Cycloserine
Cycloserine: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Cycloserine
ATX code: J04AB01
Active ingredient: cycloserine (cycloserinum)
Producer: Biocom CJSC (Russia), Valenta Pharmaceuticals OJSC (Russia), Promed Exports Pvt. Ltd (India), Dong-A Pharmaceutical Co. Ltd. (South Korea), etc.
Description and photo update: 10.07.2018
Cycloserine is a broad-spectrum antibacterial anti-tuberculosis drug.
Release form and composition
Cycloserine is released in capsule form:
- dosage 125 mg - No. 2, gelatinous solid, opaque, with a lid and white body (5, 7 or 10 pcs. in a blister strip packaging; 10, 20, 30, 40, 50 or 100 pcs. in a polymer can, in a cardboard box 1–6, 8, 10 packs or 1 can);
- dosage 250 mg - gelatinous solid; depending on the manufacturer: No. 1, dark brown with a red tint, or with a red opaque lid and an almost white or white body; No. 0, opaque white, or with a pale brown or orange lid, and a white body (7 or 10 pcs. In a non-cell contoured packaging, in a cardboard box 1, 2, 3, 10, 50, 54, 60 packs; 10 or 30 pcs. in a blister strip packaging, in a cardboard box 1-6, 8, 10 packs; 100 pcs. in a polyethylene bottle, 10 pcs. in a blister, in a cardboard box 1 bottle or 1, 5, 10 blisters; 4 or 10 pcs. in an aluminum strip, in a cardboard box 1, 5, 10 strips of 10 pcs., 1 or 10 strips of 4 pcs.; 30, 50 or 100 pcs. in a bag of low density polyethylene, in a polymer can 1 package; 10, 20, 30, 40, 50 or 100 pcs.in a polymer can, in a cardboard box 1 can);
- dosage 500 mg - No. 00, gelatinous solid, opaque, with a lid and a yellow body (5, 7 or 10 pcs. in a blister strip packaging; 10, 20, 30, 40, 50, 100 pcs. in a polymer can, in a cardboard box 1–6, 8, 10 packs or 1 can).
Capsule contents: powder or mixture of granules and powder from almost white or white to pale yellow; it is possible that the contents of the capsule are compacted in its shape, which disintegrates when pressed.
1 capsule contains:
- active substance: cycloserine - 125, 250 or 500 mg;
- additional components: 125 and 500 mg - magnesium stearate, lactose, colloidal silicon dioxide; 250 mg - the composition depends on the manufacturer;
- capsule shell; 125 mg - gelatin, titanium dioxide; 500 mg - gelatin, titanium dioxide, quinoline yellow and sunset yellow dyes; 250 mg - the composition depends on the manufacturer.
Pharmacological properties
Pharmacodynamics
Cycloserine belongs to the group of broad-spectrum antibiotics. Depending on the sensitivity of microorganisms and the concentration of the drug in the focus of inflammation, it exhibits bacteriostatic or bactericidal properties. By disrupting the synthesis of the cell membrane, the active substance manifests itself as a competitive antagonist of D-alanine. The drug inhibits the activity of enzymes that ensure the synthesis of the cell wall.
Cycloserine is active against gram-negative microorganisms, at a concentration of 10-100 mg / l - against Treponema spp. and Rickettsia spp. The minimum inhibitory concentration (MIC) in relation to Mycobacterium tuberculosis is 10–20 mg / L and higher on a solid, and 3–25 mg / L on a liquid nutrient medium. Resistance of microorganisms develops 6 months after the start of therapy in 20–80% of cases.
Pharmacokinetics
After oral administration, the absorption of cycloserine is 70–90%; it almost does not bind to plasma proteins. The maximum concentration of the drug (Cmax) in the blood plasma is proportional to the received dose of 250, 500 and 1000 mg is 6, 24 and 30 μg / l, respectively. Time to reach it (T Cmax) - 3-4 hours. In the case of taking cycloserine 250 mg every 12 hours, Cmax can vary from 25 to 30 μg / ml.
The substance penetrates well into tissues and body fluids such as breast milk, cerebrospinal fluid, lymphatic tissue, sputum, bile, lungs, pleural effusion, ascitic and synovial fluids. The placental barrier passes. The pleural and abdominal cavities may contain 50-100% of the serum concentration of the agent.
The process of metabolic transformation undergoes no more than 35% of the dose taken, the half-life against the background of normal renal function is 10 hours. The agent is excreted unchanged by glomerular filtration: 50% - after 12 hours, 65-70% within 24-72 hours; a small amount is excreted in the faeces.
