Perkirol

Approved Indications:

• Parkinson’s Disease (PD):
• As monotherapy in early-stage Parkinson’s disease.
• As an adjunct to levodopa in advanced stages to manage “on-off” motor fluctuations.
• Moderate to Severe Primary Restless Legs Syndrome (RLS):
• For the symptomatic treatment of idiopathic RLS in adults.

Clinically Accepted Off-Label Uses:

• Periodic Limb Movement Disorder (PLMD): Off-label use in select cases of PLMD, especially when associated with sleep disturbances.
• Secondary Parkinsonism: Occasionally used off-label in parkinsonism caused by drugs or cerebrovascular disease, where dopamine agonist therapy is appropriate.

For Parkinson’s Disease (Adults):

• Initial Dose: 0.25 mg three times daily.
• Titration: Increase in weekly increments based on response and tolerability:
• Week 1: 0.25 mg TID
• Week 2: 0.5 mg TID
• Week 3: 0.75 mg TID
• Week 4: 1 mg TID, and so on.
• Maintenance Dose: Usually 3 to 9 mg/day in divided doses.
• Maximum Dose: Up to 24 mg/day.

For Restless Legs Syndrome (Adults):

• Initial Dose: 0.25 mg once daily, taken 1 to 3 hours before bedtime.
• Titration:
• After 2 days, increase to 0.5 mg.
• After one week, may increase to 1 mg if needed.
• Maximum Dose: 4 mg once daily.

Special Populations:

• Elderly: Initiate at lower dose and titrate slowly due to increased sensitivity.
• Renal Impairment (CrCl <30 mL/min): Start at 0.25 mg once daily; adjust cautiously.
• Hepatic Impairment: No formal dose adjustment, but use cautiously due to hepatic metabolism.

Administration Instructions:

• Administer orally with or without food.
• To minimize nausea, take with food.
• Swallow extended-release tablets whole; do not crush or chew.

Ropinirole is a selective non-ergoline dopamine agonist that binds with high affinity to dopamine D2 and D3 receptors in the brain, particularly in the striatum and substantia nigra. In Parkinson’s disease, dopaminergic neurons degenerate, leading to motor symptoms due to dopamine deficiency. Ropinirole mimics dopamine by directly stimulating these receptors, improving motor control. In Restless Legs Syndrome, the exact mechanism is not fully understood, but it is believed that dopaminergic dysfunction in the central nervous system contributes to the symptoms, and ropinirole’s stimulation of D2 receptors helps relieve these uncomfortable sensations and urge to move.

• Absorption: Rapid and nearly complete oral absorption; peak plasma levels in 1–2 hours (immediate-release).
• Bioavailability: ~55%.
• Distribution: Wide distribution (Vd ~7.5 L/kg); ~40% plasma protein binding.
• Metabolism: Primarily hepatic via CYP1A2 to inactive metabolites.
• Elimination Half-Life: ~6 hours (immediate-release); slightly longer with extended-release formulations.
• Excretion: Predominantly via urine as metabolites (approx. 88%); ~10% excreted in feces.

• Pregnancy: Category C.
• Animal studies show fetal harm; no adequate studies in pregnant women.
• Use only if the potential benefit justifies the potential risk to the fetus.
• Lactation:
• Ropinirole may inhibit lactation by reducing prolactin levels.
• Excretion into human breast milk is unknown but observed in animals.
• Breastfeeding is not recommended during treatment due to potential adverse effects on the infant and reduction of milk production.

• Primary Class: Dopaminergic Antiparkinsonism Agent
• Subclass: Non-ergot Dopamine Receptor Agonist (D2/D3 agonist)

• Known hypersensitivity to ropinirole or any component of the formulation.
• Concurrent use with potent CYP1A2 inhibitors without proper dose adjustment.
• Severe hepatic impairment (due to uncertain metabolism).
• Pregnancy and lactation (unless benefits outweigh risks).

• Sudden Sleep Episodes: Can occur without warning; patients should avoid driving or operating machinery.
• Impulse Control Disorders: Including pathological gambling, hypersexuality, binge eating—monitor closely.
• Hallucinations and Psychotic Behavior: Especially in elderly patients or at higher doses.
• Neuroleptic Malignant Syndrome (NMS): May occur if abruptly discontinued; taper gradually.
• Orthostatic Hypotension: Monitor blood pressure during dose titration.
• Augmentation in RLS: May worsen or cause earlier onset of symptoms—adjustment of dose or discontinuation may be required.

Common (≥1%):

• CNS: Dizziness, somnolence, headache, fatigue, insomnia.
• Gastrointestinal: Nausea, vomiting, constipation, dyspepsia.
• Psychiatric: Hallucinations, abnormal dreams.

Less Common:

• Edema (peripheral), orthostatic hypotension, sweating, dry mouth.

Serious/Rare:

• Syncope, sudden onset of sleep, impulse control disorders (compulsive gambling, hypersexuality), hepatotoxicity, serotonin syndrome (when combined with serotonergic drugs).

Onset & Dose Dependence:

• Most side effects appear early during dose escalation and are dose-dependent. Titrating slowly can reduce incidence and severity.

• CYP1A2 Inhibitors (e.g., ciprofloxacin, fluvoxamine): Increase plasma levels of ropinirole—dose adjustment may be needed.
• CYP1A2 Inducers (e.g., smoking, omeprazole): May reduce efficacy by lowering drug levels.
• Dopamine Antagonists (e.g., antipsychotics, metoclopramide): May counteract therapeutic effect.
• CNS Depressants & Alcohol: Additive sedative effects; use caution.
• Estrogens: May inhibit CYP1A2 and increase ropinirole exposure.

• Impulse Control Warnings: The FDA and EMA emphasize monitoring for compulsive behaviors in patients using dopamine agonists.
• Dose Adjustments in RLS: Recommendations to periodically re-evaluate therapy to avoid augmentation.
• Guidelines for Parkinson’s Disease: Ropinirole remains a first-line agent for early-stage PD and adjunct in advanced PD, per current movement disorder society guidelines.

• Temperature: Store below 25°C (77°F).
• Humidity & Light: Protect from light and moisture; keep in original packaging.
• Handling: Extended-release tablets must not be crushed, chewed, or split.
• Refrigeration: Not required.
• Shelf Life: Check manufacturer’s label; typically 2–3 years under proper conditions.