Norflex
Norflex
Generic Name
Norflex
Mechanism
Norflex (tizanidine) is a selective α2‑adrenergic receptor agonist.
• Activates presynaptic α2‑receptors in the spinal cord and brainstem.
• Inhibits release of excitatory amino acids (glutamate) and decreases excitatory neurotransmission.
• Leads to reduced motoneuron firing and a decrease in muscle tone and spasticity.
Pharmacokinetics
- Route: Oral, immediate‑release tablets.
- Absorption: Rapid; peak plasma concentration (Cmax) reached at ~0.5 – 2 h (Tmax).
- Bioavailability: ~45 % due to significant first‑pass hepatic metabolism.
- Metabolism: Hepatic, primarily CYP1A2 (inducible by smoking); minor CYP2D6 contribution.
- Elimination: Renal excretion of metabolites; terminal half‑life ~1 – 2.5 h (shorter in smokers).
- Drug interactions: Inhibits CYP1A2 (increases levels of fluvoxamine, clozapine); is metabolized by CYP1A2 (induction by smoking lowers plasma levels).
Indications
- Spasticity associated with multiple sclerosis (MS), spinal cord injury, traumatic brain injury, or other neurologic conditions.
- Chronic low back pain where spasticity contributes to discomfort (off‑label, in some regions).
Contraindications
- Contraindications:
- Severe hepatic impairment (Child‑Pugh Class B/C).
- Hypotension or orthostatic hypotension.
- Recent use of MAO inhibitors or within 14 days of discontinuation.
- Warnings:
- Hepatotoxicity: monitor ALT/AST; discontinue if transaminases >3 × ULN.
- Central nervous system depression: avoid alcohol, benzodiazepines, opioids.
- Severe renal impairment: dose adjustment may be required.
Dosing
| Situation | Typical Regimen | Notes |
| Adults (initial) | 2.5 mg twice daily (BID) | Start low to assess tolerance. |
| Titration | Increase by 2.5–5 mg every 3–5 days | Aim for ≤ 50 mg/day (max). |
| Maintenance | 10–30 mg/day (divided) | Adjust for effect and side‑effects. |
| Children (≥ 12 yrs) | 0.25 mg/kg/day (max 10 mg/day) | Dose adjusted by weight. |
| Renal impairment | Consider ½ dose; monitor. | No formal dose‑adjustment data for severe CKD. |
• Administration: With food to reduce nausea; avoid high‑fat meals that delay absorption.
• Missed dose: Take as soon as remembered, but skip if next dose within 1 h.
Adverse Effects
- Common (≥ 10 %)
- Somnolence / dizziness
- Dry mouth, fatigue
- Hypotension (postural)
- Headache, nausea, constipation
- Serious (≤ 1 %)
- Severe hepatotoxicity (↑ transaminases, jaundice)
- Bradycardia, syncope
- Severe rash or hypersensitivity reactions
- Respiratory depression (rare, with CNS depressants)
Monitoring
- Baseline: LFTs (ALT, AST, bilirubin), CBC, electrolytes, fasting glucose.
- During therapy:
- LFTs every 4–6 weeks for first 3 months, then every 3 months if stable.
- BP and pulse at each visit; orthostatic measurements.
- Weight & liver imaging if signs of hepatotoxicity.
- Cognitive/motor function if high dose or CNS depression noted.
Clinical Pearls
- Start Slow, Go Slow: The 2.5 mg BID starter dose is critical; many patients experience hypotension or drowsiness at higher doses.
- Avoid Alcohol & CNS Depressants: Combining with alcohol, benzodiazepines, or opioids can amplify sedation and hypotension.
- Smoking Effect: Smokers metabolize tizanidine faster; consider a 30 % higher dose or monitor closely.
- Abrupt Discontinuation Risks: Sudden withdrawal may precipitate rebound spasticity; taper over 1–2 weeks if stopping.
- Hepatotoxicity Watch: A sudden rise in transaminases > 3 × ULN warrants immediate discontinuation.
- Rebound Spasticity: In chronic MS patients, consider a maintenance dose of 10–20 mg/day to avoid rebound after tapering.
- Patient Education: Emphasize the need to avoid driving or operating heavy machinery until the sedative effect is known.
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• Keywords: Norflex, tizanidine, spasticity, α2‑adrenergic agonist, muscle relaxant, dosing guidelines, hepatotoxicity, hypotension, monitoring.