Cycloserine + Pyridoxine (Cycloserinum + Pyridoxinum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Other antibiotics

Included in the formulation
  • Coxerin® Plus
    pills inwards 
    McLeodz Pharmaceuticals Co., Ltd.     India
  • Cyclo plus
    pills inwards 
    S.P.Inkomed Pvt.Ltd     India
  • Cyclomycin® Plus
    pills inwards 
    VALENTA PHARM, PAO     Russia
  • Cyclomycin® Plus
    capsules inwards 
    VALENTA PHARM, PAO     Russia
    • АТХ:

    J.04.A.B.01   Cycloserine

    A.11.H.A.02   Pyridoxine (vitamin B6)

    Pharmacodynamics:

    Combined drug.

    Cycloserin is a broad-spectrum bactericidal antibiotic; inhibits the synthesis of the cell wall of sensitive strains of gram-positive and gram-negative bacteria and mycobacteria tuberculosis.

    Pyridoxine reduces the severity of adverse reactions of cycloserine from the side of the central nervous system.

    Pharmacokinetics:

    Cycloserine is rapidly absorbed from the digestive tract. Absorption after oral administration is 70-90%. Virtually does not bind to plasma proteins. Time to reach a maximum concentration of 3-4 hours After taking 250 mg every 12 hours, the maximum concentration of 25-30 μg / ml. It penetrates well into body fluids and tissues. Penetrates into lymphoid tissue, lung tissue, pleural and ascites fluid, phlegm, bile, breast milk. In the abdominal and pleural cavities contains 50-100% of the concentration of the drug in the blood serum. Passes the placental barrier and hematoencephalic barrier (the concentration in the cerebrospinal fluid corresponds to the concentration in the plasma, determined in the amniotic fluid and fetal blood).About 35% of the administered dose is metabolized. It is allocated mainly by the kidneys in an unchanged form by glomerular filtration (50% - found in urine for 12 hours, 65-70% within 24-72 hours), small amounts are excreted by the intestine. Half-life of cycloserine with a normal kidney function of about 10 hours. In chronic kidney failure after 2-3 days, cumulation phenomena may occur.

    Pyridoxine is rapidly absorbed throughout the small intestine, more is absorbed in the jejunum. Metabolised in the liver with the formation of pharmacologically active metabolites (pyridoxal phosphate and pyridoxamine phosphate). Pyridoxal phosphate with plasma proteins binds to 90%. Well penetrates into all tissues, accumulates mainly in the liver, less - to the muscles and the central nervous system. Penetrates through the placenta, is secreted with breast milk. It is excreted by the kidneys. The half-life of pyridoxine is 15-20 days.

    Indications:

    In combination with other anti-tuberculosis drugs: active pulmonary tuberculosis, extrapulmonary tuberculosis (including kidney damage) in the case of sensitivity of the microorganisms to the drug and after an unsuccessful adequate treatment with basic medicinal drugs (rifampicin, isoniazid, streptomycin, ethambutol).The combination of tuberculosis with acute infections of the urinary tract caused by sensitive strains of gram-positive and gram-negative bacteria, in particular Klebsiella spp., Enterobacter spp., Escherichia coli with ineffectiveness of essential medicines. Atypical mycobacterial infections (including those caused by Mycobacterium avium).

    ICD-10

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

    I.A15-A19.A16.2   Tuberculosis of the lungs without mention of bacteriological or histological confirmation

    I.A15-A19   Tuberculosis

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

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

    Contraindications:
    • Hypersensitivity to the components of the drug.
    • Organic diseases of the central nervous system.
    • Epilepsy.
    • Depression.
    • Expressed state of excitation.
    • Psychosis.
    • Chronic renal failure (creatinine clearance less than 50 ml / min).
    • Acute and chronic heart failure.
    • Alcoholism.
    • Addiction.
    • Pregnancy.
    • Lactation period.
    • Children under 3 years.
    Carefully:
    • Impaired renal function (risk of cumulation of the drug).
    • Childhood.
    Pregnancy and lactation:

    Recommendations for FDA - category C. Application in pregnancy is possible only in exceptional cases, when the intended use for the mother exceeds the potential risk to the fetus.

