TRIHEXYPHENIDYL HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIHEXYPHENIDYL HYDROCHLORIDE (TRIHEXYPHENIDYL HYDROCHLORIDE).
Trihexyphenidyl is an anticholinergic agent that competitively blocks central muscarinic receptors (primarily M1) in the striatum, restoring the balance between acetylcholine and dopamine in the basal ganglia. It also has mild peripheral anticholinergic effects.
| Metabolism | Primarily metabolized by hepatic microsomal enzymes, with CYP2D6 possibly involved. Elimination half-life is approximately 3–4 hours. |
| Excretion | Renal (primarily as unchanged drug and metabolites; <15% unchanged) and biliary/fecal (minor). |
| Half-life | 10-17 hours; clinical context: steady-state concentrations achieved in 2-3 days. |
| Protein binding | Minimal; approximately 10-20% bound to plasma proteins (albumin). |
| Volume of Distribution | Approximately 0.5-1.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: approximately 80-95% (first-pass metabolism minimal). |
| Onset of Action | Oral: 1-2 hours; IM: 10-15 minutes; IV: immediate. |
| Duration of Action | Oral: 6-12 hours; IM/IV: 2-4 hours. Note: effects persist longer with chronic use. |
1 mg orally initially, then increase by 2 mg every 3-5 days up to 6-10 mg daily in 3-4 divided doses; maximum 15 mg/day.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: administer every 8-12 hours; CrCl <10 mL/min: consider alternative or reduce dose by 50%. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid use or use with extreme caution, reduce dose by 75%. |
| Pediatric use | Children 2-12 years: initial 1 mg/day, increase by 1 mg every 3-5 days; maximum 6 mg/day in divided doses. |
| Geriatric use | Start at 1 mg once or twice daily; increase slowly by 1 mg increments every 5-7 days; monitor for anticholinergic side effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIHEXYPHENIDYL HYDROCHLORIDE (TRIHEXYPHENIDYL HYDROCHLORIDE).
| Breastfeeding | No data on M/P ratio; excreted in breast milk in unknown amounts. Caution recommended; avoid if possible. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: No known specific risks; use only if clearly needed. |
| Fetal Monitoring | Monitor maternal extrapyramidal symptoms and anticholinergic adverse effects. Fetal monitoring not specifically required unless maternal toxicity occurs. |
■ FDA Black Box Warning
Not applicable.
| Serious Effects |
["Hypersensitivity to trihexyphenidyl","Narrow-angle glaucoma","Obstructive gastrointestinal disorders (e.g., pyloric stenosis, paralytic ileus)","Severe ulcerative colitis or toxic megacolon","Myasthenia gravis"]
| Precautions | ["May cause drowsiness, dizziness, or blurred vision; caution with driving or hazardous activities","Anticholinergic effects may be exacerbated in elderly patients, including confusion, constipation, urinary retention, and hyperthermia","Use cautiously in patients with glaucoma, prostatic hypertrophy, cardiac arrhythmias, or myasthenia gravis","Potential for abuse or dependence at high doses","May exacerbate tardive dyskinesia in patients on neuroleptics"] |
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| Fertility Effects | No known adverse effects on human fertility; animal studies show no impairment. |