What is Noraflex (orphenadrine citrate)?

What is Noraflex (Orphenadrine Citrate)?

Noraflex (orphenadrine citrate) is a centrally acting skeletal muscle relaxant with anticholinergic properties, structurally similar to diphenhydramine, indicated as an adjunct to rest and physical therapy for relief of discomfort associated with acute, painful musculoskeletal conditions. 1

Mechanism of Action

• The precise mechanism remains unclear but does not involve direct skeletal muscle relaxation. 2, 1
• The drug appears to work through anticholinergic properties and may have analgesic effects independent of muscle relaxation. 2, 1
• Research demonstrates both antinociceptive (pain-reducing) and muscle relaxant properties in animal models, though the exact pathways are not fully elucidated. 3

Clinical Indications

• FDA-approved as an adjunct for acute, painful musculoskeletal conditions when combined with rest and physical therapy. 1
• Evidence supports efficacy in reducing muscle cramps in cirrhotic patients, with significant improvements in frequency, duration, and pain scores. 4
• Limited controlled data suggest effectiveness in reducing spastic hypertonia in spinal cord injury patients, though onset may be delayed 30 minutes and severe spasticity may not respond. 5

Anticholinergic Adverse Effects

The anticholinergic properties produce a characteristic side effect profile that clinicians must recognize: 2

• Central nervous system: Confusion, anxiety, tremors, hallucinations, agitation, drowsiness 2, 6
• Cardiovascular: Tachycardia, cardiovascular instability 2
• Gastrointestinal: Dry mouth, constipation 2, 4
• Genitourinary: Urinary retention 2

Critical Contraindications

Orphenadrine is absolutely contraindicated in: 1

• Glaucoma
• Gastrointestinal obstruction (pyloric/duodenal obstruction, stenosing peptic ulcers)
• Prostatic hypertrophy or bladder neck obstruction
• Myasthenia gravis
• Cardiospasm (megaesophagus)
• Previous hypersensitivity to the drug

High-Risk Populations Requiring Caution

Use with extreme caution in: 2, 7

• Cardiac patients: Those with tachycardia, cardiac decompensation, coronary insufficiency, or cardiac arrhythmias 2
• Elderly patients: Increased susceptibility to anticholinergic effects 2, 7
• Patients with seizure disorders: As a centrally acting medication, theoretical concerns exist regarding CNS excitability, though no specific seizure threshold warnings appear in FDA labeling 7

Perioperative Management

The Society for Perioperative Assessment and Quality Improvement (SPAQI) recommends holding orphenadrine on the day of surgery due to its anticholinergic and sedative properties. 2, 7

Drug Interactions

• Potentiates anticholinergic effects when combined with other anticholinergic medications, creating additive toxicity risk. 2
• Should not be used in patients with myasthenia gravis as it may interfere with pyridostigmine bromide effects. 2

Toxicity Considerations

• Orphenadrine can cause profound toxicity in children after small doses (as few as two 100-mg tablets in a 3-year-old), manifesting as central anticholinergic syndrome with hallucinations and severe agitation. 6
• In adults, deliberate self-poisoning with doses up to 10 grams has been associated with antimuscarinic toxicity and sedation, but severe cardiotoxicity appears less common than historical case reports suggest. 8
• Sustained-release formulations may produce lesser acute toxicity compared to immediate-release products at similar doses. 8

Available Formulations

• Oral tablets (orphenadrine citrate extended-release)
• Injectable solution (30 mg/mL for intravenous or intramuscular administration) 1

Common Pitfalls to Avoid

• Do not prescribe in elderly patients without carefully weighing anticholinergic burden, as confusion and cardiovascular effects are more pronounced in this population. 2
• Screen for contraindications before prescribing, particularly glaucoma, urinary obstruction, and myasthenia gravis. 1
• Avoid combining with other anticholinergic medications to prevent additive toxicity. 2
• Do not expect immediate effect in spasticity—therapeutic benefit may require 30+ minutes. 5