Зерит®

General characteristics. Structure:

Active ingredient: 1 mg of a stavudin in 1 ml of the prepared solution.

Excipients: methylparahydroxybenzoate, пропилпарагидроксибензоат, sodium carboxymethylcellulose, sucrose, simetikonovy emulsion, cherry fragrance.

Pharmacological properties:

Pharmacodynamics. Stavudin (2-3-didegidro-3-dezoksitimidin) – a synthetic analog of a nucleoside of thymidine, suppresses replication of HIV in the cultivated cells of the person and in the cellular in vitro lines.

After hit in a cell ставудин under the influence of cellular enzymes triphosphate which suppresses activity of the HIV return transcriptase due to the competition to natural substrate of dioxythymidine triphosphate and breaks replication of HIV turns into an active metabolite of a stavudin. Stavudina triphosphate also strengthens termination of chains of virus DNA thanks to absence in a molecule of the Z-hydroxylic groups necessary for DNA creation. Besides, the stavudina triphosphate suppresses cellular DNA polymerases β and γ and considerably reduces synthesis of mitochondrial DNA.

Studying of overwhelming activity of a stavudin in a combination with a zidovudine of in vitro showed that both drugs are phosphorylated by a cellular thymidinekinase. And transformation of a zidovudine into an active form happens quicker, slowing down activity of a stavudin. Considering this, combined treatment by these drugs it is not recommended. According to the researches in vitro, phosphorylation of a stavudin is also slowed down in the presence of drugs of doxorubicine and a ribavarin.

Pharmacokinetics. Adults. Stavudin is quickly soaked up at intake. Absolute bioavailability makes about 86,4%. After the dose which is once accepted внтурь the maximum concentration of drug in a blood plasma is observed less, than in 1 hour. Values With max increase in proportion to increase in doses of drug. Cumulation of a stavudin at its use was not observed each 6, 8 or 12 hours.

The pharmacokinetics of a stavudin at sick HIV without the clinical manifestations accepting drug after or during meal with the high content of fat or on an empty stomach considerably did not change.

The seeming distribution volume after a single dose of drug averages 66 liters and does not depend on a dose. Drug is equally distributed between red and white blood cells. Linkng with blood proteins is insignificant. After a single peroral dose of 40 mg concentration in cerebrospinal fluid (SMZh) of healthy volunteers made 63 ng/ml (an average 44-71¡ú/ml) for 4-5 hours. SMZh attitude towards concentration in a blood plasma made about 40% (an average of 31-45%).
Metabolism of a stavudin in a human body remains not studied.

After intake the elimination half-life of drug makes 1,44 hours and does not depend on a dose. The renal clearance makes 40% of the general clearance and exceeds clearance of endogenous creatinine almost twice that indicates active canalicular secretion at removal of a stavudin through kidneys along with glomerular filtering.

Children. Absolute bioavailability of drug at children averages 76,9%.

The pharmacokinetics after a single dose of drug is similar to pharmacokinetics of adults and does not depend on a dose. Concentration of drug in SMZh after single and multiple dose inside make from 16 to 125% in relation to concentration in a blood plasma. Cumulation of a stavudin at reception of a dose of 0,125 - 2 mg/kg is not observed each 12 hours. The elimination half-life averages 1 hour. About 34,5% of drug are removed through kidneys in not changed look.

Elderly patients. The pharmacokinetics at patients is more senior than 65 years was not studied. Renal failure. At an impaired renal function the clearance of a stavudin decreases.

Abnormal liver function. The pharmacokinetics of drug has similarity at patients to the broken and normal function of a liver. With the broken function of a liver in a stable condition of correction of an initial dose of drug it is not required to patients.

Indications to use:

Treatment of HIV of infectious diseases (in a combination with other nukleozidny and nenukleozidny inhibitors of the return transcriptase and inhibitors of HIV protease).

Route of administration and doses:

Inside. Time of administration of drug does not depend on meal time. The dose of drug depends on body weight.

Adults and children are more senior than 12 years:

- at the body weight of ≥60 kg a dose: 40 mg each 12 h;

- at body weight <60 kg a dose: 30 mg each 12 h.

Children are more senior than 3 months.

- at body weight <30 kg a dose: 1 mg/kg each 12 h;

- at the body weight of ≥30 kg <60 kg a dose: 30 mg each 12 h;

- at the body weight of ≥60 kg a dose: 40 mg each 12 h.

If the proglatyvaniye of capsules is complicated, it is necessary to open accurately the capsule and to accept contents with a small amount of food.

The dose decline depending on clearance of creatinine is recommended to adults with an impaired renal function:

To children with an impaired renal function. Exact recommendations about correction of a dose of drug at children are absent. The dose decline and/or increase in an interval between administrations of drug is possible.

Preparation of solution for intake. To stir up contents in a bottle. To add 202 ml of water to a bottle and to stir up before full dissolution. The prepared solution can opalestsirovat slightly. The dose is measured the enclosed measured kopachok. Before the use to shake up.

It is necessary to store the prepared solution densely closed in the refrigerator at (2-8 °C) no more than 30 days. After a period of validity unused solution of drug is thrown out.

