Drug Detail

Cycloserine

Last Updated June 10, 2016

Trade Names

Not registered in South Africa; can be obtained from Equity Pharmaceuticals on named-patient basis following MCC approval.

Drug Classification

Broad spectrum antibiotic targeting cell envelope

Formulations

250 mg capsules

Indications and Pharmacology

Indication: treatment of tuberculosis resistant to first-line agents, when administered in combination with at least 1 or 2 other drugs to which the organism is known to be susceptible.

Mechanism of action: inhibits cell wall synthesis through enzymatic inhibition.

Pharmacokinetics: absorbed from gastrointestinal tract and widely distributed to tissues and fluids including central spinal fluid, pleural fluid, foetal blood, and breast milk; Tmax 4-6 hours, half-life 12 hours.

Dosage

Adult Dose: 10-20 mg/kg/day, usually 500-750 mg/day in divided doses; maximum 1 g/day. Take on empty stomach; give with meals if gastrointestinal intolerance occurs.*

Should be given with pyridoxine 150 mg.*

Use in Renal or Hepatic Insufficiency:

  • Contraindicated in severe renal insufficiency.
  • For renal impairment extend dose interval: for glomerular filtration rate 10-50 mL/min, 24 hours; for glomerular filtration rate < 10 mL/min, 36-48 hours.
  • No adjustments needed for hepatic insufficiency.

Use in Pregnancy and Breastfeeding*: Pregnancy Category C. No teratogenicity in animals has been reported. Use during pregnancy only if no alternatives exist; consider giving breast-fed infants concurrent pyridoxine.

Use in Children: Off-label use: 5-10 mg/kg/dose twice daily(maximum 1 g/day); used for multidrug-resistant tuberculosis and drug-resistant tuberculosis meningitis.

Warnings

Contraindicated in patients with hypersensitivity to cycloserine, neurological conditions (epilepsy, depression, severe anxiety, psychosis), severe renal insufficiency, porphyria, or excessive concurrent alcohol use.

Should be discontinued or dose reduced if allergic dermatitis or symptoms of central nervous system toxicity occur.

Patients should be monitored for haematologic, renal, blood, and liver function disturbances.

Most adverse reactions occur with higher doses of cycloserine.

Concomitant pyridoxine 150-300 mg/day may prevent or reduce central nervous system toxicity.

Use alone or failure to complete full treatment regimen may result in rapid development of resistance.

Drug–Drug Interactions

Potentiation of adverse effects of concomitant medication: ethionamide (neurotoxicity): isoniazid, efavirenz (central nervous system effects); phenytoin (levels may be increased).

Incompatible with alcohol (increased risk of epilepsy).

Cross-resistance: occurs with terizidone.

Considerations for Special Populations

For renal impairment extend dose interval: for glomerular filtration rate 10-50 mL/min, 24 hours; for glomerular filtration rate < 10 mL/min, 36-48 hours.

Adverse Effects

Central nervous system effects (dose related): dizziness, slurred speech, convulsions, headache, vertigo, drowsiness, tremor, paraesthesia, coma, insomnia, confusion, depression, anxiety suicidality, psychosis, confusion, aggression, irritability, paranoia, peripheral neuropathy; changes in liver function tests, hepatitis; hypersensitivity, allergic dermatitis; photosensitivity; megaloblastic anaemia ; heart failure at high doses.*

*Information from terizidone entry in Aurum Institute Drugs on the Go.
From US Prescribing Information.