Schedule H

Oral

Formulation Type Strengths Available

Immediate-Release Tablets 0.125 mg, 0.25 mg, 0.5 mg, 1 mg

Extended-Release Tablets 0.375 mg, 0.75 mg, 1.5 mg, 3 mg

Note: Strengths are expressed as Pramipexole dihydrochloride monohydrate (salt form). Some references may quote base equivalent doses.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Idiopathic Parkinson's Disease

Can be used as monotherapy in early disease or as adjunct to Levodopa in advanced disease with motor fluctuations.

Immediate-Release (IR) Tablets:

Parameter Dosing

Starting dose 0.125 mg three times daily

Titration Increase by 0.125 mg per dose every 5–7 days based on response and tolerability

Usual maintenance dose 0.5–1.5 mg three times daily (1.5–4.5 mg/day total)

Maximum dose 4.5 mg/day (in three divided doses)

Extended-Release (ER) Tablets:

Parameter Dosing

Starting dose 0.375 mg once daily

Titration Increase by 0.75 mg/day at weekly intervals

Usual maintenance dose 1.5–3 mg once daily

Maximum dose 4.5 mg once daily

Clinical Notes:

• When used as adjunct to Levodopa, consider reducing Levodopa dose by 20–30% as Pramipexole dose is optimised

• Taper gradually when discontinuing — do not stop abruptly (risk of dopamine agonist withdrawal syndrome)

• May take with or without food; food reduces nausea

• ER tablets must be swallowed whole — do not crush, chew, or divide

1. Moderate to Severe Primary Restless Legs Syndrome (RLS)

Immediate-Release Tablets Only:

Parameter Dosing

Starting dose 0.125 mg once daily, 2–3 hours before bedtime

Titration May increase by 0.125 mg every 4–7 days if needed

Usual maintenance dose 0.25–0.5 mg once daily

Maximum dose 0.5 mg/day

Clinical Notes:

• Not approved for secondary RLS

• Risk of augmentation (worsening of symptoms) increases with doses above 0.5 mg/day

• Treatment should be reassessed periodically — long-term use may lead to augmentation

• ER tablets are NOT recommended for RLS

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes Evidence Basis

Treatment-Resistant Depression (Augmentation) 0.125–0.5 mg/day in divided doses 6–8 weeks minimum trial OFF-LABEL; Psychiatrist supervision only Limited RCTs; not standard practice in India

Bipolar Depression (Adjunctive) 0.125 mg/day up to 1 mg/day Variable OFF-LABEL; Psychiatrist only; monitor for mania Small RCTs; use with caution

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable. Pramipexole is NOT approved for use in children and adolescents below 18 years of age for any indication.

Secondary Indications — Paediatric (Off-label)

Not applicable. No established paediatric indications or dosing.

Clear Statement: Use in patients below 18 years of age is NOT RECOMMENDED. Safety and efficacy have not been established in the paediatric population.

Creatinine Clearance (CrCl) IR Tablets ER Tablets

50 mL/min No adjustment required No adjustment required

30–50 mL/min Start 0.125 mg twice daily; max 1.5 mg/day Start 0.375 mg every other day; max 2.25 mg/day

15–30 mL/min Start 0.125 mg once daily; max 1.5 mg/day Not recommended

<15 mL/min or Haemodialysis Avoid; if essential, 0.125 mg once daily max Not recommended

Notes:

• Extended-release tablets are NOT recommended in severe renal impairment (CrCl <30 mL/min)

• Not significantly removed by haemodialysis

• Titrate slowly with close monitoring in all renal impairment categories

Note: Pramipexole is minimally metabolised hepatically; dose adjustment is generally not required based on hepatic function alone.

• Known hypersensitivity to Pramipexole or any excipient

• Severe renal impairment (CrCl <15 mL/min) — for extended-release formulation

• Renal impairment — dose adjustment essential; monitor closely

• History of or active psychiatric illness (psychosis, hallucinations, delusions)

• Pre-existing impulse control disorders — may worsen; counsel patient and caregivers

• Risk of sudden onset of sleep (sleep attacks) — caution patients about driving and operating machinery

• Cardiovascular disease — risk of orthostatic hypotension, especially during titration

• Elderly patients — increased susceptibility to CNS adverse effects

• Concurrent use with other sedating medications

• History of dyskinesias — may worsen when used with Levodopa

• Abrupt discontinuation — risk of dopamine agonist withdrawal syndrome (anxiety, depression, panic, sweating, pain)

• Ophthalmological abnormalities — periodic eye examinations recommended

Parameter Details

Risk category Limited human data; animal studies show reproductive toxicity at high doses

Preferred alternatives Levodopa-Carbidopa is preferred for Parkinson's disease in pregnancy if treatment essential

When it may be used Only if maternal benefit clearly outweighs fetal risk; specialist neurologist and obstetrician supervision mandatory

Monitoring Fetal growth parameters, maternal motor symptoms, blood pressure

Parameter Details

Compatibility Not recommended during breastfeeding

Drug levels in milk Unknown; inhibits prolactin secretion — may suppress lactation

Preferred alternatives Consider Levodopa-Carbidopa if antiparkinsonian therapy essential; or avoid breastfeeding

Monitoring in infant If inadvertent exposure: feeding difficulties, sedation, poor weight gain, irritability

Parameter Recommendation

Starting dose 0.125 mg once or twice daily (IR); 0.375 mg once daily (ER)

Titration Slower than younger adults — increase dose at intervals of 7–14 days

Extra risks Orthostatic hypotension and falls, hallucinations, confusion, somnolence, cognitive impairment

Special considerations Assess renal function before starting; regular cognitive and psychiatric assessment; educate caregivers about impulse control disorders and sleep attacks

Interacting Drug Effect Recommendation

Antipsychotics (Haloperidol, Risperidone, Olanzapine) Dopamine receptor antagonism — reduces Pramipexole efficacy Avoid; if antipsychotic essential, consider Quetiapine or Clozapine under specialist care

Metoclopramide Central dopamine antagonist — reduces efficacy, may worsen Parkinsonism Avoid; use Domperidone as alternative antiemetic

Levodopa Enhanced dopaminergic effects — increased dyskinesias Reduce Levodopa dose by 20–30% when adding Pramipexole

CNS depressants (Benzodiazepines, Opioids, Alcohol) Additive sedation; increased risk of sudden sleep episodes Use with caution; counsel about driving

Interacting Drug Effect Recommendation

Cimetidine Inhibits renal tubular secretion of Pramipexole — may increase plasma levels Monitor for adverse effects; consider dose reduction

Amantadine Combined dopaminergic effects — increased risk of hallucinations, confusion Use with caution; monitor closely

MAO-B Inhibitors (Selegiline, Rasagiline) Synergistic dopaminergic effects Can be combined; monitor for dyskinesias and psychiatric symptoms

Antihypertensives Additive hypotensive effect Monitor blood pressure; adjust antihypertensive if needed

Other Dopamine Agonists (Ropinirole, Rotigotine) Overlapping mechanism — no additional benefit Avoid combination

• Nausea, vomiting

• Dizziness, lightheadedness

• Somnolence, fatigue

• Insomnia

• Constipation

• Peripheral oedema

• Hallucinations (especially in elderly or with Levodopa)

• Headache

• Dry mouth

• Dyskinesias (when used with Levodopa)

• Sudden onset of sleep (sleep attacks) — may occur without warning; driving hazard — counsel patients; immediate dose reduction required

• Impulse control disorders — pathological gambling, hypersexuality, compulsive shopping, binge eating; requires dose reduction or discontinuation; family counselling essential

• Psychosis, severe hallucinations, delusions — may require dose reduction or discontinuation; consider Quetiapine or Clozapine if antipsychotic needed

• Severe orthostatic hypotension — risk of syncope and falls

• Dopamine agonist withdrawal syndrome — anxiety, panic attacks, depression, irritability, sweating, pain; taper gradually over weeks

• Retroperitoneal fibrosis, pulmonary fibrosis — rare; more common with ergot-derived agonists but reported with non-ergot agents; requires discontinuation

Phase Parameters to Monitor

Baseline Renal function (eGFR/CrCl), blood pressure (lying and standing), psychiatric history, cognitive assessment, ophthalmological examination (if prolonged use anticipated)

After initiation / dose change Blood pressure (lying and standing) weekly during titration, motor response, emergence of somnolence/sleep attacks, hallucinations, dyskinesias

Long-term Renal function annually, impulse control disorder screening (ask patient and caregivers), psychiatric status, periodic ophthalmological examination, motor fluctuations

Brand Name Manufacturer Formulations Available

Pramirol Sun Pharma IR: 0.125 mg, 0.25 mg, 0.5 mg, 1 mg

Pramipex Various IR: 0.125 mg, 0.25 mg, 0.5 mg

Pexola Zydus IR: 0.125 mg, 0.25 mg, 0.5 mg

Prapex Intas IR: 0.125 mg, 0.25 mg, 0.5 mg, 1 mg

Pramipexole ER Various ER: 0.375 mg, 0.75 mg, 1.5 mg

Note: Extended-release formulations have limited availability in India. Verify local availability before prescribing.

Note: Pramipexole is NOT included in NLEM India 2022; prices are not NPPA-controlled. Available in select neurology OPDs under central/state schemes.

• Preferred in younger Parkinson's patients: Consider Pramipexole as initial monotherapy in younger patients (<60 years) without cognitive impairment to delay Levodopa initiation and reduce long-term motor complications.

• RLS dosing ceiling: For Restless Legs Syndrome, do NOT exceed 0.5 mg/day — higher doses significantly increase risk of augmentation phenomenon.

• Taper, never stop abruptly: Dopamine agonist withdrawal syndrome can be severe; always taper over 1–2 weeks minimum.

• Screen for impulse control disorders: Actively ask patients and caregivers about gambling, hypersexuality, compulsive shopping at every visit — these may not be volunteered.

• Warn about sleep attacks: Document counselling about sudden onset of sleep and advise against driving/operating machinery until stable on dose.

• Elderly require lower doses: Start low, go slow — hallucinations and orthostatic hypotension are significantly more common in elderly patients.

Pramipexole; Parkinson's disease; dopamine agonist; non-ergot; Restless Legs Syndrome; RLS; impulse control disorders; sleep attacks; renal-dose-adjust; Schedule H; elderly-caution; Neurology

RxIndia v1.0 — 11 Jun 2025

• CDSCO approved product inserts

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine — Movement Disorders chapter

• AIIMS Neurology Drug Formulary

• Harrison's Principles of Internal Medicine, 21st edition

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Selected RCTs (for off-label psychiatric indications — clearly marked)