CYCLOSERINE Capsules Ref.[7208] Active ingredients: Cycloserine

Administration of cycloserine should be discontinued or the dosage reduced if the patient develops allergic dermatitis or symptoms of central nervous system toxicity such as convulsions, psychosis, somnolence, depression, confusion, hyper-reflexia, headache, tremor, vertigo, paresis or dysarthria.

Toxicity is usually associated with blood levels of greater than 30 mg/l, which may be the result of high dosage or inadequate renal clearance. The therapeutic index for this drug is low. The risk of convulsions is increased in chronic alcoholics (see ‘Precautions’ section).

Patients should be monitored by haematological, renal excretion, blood level and liver function studies.

Before treatment with cycloserine is begun, cultures should be taken and the susceptibility of the organism to the drug should be established. In tuberculous infections, sensitivity to the other anti-tuberculous agents in the regimen should also be demonstrated.

Blood levels should be determined at least weekly for patients having reduced renal function, for individuals receiving a daily dosage of more than 500 mg, and for those showing signs and symptoms suggestive of toxicity. The dosage should be adjusted to keep the blood level below 30 mg/l.

Anticonvulsant drugs or sedatives may be effective in controlling symptoms of central nervous system toxicity, such as convulsions, anxiety or tremor. Patients receiving more than 500 mg of cycloserine daily should be closely observed for such symptoms. The value of pyridoxine in preventing CNS toxicity from cycloserine has not been proven.

Administration of cycloserine and other anti-tuberculous drugs has been associated in a few instances with vitamin B₁₂ and/or folic acid deficiency, megaloblastic anaemia and sideroblastic anaemia. If evidence of anaemia develops during treatment, appropriate investigations and treatment should be carried out.

Cycloserine has been associated with clinical exacerbations of porphyria and is not recommended in porphyric patients.

Drug interactions

Concurrent administration of ethionamide has been reported to potentiate neurotoxic side-effects. Alcohol and cycloserine are incompatible, especially during a regimen calling for large doses of the latter. Alcohol increases the possibility and risk of epileptic episodes. Patients receiving cycloserine and isoniazid should be monitored for signs of CNS toxicity, such as dizziness and drowsiness, as these drugs have a combined toxic action on the CNS. Dosage adjustments may be necessary.

Pregnancy

Concentrations in fetal blood approach those found in the serum. A study in 2 generations of rats given doses up to 100 mg/kg/day demonstrated no teratogenic effect in offspring. It is not known whether cycloserine can cause fetal harm when administered to a pregnant woman or can affect reproductive capability. Cycloserine should be given to a pregnant woman only if clearly needed.

Breast-feeding

Concentrations in the mother’s milk approach those found in the serum. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Not relevant.

Most side-effects occurring during treatment with cycloserine involve the nervous system or are manifestations of drug hypersensitivity. The following side-effects have been observed: nervous system manifestations, which appear to be related to higher dosages of drug, i.e. more than 500 mg daily, can be convulsions, drowsiness, somnolence, headache, tremor, dysarthria, vertigo, confusion and disorientation with loss of memory, psychosis, possibly with suicidal tendencies, character changes, hyper-irritability, aggression, paresis, hyper-reflexia, paraesthesiae, major and minor localised clonic seizures and coma.

Other reported side-effects include allergy, rash, megaloblastic anaemia and elevated serum aminotransferases, especially in patients with pre-existing liver disease.

Sudden development of congestive heart failure, in patients receiving 1 to 1.5 g of cycloserine daily, has been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continues monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

Not applicable.