Schedule H

Oral

• Tablet: 2 mg, 4 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Spasticity Due to Multiple Sclerosis, Spinal Cord Injury, or Cerebral Origin

Parameter Recommendation

Starting dose 2 mg orally once to three times daily

Titration Increase by 2–4 mg per dose every 3–4 days based on response and tolerability

Usual maintenance dose 6–24 mg/day in 2–3 divided doses

Maximum dose 36 mg/day (in 3 divided doses; single dose should not exceed 16 mg)

Key Clinical Notes:

• Titrate slowly to minimise hypotension and sedation

• Short half-life (~2.5 hours) allows flexible dosing tailored to daily activity pattern

• Administer last dose at bedtime if nocturnal spasticity is predominant

• Avoid abrupt discontinuation — taper gradually

1. Acute Musculoskeletal Spasm (Short-Term Adjunctive Therapy)

Parameter Recommendation

Starting dose 2 mg orally twice to three times daily

Titration Not typically required for short-term use

Usual maintenance dose 4 mg three times daily

Maximum dose 12 mg/day

Key Clinical Notes:

• Intended for short-term use only (typically 2–3 days, maximum 1 week)

• Not for chronic non-spasticity-related musculoskeletal pain

• Avoid abrupt withdrawal even after short-term use if high doses used

Secondary Indications — Adults (Off-label)

Indication Dose Duration Evidence Basis Remarks

Chronic tension-type headache (prophylaxis) 2–4 mg at bedtime Intermittent or short-term Small RCTs; Indian neurology practice OFF-LABEL. Specialist (neurologist) only. Used as adjunct in refractory cases.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

NOT APPROVED for routine paediatric use in India.

Secondary Indications — Paediatric Doses (Off-label)

Severe Spasticity (Cerebral Palsy, Spinal Cord Pathology)

• Minimum age: 10 years

• Not recommended below 10 years of age except under specialist supervision

Parameter Recommendation

Starting dose 0.05 mg/kg/dose orally once or twice daily

Titration Increase by 0.05 mg/kg/dose every 3–7 days based on response and tolerability

Usual maintenance dose Individualised; typically 0.1–0.2 mg/kg/day in divided doses

Maximum dose 0.3 mg/kg/day OR 24 mg/day, whichever is lower

Safety Monitoring:

• Liver function tests at baseline and periodically during therapy

• Blood pressure monitoring (risk of hypotension)

• Sedation level assessment

• Specialist (paediatric neurologist) supervision mandatory

Remarks: OFF-LABEL use. Limited paediatric data; extrapolated from adult dosing.

Creatinine Clearance (mL/min) Recommendation

≥25 No dose adjustment required; standard dosing

<25 Start with 2 mg once daily; titrate very slowly; use longer dosing intervals (once or twice daily only)

Haemodialysis Not significantly removed by dialysis; avoid high doses; start at 2 mg once daily

Note: Close monitoring for hypotension and excessive sedation is essential in renal impairment.

• Known hypersensitivity to tizanidine or any excipient

• Severe hepatic impairment

• Concomitant use with strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) — contraindicated

• Renal impairment — increased risk of accumulation and adverse effects

• Hypotension or concurrent antihypertensive therapy — additive blood pressure lowering

• Elderly patients — increased sensitivity to CNS and cardiovascular effects

• History of cardiac disease or QT prolongation

• Abrupt withdrawal after prolonged use — risk of rebound hypertension, tachycardia, tremor, anxiety

• Sedation and impaired coordination — caution regarding driving or operating machinery

• Concurrent use of other CNS depressants

Parameter Details

Safety category Limited human data; risk not fully established

When it may be used Only if benefit clearly outweighs risk; specialist input advisable

Preferred alternatives For acute spasms: paracetamol with physiotherapy is preferred; for chronic spasticity: consider baclofen under specialist guidance

What to monitor Maternal blood pressure; fetal well-being

Parameter Details

Compatibility Use with caution — limited human data; animal studies show excretion in milk

Expected drug levels in milk Likely low but not well-quantified

Preferred alternatives Avoid if safer alternatives available; consider baclofen under specialist guidance if antispasticity agent essential

What to monitor in infant Sedation, poor feeding, irritability, weight gain

• Starting dose: 2 mg once daily

• Titration: Slower titration recommended (every 5–7 days); avoid rapid dose escalation

• Extra risks:

• Increased sensitivity to hypotension and CNS depression

• Higher risk of falls, confusion, dizziness

• Reduced renal function may impair drug clearance

• Over-sedation with daytime dosing

• Recommendation: Consider avoiding for chronic use unless clear clinical benefit; prefer lowest effective dose

