Co-careldopa

Co-careldopa is a fixed-dose combination medication consisting of:

• Levodopa (also called L-dopa): A dopamine precursor

• Carbidopa: A peripheral dopa-decarboxylase inhibitor

It is primarily used in the treatment of Parkinson’s disease and Parkinsonism, including those secondary to encephalitis, carbon monoxide or manganese poisoning. Co-careldopa improves motor symptoms by replenishing dopamine levels in the brain, while reducing peripheral side effects such as nausea by inhibiting peripheral metabolism of levodopa.

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Brand Names

Co-careldopa is available under various proprietary names, including:

• Sinemet®

• Sinemet Plus®

• Sinemet CR® (controlled release)

• Duodopa® (gel formulation for intestinal infusion)

• Kinson®

• Rytary® (extended-release capsules; US only)

Available forms:

• Immediate-release tablets

• Controlled-release tablets (CR or SR)

• Dispersible tablets

• Intestinal gel (Duodopa)

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Mechanism of Action

Levodopa (L-DOPA):

• A precursor of dopamine, capable of crossing the blood-brain barrier (BBB)

• In the central nervous system (CNS), levodopa is converted to dopamine by DOPA decarboxylase

• Increases dopaminergic neurotransmission, which is deficient in Parkinson’s disease

Carbidopa:

• Inhibits peripheral DOPA decarboxylase, preventing conversion of levodopa to dopamine in the bloodstream

• This:

  • Increases bioavailability of levodopa for the brain

  • Reduces peripheral side effects like nausea, vomiting, and cardiovascular effects

  • Allows for lower doses of levodopa

The combination allows for effective CNS dopamine replenishment while minimizing unwanted systemic effects.

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Therapeutic Uses

Co-careldopa is indicated for:

• Parkinson’s disease (idiopathic Parkinsonism)

• Post-encephalitic parkinsonism

• Parkinsonian syndrome secondary to carbon monoxide and manganese poisoning

• Restless leg syndrome (off-label, in some cases)

• Freezing episodes and motor fluctuations in advanced Parkinson’s disease

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Dosage and Administration

Dosage is individualized and titrated based on patient response and disease severity.

Initial Dose (Adults)

• Start with low dose, e.g., co-careldopa 62.5 mg (levodopa 50 mg + carbidopa 12.5 mg) 3–4 times/day

• Alternatively: 100/25 mg tablets one to three times daily

Maintenance Dose

• Most patients require 300–800 mg/day of levodopa, in divided doses

• Dose intervals: Every 4–6 hours, depending on motor fluctuations

• Adjust gradually by one tablet every 1–2 days

Max Daily Dose

• Levodopa: Up to 2 grams/day

• Carbidopa: At least 70–100 mg/day required to fully inhibit peripheral decarboxylase

Formulations

• Sinemet®: Immediate-release (100/25 mg or 250/25 mg)

• Sinemet CR®: Controlled-release, dosed less frequently but with slower onset

• Duodopa®: Intestinal gel for continuous infusion in advanced disease via PEG-J tube

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Contraindications

• Hypersensitivity to levodopa, carbidopa, or excipients

• Narrow-angle glaucoma

• History of malignant melanoma

• Concurrent use of non-selective MAO inhibitors (must discontinue ≥2 weeks prior)

• Undiagnosed skin lesions (risk of activating melanoma)

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Precautions

Use with caution in:

• Cardiovascular disease: Risk of orthostatic hypotension

• Pulmonary disease or asthma

• Psychiatric illness: May exacerbate depression, psychosis

• Peptic ulcer disease

• Diabetes mellitus

• Hepatic or renal impairment

• Open-angle glaucoma: Monitor intraocular pressure

Special care is needed during transition from other dopaminergic therapies, including monoamine oxidase inhibitors.

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Side Effects

Common

• Nausea and vomiting

• Anorexia

• Dizziness

• Orthostatic hypotension

• Somnolence

• Dry mouth

• Insomnia

Neurological

• Dyskinesias: Involuntary movements (chorea, dystonia)

• Motor fluctuations ("on-off" phenomenon)

• Wearing-off: Return of symptoms before next dose

• Freezing episodes

Neuropsychiatric

• Hallucinations, delusions

• Confusion

• Impulse control disorders: Gambling, hypersexuality, compulsive eating

• Depression, suicidal ideation

Rare but Serious

• Neuroleptic malignant syndrome-like withdrawal reaction

• Hemolytic anemia

• Angioedema

• Leukopenia

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Drug Interactions

Contraindicated

• Non-selective MAO inhibitors: Hypertensive crisis risk

• Metoclopramide: Antagonizes dopaminergic action; increases side effects

Caution

• Antihypertensives: Additive hypotensive effect

• Antipsychotics (especially typical): Dopamine antagonism reduces efficacy

• Iron supplements: May impair absorption; separate by 2 hours

• High-protein diet: Competes with levodopa absorption in the gut

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Use in Special Populations

Pregnancy

• Use only if benefit outweighs risk

• Animal studies show fetal toxicity; human data limited

Lactation

• Avoid; dopamine suppresses prolactin and may affect milk production

Elderly

• Dose adjustment often necessary due to increased sensitivity and risk of orthostatic hypotension or confusion

Pediatrics

• Not recommended; safety and efficacy not established

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Patient Counseling Points

• Take doses at the same time daily

• Do not stop abruptly – risk of severe neuroleptic malignant syndrome-like reaction

• May take with food to reduce nausea, but avoid high-protein meals

• Report new or worsening involuntary movements, hallucinations, or mood changes

• May cause drowsiness or sudden sleep attacks; avoid driving if affected

• Orthostatic hypotension risk: Get up slowly from sitting/lying

• Urine or sweat may become dark colored—harmless but can stain clothes

• Regular follow-up required for dose adjustment and motor symptom monitoring

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Storage

• Store tablets at room temperature (15–25°C)

• Keep away from moisture and light

• Do not crush controlled-release tablets