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

Composition of cap capsule: iron dye ferric oxide 0.1%, iron oxide red oxide 0.12%, iron oxide oxide yellow 0.3%, titanium dioxide 2%, gelatin 100%.

Description:

Capsules № 0: white body, lid of light brown color, opaque.The contents of the capsules are a powder or a mixture of powder and granules from white or almost white to light yellow. It is allowed to compact the contents of the capsule according to the shape of the capsule, disintegrating upon pressing.

Pharmacotherapeutic group:Antibiotic.

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.01 Cycloserine

Pharmacodynamics:

Cycloserin is a broad-spectrum antibiotic that forms during the life process Streptomyces orchidaceus. Cycloserine acts bacteriostatically

or bactericidal, depending on the concentration in the focus of infection and the sensitivity of microorganisms. Cycloserine violates the synthesis of the cell wall, acting as a competitive antagonist of D-alanine, suppresses the enzymes responsible for the synthesis of the cell wall of sensitive strains of gram-positive and gram-negative bacteria. Retards the growth of mycobacterium tuberculosis (active against Mycobacterium tuberculosis, Mycobacterium avium). The minimum inhibitory concentration in relation to M. tuberculosis is 3-25 mg / l on liquid and 10-20 mg / l and more - on a dense nutrient medium. Active with respect to Rickettsia spp., Treponema spp. in a concentration of 10-100 mg / l.

Drug resistance appears slowly (after 6 months of treatment it develops in 20-60% of cases).

Pharmacokinetics:

After oral administration, quickly and almost completely (70-90%) is absorbed from the gastrointestinal tract. Time to reach the maximum concentration in blood plasma - 3-4 hours Proportionally accepted dose of 0.25, 0.5, 1g, the maximum concentration in blood plasma is 6.24 and 30 μg / ml, respectively. After taking 250 mg every 12 hours, the maximum concentration is 25-30 μg / ml.

It penetrates well into body fluids and tissues, including cerebrospinal fluid, breast milk, bile, sputum, lymphatic tissue, lungs, ascites and synovial fluid, pleural effusion, passes through the placenta. In the abdominal and pleural cavity contains 50-100% of the concentration of the drug in the blood serum. Half-life with normal kidney function is 10 hours. It is excreted by glomerular filtration in unchanged form: 50% after 12 hours, 65-70% within 24-72 hours, small amounts through the gastrointestinal tract. With chronic renal failure, after 2-3 days, cumulation phenomena may occur.

Indications:

As part of complex therapy:

Active pulmonary tuberculosis, extrapulmonary tuberculosis (including kidney damage) in case of sensitivity of microorganisms to the drug and after unsuccessful adequate treatment with essential drugs, chronic forms of tuberculosis;
The combination of tuberculosis with acute infections of the urinary tract caused by sensitive strains of gram-positive and gram-negative bacteria, in particular Klebsiella spp., Enter obacter coli when main
Atypical mycobacterial infections (including those caused by Mycobacterium avium), urinary tract infections.

Contraindications:

Hypersensitivity to cycloserine and other components of the drug, organic diseases of the central nervous system, epilepsy, epileptic seizures (including in the anamnesis), mental disorders (anxiety, psychosis, depression, including in history), chronic heart failure, chronic renal failure (creatinine clearance less than 50 ml / min), alcoholism, lactation, children under 3 years.

Due to the presence of lactose in the composition is not recommended for patients with hereditary lactase deficiency, lactose intolerance and glucose-galactose malabsorption syndrome.

Carefully:

pregnancy.

Pregnancy and lactation:

Application during pregnancy: not set whether causes cycloserine damage to the fetus when used in pregnant women. Cycloserine should be given to pregnant women only in cases of extreme necessity.

Application in the period of breastfeeding: concentrations in human milk are close to the concentrations found in the mother's blood serum. The decision to abort breastfeeding or to stop treatment with the drug should be taken in consideration of the value of treatment with the drug for the mother.

Dosing and Administration:

Inside, immediately before meals (with irritation of the mucous membrane of the gastrointestinal tract - after eating).

Adults: The usual dose is from 500 mg to 1 g per day. The initial dose for adults is often 250 mg twice a day at 12-hour intervals during the first two weeks, then, if necessary, taking into account tolerability, the dose is carefully increased to 250 mg every 6-8 hours under the control of the concentration of the drug in the blood serum. The daily dose should not exceed 1 g.

Patients older than 60 years, as well as with a body weight of less than 50 kg, the drug is prescribed at a dose of 250 mg 2 times a day.

In children older than 3 years, the initial dose of cycloserine is 10-20 mg / kg of body weight per day in 2-3 doses (not higher than 750 mg / day, a high dose is given only in the acute phase of the tuberculosis process or with inadequate effectiveness of smaller doses).

Side effects:

Most side effects observed during treatment with cycloserine are associated with impaired central nervous system function, the use of high doses of the drug (more than 500 mg / day) or is a manifestation of hypersensitivity to the drug.

