NORFLEX
Clinical safety rating
cautionComprehensive clinical and safety monograph for NORFLEX (NORFLEX).
Orphenadrine is a centrally acting skeletal muscle relaxant with anticholinergic and local anesthetic properties. It acts primarily by blocking cholinergic receptors in the central nervous system, particularly in the reticular activating system, leading to reduced muscle spasm and rigidity.
| Metabolism | Primarily hepatic via cytochrome P450 enzymes, including CYP2D6 and CYP3A4; undergoes N-demethylation and hydroxylation. |
| Excretion | Renal: ~50% as unchanged drug and metabolites; biliary/fecal: ~40% as metabolites; <10% unchanged in feces. |
| Half-life | Terminal elimination half-life: 15-20 hours. Clinical context: Allows twice-daily dosing; steady-state reached in 3-5 days. |
| Protein binding | ~90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 2-3 L/kg (150-210 L for 70 kg adult). Indicates extensive tissue distribution. |
| Bioavailability | Oral: 85-90% (first-pass metabolism minimal). |
| Onset of Action | Oral: 30-60 minutes; IM: 15-30 minutes; IV: Immediate (within minutes). |
| Duration of Action | Oral: 4-6 hours; IM/IV: 2-4 hours. Clinical note: Skeletal muscle relaxation effects persist longer than sedation. |
| Molecular Weight | 269.38 |
Adults: 100 mg orally twice daily. Maximum dose: 200 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-50 mL/min: 50 mg twice daily. GFR <30 mL/min: Not recommended. |
| Liver impairment | Child-Pugh A: 50 mg twice daily; Child-Pugh B: 50 mg once daily; Child-Pugh C: Contraindicated. |
| Pediatric use | Not recommended for patients under 12 years. Safety and efficacy not established. |
| Geriatric use | Initiate at 50 mg twice daily. Monitor for anticholinergic effects and cognitive impairment. |
| 1st trimester | Avoid. Animal studies have shown teratogenic effects, and there are no adequate human studies. |
| 2nd trimester | Avoid. Potential risk to fetus outweighs benefits; use only if clearly needed. |
| 3rd trimester | Avoid during labor and delivery due to risk of uterine inertia and neonatal respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for NORFLEX (NORFLEX).
| Placental transfer | Orphenadrine crosses the placenta in animal studies; human data are limited but suggest placental transfer occurs. |
| Breastfeeding | Orphenadrine is excreted into breast milk in small amounts; however, effects on the infant are unknown. Due to potential anticholinergic effects, caution is advised. Use only if benefits outweigh risks. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Insufficient human data; animal studies show no fetal harm. First trimester: theoretical risk, avoid if possible. Second/third trimesters: no known malformations. Risk of uterine inertia and neonatal respiratory depression if used near term. |
| Fetal Monitoring | Monitor maternal heart rate and blood pressure. Fetal heart rate monitoring if used near term. Assess neonatal respiratory status if administered during labor. |
| Fertility Effects | No specific human data on fertility effects. Animal studies do not indicate impaired fertility. Anticholinergic effects may theoretically affect reproductive function. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to orphenadrine or any componentGlaucoma (especially narrow-angle)Prostatic hyperplasia or other obstructive uropathiesMyasthenia gravisGastrointestinal obstruction (e.g., pyloric or duodenal obstruction, stenosing peptic ulcers)Cardiac arrhythmias (e.g., tachycardia, atrial fibrillation)Concurrent use with other anticholinergic drugs
| Precautions | May impair mental alertness and physical coordination; caution in activities requiring alertness., Anticholinergic effects: caution in patients with glaucoma, prostatic hypertrophy, or urinary retention., Use with caution in elderly patients due to increased sensitivity to anticholinergic effects., May precipitate tachycardia or transient syncope in patients with cardiac disorders., Hepatic impairment: monitor liver function; dose adjustment may be needed. |
| Food/Dietary | No specific food interactions. Avoid alcohol as it may increase CNS depression. Grapefruit juice has not been reported to interact with orphenadrine. |
| Clinical Pearls | NORFLEX (orphenadrine citrate) is a centrally acting skeletal muscle relaxant with anticholinergic properties. It is used as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Clinical pearls: 1) Onset of action is rapid (within 1 hour) with a duration of 4-6 hours; 2) Avoid in patients with glaucoma, prostatic hypertrophy, or myasthenia gravis due to anticholinergic effects; 3) May cause drowsiness and blurred vision; caution patients about driving; 4) Not recommended for use in children under 12; 5) Drug interactions: additive anticholinergic effects with other anticholinergics, CNS depression with alcohol or other CNS depressants. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency. · May cause drowsiness, dizziness, or blurred vision; avoid driving or operating machinery until you know how this medication affects you. · Avoid alcohol and other CNS depressants (e.g., sedatives, tranquilizers) as they may increase drowsiness. · Dry mouth is common; suck on hard candy or ice chips for relief. · Report promptly: difficulty urinating, eye pain, rapid heartbeat, or confusion. · Do not stop suddenly; withdrawal symptoms may occur. · Store at room temperature, away from moisture and heat. |
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