Duopa - Drug Monograph

Introduction

Duopa (carbidopa-levodopa enteral suspension) is a prescription medication used for the treatment of motor fluctuations in patients with advanced Parkinson's disease. It represents a significant advancement in Parkinson's therapy by providing continuous dopaminergic stimulation through continuous intestinal infusion, offering more stable symptom control compared to oral levodopa formulations.

Mechanism of Action

Duopa contains carbidopa and levodopa in a 1:4 ratio. Levodopa is a metabolic precursor to dopamine that crosses the blood-brain barrier and is converted to dopamine in the brain, replenishing depleted dopamine stores in the substantia nigra. Carbidopa is a peripheral decarboxylase inhibitor that prevents the conversion of levodopa to dopamine in peripheral tissues, allowing more levodopa to reach the central nervous system and reducing peripheral side effects. The continuous intestinal delivery system provides more stable plasma concentrations than intermittent oral dosing.

Indications

Duopa is FDA-approved for the treatment of motor fluctuations in patients with advanced Parkinson's disease. It is specifically indicated for patients who continue to experience "off" episodes despite optimized treatment with oral carbidopa-levodopa preparations.

Dosage and Administration

Duopa is administered as a continuous intestinal infusion through a percutaneous endoscopic gastrostomy (PEG) tube with a jejunal extension (PEG-J). The typical starting dose is 20 mL of Duopa (containing 100 mg levodopa and 25 mg carbidopa) infused over 16 hours, followed by an optional morning bolus dose of 10-40 mL. Dosage is titrated based on clinical response and tolerability. The maximum recommended daily dose is 200 mL (2000 mg levodopa/500 mg carbidopa). Administration requires a CADD-Legacy Duopa Pump and specific administration sets.

Special populations:

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution
• Elderly: No specific dosage adjustment required

Pharmacokinetics

Contraindications

• Hypersensitivity to carbidopa, levodopa, or any component of the formulation
• Use with non-selective monoamine oxidase (MAO) inhibitors (must allow at least 2 weeks between therapies)
• Narrow-angle glaucoma
• History of melanoma or suspicious undiagnosed skin lesions

Warnings and Precautions

• Neuroleptic Malignant Syndrome: Abrupt withdrawal or dose reduction may precipitate NMS
• Psychosis: May exacerbate pre-existing psychosis or cause new-onset psychotic symptoms
• Impulse Control Disorders: May cause pathological gambling, increased libido, hypersexuality, compulsive spending, or binge eating
• Dyskinesia: May cause or exacerbate dyskinesias
• Melanoma: Increased risk of melanoma; regular dermatologic monitoring required
• Depression: May worsen depression with suicidal ideation
• Cardiovascular Effects: Orthostatic hypotension, syncope, and arrhythmias may occur
• PEG-J Complications: Risk of tube complications including peritonitis, pneumoperitoneum, and intestinal obstruction

Drug Interactions

• MAO inhibitors: Contraindicated with non-selective MAO inhibitors; may be used with MAO-B inhibitors
• Dopamine D2 receptor antagonists: May diminish therapeutic effects (phenothiazines, butyrophenones, risperidone)
• Iron salts: May reduce bioavailability of levodopa
• Antihypertensives: May potentiate hypotensive effects
• Protein-rich meals: May reduce absorption and efficacy

Adverse Effects

• Nausea (23%)
• Constipation (19%)
• Insomnia (18%)
• Depression (16%)
• Dyskinesia (15%)
• Peripheral edema (13%)
• Upper respiratory tract infection (11%)
• Anxiety (10%)
• Dizziness (10%)
• Fall (9%)
• Hypertension (8%)
• Vomiting (8%)
• Dyspepsia (7%)
• Orthostatic hypotension (6%)

• Neuroleptic malignant syndrome
• Psychosis
• Severe hypotension
• Cardiac arrhythmias
• PEG-J complications
• Impulse control disorders

Monitoring Parameters

• Motor function and "on/off" episodes
• Mental status and psychiatric symptoms
• Blood pressure (supine and standing)
• Signs of dyskinesia
• Skin examinations for melanoma
• Signs of impulse control disorders
• PEG-J site for infection or complications
• Nutritional status and hydration
• Complete blood count, liver and renal function

Patient Education

• Do not abruptly stop treatment; follow tapering instructions
• Be aware of potential sudden sleep episodes during activities
• Report any new or worsening mental status changes
• Monitor for signs of impulse control disorders
• Regular skin examinations are essential
• Rise slowly from sitting or lying positions
• Maintain consistent protein intake timing
• Proper PEG-J site care and recognition of complications
• Do not operate machinery until effects are known
• Inform all healthcare providers about Duopa therapy

References

1. FDA Prescribing Information: Duopa (carbidopa and levodopa) enteral suspension. 2015. 2. Olanow CW, et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 2014;13(2):141-149. 3. Fernandez HH, et al. Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results. Mov Disord. 2015;30(4):500-509. 4. Antonini A, et al. Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results. Mov Disord. 2015;30(4):500-509. 5. Nyholm D, et al. Comparison of apomorphine and levodopa infusions in advanced Parkinson's disease. Mov Disord. 2012;27(10):1272-1278. 6. Zibetti M, et al. Motor and nonmotor symptom follow-up in parkinsonian patients after duodenal levodopa infusion. Eur J Neurol. 2013;20(1):196-202.