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

The composition of hard gelatin capsules: titanium dioxide (E 171) - 1.33 mg, iron oxide (III) 0.15192 mg, gelatin 63.152808 mg, water 11.02 mg, sodium lauryl sulfate 0.114 mg, armolop 0.076 mg, povidone - 0.076 mg, methyl parahydroxybenzoate 0.057 mg, propyl parahydroxybenzoate 0.019 mg.

Description:

Capsules (No. 1) are dark brown with a reddish tinge, the contents of the capsules are white or light yellow powder.

Pharmacotherapeutic group:Antibiotic.

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.01 Cycloserine

Pharmacodynamics:

It acts bacteriostatically or bactericidal, depending on the concentration in the focus of inflammation and the sensitivity of microorganisms.

Pharmacodynamics:

Mechanism of action. A 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.

Active against gram-negative microorganisms, in a concentration of 10-100 mg / l - Rickettsia spp., Treponema spp. The minimum inhibitory concentration 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 develops in 20-60% of cases).

Pharmacokinetics:

Cycloserin is rapidly absorbed from the gastrointestinal tract (GIT) after ingestion. Time to reach the maximum concentration in the blood plasma (TC_max) - 3-4 h. The drug is distributed freely in the fluids and tissues of the body.

Cycloserin penetrates the blood-brain barrier (BBB), the concentrations in the cerebrospinal fluid are about the same as in plasma. In patients with tuberculosis cycloserine was 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.

Cycloserin is excreted by the kidneys by glomerular filtration in unchanged form (50% after 12 hours, 65-70% within 24-72 hours) and in small amounts - by the intestine.

With chronic renal failure, after 2-3 days, cumulation phenomena may occur.

About 35% is metabolized, but metabolites have not been identified to date. The half-life of cycloserine fluctuates within 8-12 hours.

Indications:

Cycloserin is used both for the treatment of pulmonary tuberculosis in active form, and for the treatment of extrapulmonary tuberculosis (including kidney tuberculosis), provided that microorganisms are sensitive to this drug and after unsuccessful adequate treatment with essential drugs (rifampicin, isoniazid, streptomycin and ethambutol). Cycloserine should be used in combination with other anti-tuberculosis drugs. Cycloserine Effective in acute infections of the urinary tract caused by sensitive strains of Gram-positive and Gram-negative bacteria, in particular Klebsiella spp. Enterobacter spp. and Escherichia coli. 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 medication has been determined.

Contraindications:

Cycloserine is contraindicated in the following cases: hypersensitivity to cycloserine, organic diseases of the central nervous system (CNS), epilepsy, epileptic seizures (including in anamnesis), mental disorders (anxiety, psychosis, depression, including in anamnesis ), severe renal failure (creatinine clearance less than 25 ml / min), alcohol abuse, lactation period, children under 3 years of age (for this dosage form), heart failure, lactase deficiency, lactose intolerance, glucose-galactose malabs Orbtion.

Carefully:

Children's age (from 3 to 18 years), chronic renal failure (creatinine clearance more than 25 ml / min).

Pregnancy and lactation:

Concentrations in fetal blood approach the concentrations found in the pregnant serum. A study in 2 generations of rats receiving doses up to 100 mg / kg body weight / day showed no teratogenic effect in newborns.Is not established whether causes cycloserine damage to the fetus when prescribing to pregnant women and whether it has an effect on reproductive capacity. Cycloserine should be given to pregnant women only in cases of extreme necessity.

Application in the period of lactation. Concentrations in human milk approach the concentrations found in serum. The decision to stop breastfeeding or 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).

The usual dose is from 500 mg to 1 g per day for several doses under the control of the level of the drug in the blood. The initial dose for adults is often 250 mg twice daily with a 12-hour interval during the first two weeks. The daily dose should not exceed 1 g.

Children (over 3 years). The usual initial dose is from 10 mg / kg body weight / day for several doses, after which it varies depending on the concentration of the drug in the blood and the therapeutic effect. The daily dose should not exceed 0.75 g.

The elderly. Patients older than 60 years, as well as with a body weight of less than 50 kg - 0.25 g 2 times a day.

The course of treatment with cycloserine in infections of the urinary tract is 7-10 days, with tuberculosis - 6 months or more.

Side effects:

Most of the side effects observed during treatment with cycloserine were associated with impaired central nervous system function or were manifestations of hypersensitivity to the drug. The following side effects were observed:

From the nervous system: convulsions, drowsiness, headache, tremor, dysarthria, dizziness, confusion and impaired orientation, accompanied by loss of memory, psychosis, possibly with suicide attempts, character changes, increased irritability, aggressiveness, peripheral paresis, hyperreflexia, paresthesia, large and small seizures clonic convulsions and coma.

