Schedule H1

Oral

• Capsules 250 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

◾ Multidrug-Resistant Tuberculosis (MDR-TB)

As part of WHO-recommended longer MDR-TB regimen under NTEP supervision

Parameter Recommendation

Starting dose 500 mg/day in 2 divided doses (for patients 30–45 kg); 750 mg/day in 2 divided doses (for patients 46–70 kg)

Titration Titrate based on tolerability, renal function, and neuropsychiatric symptoms over 1–2 weeks

Usual maintenance dose 750–1000 mg/day in 2 divided doses (15–20 mg/kg/day)

Maximum dose 1000 mg/day

Weight-Based Dosing Reference (Adults):

Body Weight Daily Dose Dosing Schedule

30–45 kg 500–750 mg 250 mg BD to 250 mg AM + 500 mg PM

46–70 kg 750 mg 250 mg AM + 500 mg PM or 375 mg BD (round to nearest capsule)

70 kg 750–1000 mg 500 mg BD

Clinical Notes:

• Never use as monotherapy — always part of intensive phase of NTEP-approved MDR-TB regimen

• Mandatory co-administration of pyridoxine (Vitamin B6) 100–150 mg/day to reduce neurotoxicity

• Round doses to nearest 250 mg capsule increment

• Duration as per NTEP protocol (typically 18–20 months in longer regimens)

Secondary Indications – Adults (Off-label, if any)

Not applicable — No accepted off-label indications in Indian practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications – Paediatric MDR-TB

Only under NTEP or tertiary care specialist supervision

Parameter Recommendation

Starting dose 10–15 mg/kg/day in 2 divided doses

Titration Increase to target dose over 1–2 weeks based on tolerability

Usual maintenance dose 15–20 mg/kg/day in 2 divided doses

Maximum dose 750 mg/day

Weight-Based Paediatric Dosing:

Body Weight Daily Dose Schedule

10–15 kg 250 mg 125 mg BD (requires capsule splitting/compounding)

16–25 kg 250–500 mg 250 mg OD to BD

26–40 kg 500–750 mg 250 mg BD to 250 mg + 500 mg

Clinical Notes:

• Not recommended for children <6 years due to lack of safety data and capsule-only formulation

• Always co-prescribe pyridoxine 10–25 mg/day (1–2 mg/kg/day)

• Weekly neuropsychiatric monitoring mandatory in first month

• Administer under directly observed therapy

Safety Monitoring:

• Baseline and monthly: Mental status, mood assessment

• Baseline and every 2 weeks initially: Renal function

• Ongoing: Monitor for peripheral neuropathy, seizures, behavioural changes

Secondary Indications – Paediatric (Off-label, if any)

Not applicable

50 mL/min No adjustment required

30–50 mL/min 500–750 mg/day in 2 divided doses; monitor closely

10–30 mL/min 250 mg BD; increased toxicity monitoring

<10 mL/min 250 mg OD; close neuropsychiatric and drug level monitoring

Haemodialysis 250 mg OD; administer dose after dialysis session

Peritoneal dialysis 250 mg OD; specialist supervision advised

Note: Terizidone/cycloserine accumulates in renal impairment — neurotoxicity risk significantly increased

• Known hypersensitivity to terizidone or cycloserine

• Active psychosis or history of severe psychiatric illness (schizophrenia, bipolar disorder with psychotic features)

• Uncontrolled epilepsy or seizure disorder

• Severe depression with suicidal ideation

• Concurrent chronic alcohol dependence (active)

• History of depression or anxiety disorders — requires close monitoring

• Previous seizures (controlled) — may lower seizure threshold

• Alcohol misuse history — increases CNS toxicity risk; strict abstinence required

• Pre-existing peripheral neuropathy — may worsen

• Concurrent use with other neurotoxic anti-TB drugs (isoniazid, ethionamide, linezolid)

• Low body weight (<40 kg) — increased toxicity risk

• Elderly patients — heightened susceptibility to neuropsychiatric effects

Parameter Details

Risk category Limited human data; potential CNS teratogenicity (extrapolated from cycloserine animal studies)

Preferred alternatives Other Group C agents (clofazimine, linezolid) may be considered where appropriate under specialist guidance

When may be used Only when MDR-TB treatment essential and alternatives unsuitable; NTEP/specialist supervision mandatory

Monitoring Fetal growth (serial ultrasound), maternal neuropsychiatric status, pyridoxine compliance

Pyridoxine requirement 100–150 mg/day mandatory if terizidone used in pregnancy

Parameter Details

Breastfeeding compatibility Not contraindicated; may continue with monitoring

Expected drug levels in milk Low (limited data; extrapolated from cycloserine)

Preferred alternatives None specifically preferred; decision based on overall MDR regimen

Infant monitoring Irritability, poor feeding, excessive sedation, seizures, developmental milestones

