Schedule H1

Oral

Form Strength

Capsule 250 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

▶ Multidrug-Resistant Tuberculosis (MDR-TB)

Use only as part of multidrug regimen under NTEP protocols or specialist supervision

Parameter Details

Starting dose 250 mg once daily for first 2 weeks

Titration Increase by 250 mg every 3–5 days based on tolerance and neuropsychiatric assessment

Usual maintenance dose 500–750 mg/day in 1–2 divided doses

Maximum dose 1000 mg/day (requires close psychiatric and seizure monitoring)

Duration Entire course of MDR-TB regimen (typically 18–20 months) as per NTEP

Key Clinical Notes:

• Must be combined with at least 4–5 other effective second-line drugs; never use as monotherapy

• Divided dosing (twice daily) may reduce peak CNS toxicity compared to single daily dose

• Mandatory pyridoxine co-administration (50–100 mg/day) to prevent neurotoxicity

• Psychiatric risk assessment essential before initiation

• Dose selection influenced by body weight, tolerability, and renal function

Secondary Indications – Adults Only (Off-label):

Not routinely used beyond MDR-TB treatment programmes in India. Historical use in urinary tract infections and other mycobacterial infections is obsolete and NOT recommended in current Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

▶ MDR-TB in Children (as per NTEP and IAP MDR-TB Guidelines)

Weight Band Starting Dose Titration Usual Maintenance Dose Maximum Dose

10–15 kg 125 mg once daily Increase gradually as tolerated 10–15 mg/kg/day in 1–2 divided doses 250 mg/day

16–25 kg 250 mg once daily Increase gradually as tolerated 10–15 mg/kg/day in 1–2 divided doses 375 mg/day

26–45 kg 250–375 mg once daily Increase gradually as tolerated 10–15 mg/kg/day in 1–2 divided doses 500 mg/day

45 kg 250–500 mg once daily Increase gradually as tolerated 10–15 mg/kg/day in 1–2 divided doses 750 mg/day

Key Clinical Notes:

• Use only under NTEP or paediatric TB specialist supervision

• Divided dosing (twice daily) preferred for tolerability

• Co-administer pyridoxine 1–2 mg/kg/day (maximum 50 mg/day) for neuroprotection

• Capsule may need to be opened and contents mixed with food for younger children (specialist guidance required)

Safety Monitoring:

• Active monitoring for behavioural changes, seizures, confusion

• Baseline and periodic mental health assessment

• Renal function monitoring

• Weight monitoring at each visit

Secondary Indications – Paediatrics (Off-label):

None routinely used in India. Not recommended outside NTEP-supervised MDR-TB programmes.

Age Restriction Statement:

Not recommended below 5 years of age except under specialist MDR-TB supervision with documented exceptional indication. Requires active monitoring for neuropsychiatric adverse effects in all paediatric patients.

50 No adjustment required Standard dosing

30–50 Use lower end of dosing range (250 mg once daily) Monitor for CNS toxicity

10–29 250 mg every 48 hours Close monitoring mandatory

<10 (not on dialysis) 250 mg every 48–72 hours Avoid if possible; specialist supervision only

Haemodialysis 250 mg after each dialysis session Drug is dialyzable; monitor serum levels if available

Peritoneal dialysis 250 mg every 48 hours Limited data; specialist supervision

• History of seizures or epilepsy not adequately controlled on antiepileptic therapy

• Known hypersensitivity to cycloserine

• Active alcoholism or alcohol use disorder

• Severe psychiatric illness (active psychosis, severe depression with suicidal ideation)

• Severe renal impairment (eGFR <10 mL/min) without specialist oversight and monitoring capability

• History of depression, anxiety, or psychosis — even if currently in remission

• Concurrent use with other neurotoxic drugs (isoniazid, ethionamide, fluoroquinolones)

• Elderly patients — increased susceptibility to CNS adverse effects

• History of alcohol misuse — strictly avoid alcohol during treatment

• Pre-existing peripheral neuropathy

• Renal impairment (eGFR <50 mL/min) — requires dose adjustment and close monitoring

• Avoid abrupt dose escalation — gradual titration essential

Parameter Recommendation

Risk category Not formally classified in India; limited human data available

Overall safety Use only if benefit clearly outweighs risk; potential for fetal harm

Preferred alternatives Avoid cycloserine if other effective second-line agents available in the regimen

When may be used In MDR-TB when resistance pattern requires and no safer alternative exists; only under expert supervision

Monitoring Maternal neurotoxicity assessment; fetal growth surveillance; ensure pyridoxine supplementation

Parameter Recommendation

Excretion in milk Yes; levels suspected to be low to moderate

Compatibility Use with caution; may continue breastfeeding if essential for MDR-TB regimen

Preferred alternatives Use only if no alternative second-line agent available in regimen

Infant monitoring Feeding behaviour, irritability, weight gain, signs of CNS effects

Additional notes Mother must receive pyridoxine supplementation

Parameter Recommendation

Starting dose 250 mg once daily

Titration Slower titration over ≥2–3 weeks; increase by 125–250 mg every 5–7 days

