Orphenadrine - Drug Monograph

Introduction

Orphenadrine is a skeletal muscle relaxant with anticholinergic properties that has been used clinically since the 1950s. It is structurally related to diphenhydramine and is primarily indicated for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine acts centrally to reduce muscle spasm without directly affecting skeletal muscle fibers.

Mechanism of Action

Orphenadrine exerts its therapeutic effects through multiple mechanisms:

• Central anticholinergic action at muscarinic receptors in the brainstem and spinal cord
• Inhibition of polysynaptic reflexes in the spinal cord
• Mild analgesic properties through central nervous system depression
• Indirect action on norepinephrine reuptake inhibition

The drug does not directly relax skeletal muscles but rather acts on the central nervous system to reduce muscle tone and spasticity.

Indications

FDA-approved indications:

• Adjunctive therapy for acute musculoskeletal conditions
• Relief of discomfort associated with painful musculoskeletal conditions

Off-label uses (not FDA-approved):

• Parkinson's disease symptoms (tremor, rigidity)
• Drug-induced extrapyramidal symptoms

Dosage and Administration

• Oral: 100 mg twice daily
• Extended-release: 100 mg once or twice daily
• Injectable: 60 mg IV or IM every 12 hours

• Initiate with lower doses due to increased sensitivity to anticholinergic effects

• Use with caution; consider dose reduction

• Contraindicated in severe hepatic impairment

Maximum daily dose: 400 mg

Pharmacokinetics

Contraindications

• Hypersensitivity to orphenadrine or any component of the formulation
• Glaucoma (angle-closure)
• Gastrointestinal obstruction
• Megacolon
• Myasthenia gravis
• Severe hepatic impairment
• Prostatic hypertrophy with urinary retention
• Achalasia

Warnings and Precautions

• May cause drowsiness; caution patients about driving or operating machinery
• Use with caution in patients with:

- Cardiovascular disease - Mild to moderate hepatic impairment - Renal impairment - Hyperthyroidism - Urinary retention - Elderly patients (increased risk of adverse effects)

• Taper gradually when discontinuing after long-term use
• Risk of anticholinergic toxicity in overdose

Drug Interactions

• Other CNS depressants (alcohol, benzodiazepines, opioids): Enhanced sedation
• Anticholinergic agents (atropine, antihistamines, tricyclic antidepressants): Additive anticholinergic effects
• MAO inhibitors: Risk of hypertensive crisis
• Metoclopramide: May counteract gastrointestinal effects

• Antipsychotics: Increased risk of extrapyramidal symptoms
• Guanethidine: Reduced antihypertensive effect

Adverse Effects

• Dry mouth
• Drowsiness
• Dizziness
• Blurred vision
• Constipation
• Urinary retention

• Tachycardia
• Hypotension or hypertension
• Anaphylaxis
• Seizures
• Acute angle-closure glaucoma
• Neuroleptic malignant syndrome (rare)
• Hepatitis (rare)

Monitoring Parameters

• Liver function tests
• Renal function
• Complete blood count
• Intraocular pressure (if history of glaucoma)

• Therapeutic response
• Adverse effects (especially anticholinergic effects)
• Mental status changes
• Signs of overdose (tachycardia, hyperthermia, delirium)
• Liver function (periodically with long-term use)

Patient Education

• May cause drowsiness; avoid alcohol and other sedating medications
• Do not drive or operate machinery until effects are known
• Maintain adequate hydration to prevent constipation
• Report any vision changes, difficulty urinating, or palpitations
• Do not crush or chew extended-release formulations
• Inform all healthcare providers about orphenadrine use
• Store at room temperature away from moisture

• Take as soon as remembered unless close to next dose
• Do not double doses

References

1. Micromedex® Solutions. Orphenadrine. Truven Health Analytics. 2023. 2. Lexicomp Online®. Orphenadrine: Drug Information. Wolters Kluwer. 2023. 3. Gilman AG, Goodman LS, Gilman A. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th ed. New York: McGraw-Hill; 2018. 4. Orphenadrine citrate prescribing information. FDA-approved labeling. 5. Browne BJ. Muscle relaxants: a review. Am J Emerg Med. 1996;14(4):385-391. 6. See S, Ginzburg R. Skeletal muscle relaxants. Pharmacotherapy. 2008;28(2):207-213.