Additional measures Pyridoxine supplementation for infant (1–2 mg/kg/day) recommended if breastfeeding continued

Parameter Recommendation

Starting dose 250 mg/day in single dose or 250 mg BD

Titration Slower titration over 2–4 weeks; increase by 250 mg weekly if tolerated

Maximum dose 750 mg/day (rarely 1000 mg/day)

Special risks Increased susceptibility to: psychosis, confusion, seizures, falls, peripheral neuropathy

Additional monitoring Baseline and periodic renal function; weekly neuropsychiatric review; fall risk assessment

Interacting Drug Effect Management

Alcohol Significantly increases risk of CNS toxicity and seizures Strictly contraindicated during treatment

Isoniazid (high-dose) Additive neurotoxicity; increased seizure and neuropathy risk Avoid concurrent high-dose isoniazid; if used, ensure adequate pyridoxine

Ethionamide Additive CNS and peripheral neurotoxicity Monitor closely; consider dose reduction of one or both agents

Cycloserine Same active metabolite — overlapping toxicity Never use together (pharmacologically redundant)

Interacting Drug Effect Management

Fluoroquinolones (moxifloxacin, levofloxacin) May potentiate CNS effects; both lower seizure threshold Monitor mental status; use with standard caution in MDR regimens

Linezolid Additive neurotoxicity (peripheral neuropathy, CNS effects) Monitor closely; both commonly used in MDR regimens

Carbamazepine/Phenytoin May induce metabolism; also lower seizure threshold Monitor for reduced efficacy and seizure control

Pyridoxine (Vitamin B6) Protective — reduces neurotoxic effects Always co-administer (100–150 mg/day in adults)

• Headache

• Drowsiness and somnolence

• Dizziness

• Mood changes (irritability, anxiety)

• Tremors

• Nausea and abdominal discomfort

• Peripheral neuropathy (dose-related, preventable with pyridoxine)

• Insomnia

Adverse Effect Clinical Action

Psychosis (hallucinations, paranoia, severe behavioural change) Immediate discontinuation; psychiatric evaluation

Seizures Discontinue; anticonvulsant management; do not rechallenge

Suicidal ideation or behaviour Immediate discontinuation; urgent psychiatric referral

Severe depression Consider discontinuation; psychiatric evaluation

Hypersensitivity reactions (rare) Discontinue; supportive management

Phase Parameters

Baseline Mental status examination; renal function (serum creatinine, eGFR); LFTs; peripheral neuropathy assessment; document any psychiatric history

After initiation (first month) Weekly neuropsychiatric review; renal function every 2 weeks; assess for neuropathy symptoms

Ongoing (monthly) Mental status; mood assessment; peripheral neuropathy screening; renal function; pyridoxine compliance

Long-term Cognition assessment; monitor for cumulative neurotoxicity; adjust dose if renal function declines

• Terijox® (Macleods Pharmaceuticals)

• Tracetriz® (Lupin)

• Generic formulations supplied under NTEP

Source Price (per 250 mg capsule)

Private market ₹18–30

Government/NTEP supply Free for enrolled MDR-TB patients

Note: Not listed under NLEM; procurement primarily through NTEP for MDR-TB management

1. Pyridoxine is mandatory — Never prescribe terizidone without concurrent pyridoxine (100–150 mg/day adults; 10–25 mg/day children); omission significantly increases neurotoxicity risk

1. Structurally a prodrug of cycloserine — Terizidone consists of two cycloserine molecules; identical antimicrobial spectrum and toxicity profile but better gastrointestinal tolerance

1. Neuropsychiatric toxicity is dose-limiting — Start low, titrate slowly; err on side of lower dosing in patients with low body weight, elderly, or renal impairment

1. Immediate discontinuation required for psychosis, hallucinations, or suicidal ideation — Do not attempt dose reduction; these warrant permanent discontinuation

1. Not interchangeable with cycloserine in same regimen — Pharmacologically equivalent; never combine

1. Only for supervised MDR-TB treatment — Not suitable for drug-susceptible TB or empirical use; always part of complete NTEP-approved regimen

Terizidone; MDR-TB; XDR-TB; second-line antitubercular; antimycobacterial; NTEP India; neurotoxic; pyridoxine-dependent; renal-adjustment; Schedule H1; cycloserine-derivative

RxIndia v1.0 — 07 May 2024

• CDSCO (Central Drugs Standard Control Organisation)

• IP/NFI (Indian Pharmacopoeia / National Formulary of India)

• NTEP India Guidelines for Programmatic Management of Drug-Resistant TB (2021)

• ICMR MDR/XDR TB Management Guidelines

• AIIMS Department of Pulmonary Medicine dosing protocols

• WHO Consolidated Guidelines on Drug-Resistant Tuberculosis Treatment (supportive reference for Group C classification)