What is the purpose of this medication?

Cycloserine: Purpose and Clinical Use

Cycloserine is a second-line antibiotic medication primarily used for treating drug-resistant tuberculosis in patients with organisms that have known or presumed susceptibility to the agent. 1

Primary Indications

• Treatment of drug-resistant tuberculosis (TB)
• Temporary treatment for TB patients with acute hepatitis when combined with other non-hepatotoxic drugs 1

Mechanism and Dosing

Cycloserine is an oral antibiotic that works by inhibiting bacterial cell wall synthesis. The recommended dosing is:

• Adults: 10-15 mg/kg per day (maximum 1,000 mg), usually given as 500-750 mg/day in two divided doses 1
• Children: 10-15 mg/kg per day (maximum 1.0 g/day) 1
• Available as 250 mg capsules 1

Safety Considerations

Neuropsychiatric Effects

Cycloserine has significant neuropsychiatric side effects that require careful monitoring:

• Central nervous system effects range from mild (headache, restlessness) to severe (psychosis, seizures) 1, 2
• Seizure risk is dose-dependent:
  • 16% risk with 500 mg twice daily
  • Only 3% risk with 500 mg once daily 1, 2
• May exacerbate underlying seizure disorders or mental illness 1, 2
• Pyridoxine (vitamin B6) supplementation at 100-200 mg/day is recommended to prevent and treat neurotoxic side effects 1, 2

Special Populations

1. Renal Impairment:

   • Drug accumulates in patients with impaired renal function
   • Avoid in patients with creatinine clearance <50 ml/minute unless on hemodialysis
   • For hemodialysis patients: 500 mg three times weekly or 250 mg daily 1, 2
   • Serum concentration monitoring recommended 2

2. Hepatic Disease:

   • No specific precautions except in patients with alcohol-related hepatitis who have increased seizure risk 1, 2

3. Pregnancy:

   • Crosses the placenta
   • Limited safety data in pregnancy
   • Use only when no suitable alternatives exist 1, 2

Monitoring Requirements

• Neuropsychiatric status assessment at least monthly and more frequently if symptoms develop 1, 2
• Serum concentration measurements aiming for peak concentration of 20-35 mg/ml may be necessary to determine optimal dosing 1, 2
• For patients taking phenytoin, monitor serum phenytoin concentrations due to potential interactions 1, 2

Clinical Pearls and Pitfalls

• Start with lower doses and titrate slowly to minimize neuropsychiatric side effects 2
• Higher doses (>500 mg/day) are associated with increased toxicity 2
• Patient education about potential neuropsychiatric symptoms is essential, with instructions to report them immediately 2
• If severe neuropsychiatric symptoms develop, dose reduction or discontinuation may be necessary 2
• Patients with alcohol-related hepatitis have increased risk of seizures when taking cycloserine 2

Fixed-Dose Combinations for TB

It's worth noting that cycloserine is not included in the fixed-dose combination preparations used for standard TB treatment. The fixed-dose combinations (Rifamate® and Rifater®) contain different medications:

• Rifamate®: Contains rifampin (300 mg) and isoniazid (150 mg)
• Rifater®: Contains rifampin (120 mg), isoniazid (50 mg), and pyrazinamide (300 mg) 1

These fixed-dose combinations help minimize inadvertent monotherapy and reduce the risk of acquired drug resistance, particularly when directly observed therapy is not possible 1.