount of fatty tissue in a face and extremities, increase in visceral fat, increase in mammary glands and an adiposity on the back surface of a neck and back ("buffalo hump"), and also increase in concentration of lipids in serum and concentration of glucose in blood.

Though one or several of the listed above undesirable reactions connected with the general syndrome which is often called a lipodystrophy drugs from classes of inhibitors of protease and nukleozidny inhibitors of the return transcriptase can cause weight, the saved-up data confirm existence of distinctions between certain representatives of the specified classes of drugs in ability to cause these undesirable reactions.

In addition, a syndrome of a lipodystrophy has a multifactorial etiology; for example, the HIV infection stage, advanced age and duration of anti-retrovirus therapy play important, perhaps exponential, a role in development of this complication. Long-term effects of the specified undesirable reactions are not established now. Clinical inspection of patients has to include survey for identification of signs of redistribution of fatty tissue. It is also necessary to control concentration of lipids and glucose in blood serum. Disturbances of lipidic exchange need to be adjusted according to clinical indications.

Myopathy. It is necessary to consider that development of symptoms of a myopathy (a mialgiya, weakness, increase in activity of KFK) at HIV-positive patients can be connected with a basic disease. At use of a zidovudine in doses of 500 mg or 600 mg a day the myopathy connected with administration of drug is observed seldom. In case of development of the myopathy caused by reception of a zidovudine, drug should be cancelled.

Immunity recovery syndrome. At HIV-positive patients with a heavy immunodeficiency during the beginning of aitiretrovirusny therapy the aggravation of inflammatory process against the background of asymptomatic or a slow opportunistic infection is possible that can become the reason of a serious aggravation of symptoms or aggravation of symptomatology. Usually similar reactions were observed in the first weeks or months after the beginning of aitiretrovirusny therapy. The most significant examples - a Cytomegaloviral retinitis, a generalized and/or focal mikobakterialny infection and pneumocystic pneumonia. Any symptoms of an inflammation need to be revealed immediately and to timely begin treatment. Autoimmune diseases (such as Greyvs's disease, nolimiozit also a syndrome to Giyena-Barra) were observed against the background of immunity recovery, however time of primary manifestations varied, and the disease could arise in many months after the beginning of therapy and have an atypical current.

The patients infected at the same time with HIV and the hepatitis C virus (HCV). The researches in vitro showed what рибавирин can reduce phosphorylation of analogs of pirimidinovy nucleosides, including a zidovudine. Though obvious proofs of pharmacokinetic and pharmakodinamichesky interaction of a ribavirin and zidovudine at patients with the combined infection (VICh-1/VGS) are not revealed.

It was reported about an exacerbation of the ribavirin-induced anemia at the HIV-positive patients receiving at the same time therapy by a zidovudine. The mechanism of development of this effect is unknown now. Therefore simultaneous use of a ribavirin and zidovudine is not recommended. It is necessary to replace the scheme of anti-retrovirus therapy on alternative, not containing a zidovudine, especially in the presence in the anamnesis from the anemia connected with reception of a zidovudine.

It was reported about cases of a liver failure (sometimes with a lethal outcome) at the patients infected with VICh-1 with the accompanying hepatitis C, receiving the combined anti-retrovirus therapy for VICh-1 and interferon an alpha with ribaviriny or without ribavirin. At simultaneous use of a zidovudine and interferon an alpha with ribaviriny or without ribavirin it is necessary to make careful observation of patients regarding identification of signs of toxicity, especially liver failure, a neutropenia and anemia. At increase of clinical manifestations of toxicity, especially liver failure (> 6 points on a scale of Chayld-Pyyu) it is necessary to lower doses or to cancel interferon an alpha, рибавирин or both drugs. In case of development of a miyelosupressiya it is necessary to consider the possibility of interruption or cancellation of therapy by a zidovudine.

Influence on ability to manage vehicles and mechanisms. During treatment it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. At emergence of such undesirable phenomena as dizziness, drowsiness, block, spasms, it is necessary to refrain from performance of the specified types of activity.

Side effects:

The undesirable reactions arising at treatment by a zidovudine are identical at children and adults.

For assessment of frequency of emergence of undesirable reactions the following gradation are used: very often (> 1/10), it is frequent (> 1/100, <1/10), infrequently (> 1/1000, <1/100), is rare (> 1/10000, <1/1000), is very rare (<1/10000).

From bodies of a hemopoiesis: often - anemia (which can demand hemotransfusions), a neutropenia, a leukopenia, infrequently - thrombocytopenia, a pancytopenia with a marrow hypoplasia, it is rare - an erythrocyte aplasia, is very rare - aplastic anemia.

From a GIT: very often - nausea, it is frequent - vomiting, pains in upper parts of a stomach, diarrhea, infrequently - a meteorism, is rare - dyspepsia, a food faddism, pigmentation of a mucous membrane of an oral cavity, pancreatitis, anorexia.

From gepatobiliarny system: often - a hyperbilirubinemia, increase in activity of liver enzymes, it is rare - the expressed hepatomegalia with a steatosis.

From a nervous system: very often - a headache, it is frequent - dizziness, is rare - paresthesias, sleeplessness, drowsiness, decrease in intellectual working capacity, a spasm, alarm, a depression.

