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

Contents of capsules: powder or mixture of powder and granules from white or almost white to light yellow color. It is allowed to compact the contents of the capsule in the form of a capsule, disintegrating when pressed with a glass rod.

Pharmacotherapeutic group:Antibiotic

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.01 Cycloserine

Pharmacodynamics:

Cycloserin is a broad-spectrum antibiotic that disrupts the synthesis of the cell wall, acting as a competitive antagonist D-alanine, suppresses the enzymes responsible for the synthesis of the cell wall of sensitive strains of microorganisms. It acts bacteriostatically or bactericidal, depending on the concentration in the focus of inflammation and the sensitivity of microorganisms.

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. Active with respect to Rickettsia spp., Treponema spp. in a concentration of 10-100 mg / l. Also active in relation to Enterobacter spp., Escherichia coli, Klebsiella spp., Mycobacterium avium. 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 the blood plasma (TCmah) 3-4 hours After taking 250 mg every 12 hours Cmah 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. Concentrations of cycloserine in the cerebrospinal and pleural fluid, in fetal blood and in breast milk reach this value in blood plasma.

Partially (35%) is biotransformed in the liver to non -identified metabolites.

The half-life (T1 / 2) 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 h, small amounts - through the gastrointestinal tract. With chronic renal failure, after 2-3 days, cumulation phenomena may occur.

Indications:

In the combination therapy:

- Tuberculosis: active pulmonary tuberculosis, extrapulmonary tuberculosis (including kidney damage) in case of susceptibility of microorganisms to cycloserine, and after unsuccessful adequate treatment with essential drugs (rifampicin, isoniazid, streptomycin, ethambutol).

- Atypical mycobacterial infections (including those caused by Mycobacterium avium). Acute urinary tract infections caused by sensitive strains of Gram-positive and Gram-negative bacteria, in particular Klebsiella spp., Enterobacter spp. and Escherichia coli. Use cycloserine in this case it follows only after the ineffectiveness of the main means of treatment is shown and when the sensitivity of microorganisms to cycloserine is determined.

Contraindications:

Hypersensitivity to cycloserine and other components of the drug, epilepsy, epileptic seizures (including in the anamnesis), mental disorders (anxiety, depression, a state of excitement or psychosis, including in an anamnesis), organic diseases of the central nervous system (CNS), chronic renal failure (creatinine clearance less than 50 ml / min), acute and chronic heart failure, alcoholism,children under 3 years old, lactose intolerance, lactase deficiency, glucose-galactose malabsorption, porphyria.

Carefully:

Children age from 3 to 18 years.

Pregnancy and lactation:

The use of the drug in pregnancy is possible only in exceptional cases, when the expected benefit for the mother exceeds potential risk to the fetus. If you need to use the drug in the period lactation, breastfeeding should be discontinued.

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 1000 mg 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 and taking into account tolerability, the dose is gradually increased to 250 mg every 6-8 hours under the control of cycloserine concentration in the blood plasma. The daily dose should not exceed 1000 mg.

In the case of impaired renal function, the dose is reduced.

Children over 3 years old prescribe 10-20 mg / kg of body weight per day in 2-3 doses (not higher than 750 mg / day, a large dose is prescribed only in the acute phase of the tuberculosis process or with insufficient effectiveness of smaller doses).

Elderly patients

Patients over 60 years of age, as well as with a body weight of less than 50 kg, are prescribed 250 mg twice daily.

The course of treatment of urinary tract infections is 7-10 days, mycobacterial infections - more than 6 months.

Side effects:

From the central nervous system and the peripheral nervous system: headache, dizziness, insomnia or drowsiness, "nightmarish" dream, anxiety, irritability, aggression, memory loss, paresthesia, peripheral neuritis, muscle twitching, tremors, dysarthria, euphoria, depression, suicidal thoughts, confusion, disorientation, accompanied by memory loss, psychosis, epileptiform convulsions, coma, confusion, paresis, stupor, changing nature, hyperreflexia, large and small attacks clonic seizures, suicidal attempts.

