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

Capsule shell composition: Capsule body: gelatin up to 100%, titanium dioxide (E 171) 2.11%; Capsule cap: gelatin up to 100%, dye Ponso 4R (E 124) 0.49%, dye quinoline yellow (E 104) 0.00999%, titanium dioxide (E 171) 2.16%.

Description:

Hard gelatin capsules № 1 with opaque white body, opaque cap of red color.

The contents of capsules are white or almost white powder.

Pharmacotherapeutic group:Antibiotic.

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.01 Cycloserine

Pharmacodynamics:

A bactericidal broad-spectrum antibiotic that disrupts 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.

It is active against Gram-positive and Gram-negative microorganisms, in a concentration of 10-100 mg / l - Rickettsia spp., Treponema spp. The minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis is 3-25 mg / L for liquid and 10-20 mg / L and more for a dense nutrient medium. Drug resistance appears slowly (after 6 months of treatment it develops in 20-60% of cases).

Pharmacokinetics:

Cycloserin is rapidly absorbed from the gastrointestinal tract (GIT) after ingestion, the concentrations determined are created in the plasma for 1 hour. Absorption after oral administration is 70-90%. Virtually does not bind to the proteins of the plaza. Time to reach the maximum concentration (TC_max) - 3-4 hours; after taking in a dose of 0.25, 0.5 and 1 g, the maximum concentration (C_max) is about 6, 24 and 30 mg / l, respectively. After taking a dose of 250 mg every 12 hours C_max 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 cavities contains 50-100% of the concentration of the drug in the blood serum. Partially metabolized (up to 35% of the administered dose); metabolites are not established. The half-life (T1 / 2) with normal kidney function is 10 hours.

It is excreted by glomerular filtration in unchanged form, small amounts with feces. With chronic renal failure (CRF), cumulation phenomena may appear in 2-3 days; is output by dialysis. The violation of liver function does not affect the kinetics of cycloserine.

Indications:

Tuberculosis caused by sensitive strains of Mycobacterium tuberculosis (as part of a combination therapy): active pulmonary tuberculosis, extrapulmonary tuberculosis (including kidney damage) after unsuccessful adequate treatment with essential drugs, chronic forms of tuberculosis.

Atypical mycobacterial infections (including those caused by Mycobacterium avium) in combination therapy.

Urinary tract infections caused by sensitive strains of Gram-positive and Gram-negative bacteria, such as Enterobacter spp. and Escherichia coli.

Contraindications:

Hypersensitivity to cycloserine, etc.(including anxiety, psychosis, depression, including history), chronic heart failure, chronic renal failure insufficiency (creatinine clearance less than 50 ml / min), alcoholism, lactation, children under 12 years (for this dosage form).

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, or whether it affects reproductive capacity. Cycloserine should be given to pregnant women only in cases of extreme necessity.

Application during lactation: 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 with a 12-hour interval during the first two weeks. Periodically (after several procedures, it is necessary to monitor the concentration of cycloserine in the blood). 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 12 years, the initial dose of cycloserine is 10-20 mg / kg of body weight per day in 2-3 doses (not more than 750 mg / day, a high dose is given only in the acute phase of the tuberculosis process or with insufficient effectiveness of smaller doses).

Side effects:

Most of the side effects observed during treatment with cycloserine are associated with impaired CNS 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: convulsions, drowsiness, sleeplessness, sopor, headache, tremor, dysarthria, dizziness, confusion and impaired orientation, accompanied by loss of memory, anxiety, peripheral neuritis, psychosis, possibly 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 side of the digestive system, nausea, heartburn, diarrhea, especially in the elderly 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.

Other: fever, coughing.

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 side of 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

contributes to a decrease in resistance to isoniazid, streptomycin and paraaminosalicylic acid (PASC). Patients receiving cycloserine and isoniazid, should be under control, since these drugs have a combined toxic effect on the central nervous system (CNS).
increases the speed of excretion pyridoxine kidneys (may cause the development of anemia and peripheral neuritis, an increase in the dose of pyridoxine is required).
Simultaneous administration 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 direct medical supervision because of the possible development of side effects from the CNS.

Treatment with cycloserine should be canceled or the dose should be reduced if the patient develops allergic dermatitis or symptoms of CNS intoxication, 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 (see section "Contraindications").

Anticonvulsants or sedatives can be effective in preventing neurotoxic reactions, such as 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.

Toxic effect is usually observed with the use of high doses of the drug in the blood (500 mg / day), as well as in patients with reduced renal function. In this case, weekly monitoring of kidney function is necessary (concentration of creatinine and urea nitrogen in the blood). 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 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).

In connection with the rapid development of stability with monotherapy with cycloserine, it is recommended that it be combined with other anti-tuberculosis drugs.

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

Not installed. However, taking into account the possible development of side effects from the central nervous system, during the treatment it is recommended to refrain from driving motor vehicles and practicing other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules 250 mg.

Packaging:

10 capsules in an aluminum strip. For 1, 5 or 10 aluminum strips, together with the instructions for use are placed in a cardboard box.

Storage conditions:

In dry, 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000921

Date of registration:18.10.2011

The owner of the registration certificate:Rowecq LimitedRowecq Limited United Kingdom

Manufacturer: & nbsp

BELCO PHARMA India

REDKINSKY EXPERIMENTAL FACTORY, CJSC Russia

Representation: & nbspROUTEC LIMITEDROUTEC LIMITEDUnited Kingdom

Illustrated instructions

Instructions

Cycloserine (Cycloserine)