Carlev CR

Approved Indications:

• Parkinson’s Disease (Idiopathic Parkinsonism):
• First-line treatment for all stages—early and advanced.
• Effective in controlling symptoms such as bradykinesia, rigidity, tremor, and gait disturbances.
• Post-Encephalitic Parkinsonism
• Symptomatic Parkinsonism Due to:
• Carbon monoxide poisoning.
• Manganese intoxication.
• Motor Fluctuations in Parkinson’s Disease:
• Management of "on-off" phenomena and end-of-dose "wearing-off" symptoms.

Clinically Accepted Off-Label Use:

• Restless Legs Syndrome (RLS):
• Used in selected cases unresponsive to dopaminergic agonists. Caution is required due to potential for symptom augmentation.

Route of Administration: Oral (tablet, controlled-release tablet, dispersible tablet)

Adults with Parkinson’s Disease:

• Immediate-Release Formulations:
• Initial dose: Levodopa 100 mg + Carbidopa 25 mg, 3 times daily.
• Titrate every 1–2 days based on response.
• Usual maintenance: Levodopa 300–800 mg/day, in divided doses.
• Maximum Levodopa dose: 800–1000 mg/day.
• Controlled-Release (CR) Tablets:
• Initial dose: Levodopa 200 mg + Carbidopa 50 mg, twice daily.
• Dosage may be increased as needed, but intervals should be at least 6 hours apart.
• Do not crush or chew CR tablets.

Special Populations:

• Elderly:
• Start with lower doses (e.g., Levodopa 50 mg + Carbidopa 12.5 mg, 2–3 times daily).
• Adjust gradually based on tolerance and response.
• Pediatric Use:
• Not recommended; safety and efficacy have not been established.
• Renal Impairment:
• No dosage adjustment required, but monitor for accumulation.
• Hepatic Impairment:
• Use with caution; no formal adjustment guidelines, but clinical monitoring is advised.

Administration Notes:

• May be taken with or without food.
• Avoid high-protein meals around dosing times to prevent reduced absorption.
• Dispersible tablets may be dissolved in a small amount of water before administration.

Levodopa is the metabolic precursor of dopamine. It crosses the blood–brain barrier and is converted to dopamine by aromatic L-amino acid decarboxylase (AADC), thereby replenishing depleted dopamine levels in the brain, particularly in the striatum. Carbidopa is a peripheral AADC inhibitor that does not cross the blood–brain barrier. It prevents the peripheral metabolism of Levodopa to dopamine, which increases the availability of Levodopa to the brain and reduces peripheral side effects such as nausea and hypotension. The combination results in enhanced central dopaminergic activity, improving motor symptoms in Parkinson’s disease.

• Absorption:
  Levodopa is rapidly absorbed from the small intestine. Co-administration with Carbidopa enhances Levodopa’s bioavailability.
• Bioavailability:
  Approximately 30% (for Levodopa with Carbidopa).
• Onset of Action:
  15 to 60 minutes for immediate-release formulations.
• Peak Plasma Concentration:
  1 to 2 hours (immediate-release); 2.5 to 3 hours (controlled-release).
• Distribution:
  Widely distributed; minimal protein binding.
• Metabolism:
  Levodopa is metabolized primarily by AADC and catechol-O-methyltransferase (COMT).
  Carbidopa undergoes minimal metabolism.
• Half-Life:
  Levodopa: ~1.5 hours (prolonged to 2–3 hours with Carbidopa).
• Excretion:
  Mostly via the urine as metabolites; <1% excreted unchanged.

• Pregnancy:
  FDA Category C.
  Animal studies have shown potential fetal harm. There are no well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk.
• Lactation:
  Levodopa is excreted into breast milk in small amounts. Safety during breastfeeding is not established. It may inhibit lactation and could potentially affect the nursing infant. Use with caution.

• Primary Class: Anti-Parkinsonian Agent
• Subclass: Dopaminergic Agent (Levodopa) and Peripheral Decarboxylase Inhibitor (Carbidopa)

• Known hypersensitivity to Levodopa, Carbidopa, or any formulation excipients
• Narrow-angle glaucoma
• Concurrent use with non-selective monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing such agents
• Suspicious or diagnosed malignant melanoma
• History of severe psychosis

• Neuropsychiatric Effects: May cause hallucinations, confusion, and psychosis, particularly in elderly patients.
• Impulse Control Disorders: Monitor for pathological gambling, hypersexuality, or compulsive behaviors.
• Motor Complications: May induce dyskinesia or “on-off” fluctuations with long-term use.
• Orthostatic Hypotension: Monitor blood pressure, especially during dose initiation and titration.
• Melanoma Risk: Levodopa may activate latent melanoma; regular skin examinations are recommended.
• Withdrawal Risk: Abrupt discontinuation may lead to neuroleptic malignant syndrome-like symptoms.
• Monitoring Requirements: Regular assessments of blood pressure, mental status, liver/renal function, and skin health.

Common Side Effects:

• Neurological: Dyskinesia, dizziness, headache, confusion, hallucinations
• Gastrointestinal: Nausea, vomiting, dry mouth, constipation
• Cardiovascular: Orthostatic hypotension, palpitations
• Psychiatric: Anxiety, agitation, vivid dreams

Serious Adverse Effects:

• Severe involuntary movements (dyskinesia)
• Psychosis or suicidal ideation
• Neuroleptic malignant syndrome (if abruptly discontinued)
• Hemolytic anemia
• Agranulocytosis (rare)

• Non-selective MAOIs: Contraindicated due to risk of hypertensive crisis
• Antipsychotics (e.g., haloperidol): May reduce Levodopa's effectiveness
• Iron Supplements: May reduce Levodopa absorption—administer at different times
• High-Protein Meals: Compete with Levodopa for transport across intestinal wall
• Antihypertensive Agents: May enhance hypotensive effects
• CYP450 Interactions: Not significantly involved; metabolism mainly via AADC and COMT

• AAN/NICE Recommendations: Emphasize individualized therapy based on symptom burden and motor complications.
• New Formulations: Introduction of extended-release and dispersible combinations for improved symptom control.
• Safety Alerts: Reinforced warnings for impulse control disorders and melanoma risk.

• Immediate-Release Tablets:
  Store below 25°C (77°F) in a tightly closed container. Protect from moisture and light.
• Controlled-Release Tablets:
  Store at 20°C to 25°C (68°F to 77°F). Avoid exposure to excessive humidity and temperature variations.
• Dispersible Tablets (if applicable):
  Store at room temperature. Prepare solution freshly; do not store after reconstitution.