From the digestive system: increased activity of "liver" transaminases, nausea, heartburn, diarrhea, particularly in elderly patients with pre-existing liver disease.

From the cardiovascular system and hematopoiesis system: development congestive heart failure (noted when applied at a dose of 1000-1500 mg / day).

Allergic reactions: skin rash, itching.

Other: fever, coughing, megaloblastic or sideroblastic anemia, deficiency of cyanocobalamin and folic acid.

Overdose:

Acute overdose is observed when cycloserine is used by patients with impaired renal function or when ingesting more than 1000 mg / day. Overdose phenomena can be observed at a plasma cycloserine concentration of 25-30 μg / ml.

Symptoms: headache, dizziness, confusion, increased irritability, paresthesia, psychosis, dysarthria, peripheral paresis, convulsions, coma.

Treatment is symptomatic and supportive: Activated carbon, anticonvulsants. To reduce the absorption of the drug, it is more preferable to use Activated carbon, rather than induction of vomiting and gastric lavage. For the prevention of neurotoxic effects are introduced pyridoxine in a dose of 200-300 mg / day. preparations of benzodiazepine series (diazepam). When conducting hemodialysis cycloserine is derived from the blood,but it does not exclude the risk of life-threatening intoxication.

Interaction:

Reduces resistance to isoniazid, streptomycin and aminosalicylic acid. Enhances the neurotoxic effect of ethionamide.

Ethanol increases the risk of epileptic seizures.

Isoniazid enhances the toxic effect of the drug on the central nervous system. Patients receiving cycloserine and isoniazid, should be under the control of the doctor regarding signs of toxic effects on the central nervous system (for example: drowsiness, dizziness).

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:

Before treatment, it is necessary to determine sensitivity strains of microorganisms to cycloserine and other anti-tuberculosis drugs.

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.

In the case of development against the background of treatment of allergic dermatitis or symptoms of damage to the central nervous system(convulsions, psychosis, drowsiness, confusion, hyperreflexia, headache, dizziness, tremor, peripheral paresis, dysarthria) drug treatment should stop or reduce the dose.

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

When taking the drug should monitor the indicators of electroencephalography, 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 mcg / ml.

In the treatment of patients with reduced renal function, taking more than 500 mg of the drug per day and who are suspected to have signs and symptoms of an overdose, the concentration of cycloserine in the blood should be monitored at least once a week. The dose should be adjusted in such a way as to maintain a concentration of cycloserine in the blood below 30 μg / ml.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 such symptoms.

In some cases, the use of cycloserine and other anti-tuberculosis drugs can cause deficiency of vitamin B12 and folic acid in the body, the development of megaloblastic and sideroblastic 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 500 mg 3-4 times daily (before meals) and daily intramuscular injections of pyridoxine at a dose of 200-300 mg / day during the treatment period.

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

In connection with the rapid development of resistance with monotherapy with cycloserine, it is recommended to combine it with other anti-TB drugs.

The use of cycloserine may cause an exacerbation of the disease in patients with porphyria.

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

During the period of treatment it is recommended to abandon the management of vehicles, mechanisms requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules 125 mg and 500 mg.

Packaging:

For 5, 7, 10 capsules in a contour mesh box made of a polyvinylchloride film and aluminum foil printed lacquered.

10, 20, 30. 40, 50 or 100 capsules in cans of polyethylene terephthalate for medicines or polypropylene for drugs sealed with high-pressure polyethylene lids with a control of the first opening, or polypropylene caps with a "push-turn" system or lids made of low pressure polyethylene with control of the first opening.

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:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004416

Date of registration:16.08.2017

Expiration Date:16.08.2022

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

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp11.09.2017

Illustrated instructions

Instructions

Cycloserine (Cycloserine)