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

Cycloserine is a broad-spectrum bactericidal antibiotic. Cycloserine inhibits the synthesis of the cell membrane of sensitive strains of Gram-positive and Gram-negative bacteria and Mycobacterium tuberculosis. Active against gram-negative microorganisms, in a concentration of 10-100 mg / l - Rickettsia spp., Treponema spp .. IPC in relation to Mycobacterium tuberculosis is 3-25 mg / l on liquid and 10-20 mg / l and more - on a dense nutrient medium. Drug resistance appears slowly (after 6 months of treatment, it is observed in 20-60% of cases).

Pharmacokinetics:

Cycloserine is rapidly absorbed from the digestive tract after ingestion, reaching the determined plasma concentrations within one hour, is distributed freely in body fluids and tissues.

Cycloserin penetrates the BBB, the concentrations in the cerebrospinal fluid are about the same as in the blood plasma. In patients with tuberculosis Cycloserine is found in sputum, as well as in pleural and ascitic fluids, in bile, amniotic fluid and fetal blood, in breast milk, lung tissue and lymphoid tissue.

About 66% of the dose is excreted unchanged in urine within 24 hours. 10% for the next 48 hours. With feces are excreted in small amounts.About 35% are metabolized, but metabolites have not been identified to date.

The half-life of cycloserine is within 8-12 hours.

Cycloserine penetrates the placenta. In the abdominal and pleural cavity contains 50-100% of the concentration of the drug in the blood serum.

T1 with normal kidney function - 10 hours. In chronic renal failure after 2-3 days, cumulation phenomena may occur.

Indications:

Tuberculosis of the lungs in active form; extrapulmonary tuberculosis (including kidney disease), provided that microorganisms are sensitive to this drug and after ineffective treatment with adequate doses of essential drugsstreptomycin, isoniazid, rifampicin and ethambutol). The drug should be used in combination with other chemotherapeutic agents, and not as monotherapy.

Atypical bacterial infections (including those caused by Mycobacterium avium).

Acute infections of the urinary tract caused by sensitive strains of Gram-positive and Gram-negative bacteria, especially the Klebsiella / Enterobacter and Escherichia coli species. In the treatment of urinary tract infections caused by bacteria other than mycobacteria, cycloserine is usually effective in the same way as other antimicrobials. Use cycloserine for the treatment of these infections should only after all conventional means of treatment have been exhausted and when the sensitivity of the microorganisms to this drug has been established.

Contraindications:

Hypersensitivity to cycloserine;
Epilepsy, epileptic seizures (including in history);
Depression;
Expressed states of excitement or psychosis;
Heart failure;
Severe renal insufficiency;
Alcohol abuse;
Children up to 3 years.

Carefully:

Children's age (see section "method of administration and dose").

Treatment with cycloserine should be canceled or the dose should be reduced if the patient develops allergic dermatitis or symptoms of the central nervous system, for example, convulsions, psychoses, drowsiness, depression, confusion, hyperreflexia, headache, tremor, dizziness, paresis or dysarthria. Poisoning is usually observed at a drug concentration in the blood of more than 30 g / ml, which can be the result of an overdose or impaired renal clearance.

The therapeutic index of this drug is low. The risk of seizures increases in patients with chronic alcoholism.

When taking the drug should be monitored hematological indicators, excretory function of the kidneys, the level of the drug in the blood and the state of liver function. Before starting treatment with cycloserine, it is necessary to isolate the culture of microorganisms and determine the sensitivity of the strains to this preparation. In the case of tuberculosis infection, it is necessary to determine the sensitivity of the strain to other anti-tuberculosis drugs.

In the treatment of patients with reduced renal function, taking a daily dose of more than 500 mg, which are suspected to show signs and symptoms of poisoning, 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 as to maintain the level of the drug in the blood below 30 mg / ml.

Anticonvulsants or sedatives can be effective in preventing central nervous system poisoning symptoms, such as seizures, arousal or tremor.