Features of use:

Pregnancy and period of a lactation. It is necessary to apply Zerit during pregnancy only in the presence of strict indications and only when the potential advantage of treatment outweighs possible risk. Researches on animals showed that ставудин and/or its metabolites pass through a placenta. It is unknown whether passes drug into breast milk. During treatment by drug it is not necessary to nurse.

Drug should be used with care at patients with the increased risk of development of peripheral neuropathy, at the progressing HIV infection, with peripheral neuropathy in the anamnesis, and also at use in a combination with didanoziny. The feeling of numbness, a pricking or extremity pain can indicate development of peripheral neuropathy which can disappear right after the termination of administration of drug. At emergence of the specified symptoms it is necessary to stop temporarily treatment by drug. It is possible to resume treatment by drug only after total disappearance of symptoms. Reduction of a dose to the half recommended can be required.

Drug should be used with care at patients with the increased risk of development of pancreatitis, at the progressing HIV infection, at co-administration with didanoziny. At emergence of symptoms of pancreatitis treatment by drug should be suspended, At repeated purpose of drug to exclude simultaneous use of a didanozin and hydroxurea.

Irrespective of the fact how drug of Zerit in the form of monotherapy or in a combination with other drugs is used, biochemical indicators of function of a liver can raise. For the purpose of early identification of development of pancreatitis the thicket needs to check function of a pancreas.

Side effects:

At use with other medicines with similar toxicity the risk of development of side effects of drug of Zerit increases in a combination.

Peripheral neuropathy is heavy and dozozavisimy side effect of use of drug. The risk of development of this effect increases at simultaneous use with didanoziny. Peripheral neuropathy usually is followed by bilateral symmetric feeling of numbness of extremities: a pricking and pains in ступнях legs less in hands. In clinical trials the frequency of manifestation of these reactions depended on a dose and/or on a disease stage. At early stages of a disease these phenomena less frequent.
Pancreatitis of varying severity, including a lethal outcome, can develop at the patient at different stages of treatment and does not depend on whether drug in the form of monotherapy or in a combination with other drugs, or from immunosuppression degree is used. At use of drug in a combination with didanoziny or other drugs possessing toxic action on a pancreas, the risk of development of pancreatitis increases.

Lactic acidosis / Severe form of a steatosis with a hepatomegalia, including cases of a lethal outcome, were noted at use of nukleozidny analogs at monotherapy or in a combination with other anti-virus drugs, including ставудин. The lethal outcome of the pregnant woman with the diagnosis lactic acidosis was registered at treatment by drugs of Zerit and диданозин in a combination with other anti-virus drugs. At use of drug of Zerit with didanoziny the risk of an abnormal liver function considerably increases in a combination.

Nausea, vomiting, pains in abdominal area, hurried breathing or an asthma, or muscular weakness can indicate development of lactic acidosis.

Other side effects: thrombocytopenia, hepatitis, abnormal liver functions, adynamy, headache, sleeplessness, dizziness; dryness in a mouth, a loss of appetite, diarrhea, pancreatitis; increase in activity of "hepatic" transaminases, hyperbilirubinemia, neutropenia, allergic reactions (skin rash, fever), arthralgia, mialgiya, fever.

Children. In clinical trials children and adult patients had similar side effects of drug. Development of peripheral neuropathy in children was observed less than at adults. However symptoms of peripheral neuropathy at children were more difficult to be revealed.

Interaction with other medicines:

Zerit does not rekomenudtsya to apply a zidovudine along with drug. Transformation of a stavudin into an active metabolite decreases in the presence of a zidovudine.

At the same time accepted диданозин, ламивудин or нелфинавир do not influence efficiency of drug of Zerit. The risk of development of side effects of drug of Zerit increases at simultaneous use with didanoziny.

Stavudin almost does not contact blood proteins that indicates small probability of medicinal interactions with participation of the mechanism of replacement from places of binding.

The accompanying administration of drugs, causing peripheral neurologic frustration is not recommended (chloramphenicol, Cisplatinum, dapsone, Ethambutolum, Etioniamidum, гидралазин, an isoniazid, lithium, metronidazole, nitrofurantoin, Phenytoinum, Vincristinum, залцитабин).

Contraindications:

Hypersensitivity to a stavudin and/or any of drug excipients, children's age up to 3 months.

With care. Alcoholism, a chronic renal failure (clearance of creatinine less 50ml/mines), a liver failure, peripheral neuropathy, use in a combination with didanoziny, pancreatitis.

Overdose:

Peripheral neuropathy and abnormal liver function.

Treatment: symptomatic. Stavudin leaves at a hemodialysis (speed of removal makes 120±18мл/мин). Peritonialny dialysis is not effective.

Storage conditions:

To store powder for preparation of solution for intake at a temperature of 15-30 °C. The prepared solution should be stored densely closed in the refrigerator at a temperature of 2-8 °C no more than 30 days. After a period of validity unused solution of drug is thrown out. To store in the place, unavailable to children! A period of validity - 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for intake with concentration of 1 mg/ml. On 12,6 g in a bottle from polyethylene of high pressure of 260 ml (calculated for preparation of 200 ml of solution for intake), with the neck soldered by a foil with the put BMS logo, corked by the screwing-up polypropylene cover unavailable to opening by children. Two arrows and texts of "Close tightly" and "While pushing down turn" are applied on a cover of a bottle. One bottle complete with a measured cap and the instruction on a medical use in a box cardboard.