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

It acts bacteriostatically or bactericidal, depending on the concentration in the focus of infection and the sensitivity of microorganisms. It is an analog of the amino acid D-alanine. The activity of L-alanine-racemase enzymes, which converts L-alanine to D-alanine, and D-alanyl-D-alanine synthetase, including D-alanine, into a pentapeptide necessary for constructing the bacterial cell wall, has been competitively inhibited.

Active with respect to Mycobacterium tuberculosis, Mycobacterium avium.

Pharmacokinetics:

Quickly absorbed in the digestive tract, the therapeutic concentration in the plasma is created after 1 hour. It is evenly distributed, penetrates into the lymphoid tissue, lung tissue, pleural and ascitic fluids, sputum, bile. Passes the placental barrier and the blood-brain barrier (concentration in the cerebrospinal fluid corresponds to the concentration in the plasma, determined in the amniotic fluid and fetal blood). Metabolised in the liver (30%). It is allocated mainly by the kidneys (66% - found in the urine within 24 hours, another 10% - in the next 48 hours) in unchanged form and is excreted with feces. Some amount is excreted with milk.

Indications:

Tuberculosis of lungs (active form), extrapulmonary tuberculosis (including kidney disease) as part of combination therapy; acute urinary tract infections.

ICD-10

I.A15-A19.A18.1 Tuberculosis of the urogenital organs

I.A15-A19.A18 Tuberculosis of other organs

I.A15-A19.A17.0 Tuberculous meningitis (G01 *)

I.A15-A19.A15.8 Tuberculosis of other respiratory organs, confirmed bacteriologically and histologically

XIV.N30-N39.N39.0 Urinary tract infection without established localization

I.A30-A49.A31.0 Pulmonary infection caused by Mycobacterium

Contraindications:

Hypersensitivity, epilepsy, depression, severe agitation, psychosis, severe renal failure, alcoholism.

Carefully:

Childhood.

Elderly patients are prescribed smaller doses on the background of impaired renal function.

Pregnancy and lactation:

Recommendations FDA category C. Contraindicated in pregnancy.

Cycloserine excreted in breast milk, so if you need to use during lactation, you should decide whether to stop breastfeeding.

Dosing and Administration:

Inside the adults, the initial dose is 500 mg per day with an interval of 12 hours, under the control of the level of cycloserine in the blood, the maximum daily dose is 1 g; in children the initial dose is from 10 mg / kg / day, then the dose varies depending on the level of cycloserine in the blood and the therapeutic effect.

Side effects:

From the nervous system and sensory organs: headache, tremor, dysarthria, dizziness, convulsions, drowsiness, semi-unconsciousness, confusion of thoughts, disorientation accompanied by loss of memory, psychosis with suicidal attempts, change in character, increased irritability, aggressiveness, paresis, hyperreflexia, paresthesia, seizures of clonic convulsions, coma .

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): congestive heart failure (at doses of 1000-1500 mg per day), megaloblastic anemia.

Other: an increase in the level of aminotransferases in the serum (especially in elderly patients with liver diseases), allergic reactions (itching).

Overdose:

Symptoms: headache, dizziness, irritability, paresthesia, dysarthria, paresis, convulsions, psychosis, semi-unconsciousness, confusion, coma.

Treatment: reception of activated charcoal, symptomatic and maintenance therapy, including the administration of pyridoxine (200-300 mg per day) with the aim of arresting neurotoxic effects. Effective hemodialysis.

Interaction:

Ethionamide and isoniazid increase neurotoxicity.

Incompatible with alcohol (increases the risk of epileptic seizures).

Special instructions:

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

With monotherapy with cycloserine, the rapid development of mycobacterial resistance is possible, so only combination therapy should be used.

During the treatment period, the level of cycloserine in the blood should be monitored (at concentrations above 30 mg / ml, toxicity is likely), hematologic parameters, kidney and liver function. To prevent symptoms of neurotoxicity (including tremors, seizures, arousal), it is possible to prescribe anticonvulsants or sedatives.

Instructions

Cycloserine (Cycloserinum)