    If you need to use the drug during 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 are prescribed 12.5 mg / kg body weight or 500-750 mg per day (cycloserine) in 2-3 doses (initial dose of cycloserine 250 mg every 12 hours during the first week, then, if necessary taking into account the tolerability dose carefully increase up to 250 mg every 6-8 hours under the control of the level of cycloserine in the blood). The highest single dose of cycloserine for adults is 250 mg; the maximum daily dose is 1 g. Patients over 60 years of age, and also with a body weight of less than 50 kg are prescribed 250 mg (cycloserine) 2 times a day.

    In children, the initial dose of cycloserine is 10-20 mg / kg of body weight per day, the maximum daily dose is 750 mg.

    Side effects:

    In treatment, side effects can occur, mainly due to the effect of cycloserine on the nervous system. These phenomena usually occur when the dose is reduced or the drug is withdrawn.

    From the side central and peripheral nervous system: cramps, drowsiness, headache, tremor, dysarthria, dizziness, confusion and impaired orientation, accompanied by loss of memory, psychoses (including suicidal attempts), irritability, aggressiveness, peripheral paresis, hyperreflexia, paresthesia, large and small attacks of clonic seizures , a coma.

    From the side digestive system: nausea, heartburn, diarrhea, increased activity of "hepatic" aminotransferases in the serum.

    From the side cardiovascular system and hematopoiesis system: sideroblastic and megaloblastic anemia, when applied at a dose of 1 g per day exacerbation of chronic heart failure.

    Other: deficiency of cyanocobalamin and folic acid, allergic reactions (skin rash, itching, fever, coughing).

    If any of the side effects listed in the manual are aggravated or any other side effects not indicated in the instructions are noted, the doctor should be informed immediately.

    Overdose:

    Overdosage is observed at a plasma cycloserine concentration of 25-30 mg / ml (high doses, impaired renal clearance).Acute poisoning can occur when ingested more than 1 g per day. Symptoms of chronic intoxication occur with long-term administration of cycloserine in a dose of more than 500 mg per day.

    Symptoms: headache, dizziness, increased irritability, paresthesia, dysarthria, paresis, convulsions, psychosis, confusion or loss of consciousness (coma).

    Treatment: symptomaticActivated carbon, anticonvulsant and sedatives). Effective hemodialysis. For the prevention of neurotoxic effects are introduced pyridoxine at a rate of 200-300 mg per day. All activities are conducted against the background of drug withdrawal.

    Interaction:

    Reduces resistance to isoniazid, streptomycin and PASC.

    Enhances the neurotoxic effect of ethionamide.

    Ethanol increases the risk of seizures.

    Isoniazid increases the toxic effect on the central nervous system.

    Pyridoxine (in combination cycloserine + pyridoxine) with combined application weakens the activity of levodopa.

    Penicillamine, when combined, weakens the effect of pyridoxine (in combination cycloserine + pyridoxine).

    Ethionamide enhances the neurotoxic effect of cycloserine (in combination cycloserine + pyridoxine): simultaneous administration of ethionamide increases the risk of side effects from the CNS, especially convulsive syndrome.

    Special instructions:

    In case of development against the background of treatment of allergic dermatitis or symptoms of CNS damage (cramps, psychosis, drowsiness, confusion, hyperreflexia, headache, dizziness, tremor, peripheral paresis, dysarthria), the drug should be discontinued.

    During the treatment period, EEG, hematologic parameters, kidney and liver function should be monitored. In the treatment of patients with reduced renal function, taking a daily dose of more than 500 mg, it is necessary to monitor urinalysis weekly. Anticonvulsants or sedatives can be effective in preventing symptoms of CNS damage (including seizures, agitation, tremors). 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 neurotoxic effects prescribe drugs benzodiazepine series (diazepam), nootropic drugs (piracetam, glutamic acid).

    In some cases, the use of cycloserine and other anti-TB drugs can lead to the development of insufficiency of cyanocobalamin and folic acid, megaloblastic anemia.

    Given the possible side effects, when taking the drug should be careful during work drivers of vehicles and people whose profession requires increased concentration and speed of psychomotor reactions.

    Instructions
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