Carbidopa
Carbidopa
Generic Name
Carbidopa
Mechanism
Carbidopa is a peripheral aromatic L‑dopa decarboxylase (AADC) inhibitor.
• Inhibits AADC in the gastrointestinal wall and the blood‑brain barrier, preventing peripheral metabolism of L‑dopa into dopamine.
• Preserves systemic L‑dopa for transport across the blood‑brain barrier, where it is converted to dopamine and exerts therapeutic effects.
• Does not cross the blood‑brain barrier itself; its action is strictly peripheral, thus minimizing dopamine‑mediated side effects outside the CNS.
> *Key pharmacology concept*: Carbidopa “shields” levodopa from peripheral decarboxylation, increasing its bioavailability to the brain and allowing lower levodopa doses.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Oral, peak plasma 1–3 h | Rapid absorption after meal; mixed with levodopa improves overall bioavailability. |
| Distribution | Vol. of distribution ~1 L/kg | Does not cross blood‑brain barrier; primarily in plasma. |
| Metabolism | Minimal hepatic metabolism | Metabolites inactive; negligible hepatic clearance. |
| Elimination | Renal excretion | Renal clearance ~50 mL/min; dose adjustment not routinely required in mild–moderate CKD. |
| Half‑life | 1–2 h orally | Short t½; steady‑state achieved within 1–2 days. |
| Protein binding | < 10 % | Limited plasma protein binding. |
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Indications
- Parkinson’s disease: Used *in combination with levodopa* to treat motor symptoms (rest tremor, rigidity, bradykinesia).
- Shankman syndrome (post‑traumatic neuroregeneration) – In select cases, used adjunctively.
- Primary motor neuron disease & other dopaminergic inadequacies – Off‑label, usually with levodopa.
> Standard prescription: Carbidopa 25 mg + levodopa 100 mg (levodopa/carbidopa 100/25 mg) as the most common tablet strength.
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Contraindications
| Category | Details |
| Absolute Contraindications | • Hypersensitivity to carbidopa/levodopa. |
| Relative Contraindications | • Seizure disorder (may lower seizure threshold). |
| Warnings |
• Serotonin syndrome: when combined with serotonergic agents (SSRIs, SNRIs, MAO‑I). • Neuroleptic malignant syndrome (NMS) risk with antipsychotics – avoid concomitant use. • Hypertension: monitor BP due to potential vasodilatory effects. |
| Drug Interactions |
• MAO‑I (phenelzine, selegiline) – contraindicated. • Monoamine‑oxidase inhibitors or serotonergic drugs increase risk of serotonin syndrome. • Antipsychotics: may worsen Parkinsonian symptoms. |
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Dosing
| Setting | Typical Regimen | Notes |
| Adults (Parkinson’s) | 25 mg carbidopa / 100‑200 mg levodopa PO q4–6 h | Start at low dose; titrate to symptom control. |
| Children (age < 12 y) | 25 mg carbidopa / 100 mg levodopa PO q4–6 h | Dose adjusted per weight (1 mg levodopa/kg). |
| Split‑dose strategy | 25 mg carbidopa + 200 mg levodopa PO q6–8 h | Allows smoother dopamine levels; reduces “off” periods. |
| Intra‑operative | 25 mg carbidopa PO prior to levodopa infusion | Reduces peripheral side effects during surgery. |
• Formulations: Immediate‑release tablets, extended‑release (e.g., pericyclic).
• Take with/without food: Absorption slightly reduced with high‑fat meals; can be taken with food to lessen GI upset.
• Missed dose: Skip; do not double the next dose.
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Adverse Effects
| Category | Adverse Effect | Frequency | Management |
| Common | Nausea & Vomiting (10–20 %) | • Gaviscon, ondansetron | Counsel to take with food; antiemetic if needed. |
| Dyskinesia / “on/off” fluctuations (15–30 %) | • Reduce dose or add dopamine agonists | Reevaluate dosing schedule. | |
| Dry mouth, orthostatic hypotension (5–15 %) | • Hydration, graded dosing | Monitor BP; consider anticholinergic sparing. | |
| Headache (5–10 %) | • NSAIDs, acetaminophen | Check hydration status. | |
| Serious | Serotonin syndrome (rare) | • Aggressive monitoring with serotonergic drugs | Discontinue interacting drugs. |
| Neuroleptic malignant syndrome (≤ 1 %) | • Immediate medical attention | Discontinue levodopa. | |
| Agranulocytosis (very rare) | • CBC monitoring in long‑term therapy | Referral to hematology if abnormal. |
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Monitoring
| Parameter | Target / Frequency | Rationale |
| Motor function | Unified Parkinson's Disease Rating Scale (UPDRS) monthly | Gauge therapeutic responsiveness. |
| Blood pressure | Every visit, especially first 6 weeks | Detect orthostatic hypotension. |
| Weight & nutrition | Every 3 months | Prevent weight loss due to appetite suppression. |
| CBC (long‑term) | Every 4–6 months | Detect rare agranulocytosis. |
| Serotonin syndrome signs | Clinical evaluation when on serotonergic drugs | Early detection imperative. |
| Plasma levodopa levels (as needed) | In research settings | Ensures optimal dosing without toxicity. |
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Clinical Pearls
- “Carbidopa first” – Starting with carbidopa alone is generally unnecessary; the levodopa/carbidopa combo tablets provide integrated dosing.
- Avoid MAO‑I overlap – Even short‑term overlap with phenelzine/sertraline can precipitate life‑threatening serotonin syndrome.
- Add “up‑titration” with meal time – Give during meals to minimize nausea while maintaining levodopa absorption.
- Manage dyskinesia with dose timing – Splitting doses (e.g., 200 mg levodopa every 8 h) smooths plasma curves and reduces peak‑induced dystonia.
- Patient education – Reinforce “off” periods often occur when plasma levodopa falls below 200 ng/mL; early dosing can preempt symptoms.
- Reversible off‑set – If severe hypotension or nausea occurs, reduce carbidopa dose; the levodopa effect may persist because levodopa levels are not as rapidly diminished.
- Extended‑release formulations – Ideal for patients with erratic compliance; still require monitoring for dyskinesia due to sustained dopamine exposure.
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• *Carbidopa remains a cornerstone in Parkinsonian therapy by mitigating peripheral dopamine production and improving levodopa bioavailability. Mastery of its pharmacology, dosing nuances, and monitoring needs equips clinicians to optimize outcomes and mitigate adverse effects.*