Antiparkinsonian (dopamine precursor + decarboxylase inhibitor) Pregnancy: Avoid unless essential — limited data; teratogenic in animals.

Co-careldopa (carbidopa + levodopa)

Brand names: Sinemet, Sinemet CR, Sinemet Plus, Caramet CR, Half Sinemet CR

Adult dose

Dose: Initiation (Parkinson's disease): 12.5/50 mg TDS (Sinemet 62.5 = ¼ of 25/100; or Half Sinemet); titrate every 2–3 days as tolerated. Maintenance: 50/200 mg TDS to QDS, individualised. Sinemet CR (controlled-release): 50/200 mg BD initially, titrate; useful for nocturnal / off-period symptoms. Always preserve carbidopa:levodopa ratio.

Route: Oral

Frequency: TDS to 5 times daily depending on stage

Max: Levodopa 8 g/day in advanced disease (rare — specialist dosing); 'standard' practical max 1.6 g levodopa/day for most patients

Take 30 min before food (high-protein meals reduce absorption — competition for amino acid transporters). Convert to/from co-beneldopa using approximate 4:5 levodopa equivalence (Madopar 100 mg ≈ Sinemet 80 mg).

Dose adjustments

Renal

No specific adjustment; caution.

Hepatic

Caution; reduce dose.

Clinical pearls

Levodopa is the most effective symptomatic therapy for Parkinson's disease — 'gold standard'. Carbidopa is a peripheral DOPA-decarboxylase inhibitor preventing peripheral conversion (and thus nausea) without crossing BBB.
Start low and titrate slowly — 'start low, go slow' applies. Most patients need 50–200 mg levodopa TDS by 6 months.
Wearing-off and dyskinesias emerge typically 3–7 years in — manage with: more frequent smaller doses, MAO-B inhibitor add-on, COMT inhibitor (entacapone), dopamine agonist add-on, or apomorphine.
For nausea: ALWAYS use domperidone (peripheral dopamine antagonist, doesn't cross BBB) NOT metoclopramide or prochlorperazine.
DO NOT abruptly stop — risk of neuroleptic malignant-like syndrome. Even peri-operatively, give via NG tube or rotigotine patch.
Discuss impulse control disorders explicitly with patient AND family — patients often don't volunteer.
Sinemet 'numbers': 25/100 = 25 mg carbidopa + 100 mg levodopa. Half Sinemet CR = 25/100 controlled release. Sinemet Plus = 25/100 immediate release.

Contraindications

Narrow-angle glaucoma
Severe psychotic illness (active psychosis)
Suspicious skin lesion / undiagnosed melanoma (relative — levodopa may activate)
MAOI within 14 days (except selegiline/rasagiline — selective MAO-B inhibitors)
Severe cardiovascular disease (relative)
Phaeochromocytoma

Side effects

Nausea, vomiting (common — give domperidone NOT metoclopramide; metoclopramide is dopamine antagonist and worsens PD)
Postural hypotension
Dyskinesias (chorea, dystonia — usually peak-dose; develop in 50% by 5 years)
Motor fluctuations (wearing-off, on-off phenomena)
Hallucinations, confusion, vivid dreams (especially elderly)
Impulse control disorders (gambling, hypersexuality, binge eating — class effect, more with dopamine agonists than levodopa)
Dopamine dysregulation syndrome
Excessive daytime sleepiness, sudden-onset sleep
Reddish discolouration of urine, sweat, saliva (harmless)
Punding (repetitive purposeless behaviour)

Interactions

Non-selective MAOIs: hypertensive crisis — contraindicated within 14 days
Metoclopramide / prochlorperazine: dopamine antagonism — worsens PD; use ondansetron or domperidone for nausea
Antipsychotics (especially haloperidol, risperidone): worsen parkinsonism; quetiapine or clozapine preferred if needed in PD
Iron salts: chelate levodopa — separate by 2 hours
High-protein meals: ↓ absorption
Antihypertensives: additive hypotension
Selegiline/rasagiline: synergistic — useful, but watch for hypertension and dyskinesias

Monitoring

Motor diary (on/off times)
BP (postural)
Mental state — hallucinations, ICDs
Skin (melanoma surveillance)

Reference: BNF 90; SmPC Sinemet; NICE NG71 (Parkinson's disease 2017); MDS Movement Disorders Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways