Schedule H

Oral

Formulation Strengths

Tablets (combination) Levodopa 100 mg + Carbidopa 10 mg; Levodopa 100 mg + Carbidopa 25 mg; Levodopa 250 mg + Carbidopa 25 mg

Controlled-Release Tablets Levodopa 200 mg + Carbidopa 50 mg

Orally Disintegrating Tablets Levodopa 100 mg + Carbidopa 25 mg; Levodopa 250 mg + Carbidopa 25 mg

Levodopa + Benserazide Levodopa 100 mg + Benserazide 25 mg; Levodopa 200 mg + Benserazide 50 mg

Important: Pure Levodopa monotherapy tablets are NOT AVAILABLE in India for routine prescribing. Standard of care mandates co-administration with a peripheral DOPA decarboxylase inhibitor (DDCI) — Carbidopa or Benserazide.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Parkinson's Disease (Idiopathic Parkinsonism)

Always prescribed in combination with DDCI (Carbidopa or Benserazide).

Parameter Levodopa + Carbidopa

Starting dose 100 mg Levodopa + 25 mg Carbidopa once or twice daily

Titration Increase by 100 mg Levodopa every 3–7 days based on response and tolerability

Usual maintenance dose 300–600 mg/day Levodopa (divided into 3–4 doses) with 75–150 mg/day Carbidopa

Maximum dose 800–1000 mg/day Levodopa; doses exceeding 1000 mg require specialist supervision

Clinical Notes:

• Administer 30–60 minutes before meals for optimal absorption

• If nausea is prominent, may give with low-protein snack initially

• Controlled-release formulations useful for managing "wearing-off" phenomena

• Minimum Carbidopa requirement: 70–100 mg/day to adequately inhibit peripheral decarboxylation

1. Secondary Parkinsonism (Post-encephalitic, Carbon Monoxide Poisoning, MPTP-induced)

Parameter Dosing

Starting dose Same as idiopathic Parkinson's disease

Titration Individualised based on aetiology and response

Usual maintenance dose 300–800 mg/day Levodopa (divided doses)

Maximum dose As per specialist discretion

Clinical Notes:

• Specialist management mandatory

• Response may differ from idiopathic Parkinson's disease

• Evaluate for reversibility of underlying cause

Secondary Indications — Adults (Off-label)

Not applicable. No major evidence-based off-label indications are established in Indian practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Juvenile Parkinsonism

Parameter Dosing (Levodopa component)

Starting dose 1–2 mg/kg/day in 2–3 divided doses

Titration Increase gradually every 5–7 days based on response

Usual maintenance dose 4–8 mg/kg/day in 3–4 divided doses

Maximum dose 10 mg/kg/day

1. Dopa-Responsive Dystonia (Segawa Syndrome)

Parameter Dosing (Levodopa component)

Starting dose 1 mg/kg/day in 2 divided doses

Titration Gradual increase every 5–7 days

Usual maintenance dose 4–5 mg/kg/day (often dramatic response at low doses)

Maximum dose 10 mg/kg/day

Safety Monitoring:

• Monitor for dyskinesias and dose-related involuntary movements

• Assess for behavioural changes, sleep disturbance

• Regular neurological evaluation for motor response

Minimum Age: Not routinely recommended below 2 years of age; use only under specialist supervision with confirmed diagnosis.

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes Evidence Basis

Other Dopa-responsive movement disorders 1–5 mg/kg/day in divided doses Long-term Specialist paediatric neurologist only; OFF-LABEL Case series, established specialist practice

Severe impairment (eGFR <30) Use with caution; monitor for accumulation of DDCI component

Haemodialysis No specific data; Levodopa may be partially dialysable; monitor clinical response

Peritoneal dialysis No specific data; use standard dosing with monitoring

• Narrow-angle glaucoma (uncontrolled)

• Concurrent use with non-selective monoamine oxidase inhibitors (Phenelzine, Tranylcypromine, Isocarboxazid) — must discontinue MAO inhibitor at least 14 days before initiating Levodopa

• Known hypersensitivity to Levodopa, Carbidopa, Benserazide, or any excipient

• History of malignant melanoma or suspicious undiagnosed skin lesions

• Severe uncontrolled psychosis

• Cardiovascular disease (risk of orthostatic hypotension, arrhythmias)

• History of myocardial infarction with residual arrhythmia

• Active peptic ulcer disease (risk of upper GI bleeding)

• Pre-existing psychosis, dementia, or cognitive impairment (may worsen hallucinations)

• Chronic wide-angle glaucoma (monitor intraocular pressure)

• History of seizures

• Pulmonary disease, bronchial asthma

• Endocrine disorders (diabetes mellitus, osteomalacia)

• High-protein diet (reduces Levodopa absorption via amino acid competition)

• Abrupt discontinuation (risk of neuroleptic malignant syndrome-like reaction)

Parameter Details

Risk category Limited human data; animal studies suggest possible embryotoxicity and skeletal abnormalities

Preferred alternatives No clearly established safer alternative for Parkinson's disease in pregnancy

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

Monitoring Fetal growth parameters, maternal blood pressure, signs of motor deterioration

Parameter Details

Compatibility Not recommended; insufficient data

Drug levels in milk Unknown; possibly low based on pharmacokinetics

Effects on infant Unclear; theoretical concern of prolactin suppression affecting lactation

Preferred alternatives Consider alternative therapy if breastfeeding is essential

Monitoring in infant Feeding tolerance, weight gain, sedation, irritability

Parameter Recommendation

Starting dose 50 mg Levodopa + 12.5 mg Carbidopa once or twice daily

Titration Slower than adults; increase every 5–7 days in small increments

Extra risks Orthostatic hypotension, falls, confusion, hallucinations, vivid dreams, increased sensitivity to dyskinesias

Special considerations Prefer controlled-release formulations to reduce motor fluctuations; regular cognitive and psychiatric assessment

Interacting Drug Effect Recommendation

Non-selective MAO inhibitors (Phenelzine, Tranylcypromine) Hypertensive crisis risk Contraindicated; stop MAO inhibitor ≥14 days before Levodopa

Antipsychotics (Haloperidol, Risperidone, Olanzapine) Dopamine receptor blockade antagonises Levodopa efficacy Avoid; if essential, consider Clozapine or Quetiapine under specialist care

Metoclopramide Dopamine antagonist; reduces Levodopa efficacy and worsens Parkinsonism Avoid; use Domperidone as alternative antiemetic

Isoniazid May reduce Levodopa efficacy Monitor response; consider dose adjustment

Interacting Drug Effect Recommendation

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

Iron salts Chelation reduces Levodopa absorption Separate administration by ≥2 hours

Pyridoxine (Vitamin B6) High doses (>10 mg/day) reduce Levodopa efficacy when used without DDCI Not clinically significant when Carbidopa/Benserazide is co-administered

Selegiline, Rasagiline MAO-B inhibitors; potential for increased dopaminergic effects Can be combined; monitor for dyskinesias and hypotension

Tricyclic antidepressants Synergistic CNS effects; may worsen orthostatic hypotension Use with caution; monitor

High-protein meals Amino acid competition reduces Levodopa absorption Advise consistent, moderate protein intake; take medication before meals

Phenytoin, Papaverine May reduce Levodopa efficacy Monitor therapeutic response

• Nausea, vomiting, anorexia (improves with DDCI co-administration and food)

• Orthostatic hypotension, dizziness

• Drowsiness, fatigue

• Dyskinesias (choreiform, dystonic movements) — dose-related

• Motor fluctuations: "wearing-off," "on-off" phenomenon

• Vivid dreams, insomnia

• Dry mouth

• Dark discolouration of urine, sweat (harmless)

• Psychiatric disturbances: hallucinations, delusions, psychosis (especially elderly)

• Neuroleptic malignant syndrome-like reaction (with abrupt withdrawal)

• Severe dyskinesia

• Cardiac arrhythmias (rare)

• Impulse control disorders (pathological gambling, hypersexuality, compulsive shopping)

• Depression, suicidal ideation

• Haemolytic anaemia (rare)

• Hepatotoxicity (rare; monitor LFTs in long-term use)

Phase Parameters

Baseline Liver function tests, renal function, ECG (if elderly or cardiac history), blood pressure, complete blood count, psychiatric assessment

During titration Blood pressure (lying and standing), motor response, dyskinesias, psychiatric symptoms (hallucinations, confusion)

Long-term Motor fluctuations ("wearing-off," "on-off"), dyskinesias, psychiatric status, impulse control disorders, LFTs annually, bone health assessment

Brand Name Manufacturer Composition

Tidomet Intas Levodopa + Carbidopa

Sinemet MSD (limited availability) Levodopa + Carbidopa

Madopar Roche (limited availability) Levodopa + Benserazide

Levopa-C Micro Labs Levodopa + Carbidopa

Note: Levodopa-Carbidopa combination is included in NLEM India 2022; prices may be regulated under DPCO for scheduled formulations.

• Never prescribe Levodopa without a DDCI — monotherapy leads to excessive peripheral side effects and poor CNS availability.

• Timing matters: Administer 30–60 minutes before meals; high-protein meals significantly reduce absorption.

• "Start low, go slow" in elderly — they are highly susceptible to neuropsychiatric adverse effects.

• Motor complications are inevitable with long-term use; consider early addition of dopamine agonists or COMT inhibitors in younger patients to delay Levodopa.

• Never withdraw abruptly — risk of neuroleptic malignant syndrome-like reaction; always taper gradually.

• Domperidone is the antiemetic of choice for Levodopa-induced nausea (does not cross blood-brain barrier); avoid Metoclopramide.

• Impulse control disorders are increasingly recognised — counsel patients and caregivers to report compulsive behaviours.

Levodopa; Parkinsonism; dopaminergic; Levodopa-Carbidopa; antiparkinsonian; Schedule H; elderly-caution; pregnancy-uncertain; renal-safe; NLEM India

RxIndia v1.0 — 11 Jun 2025

• CDSCO approved product inserts

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Neurology Parkinson's Disease Protocol

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

• NLEM India 2022

• WHO Guidelines (supportive reference for paediatric dystonia)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics