Safety Concerns with Orphenadrine
Orphenadrine is not considered safe for general use due to its significant anticholinergic effects and potential for serious adverse events, particularly in elderly patients, those with certain comorbidities, and in overdose situations. 1, 2
Mechanism and Safety Profile
- Orphenadrine is a centrally acting skeletal muscle relaxant with anticholinergic properties, structurally similar to diphenhydramine 1
- It has both peripheral and central anticholinergic effects with known cardiotoxic effects when taken in large doses 3
Contraindications
Orphenadrine is contraindicated in patients with:
- Gastrointestinal tract obstruction 1
- Stenosing peptic ulcer disease 1
- Prostatic hypertrophy or bladder outlet obstruction 1
- Glaucoma 1
- Myasthenia gravis 1
Cautions and Risk Factors
Orphenadrine should be used with extreme caution in:
- Elderly patients (listed in the 2019 AGS Beers Criteria® as potentially inappropriate for older adults due to anticholinergic effects) 1
- Patients with cardiac conditions including tachycardia, cardiac decompensation, coronary insufficiency, and cardiac arrhythmias 1, 2
- Patients taking other medications with anticholinergic properties (potential for additive effects) 1
- Patients with renal or hepatic dysfunction 2
Adverse Effects
Common adverse effects include:
- Anticholinergic symptoms: confusion, anxiety, tremors 1
- Urinary retention, dry mouth, constipation 1
- Cardiovascular instability 1
- Drowsiness and dizziness 1
Toxicity and Overdose
- The minimum lethal dose is reported to be 2-3 grams for adults, though toxicity is variable and unpredictable 2
- Overdose typically induces anticholinergic effects that can be severe 2
- Case reports document severe outcomes including seizures, coma, ventricular tachycardia, and respiratory failure requiring intubation 3, 4
- A recent retrospective study found that while severe toxicity can occur, many patients with overdoses up to 10g experienced primarily antimuscarinic toxicity and sedation without severe cardiotoxicity 5
Special Populations
- Safety in children has not been established; not recommended for pediatric use 2
- Pregnancy Category C: should only be given to pregnant women if clearly needed 2
- Long-term safety has not been established; periodic monitoring of blood, urine, and liver function values is recommended for prolonged use 2
Perioperative Considerations
- The Society for Perioperative Assessment and Quality Improvement (SPAQI) consensus recommendation is to hold orphenadrine on the day of operation 1
Drug Interactions
- Concomitant use with propoxyphene may cause confusion, anxiety, and tremors 2
- May potentiate anticholinergic effects when used with other medications that have anticholinergic properties 1
- Can lower plasma concentrations of chlorpromazine when used concomitantly 6
In conclusion, orphenadrine carries significant safety concerns due to its anticholinergic properties and potential for toxicity, particularly in vulnerable populations and in overdose situations. Alternative muscle relaxants with better safety profiles should be considered when clinically appropriate.