Perkinil

Approved Indications

• Idiopathic Parkinson’s Disease (Early to Moderate Stage)
  • Used as adjunctive therapy to reduce tremor, muscle rigidity, drooling, and akinesia.
  • Most effective when tremor is the predominant symptom.
• Drug-Induced Extrapyramidal Symptoms (EPS)
  • Treatment of acute or chronic extrapyramidal side effects caused by antipsychotic drugs such as dystonia, pseudoparkinsonism, and akathisia.
  • Commonly used in psychiatric settings during ongoing antipsychotic treatment.

Clinically Accepted Off-Label Uses

• Acute Dystonic Reactions (Emergency Use)
  • Used intramuscularly for rapid reversal of acute dystonia due to antipsychotics or antiemetics.
  • Often administered in emergency departments or psychiatric facilities.

Route of Administration: Oral and Intramuscular (IM)

Adults

• Parkinson’s Disease (Oral):
  • Start with 2.5 mg three times daily.
  • Increase by 2.5 mg every 2–3 days as needed.
  • Usual maintenance dose: 10–20 mg/day in divided doses.
• Drug-Induced EPS (Oral):
  • Initial dose: 2.5–5 mg three times daily.
  • Adjust based on clinical response.
  • Maximum: 20 mg/day.
• Acute Dystonia (IM):
  • 5–10 mg as a single intramuscular injection.
  • Onset of relief within 20–30 minutes.

Elderly

• Begin with 2.5 mg once or twice daily.
• Increase slowly and cautiously.
• Monitor closely for confusion, hallucinations, and urinary retention.

Pediatric Use

• Not routinely recommended.
• May be used in children ≥1 year only under specialist supervision for acute dystonic reactions.

Renal or Hepatic Impairment

• Use with caution; start at the lowest effective dose.
• Monitor for signs of drug accumulation or toxicity.

Treatment Duration

• As long as clinical benefits persist.
• Taper gradually if discontinuation is necessary to avoid withdrawal symptoms (e.g., rebound EPS or tremor).

Procyclidine Hydrochloride is a centrally acting antimuscarinic agent. It blocks muscarinic cholinergic receptors, primarily the M1 subtype, in the central nervous system, especially within the basal ganglia and striatum. This reduces the relative excess of acetylcholine that results from dopamine deficiency in Parkinson’s disease or dopamine receptor blockade in antipsychotic-induced EPS. By restoring the dopamine-acetylcholine balance, it alleviates symptoms such as tremor, rigidity, and dystonia.

• Absorption: Rapid and nearly complete absorption from the gastrointestinal tract following oral administration.
• Distribution: Widely distributed in body tissues; crosses the blood-brain barrier.
• Metabolism: Extensively metabolized in the liver.
• Elimination: Primarily via renal excretion (urine), both unchanged and as metabolites.
• Onset of Action:
  • Oral: Within 1 hour
  • IM: Within 20–30 minutes
• Time to Peak Plasma Concentration: 1–2 hours
• Half-Life: Approximately 12 hours
• Bioavailability: High oral bioavailability (not extensively affected by first-pass metabolism).

• Pregnancy:
  • No FDA pregnancy category (previously not assigned).
  • Human data are limited; animal studies are insufficient.
  • Use only if potential benefit justifies potential fetal risk.
• Lactation:
  • Unknown whether Procyclidine is excreted in human milk.
  • Risk of anticholinergic effects (e.g., dry mouth, sedation) in breastfed infants.
  • Caution advised during breastfeeding; monitor infant if used.

• Primary Class: Antiparkinsonian Agent
• Subclass: Centrally Acting Anticholinergic
• Pharmacological Type: Muscarinic Receptor Antagonist (M1-selective)

• Hypersensitivity to Procyclidine or its excipients
• Narrow-angle (closed-angle) glaucoma
• Gastrointestinal obstruction or paralytic ileus
• Urinary retention
• Severe prostatic hypertrophy with obstructive symptoms
• Myasthenia gravis

• Cognitive Impairment: Risk of confusion, hallucinations, and memory disturbances, particularly in the elderly.
• Psychosis: May worsen psychotic symptoms in patients with schizophrenia.
• Abuse Potential: May be misused for its mild euphoric effects, especially in psychiatric patients.
• Tardive Dyskinesia: Not effective; may exacerbate symptoms—avoid use.
• Hyperthermia Risk: May impair heat regulation due to reduced sweating; caution in hot environments.
• Ophthalmic Caution: Avoid in patients with known or suspected angle-closure glaucoma; monitor intraocular pressure.
• Cardiac Monitoring: Use cautiously in patients with tachyarrhythmia or cardiovascular disease.
• Urinary Symptoms: Monitor for urinary hesitancy or retention, especially in older males.

Common Side Effects (by System):

• Central Nervous System:
  • Drowsiness, dizziness, confusion, disorientation
  • Nervousness, mild euphoria, hallucinations (at high doses)
• Gastrointestinal:
  • Dry mouth, constipation, nausea
• Ophthalmologic:
  • Blurred vision, dilated pupils (mydriasis)
• Genitourinary:
  • Urinary retention, difficulty urinating
• Cardiovascular:
  • Palpitations, tachycardia

Serious or Rare Side Effects:

• Delirium or psychosis in vulnerable patients
• Allergic reactions (e.g., rash, pruritus)
• Worsening of glaucoma
• Slurred speech, ataxia at high doses

Onset and Severity:

• Most side effects occur early in therapy or during dose escalation.
• Severity is dose-dependent; more pronounced in elderly or those with CNS sensitivity.

• Additive Anticholinergic Effects:
  • Antihistamines, tricyclic antidepressants, other antimuscarinics (↑ dry mouth, confusion, constipation)
• CNS Depressants (e.g., alcohol, sedatives, benzodiazepines):
  • Increased risk of sedation, cognitive dulling
• Antipsychotics:
  • May mask symptoms of tardive dyskinesia; should be avoided in patients with established TD
• Cholinesterase Inhibitors (e.g., donepezil, rivastigmine):
  • Opposing actions—may reduce effectiveness in dementia treatment
• Unknown CYP Involvement:
  • While exact CYP enzymes are unclear, hepatic metabolism suggests potential for interactions with CYP3A4-modulating agents; use caution.

• Updated Clinical Guidance:
  • Continued recommendation as a second-line agent for Parkinson’s-related tremor when dopaminergic drugs are ineffective.
  • Highlighted in psychiatric treatment protocols for management of acute EPS and dystonia.
  • Recent emphasis on limiting long-term use in elderly due to cognitive risk and anticholinergic burden.
• Safety Monitoring Advice:
  • Regular review advised in elderly and psychiatric patients to minimize misuse or cognitive side effects.

• Temperature: Store below 25°C (77°F)
• Light Protection: Keep in original container; protect from direct sunlight
• Humidity: Store in a dry place
• Handling: Do not freeze. Keep tightly closed.
• Shelf Life: Refer to specific manufacturer’s label; typically 2–3 years if unopened
• Reconstitution: Not applicable (oral and IM formulations are pre-prepared)