From respiratory system: infrequently - an asthma, it is rare - cough.

From cardiovascular system: cardiomyopathy.

From outside мочевыделителыюй systems: seldom - the speeded-up urination.

From endocrine system and a metabolism: often - a giperlaktatemiya, it is rare - a lactacidemia, a gynecomastia.

From a musculoskeletal system: often — a mialgiya, infrequently - a myopathy.

From integuments: infrequently - skin rash, a skin itch, it is rare - pigmentation of nails and skin, the increased sweating, a small tortoiseshell.

Others: often - the indisposition, infrequently - fever, an adynamy, a generalized pain syndrome, is rare - a grippopodobiy syndrome. Fever, thorax pains, redistribution/accumulation of a hypodermic fatty tissue.

The side reactions arising at use of a zidovudine of day of prevention of transfer of HIV infection from mother to a fruit.

Pregnant women well transfer a zidovudine in the recommended doses. At children decrease in a hemoglobin content which, however, does not demand carrying out hemotransfusions is observed. Anemia disappears in 6 weeks after completion of therapy by a zidovudine.

Interaction with other medicines:

The zidovudine is applied as a part of the combined anti-retrovirus therapy together with other nukleozidny inhibitors of the return transcriptase and drugs from other groups (inhibitors of proteases, nenukleozidny inhibitors of the return transcriptase). The list of the interactions which are listed below should not be considered exhaustive, however they are characteristic of drugs which demand careful use together with a zidovudine.

Lamivudin: moderate increase in the maximum concentration in blood (28%) for a zidovudine at appointment is observed together with lamivudiny, however, the general exposure (AUC) at the same time is not broken. The zidovudine does not exert impact on pharmacokinetics of a lamivudin.

Phenytoinum: the zidovudine reduces concentration of Phenytoinum in blood that demands observation of concentration of Phenytoinum in blood at its simultaneous appointment with a zidovudine.

Probenitsid: reduces a glyukuronization and raises an average elimination half-life and AUC of a zidovudine. Renal excretion of a glucuronide and the zidovudine decreases in the presence of a probenitsid.

Atovakhon: the zidovudine does not influence pharmacokinetic parameters of an atovakhon. Atovakhon slows down a zidovudine glyukuronization (AUC of a zidovudine in an equilibrium state increases by 33%, the maximum concentration of a glucuronide decrease by 19%). Change of a profile of safety of the zidovudine appointed in doses of 500 or 600 mg a day at simultaneous use with atovakhony within three weeks is improbable.

In need of more prolonged simultaneous use of these drugs careful observation of a clinical condition of the patient is recommended.

Klaritromitsin: reduces absorption of a zidovudine. The break between administrations of drugs has to make not less than 2 hours.

Valproic acid, флуконазол, methadone: reduce clearance of a zidovudine owing to what its system exposure increases.

Ribavirin: the nukleozidny analog рибавирин is an antagonist of a zidovudine. It is necessary to avoid simultaneous use of a zidovudine and a ribavirin.

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

Stavudin: the zidovudine can suppress intracellular phosphorylation of a stavudin. It is not necessary to apply ставудин along with a zidovudine.

Others: such medicines as paracetamol, acetylsalicylic acid, codeine, methadone, morphine, indometacin, ketoprofen, Naproxenum, oxazepam, lorazepam, Cimetidinum, Clofibratum, dapsone, изопринозин, can break metabolism of a zidovudine by competitive inhibition of a glyukuronization or direct suppression of microsomal metabolism in a liver. To a possibility of use of these drugs in a combination with a zidovudine, especially for long therapy, it is necessary to approach with care. A zidovudine combination, especially at emergency treatment, with potentially nephrotoxic and myelotoxic drugs (for example, pentamidine, dapsone, Pyrimethaminum, co-trimoxazole, Amphotericinum, flutsitoziny, gantsikloviry, interferon, Vincristinum. vinblastine, doxorubicine) increases risk of development of side reactions on a zidovudine. Observation of function of kidneys and indicators of blood and a dose decline of drugs is necessary if it is required.

Contraindications:

— hypersensitivity to a zidovudine or any other component of drug;

— a neutropenia/leukopenia (the number of neutrophils are lower 0.75×109/л); anemia (hemoglobin is lower than 75 g/l);

— a concomitant use with stavudiny, the doxorubicine, other medicines reducing antiviral activity of a zidovudine;

— children's age (at body weight less than 30 kg).

With care. Oppression of a marrowy hemopoiesis, deficit of cyanocobalamine or folic acid, liver failure, advanced age, obesity, hepatomegalia. hepatitis or any risk factors of diseases of a liver, neutropenia/leukopenia (number of neutrophils 0,75-1,0 ×109/л): anemia (hemoglobin of 75-90 g/l).

Overdose:

Symptoms: fatigue, headache, vomiting, disturbance of hematologic indicators.

Treatment: symptomatic. The hemodialysis and peritoneal dialysis are a little effective for removal of a zidovudine from an organism, but accelerate removal of its metabolite - a glucuronide.

Storage conditions:

At a temperature not above 25 °C, in an original packing. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, on 100 mg and 300 mg. On 20, 50, 60, 100, 200 or 500 tablets (for hospitals) place in a polymeric can.