Generic Name

Zanaflex

Mechanism

• Selective α₂‑adrenergic agonist: Enhances inhibitory α₂‑receptor activity in the spinal cord, which ↓ the excitability of motoneurons, leading to reduced muscle tone.
• Acts on both pre‑ and postsynaptic receptors, decreasing excitatory neurotransmitter release.
• This postsynaptic effect is responsible for the tonic reduction in spasticity without the prolonged paralysis seen with other agents.

Pharmacokinetics

• Absorption: Rapid oral uptake, peak plasma concentration in 0.5‑2 h.
• Bioavailability: ~30% due to first‑pass hepatic metabolism.
• Metabolism: Primarily via CYP1A2; minimal CYP3A4 involvement.
• Half‑life: 1‑2 h; adequate for a 3‑dose-per‑day schedule.
• Elimination: Renal (≈ 30%) and hepatic (~ 70%).
• Drug interactions: Increases with CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine); decreases with CYP1A2 inducers (e.g., rifampin, carbamazepine).

Indications

• Spasticity secondary to:
• Spinal cord injury
• Multiple sclerosis
• Amyotrophic lateral sclerosis
• Adjunctive therapy for:
• Chronic spinal central pain
• Spasticity related to cerebral palsy (in adolescents, not approved in adults)

Contraindications

• Severe hepatic impairment: Contraindicated (risk of hepatotoxicity).
• Hypotension or orthostatic dizziness: Use with caution; may worsen BP.
• Alcohol use: Contraindicated; additive CNS depression.
• Pregnancy: Category B; minimal data—use only if benefits outweigh risks.
• Depression, suicidal ideation: Monitor for psychiatric symptoms; report promptly.

Dosing

• Adults:
• Initiate at *1.25 mg orally three times daily (TID)*, 2‑4 h before meals.
• Incrementally titrate by *0.5‑1 mg* every 3–7 days based on tolerance and efficacy.
• Maximum: 40 mg/day (split across meals).
• Children (≥ 5 yrs): Off‑label use; 0.5–1 mg/kg/day divided TID.
• Special populations:
• Renal impairment: No dose adjustment needed; monitor renal function.
• Hepatic impairment: Avoid in severe disease; mild/moderate impairment may require reduction.
• Timing with food: Does not require, but can be taken with light meals.
• Dose scheduling: Avoid prolonged dosing beyond 1–2 months *unless* S‑band therapy bridges to long‑acting agents.

Adverse Effects

• Common:
• Dry mouth
• Dizziness
• Nausea
• Somnolence
• Rash or pruritus
• Serious:
• Elevation of ALT/AST → hepatic injury
• Persistent bradycardia or hypotension
• Rhabdomyolysis (rare)
• Severe allergic reactions (anaphylaxis)
• Psychiatric: mood changes, depression, anxiety, suicidality

Monitoring

Clinical Pearls

• Tizanidine is the gold‑standard non‑benzodiazepine for acute spasticity, especially in short‑term settings or when rapid titration is necessary.
• Use of pharmacogenetic testing (CYP1A2 phenotyping) may predict metabolism rates; patients with reduced CYP1A2 activity may require lower initial doses to avoid hypotension.
• When co‑prescribed with amlodipine for hypertension, start in the gym; 10‑15 % of patients may experience profound hypotension—monitor BP closely.
• The ‘post‑dose ‘Hold‑down’ principle: Teach patients to rest for 2–4 h after the medication to avoid falls during reflex activity.
• Rapid titration in spasticity flare: Increase dose by *0.5 mg every 2 days* if clinically needed, monitoring for side effects.
• Hepatotoxic monitoring: Check baseline LFTs before initiating therapy; a repeated test after 4 weeks is typically sufficient because most hepatotoxic events occur early.
• Switching strategy: For prolonged therapy, transition to a long‑acting agent (e.g., baclofen) after 1–2 months of tizanidine to avoid chronic side effects.

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• Key takeaways for clinicians:
• Start low, go slow—be vigilant for hypotension and hepatic injury.
• Patients with psychiatric histories require a risk–benefit assessment.
• Regular monitoring is essential for safe therapy.

By adhering to these guidelines, Zanaflex delivers potent, rapid relief of spasticity while maintaining a manageable safety profile for patients and prescribers alike.