In the presence of chronic renal failure (CRF), cumulation may occur in 2–3 days.
Indications for use
- tuberculosis: chronic forms, active pulmonary tuberculosis, extrapulmonary tuberculosis (including kidney damage) - with the sensitivity of pathogens to the drug and after ineffective therapy with essential drugs (as part of a combination treatment);
- urinary tract infections caused by susceptible strains of gram-negative and gram-positive bacteria (Escherichia coli, Enterobacter spp.);
- atypical mycobacterial infections, including those caused by Mycobacterium avium (as part of a combination treatment).
Contraindications
- chronic heart failure;
- epileptic seizures (including history);
- epilepsy;
- organic diseases of the central nervous system (CNS);
- CRF with creatinine clearance (CC) less than 25 or less than 50 ml / min (depending on the manufacturer);
- alcoholism;
- mental disorders (anxiety, depression, psychosis, including a history);
- hypersensitivity to the constituents of Cycloserine.
Additional contraindications, depending on the manufacturer:
- porphyria;
- addiction;
- pregnancy and the period of breastfeeding;
- age up to 3 or up to 12 years;
- glucose-galactose malabsorption, lactose intolerance, lactase deficiency (if lactose is present in capsules).
According to the instructions, Cycloserine should be used with extreme caution in children.
Instructions for the use of Cycloserine: method and dosage
Cycloserine is taken orally, immediately before meals, in case of irritation of the mucous membrane of the digestive tract - after meals.
The initial dose for adults, as a rule, is 250 mg taken 2 times a day (every 12 hours) for the first two weeks. In the future, if appropriate, depending on tolerance, the dose is carefully increased to 250 mg 3-4 times a day (every 6-8 hours), while monitoring the concentration of the substance in the blood serum.
The maximum daily dose of Cycloserine is 1000 mg, with functional disorders of the kidneys, a dose reduction is required.
Patients with a body weight of less than 50 kg, as well as over 60 years old, should take the drug 2 times a day, 250 mg.
The duration of therapy for urinary tract infections is 7-10 days, for mycobacterial infections - from 6 months or more.
Children after 3 years (or after 12 years - depending on the manufacturer) are recommended to take the drug in a daily dose of 10–20 mg / kg of body weight in 2–3 doses, but not exceeding 750 mg per day. Reception of large doses of Cycloserine is allowed only in the treatment of the acute phase of the tuberculous process or with insufficient effect of the above doses.
Side effects
- cardiovascular system and hematopoietic organs: the onset of congestive heart failure (when using daily doses of 1000-1500 mg);
- nervous system: dizziness, headache, nightmares, insomnia / drowsiness, increased irritability, anxiety, aggressiveness, memory impairment, peripheral neuritis, tremor, paresthesia, muscle twitching, dysarthria, depression, euphoria, disorientation with memory loss, mental confusion, psychosis, confusion, character change, epileptiform seizures, paresis, stupor, suicidal tendencies, major and minor seizures of clonic seizures, hyperreflexia, suicidal attempts, coma;
- allergic reactions: itching, skin rash;
- digestive system: heartburn, nausea, diarrhea, increased activity of hepatic aminotransferases (mainly in elderly patients with pre-existing liver disease);
- others: increased cough, fever, megaloblastic / sideroblastic anemia, folic acid and cyanocobalamin deficiency.
Overdose
Overdose can be observed when the plasma concentration of cycloserine is 25-30 mg / ml, resulting from impaired renal clearance or taking large doses of the drug. Oral use of the drug in a daily dose of more than 1000 mg increases the likelihood of acute poisoning. Symptoms of chronic intoxication against the background of long-term administration of the drug at 500 mg per day include the following disorders: dizziness, headache, irritability, confusion, psychosis, dysarthria, paresthesia, convulsions, paresis, coma.
In this condition, symptomatic and supportive therapy is recommended. Taking activated charcoal is more effective in reducing absorption than gastric lavage and induction of vomiting. For convulsions, antiepileptic drugs are prescribed, in order to prevent neurotoxic reactions, pyridoxine is administered at a rate of 200-300 mg per day, as well as sedative and anticonvulsant drugs. Hemodialysis ensures the removal of cycloserine from the blood, but cannot exclude the occurrence of life-threatening intoxication.
special instructions
Before starting therapy, it is required to isolate cultures of microorganisms and establish the sensitivity of the strains to the drug. If tuberculosis infection is detected, the sensitivity of the strain to other anti-tuberculosis drugs should be determined.
