Aparkin

Approved Indications:

• Idiopathic Parkinson’s Disease: For the treatment of all stages of Parkinson’s disease to relieve symptoms such as tremor, rigidity, bradykinesia, and postural instability.
• Post-encephalitic Parkinsonism
• Symptomatic Parkinsonism resulting from:
• Manganese intoxication
• Carbon monoxide poisoning
• Parkinsonism due to arteriosclerosis of cerebral vessels

Off-label (Clinically Accepted) Uses:

• Restless Legs Syndrome (RLS): In selected refractory cases when other first-line agents are ineffective or poorly tolerated.

Route: Oral

Adults:

• Initial dose: 62.5 mg (Levodopa 50 mg + Benserazide 12.5 mg) two to three times daily, taken with meals to reduce GI side effects.
• Titration: Dose may be increased every 3–7 days based on response.
• Maintenance dose: Commonly Levodopa 300–800 mg/day (with Benserazide in a 4:1 ratio), in divided doses.
• Maximum daily dose: Levodopa up to 1000 mg/day, as tolerated.

Elderly:

• Initiate treatment with caution. Start with lower doses and adjust slowly based on tolerability and response.

Pediatrics:

• Not recommended for use in children under 18 years.

Renal Impairment:

• Use with caution; dose adjustment may be necessary. Monitor renal function closely.

Hepatic Impairment:

• No specific adjustment recommended, but clinical monitoring is advised.

Administration Notes:

• Take with food to reduce nausea but avoid high-protein meals close to dosing, as amino acids may interfere with Levodopa absorption.

Levodopa is a metabolic precursor of dopamine. Once absorbed and transported into the brain, it is decarboxylated to dopamine, replenishing deficient dopamine levels in the striatum of Parkinson’s patients. Benserazide is a peripheral dopa-decarboxylase inhibitor that prevents the premature conversion of Levodopa to dopamine outside the central nervous system. This allows more Levodopa to enter the brain and minimizes peripheral side effects such as nausea and hypotension. Benserazide does not cross the blood–brain barrier, thus enhancing Levodopa’s central efficacy while reducing peripheral adverse effects.

• Absorption: Rapid from the gastrointestinal tract.
• Bioavailability: Levodopa ~30% (in combination with Benserazide).
• Time to peak plasma concentration: 1–2 hours.
• Distribution: Levodopa crosses the blood-brain barrier; Benserazide does not.
• Protein Binding: Levodopa ~10–30%.
• Metabolism:
• Levodopa: Decarboxylated to dopamine in CNS.
• Benserazide: Extensively metabolized in the liver and gut wall.
• Half-life:
• Levodopa: ~1.5 hours (prolonged with Benserazide).
• Elimination: Primarily via urine (as metabolites).
• Dialysis: Not significantly removed by hemodialysis.

• Pregnancy: Use is not recommended. Animal studies show embryotoxic effects. Human data are limited.
• Lactation: Both components are excreted into breast milk. May suppress lactation and potentially affect the nursing infant.
• Recommendation: Avoid use in pregnancy and breastfeeding unless no safer alternative exists and benefits clearly outweigh risks.

• Primary Class: Anti-Parkinsonian Agent
• Subclass: Dopaminergic Agent (Levodopa is a dopamine precursor; Benserazide is a peripheral dopa-decarboxylase inhibitor)

• Known hypersensitivity to Levodopa, Benserazide, or any excipients
• Narrow-angle glaucoma
• Severe hepatic or renal dysfunction
• Cardiac arrhythmias or recent myocardial infarction
• Active psychosis or history of psychotic episodes
• Use with non-selective MAO inhibitors (must be discontinued at least 2 weeks before treatment)

• Motor Fluctuations: Long-term use may lead to "on-off" phenomena and dyskinesia.
• Neuropsychiatric Effects: Monitor for hallucinations, confusion, and behavioral changes.
• Orthostatic Hypotension: Monitor blood pressure, especially at treatment initiation.
• Abrupt Discontinuation: Risk of neuroleptic malignant-like syndrome.
• Impulse Control Disorders: Monitor for compulsive behaviors (gambling, hypersexuality).
• Melanoma Risk: Levodopa may activate malignant melanoma; monitor skin lesions.

Common:

• Nausea, vomiting
• Drowsiness
• Orthostatic hypotension
• Dyskinesia (involuntary movements)
• Loss of appetite

Uncommon:

• Confusion
• Anxiety, agitation
• Hallucinations, vivid dreams
• Dry mouth

Serious (Rare):

• Cardiac arrhythmias
• Depression with suicidal ideation
• Hemolytic anemia
• Hepatic enzyme elevations
• Neuroleptic malignant syndrome (on abrupt withdrawal)

• Non-selective MAO inhibitors: Contraindicated due to risk of hypertensive crisis.
• Antipsychotics: May reduce Levodopa’s efficacy and worsen Parkinsonian symptoms.
• Iron supplements: May reduce Levodopa absorption; stagger dosing.
• Protein-rich foods: May interfere with Levodopa transport across the BBB.
• Methyldopa & Reserpine: May increase CNS dopamine levels unpredictably.
• Antihypertensives: Additive hypotensive effect possible.

• Updated Guidelines (2024):
  Levodopa remains the most effective symptomatic treatment for Parkinson’s disease.
  Newer guidelines emphasize combining it with dopamine agonists or MAO-B inhibitors to manage motor fluctuations.
• Motor Complication Management:
  Controlled-release or individualized dosing regimens are now recommended to reduce “wearing-off” and peak-dose dyskinesias.
• Monitoring Recommendations:
  Skin exams for melanoma and regular psychiatric assessments are advised with long-term therapy.

• Temperature: Store below 30°C (86°F).
• Protection: Keep in a dry place, protected from moisture and direct light.
• Container: Keep tablets in original container, tightly closed.
• Handling: Do not crush or chew modified-release tablets unless advised.