ARTANE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARTANE (ARTANE).
Artane (trihexyphenidyl) is a centrally acting anticholinergic agent that competitively blocks muscarinic acetylcholine receptors in the basal ganglia, reducing cholinergic overactivity relative to dopaminergic deficiency in Parkinson disease and extrapyramidal disorders.
| Metabolism | Primarily hepatic via oxidative metabolism (CYP450 enzymes, specifically CYP2D6 and CYP3A4); metabolites are excreted in urine with minimal unchanged drug. |
| Excretion | Primarily renal excretion of unchanged drug and metabolites; approximately 56-70% of a dose is excreted in urine within 24 hours, with about 30% as unchanged trihexyphenidyl and the remainder as metabolites. Biliary/fecal elimination accounts for a minor fraction (estimated <5%). |
| Half-life | Terminal elimination half-life is approximately 12-15 hours in adults with normal renal function. In geriatric patients or those with renal impairment, half-life may be prolonged up to 30 hours. Clinical context: Steady-state is achieved within 2-4 days. |
| Protein binding | Approximately 30-40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 1.0-1.5 L/kg, indicating extensive tissue distribution. Clinical meaning: High Vd suggests significant penetration into tissues, including CNS, which correlates with its central anticholinergic effects. |
| Bioavailability | Oral bioavailability is approximately 100% for immediate-release tablets; extended-release formulations have approximately 80% bioavailability relative to immediate-release due to first-pass metabolism. |
| Onset of Action | Oral (immediate-release): 1-2 hours; Oral (extended-release): 2-4 hours. Parenteral routes are not typically used clinically. |
| Duration of Action | Oral immediate-release: 6-8 hours; Oral extended-release: 12-24 hours. Duration may be shorter in patients with hepatic enzyme induction or longer in renal impairment. |
| Molecular Weight | 337.5 |
1 mg orally initially, then 2 mg every 3-4 hours as needed; maintenance: 6-10 mg daily in divided doses.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No specific GFR-based dose adjustment guidelines; use with caution in severe renal impairment. |
| Liver impairment | No specific Child-Pugh based modifications; use with caution in severe hepatic impairment. |
| Pediatric use | For parkinsonism: 1-2 mg orally 3 times daily initially, titrate as needed; maximum dose determined by response. |
| Geriatric use | Initiate at lower doses (e.g., 1 mg twice daily) and titrate slowly due to increased sensitivity to anticholinergic effects. |
| 1st trimester | Avoid; teratogenic effects (orofacial clefts) reported in animal studies and limited human data. Use only if benefit outweighs risk. |
| 2nd trimester | Use with caution; may cause fetal anticholinergic effects. Consider alternative agents. |
| 3rd trimester | Avoid near term; may cause neonatal anticholinergic toxicity (e.g., ileus, respiratory depression). |
Clinical note
Comprehensive clinical and safety monograph for ARTANE (ARTANE).
| Placental transfer | Crosses placenta; limited data suggest detectable fetal levels. |
| Breastfeeding | Trihexyphenidyl is excreted in breast milk in small amounts. Monitor infant for anticholinergic effects (e.g., irritability, dry mouth, constipation). Use with caution in breastfeeding women, especially with high doses or prolonged therapy. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to trihexyphenidylNarrow-angle glaucomaPyloric or duodenal obstructionStenosing peptic ulcerProstatic hypertrophyBladder neck obstructionMyasthenia gravis
| Precautions | May exacerbate angle-closure glaucoma, May cause urinary retention in patients with prostatic hypertrophy, May precipitate delirium or cognitive impairment in elderly, Caution in patients with cardiac arrhythmias, hypertension, or hyperthyroidism, May impair heat dissipation leading to hyperthermia, especially in hot environments, Possible development of tachyphylaxis; dose adjustment may be required |
| Food/Dietary | No significant food interactions. Take with food if gastrointestinal upset occurs. Avoid excessive caffeine intake as it may counteract anticholinergic effects. |
Loading safety data…
| Lactation Rating |
| L3 (Moderate Safety) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: No specific fetal risks documented; use only if clearly needed. |
| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and urinary retention; assess fetal heart rate and growth if prolonged use. |
| Fertility Effects | No known effects on human fertility; anticholinergic effects may theoretically affect reproductive function via altered glandular secretions. |
| Clinical Pearls | ARTANE (trihexyphenidyl) is an anticholinergic agent used for Parkinson's disease and drug-induced extrapyramidal symptoms. Onset of action is within 1 hour after oral administration. May exacerbate tardive dyskinesia. Avoid abrupt discontinuation to prevent withdrawal symptoms. Use with caution in patients with glaucoma, prostatic hypertrophy, or tachyarrhythmias. Monitor for cognitive impairment in elderly. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly. · Avoid alcohol and CNS depressants. · May cause drowsiness; avoid driving until effects known. · Drink plenty of fluids to reduce dry mouth. · Report blurred vision, difficulty urinating, or rapid heartbeat. |