Patients receiving more than 500 mg of cycloserine per day should be under direct observation because of the possible development of such symptoms. The significance of pyridoxine in preventing the poisoning of the Cp C cycloserine is not established. In some cases, the use of cycloserine and other anti-tuberculosis drugs caused the development of vitamin B12 and / or folic acid deficiency, megaloblastic and sideroblastic anemia. In case of anemia during treatment, it is necessary to conduct an appropriate examination and treatment of the patient.

Pregnancy and lactation:

Application during pregnancy. Concentration in fetal blood approaches the concentrations found in serum. Studies on 2 generations of rats given doses up to 100 mg / kg body weight / day showed no teratogenic effect in newborns. It is not established whether cycloserine damage to the fetus when administered to pregnant women only in cases of extreme necessity.

Application in the period of breastfeeding. Concentrations in human milk approach the concentrations found in serum.The decision on the abolition of breastfeeding or the cessation of drug treatment should be taken taking into account 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 - 0.25 g every 12 hours for the first 12 hours, then if necessary taking into account the tolerability dose carefully increased to 250 mg every 6-8 hours under the control of the concentration of the drug in the blood serum.

The maximum daily dose is 1 g. Patients older than 60 years, and also with a body weight of less than 50 kg - 0.25 g 2 times a day. The daily dose for children is 0.01-0.02 g / kg (not more than 0.75 g / day).

Side effects:

Most of the side effects observed during treatment with cycloserine were associated with the nervous system or were manifestations of hypersensitivity to the drug.

From the nervous system (due to high doses of the drug (more than 500 mg per day)): convulsions, drowsiness, insomnia, nightmares, a semi-unconscious condition, headache, tremor, dysarthria, dizziness, confusion of thoughts and disorientation accompanied by loss of memory, anxiety,peripheral neuritis, psychosis, possibly with suicide attempts, character change, euphoria, depression, increased irritability, aggressiveness, paresis, hyperreflexia, paresthesia, large and small seizures of clonic convulsions and coma.

From the digestive system: nausea, heartburn, diarrhea.

Other established side effects include allergic reactions, pruritus, megaloblastic anemia and an increase in aminotransferases in the serum, especially in elderly patients with pre-existing liver diseases.

There was a sudden development of congestive heart failure in patients taking from 1 to 1.5 g of cycloserine per day.

Other: fever, coughing.

Overdose:In case of an overdose, symptomatic treatment is recommended.

Interaction:

Cycloserin increases the rate of excretion of pyridoxine by the kidneys (may cause the development of anemia and peripheral neuritis, which requires an increase in the dose of pyridoxine). Alcohol and cycloserine incompatible, especially when treated with high doses of cycloserine. Alcohol increases the possibility and danger of epileptic seizures. Patients receiving cycloserine and isoniazid, should be monitored for signs of CNS poisoning, for example, dizziness and drowsiness, since these drugs have a combined toxic effect on the central nervous system. Ethionamide increases the risk of side effects from the central nervous system, especially convulsive syndrome.

Special instructions:

It is possible to prevent or reduce the toxic effect of cycloserine by prescribing glutamic acid 0.5 g 3-4 times per day (before meals) during the treatment period, and daily iv administration of the sodium salt of ATP (1 ml of a 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 resistance 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.

Form release / dosage:

Capsules 250 mg.

Packaging:

100 capsules per bottle of high density polyethylene with a screw cap (with a picture of a schematic drawing - instructions for opening the bottle),equipped with the protection of the first opening in the form of a ring and the induction welding of the foil.

1 bottle with instructions for use in a pack of cardboard.

Storage conditions:In a dry, the dark place at a temperature of no higher than 25 ° C.

Shelf life:

2 years.

Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-007957/08

Date of registration:08.10.2008

The owner of the registration certificate:BIOKOM, CJSC BIOKOM, CJSC Russia

Manufacturer: & nbsp

BIOKOM, CJSC Russia

Information update date: & nbsp12.10.2015

Illustrated instructions

Instructions

Cycloserine (Cycloserine)