From the cardiovascular system and the organs of hematopoiesis: exacerbation of heart failure (at doses of 1000-1500 mg / day), sideroblastic and megaloblastic anemia.

From the side of the digestive system, nausea, heartburn, diarrhea especially in elderly patients with pre-existing liver disease.

Allergic reactions: skin rash, itching.

Laboratory indicators: increased activity of "hepatic" aminotransferases.

Other: deficiency of cyanocobalamin and folic acid.

Overdose:

Signs and symptoms. Acute poisoning can be observed if the adult patient has ingested more than 1 g. Chronic toxicity is dose dependent and can be observed if more than 500 mg of cycloserine is administered daily to the body. When used in patients with impaired renal function, see the sections "Contraindications" and "Special instructions". Typically, toxic effects are noted from the central nervous system. These may include headache, dizziness, confusion, increased irritability, paresthesia, dysarthria and psychosis. At the use of high doses, peripheral paresis, convulsions and coma can be observed. Ethanol may increase the risk of epileptic seizures.

Treatment. It is recommended that symptomatic and supportive treatment be provided. Activated carbon may be more effective in reducing absorption of the drug than causing vomiting and gastric lavage. With the development of neurotoxic effects, 200-300 mg of pyridoxine per day is indicated. During hemodialysis cycloserine is excreted from the blood, but the development of a toxic effect that threatens life is not ruled out.

Interaction:

It is reported that the simultaneous use of ethionamide enhances the neurotoxic effects of the drug. 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 under the supervision of a physician, since with these combinations it is possible to increase the toxic effect on the central nervous system. A dose adjustment may be required. Cycloserine 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).

Special instructions:

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).

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

Intoxication is usually observed at a drug concentration in the blood of more than 30 mg / l, which can be the result of an overdose or a decrease in kidney clearance. The therapeutic index of cycloserine is low. The risk of seizures increases in patients with chronic alcoholism.

When taking cycloserine should monitor hematological indicators, excretory function of the kidneys, the concentration of the drug in the blood and the state of liver function.

Before starting treatment with cycloserine, it is necessary to isolate cultures of microorganisms and determine the sensitivity of 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, who are suspected to have signs and symptoms of an overdose, the concentration 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 keep the concentration of the drug in the blood below 30 mg / l.

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

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).

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 such symptoms. For the prevention of adverse neurotoxic effects, psychotropic drugs of benzodiazepine diazepam (5 mg) or phenazepam (1 mg) overnight; nootropic drugs - piracetam 800 mg twice a day, pyridoxine (vitamin B₆), glutamic acid 1 g 3 times a day.

In some cases, the use of cycloserine and other anti-tuberculosis drugs can cause the development of vitamin B deficiency₁₂ and / or folic acid in the body, megaloblastic and sideroblastic anemia. In case of anemia during treatment, it is necessary to conduct an appropriate examination and treatment of the patient.

During the treatment with cycloserine, care must be taken when dealing with potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

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

During the treatment with cycloserine, care must be taken when driving vehicles and mechanisms.

Form release / dosage:

Capsules of 250 mg.

Packaging:

Primary packaging of medicinal product.

4 or 10 capsules in an aluminum strip. Secondary packaging of medicinal product.

1 strip (4 capsules each) together with instructions for use in a cardboard bundle. For 5 or 10 strips (10 capsules each) together with instructions for use in a cardboard pack.

At packing at the enterprise Open Society "Farmasintez" (Russia):

Secondary packaging of medicinal product.

For 1 or 10 strips (4 capsules each), together with the instructions for use are placed in a pack of cardboard.

At packing and packing at the enterprise of Open Society "Farmasintez" (Russia).

Primary packaging of medicinal product.

For 30, 50 or 100 capsules in a package of low-density polyethylene. A label is attached to the package from paper label or written or from polymer materials, self-adhesive.

Secondary packaging of medicinal product.

One packet, together with the instruction for use, is placed in a polymer can with the lid of a pull-up with the control of the first opening. Labels are applied to cans from paper label or writing or from polymeric materials, self-adhesive.

Storage conditions:

In dry, 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 time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001108

Date of registration:23.09.2011

The owner of the registration certificate:Lock-Beta Pharmaceuticals (I) Pvt.LtdLock-Beta Pharmaceuticals (I) Pvt.Ltd India

Manufacturer: & nbsp

LOK-BETA PHARMACEUTICALS (I), Pvt. Ltd. India

Representation: & nbspFARMSINTEZ, PAO FARMSINTEZ, PAO Russia

Information update date: & nbsp09.10.2015

Illustrated instructions

Instructions

Cycloserine (Cycloserine)