Cycloserine

Cycloserine Chemical Structure

Mode of Action

Cycloserine works as an antibiotic by inhibiting cell-wall biosynthesis in bacteria. As a cyclic analogue of D-alanine, cycloserine acts against two crucial enzymes important in the cytosolic stages of peptidoglycan synthesis: alanine racemase (Alr) and D-alanine:D-alanine ligase (Ddl).

Drug Label Information | Brands:

Brands of Cycloserine in Kenya

Coxerin, Macleods Pharmaceuticals Limited
Cycloserine, Eli Lilly

INDICATIONS:

Cycloserine is indicated in the treatment of active pulmonary and extra-pulmonary tuberculosis (including renal disease) when the organisms are susceptible to this drug and after failure of adequate treatment with the primary medications (streptomycin, isoniazid, rifampicin and ethambutol). Like all anti-tuberculous drugs, cycloserine should be administered in conjunction with other effective chemotherapy and not as the sole therapeutic agent.

Cycloserine may be effective in the treatment of acute urinary tract infections caused by susceptible strains of Gram-positive and Gram-negative bacteria, especially Klebsiella/Enterobacter species and Escherichia coli. It is generally no more and may be less effective than other antimicrobial agents in the treatment of urinary tract infections caused by bacteria other than mycobacteria. Use of cycloserine in these infections should be considered only when the more conventional therapy has failed and when the organism has been demonstrated to be sensitive to the drug.

POSOLOGY / ADMINISTRATION

Adults: the usual dosage is 500 mg to 1 g daily in divided doses, monitored by blood level determinations. The initial adult dosage most frequently given is 250 mg twice daily at 12-hour intervals for the first two weeks. A daily dosage of 1g should not be exceeded.

The elderly: as for adults but reduce dosage if renal function is impaired.

Paediatric population

The usual starting dose is 10 mg/ kg/ day, then adjusted according to blood levels obtained and therapeutic response.

Method of administration

For oral administration.

CONTRAINDICATIONS:

Hypersensitivity to this drug or exepients.

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.

ADVERSE DRUG REACTIONS:

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.