If, against the background of drug therapy, the development of allergic dermatitis or symptoms of CNS intoxication (dizziness, tremor, headache, drowsiness, convulsions, depression / confusion, paresis / dysarthria, hyperreflexia) is noted, its use must be stopped or the dose reduced. In patients with chronic alcoholism, due to the low therapeutic index of cycloserine, the risk of seizures increases.
During treatment, it is necessary to monitor kidney function (the level of creatinine and urea nitrogen in the blood), hematological parameters, liver activity and the concentration of the drug in the blood.
Anticonvulsants or sedatives can be used to prevent the development of CNS symptoms such as tremors, agitation, or seizures. Patients taking cycloserine in a daily dose of more than 500 mg should be under the direct supervision of a physician due to the risk of such undesirable effects.
To reduce or prevent the toxic effect of cycloserine, it is recommended during the course to take 3-4 times a day (before meals) glutamic acid at a dose of 500 mg and inject intramuscularly sodium salt of ATP (adenosine triphosphate) 1 ml of a 1% solution and pyridoxine, 200-300 mg per day.
To prevent the development of neurotoxic disorders, psychotropic drugs of the benzodiazepine series are used - phenazepam (at a dose of 1 mg) or diazepam (at a dose of 5 mg) at night, as well as piracetam 2 times a day at a dose of 800 mg.
Sometimes taking cycloserine and other anti-tuberculosis drugs can lead to a deficiency of folic acid and cyanocobalamin (vitamin B 12) in the body, as well as to the development of sideroblastic and megaloblastic anemia. If anemia occurs against the background of drug therapy, it is necessary to prescribe an appropriate examination and treatment.
During the period of application of the remedy, it is recommended to limit the neuropsychic stress of patients and exclude such possible factors of overheating as a hot shower and exposure to the sun with an uncovered head.
In view of the rapid development of resistance when using cycloserine as a monotherapy drug, it should be combined with other anti-TB drugs.
Influence on the ability to drive vehicles and complex mechanisms
The influence of cycloserine on the ability to drive a car and other complex equipment has not been established, but due to the possible development of undesirable reactions from the central nervous system, patients should refrain from potentially hazardous activities that require concentration of attention and speed of reactions.
Application during pregnancy and lactation
The concentrations of cycloserine in fetal blood and in breast milk are close to those found in the serum of a pregnant or breastfeeding woman (respectively). There is no information confirming the negative effect of the drug on the fetus when taken during pregnancy.
Cycloserine application:
- pregnancy: allowed only in extremely rare cases, with a vital need;
- lactation period: you should stop breastfeeding.
Some manufacturers of Cycloserine indicate pregnancy in the list of absolute contraindications for taking the drug, so you should carefully study the attached instructions.
Pediatric use
The drug is contraindicated for use in children under 3 or 12 years old (depending on the manufacturer). Taking cycloserine in childhood should be done with extreme caution.
With impaired renal function
In the presence of chronic renal failure (CC below 25 or 50 ml / min - depending on the manufacturer), therapy is contraindicated. In patients with reduced renal function receiving the drug in a daily dose of more than 500 mg, against the background of possible symptoms and signs of overdose, the level of cycloserine in the blood must be monitored at least 1 time per week. The dose in this case should be selected so that the concentration of the drug in the blood is below 30 mg / l.
For violations of liver function
Functional liver disorders do not affect the kinetics of cycloserine.
Use in the elderly
Elderly patients (over 60 years old) are recommended to take the drug 2 times a day, 250 mg.
Drug interactions
- pyridoxine: the rate of excretion of this agent by the kidneys increases (the development of peripheral neuritis and anemia is possible, the dose of pyridoxine should be increased);
- isoniazid: the incidence of drowsiness, dizziness increases (patients require careful observation);
- ethionamide: the threat of the appearance of neurotoxic effects of the drug is aggravated, the likelihood of a convulsive syndrome increases;
- streptomycin, isoniazid, paraaminosalicylic acid (PASK): resistance to these drugs decreases;
- ethanol: the risk of developing epileptic seizures increases (especially in patients with chronic alcoholism).
Analogs
Cycloserine analogs are: Kansamin, Coxerin, Maizer, Cyclorin, Cycloserine-Ferein.
Terms and conditions of storage
Store in a place protected from moisture and light, out of reach of children, at a temperature not exceeding 25 ° C.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Cycloserine
According to reviews, Cycloserine shows good results in the treatment of tuberculosis, mainly as part of combination therapy. However, it is indicated that with prolonged use there is a lack of vitamin B 12 and folic acid. And also patients note the neurotoxicity of the drug.
The price of Cycloserine in pharmacies
The price of Cycloserine is approximately 4900–5800 rubles per pack containing 100 capsules.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