Additional risks Increased risk of cognitive impairment, confusion, dizziness, falls, seizures; reduced renal clearance common

Special considerations Assess renal function before dosing; ensure pyridoxine co-administration; close neuropsychiatric monitoring mandatory

Interacting Drug/Class Mechanism / Risk Recommendation

Isoniazid Additive neurotoxicity — significantly increased risk of seizures, psychosis, peripheral neuropathy Avoid concurrent use if possible; if essential, monitor very closely with pyridoxine supplementation

Alcohol Markedly increases CNS toxicity; may precipitate seizures and psychosis Contraindicated — strict alcohol avoidance mandatory

Ethionamide / Prothionamide Additive CNS toxicity (confusion, psychosis) Avoid combination if possible; if used together, intensive neuropsychiatric monitoring

Phenytoin Altered phenytoin levels; lowered seizure threshold Monitor phenytoin levels closely; avoid if possible

Interacting Drug/Class Mechanism / Risk Recommendation

Pyridoxine (Vitamin B6) Reduces cycloserine-induced neurotoxicity Mandatory co-prescription — 50–100 mg/day in adults; 1–2 mg/kg/day in children

Fluoroquinolones (levofloxacin, moxifloxacin) Cumulative CNS effects; both may lower seizure threshold Monitor for seizures; part of standard MDR-TB regimens — use with caution

SSRIs / SNRIs Additive CNS effects; potential for serotonergic symptoms Monitor closely for psychiatric symptoms

Carbamazepine Lowered seizure threshold; potential for interaction Avoid if possible; monitor antiepileptic levels

Linezolid Cumulative peripheral neuropathy risk Monitor neuropathy symptoms; ensure pyridoxine

Bedaquiline / Delamanid Part of MDR-TB regimens; monitor for overlapping CNS toxicities Use as per NTEP protocols with appropriate monitoring

• Headache

• Drowsiness and somnolence

• Dizziness

• Confusion

• Tremor

• Irritability

• Insomnia

• Anxiety

• Difficulty concentrating

Adverse Effect Notes

Seizures May require immediate discontinuation; more common with renal impairment or high doses

Psychosis and hallucinations Requires immediate dose reduction or drug withdrawal; psychiatric consultation

Severe depression May include suicidal ideation; can occur even weeks after starting therapy; requires discontinuation

Suicidal behaviour Immediate discontinuation and psychiatric evaluation mandatory

Peripheral neuropathy May be irreversible; ensure pyridoxine prophylaxis

Coma Rare; associated with overdose or severe toxicity; requires hospitalisation

During titration (weeks 1–8) Weekly neuropsychiatric assessment; monitor for behavioural changes, confusion, sleep disturbances; renal function at week 4

Maintenance (monthly) Mental health review; neurological examination; renal function every 2–3 months

Long-term Ongoing psychiatric follow-up throughout treatment; neurological assessment every 4–8 weeks; ensure continued pyridoxine co-administration

Note: Therapeutic drug monitoring (serum cycloserine levels) should be performed where available, particularly in renal impairment. Target trough levels: 20–35 mcg/mL.

• Cyclorin (Macleods)

• Seromycin (Lilly — limited availability)

• Cycloserine capsules (NTEP/Government supply — generic labels)

Note: Supplied free of cost under NTEP for eligible patients enrolled in MDR-TB treatment programmes. Private market availability may be limited.

NLEM Status: Not currently listed under NLEM 2022 price control

Government Supply: Available free under NTEP for patients on programmatic MDR-TB treatment

• Always co-administer pyridoxine (vitamin B6) — 50–100 mg/day in adults, 1–2 mg/kg/day in children — this is mandatory, not optional

• Psychiatric screening before initiation is essential — document baseline mental health status; high-risk patients need close follow-up

• Inform caregivers to actively watch for behavioural changes (irritability, confusion, sleep disturbances) — these may be early signs of CNS toxicity

• Divided dosing (twice daily) reduces peak CNS side effects compared to single higher doses

• In renal impairment, dose adjustment is critical — reduced clearance significantly increases neurotoxicity risk; therapeutic drug monitoring where available

• Alcohol is strictly contraindicated throughout therapy — counsel patients explicitly at each visit

cycloserine; MDR-TB; tuberculosis; second-line antitubercular; neurotoxicity; seizure-risk; CNS-effects; renal-adjust; NTEP; pyridoxine; Schedule H1

RxIndia v1.0 — 28 May 2025

• CDSCO approved formulations

• Indian Pharmacopoeia / National Formulary of India

• NTEP (National Tuberculosis Elimination Programme) Guidelines for Programmatic Management of Drug-Resistant TB

• IAP MDR-TB Paediatric Guidelines

• API Textbook of Medicine

• AIIMS Pharmacology Formulary

• Harrison's Principles of Internal Medicine

• WHO Consolidated Guidelines on Drug-Resistant Tuberculosis Treatment (2020) — adapted for India (supportive reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (pharmacology reference)