Parkifen

• Approved Indications:
• Treatment of Parkinson’s disease (idiopathic and secondary parkinsonism).
• Management of extrapyramidal symptoms (EPS) caused by neuroleptic and antipsychotic medications, including drug-induced parkinsonism, dystonia, and akathisia.
• Off-label Uses:
• Adjunctive therapy in certain movement disorders.
• Occasionally used for treatment of dystonia of various etiologies.

• Adults:
• Initial dose: 1 mg two or three times daily.
• Maintenance dose: 4–10 mg daily in divided doses.
• Maximum dose: Up to 15 mg daily depending on clinical response and tolerability.
• Elderly:
• Start with lower doses due to increased susceptibility to side effects, typically 1 mg once or twice daily; titrate cautiously.
• Pediatrics:
• Use with caution; dosing individualized and generally lower than adult doses.
• Special Populations:
• No standard dose adjustments recommended for mild to moderate renal or hepatic impairment, but caution advised.
• Administration Route:
• Oral tablets taken with or without food, preferably at evenly spaced intervals.

Trihexyphenidyl is an anticholinergic agent that blocks central muscarinic cholinergic receptors. In Parkinson’s disease and drug-induced extrapyramidal symptoms, there is an imbalance between dopamine and acetylcholine in the basal ganglia, with relative cholinergic overactivity. Trihexyphenidyl restores this balance by inhibiting acetylcholine’s excitatory effects on neurons, reducing tremor, rigidity, and dystonia, thereby improving motor function.

• Absorption: Well absorbed orally with peak plasma concentrations occurring approximately 1–2 hours after administration.
• Distribution: Widely distributed; crosses the blood-brain barrier to exert central effects.
• Metabolism: Extensively metabolized in the liver through hydrolysis and conjugation.
• Elimination: Metabolites and unchanged drug excreted primarily via urine.
• Half-life: Approximately 3 to 4 hours, allowing dosing two to three times daily.

• Pregnancy:
• FDA Pregnancy Category C.
• Animal studies have shown adverse effects on the fetus; use only if clearly needed and benefits outweigh risks.
• Lactation:
• Excreted in breast milk; caution advised. Breastfeeding is generally not recommended during treatment.

• Primary Class: Anticholinergic agent
• Subclass: Centrally acting antimuscarinic

• Known hypersensitivity to trihexyphenidyl or any excipients.
• Narrow-angle glaucoma.
• Myasthenia gravis.
• Severe gastrointestinal obstruction or urinary retention.
• Severe ulcerative colitis.
• Toxic megacolon or paralytic ileus.

• Use with caution in elderly patients due to increased risk of confusion, hallucinations, and cognitive impairment.
• Monitor for anticholinergic side effects such as dry mouth, blurred vision, constipation, urinary retention, and tachycardia.
• Avoid abrupt discontinuation to prevent cholinergic rebound symptoms.
• Use cautiously in patients with cardiovascular disease, prostatic hypertrophy, or gastrointestinal obstructive disorders.
• May impair heat regulation; caution in hot climates or during exercise.
• Monitor mental status for worsening confusion or hallucinations.

• Common:
• Dry mouth, blurred vision, constipation, nausea.
• Dizziness, drowsiness, headache.
• Urinary retention.
• Tachycardia.
• Serious/Rare:
• Confusion, hallucinations, memory impairment, especially in elderly.
• Glaucoma exacerbation.
• Severe constipation or paralytic ileus.
• Allergic reactions (rash, angioedema).
• Timing & Dose-Dependence:
• Side effects often appear early in therapy and may be dose-dependent.

• Additive anticholinergic effects with other anticholinergic drugs (e.g., antihistamines, tricyclic antidepressants).
• May reduce the efficacy of cholinesterase inhibitors used in dementia.
• Potential increased risk of CNS depression when combined with alcohol or CNS depressants.
• Use caution when combined with drugs causing urinary retention or constipation.

• Continued endorsement as first-line adjunct therapy for Parkinson’s disease tremor and drug-induced EPS in recent clinical guidelines.
• Recommendations emphasize cautious use in elderly and monitoring for cognitive side effects.
• No significant recent changes in dosing or contraindications.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in tightly closed container.
• Keep out of reach of children.
• No refrigeration or reconstitution needed.