Interacting Drug(s) Effect Mechanism Management

Ciprofloxacin Marked increase in tizanidine levels (up to 10-fold); profound hypotension, sedation Strong CYP1A2 inhibition CONTRAINDICATED — do not co-administer

Fluvoxamine Marked increase in tizanidine levels (up to 33-fold); severe hypotension, sedation Strong CYP1A2 inhibition CONTRAINDICATED — do not co-administer

Oral contraceptives (ethinyl estradiol-containing) Increased tizanidine levels CYP1A2 inhibition Use with caution; consider lower tizanidine dose; monitor for hypotension and sedation

Clonidine or other alpha-2 agonists Additive hypotensive effect; risk of severe hypotension and bradycardia Pharmacodynamic synergy Avoid combination if possible; if necessary, monitor blood pressure closely

Interacting Drug(s) Effect Management

Antihypertensives (amlodipine, losartan, etc.) Additive blood pressure lowering Monitor blood pressure; adjust antihypertensive dose if needed

Benzodiazepines, opioids Enhanced CNS depression and sedation Use with caution; reduce doses if necessary

Baclofen Additive muscle relaxant effect; increased sedation Use with caution; monitor for excessive weakness and sedation

Alcohol Enhanced sedation and hypotension Advise avoidance

Other fluoroquinolones (norfloxacin, ofloxacin) Possible CYP1A2 inhibition (weaker than ciprofloxacin) Use with caution; monitor for adverse effects

Rifampicin May reduce tizanidine levels Monitor therapeutic response; dose adjustment may be needed

• Drowsiness, sedation

• Dry mouth

• Dizziness, lightheadedness

• Hypotension

• Weakness, fatigue

• Asthenia

• Nausea

• Bradycardia

• Liver enzyme elevation (with prolonged use)

Adverse Effect Clinical Notes

Severe hypotension May occur especially with CYP1A2 inhibitors or rapid titration; may require discontinuation

Hepatotoxicity Elevated ALT/AST; rare cases of hepatic failure reported; monitor LFTs; discontinue if significant elevation (>3× ULN) or clinical hepatitis

Hallucinations, psychosis Rare; more common at higher doses or in elderly; discontinue if severe

Severe bradycardia Rare; monitor in patients with cardiac disease

Withdrawal syndrome Rebound hypertension, tachycardia, tremor, anxiety — taper gradually after prolonged use

Phase Parameter Frequency

Baseline LFTs (ALT, AST), renal function, blood pressure Before initiation

After initiation/dose change Blood pressure (especially within 2–3 hours of dosing); sedation level First few days of therapy or after dose changes

After 4 weeks LFTs If continuing therapy

Long-term LFTs Every 1–2 months if therapy continued beyond 1 month

Long-term Blood pressure, clinical assessment for hepatic impairment At each visit

• Tizan (Sun Pharma)

• Tizalore (Abbott)

• Tizalud (Dr. Reddy's)

• Tizlac (Intas)

• Sirdalud (Novartis — limited availability)

FDCs (note: not for routine use):

• Not included in NLEM

• Not under NPPA price control

• Prices vary across brands

1. Short duration of action: Half-life of ~2.5 hours allows flexible dosing — useful for targeting specific times of spasticity (e.g., bedtime dosing for nocturnal spasticity reduces daytime sedation).

1. Ciprofloxacin is absolutely contraindicated: This is a commonly missed interaction in Indian practice; even a single dose of ciprofloxacin can cause severe hypotension and sedation with tizanidine.

1. Taper gradually: Abrupt discontinuation after prolonged use can precipitate rebound hypertension, tachycardia, and anxiety — always taper over several days.

1. Hepatic monitoring is essential: LFTs should be checked at baseline and after 4 weeks of continuous therapy, then periodically — hepatotoxicity is a recognised risk.

1. Comparison with baclofen: Tizanidine may cause less muscle weakness than baclofen but has more pronounced hypotensive effects — choose based on individual patient profile and tolerability.

1. Oral contraceptive users: Women on combined oral contraceptives may have higher tizanidine levels — start at lower doses and titrate cautiously.

spasticity; muscle relaxant; alpha-2 agonist; CNS depressant; hepatic-risk; CYP1A2; hypotension; elderly-caution; renal-adjust; pregnancy-caution

RxIndia v0.9 — 17 Mar 2025

• CDSCO product inserts

• Indian Pharmacopoeia

• NFI 2021

• API Textbook of Medicine

• AIIMS Drug Formulary

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Indian neurology hospital protocols

• WHO Essential Medicines List (supportive)

• Small RCTs for tension-type headache (off-label use — supportive only)