Makindo Medical Notes

Important: Levodopa is always co-administered with a peripheral decarboxylase inhibitor (benserazide or carbidopa) to minimize peripheral side effects such as nausea.

About: Always check the BNF link here for detailed prescribing guidance.

• Historical Significance: Levodopa, introduced in the late 1960s, revolutionized Parkinson’s disease (PD) management.
• Effectiveness Over Time: Benefits can diminish over the years, and side effects may become more pronounced.
• Pathophysiology: PD involves dopamine depletion in the corpus striatum; Levodopa helps replenish this deficiency.

Mode of Action

• BBB Penetration: Levodopa crosses the blood–brain barrier (BBB), whereas dopamine itself cannot.
• Central Conversion: Once within the CNS, Levodopa is decarboxylated to dopamine, replenishing depleted striatal dopamine stores.
• Peripheral Decarboxylase Inhibitor: Benserazide or carbidopa blocks peripheral conversion of Levodopa to dopamine, reducing systemic side effects (e.g., nausea, vomiting).

Indications

• Idiopathic Parkinson’s disease
• Post-encephalitic parkinsonism (as documented in Oliver Sacks’ Awakenings)
• Other parkinsonian syndromes, e.g., those arising from neurotoxic insults (CO or manganese)

Formulations & Typical Doses

Doses are individualized based on symptom control, side effects, and patient tolerance. Always start low and titrate gradually.

• Co-Beneldopa (Madopar®)
  • Madopar 62.5 mg (50 mg Levodopa + 12.5 mg Benserazide)
  • Madopar 125 mg (100 mg Levodopa + 25 mg Benserazide)
  • Madopar CR (Controlled Release): 100 mg Levodopa + 25 mg Benserazide (or other CR strengths)
  • Madopar Dispersible: 100 mg Levodopa + 25 mg Benserazide
  • Common Starting Regimen: 62.5 mg (50/12.5) TDS, with the goal of reaching an effective dose (often 300–800 mg Levodopa daily in divided doses).
• Co-Careldopa (Sinemet®)
  • Sinemet 62.5 mg (50 mg Levodopa + 12.5 mg Carbidopa)
  • Sinemet 110 mg (100 mg Levodopa + 10 mg Carbidopa)
  • Sinemet 125 mg (100 mg Levodopa + 25 mg Carbidopa)
  • Sinemet Plus 125 mg, Sinemet CR (Controlled Release) in various strengths.
  • Common Starting Regimen: 62.5 mg TDS, then titrate. Many patients eventually require 400–800 mg Levodopa per day in divided doses.
• Usual Therapeutic Range:
  • Total Levodopa: ~400–800 mg/day, though some patients may need higher or lower amounts.

Contraindications

• Drug-induced parkinsonism (e.g., antipsychotic-induced) — Levodopa typically offers little benefit.

Side Effects

• Gastrointestinal: Nausea, vomiting (especially if peripheral inhibitor dose is inadequate).
• Cardiovascular: Orthostatic hypotension.
• Neurological/Psychiatric: Confusion, delirium, hallucinations (visual > auditory).
• Motor Complications: Dyskinesias, “on–off” phenomena with prolonged use.
• Neuroleptic Malignant Syndrome–like Reaction: Possible with abrupt withdrawal.

Interactions

• Protein-Rich Meals: Can compete with Levodopa for gut absorption and reduce its effectiveness.
• Pyridoxine (Vitamin B₆): High doses can increase peripheral breakdown of Levodopa if not given with an inhibitor, but this is rarely an issue with modern co-formulations.
• Dopamine Antagonists (e.g., Antipsychotics): May oppose Levodopa’s effects.

References

• Co-beneldopa (BNF)
• Co-careldopa (BNF)