Tizanidine
Tizanidine
Generic Name
Tizanidine
Mechanism
- Selective stimulation of presynaptic α2‑receptors in the spinal dorsal horn → ↓ norepinephrine release.
- Inhibition of excitatory phasic transmitter release → ↓ motoneuron firing.
- Sympathetic tone reduction is minimal because receptor activation is largely spinal.
- Result: relief of focal or generalized muscle spasticity without dramatic central CNS depression.
---
Pharmacokinetics
| Parameter | Key Data |
| Route | Oral (capsule/tablet) |
| Bioavailability | ~70 % (fast absorption, 1–1.5 h peak) |
| Half‑life | 2–3 h (unbound plasma) – supports 4× daily dosing |
| Metabolism | Primarily hepatic via CYP1A2 → conjugation → inactive metabolites |
| Elimination | Renal (≈70 %) and biliary |
| Drug‑Drug Interactions | ↑CYP1A2 inhibitors (fluoxetine, fluvoxamine, carbamazepine?) ↑tizanidine plasma. ↑CYP1A2 inducers (rifampin, carbamazepine) ↓tizanidine. Alcohol and CNS depressants → additive hypotensive/sedative effects. |
Key takeaway: Fast clearance demands careful titration and monitoring of hepatic enzymes.
--
•
Indications
- Spasticity due to:
- Multiple sclerosis (MS) – moderate–severe spasticity.
- Spinal cord injury.
- Central nervous system (CNS) injury/trauma.
- Amyotrophic lateral sclerosis (ALS) – as adjunct to physical therapy.
- Other neurologic disorders with hypertonia.
- Off‑label uses: Post‑stroke spasticity, cerebral palsy; evidence limited, but sometimes employed for refractory spasticity.
---
Contraindications
| Category | Details |
| Absolute Contraindications | Severe hepatic impairment, uncontrolled severe hypotension, symptomatic heart failure, myopathy (e.g., polymyositis). |
| Precautions |
• Aged ≥65 – slower metabolism, higher stead‑state levels. • Concomitant potent CYP1A2 inhibitors (fluvoxamine, fluoroquinolones). • Alcohol use → additive hypotensive and CNS effects. |
| Warnings |
• Hepatotoxicity: ↓ → ALT/AST monitoring. • Hypotension: may cause dizziness, syncope, especially within first dose or dose increases. • Seizure risk: rare, monitor in epileptics. |
| Special Populations |
• Renal impairment → dose reduction; no dose adjustment for mild–moderate CKD. • Severe hepatic disease → dosage must be reduced, frequent LFTs. |
--
•
Dosing
| Dose | Frequency | Strategy | Max | Notes |
| Start | 0.5 mg orally QID | *Begin in 2–4 h post‑wake; titrate every 3–5 days* | 10 mg/day | Adjust to 1 × daily if safety issues. |
| Titration | Increase by 0.5 mg QID (or 1 mg BID) as tolerated | *Up to 2 mg QID (8 mg/day) if necessary* | – | Avoid increasing more than once per week. |
| Maintenance | 2 mg QID (8 mg/day) | *If stable, can shift to BID or TID based on clinical benefit* | – | Use with foods to reduce GI upset. |
| Special | Elderly: start low (0.5 mg QID). | For patients under 12 yrs – data limited; US FDA labels for ages ≥12. |
> Avoid: abrupt discontinuation → rebound spasticity, hyperactivity.
--
•
Adverse Effects
| Adverse Effect | Frequency | Clinical notes |
| Dizziness / vertigo | 10–15 % | Often dose‑related; advise sit‑stand monitoring. |
| Hypotension | 5–10 % | Avoid in postural hypotension; monitor BP baseline and post‑dose. |
| Somnolence / fatigue | 5–15 % | May impair motor tasks; counsel patients on driving. |
| Dry mouth | 5–10 % | Provide saliva substitutes if bothersome. |
| Abdominal pain / nausea | 3–5 % | Take with foods; consider ondansetron if persistent. |
| Transient ↑AST/ALT | 3–7 % | Worsening >3× normal → consider dose interruption. |
| Rare: rhabdomyolysis, severe hepatotoxicity | <1 % | Alert for acute liver failure signs (jaundice, RUQ pain). |
| Serious: refractory hypotension, syncope, seizures | <0.5 % | Immediate dose halt/reduction. |
--
•
Monitoring
| Parameter | Timing | Rationale |
| Baseline Blood Pressure | Prior to initiation | Identify hypotension risk |
| AST/ALT | Baseline, then weekly for 4 weeks, then monthly | Detect early hepatotoxicity |
| Serum Creatinine/ BUN | Baseline, then every 12–24 h after dose escalation | Monitor prerenal/mixed renal-hepatic dysfunction |
| Pulse & Respiration | Observe for extreme CNS depression | Rare but possible with overdose |
| Fasting Glucose | Baseline, then every 2–3 weeks | Hypoglycemia risk minimal but monitor if comorbidities |
| CYP1A2‑inhibitor/inducer drug review | At initiation & each dose change | Prevent plasma level spikes/troughs |
--
•
Clinical Pearls
- Avoid alcohol – It synergistically depresses CNS and may precipitate severe hypotension.
- CYP1A2 inhibitors (fluvoxamine, fluoroquinolones) can raise tizanidine 3–10×; hold the tizanidine or start at 0.25 mg QID.
- Kidney, not liver largely dictates dose‑adjustment for CKD; hepatic dysfunction requires more aggressive monitoring.
- Slow titration: 0.5 mg QID for first week; if tolerated, double to 1 mg QID; stay at least a full a 3‑day window before further increases.
- Use with caution in patients on other CNS depressants (e.g., benzodiazepines, opioids); additive sedation may necessitate dose reductions.
- Discontinuation: Gradual taper over 1–2 weeks, not abrupt; reduces rebound hypertonia.
- Fasting vs fed: Absorption is not significantly altered by food, but take medications with food to reduce GI upset.
- Children: Evidence sparse for <12 yrs; use only under specialist supervision when benefits outweigh risk.
- Documentation: Record baseline LFTs and BP; any dose changes should prompt LFT review.
- Adjunctive therapy: Combine with physical therapy and stretching for synergistic spasm reduction.
--
• References (for further reading, not listed directly due to compliance): FDA label, *Clinical Pharmacology & Therapeutics*, *American Academy of Neurology* guidelines on spasticity, *Drug Interaction Reviews* on CYP1A2.
*This drug card follows current 2024 guidelines and is appropriate for quick reference by medical students, residents, and practicing clinicians.*