From the nervous system: epileptic convulsions, drowsiness, insomnia, sopor, headache, tremor, dysarthria, dizziness, confusion and disorientation accompanied by loss of memory; anxiety, peripheral neuritis, psychosis is possible with suicide attempts, changes in character, euphoria, depression, increased irritability, aggressiveness, paresis, hyperreflexia, paresthesia, large and small seizures of clonic convulsions and coma.

From the digestive system: nausea, heartburn, diarrhea, especially in elderly people with pre-existing liver disease.

From the cardiovascular system: there was a development of congestive heart failure in patients taking from 1 to 1.5 g of cycloserine per day.

Other established side effects include: allergic reactions, pruritus, megaloblastic and sideroblastic anemia and increased activity of liver aminotransferases, fever, increased cough.

Overdose:

Symptoms. Acute overdose can occur when cycloserine is administered at a dose of more than 1 g. Overdose phenomena can be observed with a plasma cycloserine concentration of 25-30 mg / ml (high-dose administration, impaired renal clearance).

Usually, toxic effects occur from the central nervous system. They can include headache, dizziness, confusion, increased irritability, paresthesia, dysarthria and psychosis. When high doses are used, paresis, convulsions and coma may occur. Ethanol may increase the risk of epileptic seizures.

Treatment. It is recommended that symptomatic and supportive treatment be provided. With cramps - antiepileptic drugs. For the prevention of neurotoxic effects are introduced pyridoxine in a dose of 200-300 mg / day, preparations of benzodiazepine series (diazepam), nootropic drugs (piracetam, glutamic acid). Activated carbon may be more effective in reducing absorption than induction of vomiting and gastric lavage. Carrying out of a hemodialysis deduces cycloserine from the blood, but does not exclude the development of life-threatening intoxication.

Interaction:

Cycloserine promotes a decrease in resistance to isoniazid, streptomycin and paraaminosalicylic acid (PASC). Patients receiving cycloserine and isoniazid, should be controlled, as these drugs have a combined toxic effect on the central nervous system.

Increases the rate of excretion of pyridoxine by the kidneys (may cause the development of anemia and peripheral neuritis, an increase in the dose of pyridoxine is required).

Simultaneous administration of ethionamide potentiates neurotoxic side effects, increases the risk of side effects from the central nervous system, especially convulsive syndrome.

Ethanol increases the risk of epileptic seizures.

Special instructions:

Before starting treatment with cycloserine, isolate cultures of microorganisms and determine the sensitivity of strains to cycloserine. Patients who receive more than 500 mg of cycloserine per day should be under the direct supervision of a doctor because of the possible development of side effects from the central nervous system.

Treatment with cycloserine should be canceled or the dose should be reduced if the patient develops allergic dermatitis or symptoms of intoxication of the central nervous system, for example: convulsions, psychosis, drowsiness, oppression or confusion, hyperreflexia, headache, tremor, dizziness, paresis or dysarthria.

The risk of developing convulsive syndrome increases in patients with chronic alcoholism, so the use of cycloserine in this condition is contraindicated. Anticonvulsants or sedatives can be effective in preventing neurotoxic reactions, for example: seizures, arousal or tremor.

When taking the drug should be monitored hematological indicators, excretory function of the kidneys, the concentration of cycloserine in the blood and the state of liver function. The concentration of cycloserine in the blood should not exceed 30 mg / ml.

In the treatment of patients with reduced renal function, taking a daily dose of more than 500 mg and who are suspected to have signs and symptoms of an overdose, the level of the drug in the blood should be monitored at least once a week. The dose should be adjusted in such a way thatddKeep blood level in the blood below 30 mg / l. Such patients should be under the direct supervision of a doctor because of the possible development of symptoms of toxicity.

In some cases, the use of cycloserine and other anti-tuberculosis drugs can cause deficiency of cyanocobalamin (vitamin B12) and folic acid in the body, the development of megaloblastic anemia. In case of anemia during treatment, it is necessary to conduct an appropriate examination and treatment of the patient.

It is possible to prevent or reduce the toxic effect of cycloserine by prescribing glutamic acid 0.5 g 3 to 4 times daily (before meals) during the treatment period, and daily intramuscular administration of the sodium salt of adenosine triphosphate (1 ml of 1% solution), pyridoxine 200-300 mg / day.

It is necessary to limit the mental tension of patients and exclude possible factors of overheating (exposure to the sun with an uncovered head, hot shower).

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

During the treatment period it is necessary to refrain from engaging in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules 250 mg.

Packaging:

For 10, 30 capsules in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50 or 100 capsules in cans of polymeric for medicines.

One jar or 1, 2, 3, 4, 5, 6, 8 or 10 contour squares, together with the instructions for use, are 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-002143

Date of registration:15.07.2013

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

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp07.10.2015

Illustrated instructions

Instructions

Cycloserine (Cycloserine)