Carbidopa + Levodopa


Concise Prescribing Info
Indications/Uses
Parkinson's disease.
Dosage/Direction for Use
Adult : PO Dosage is individualised based on patient’s age, cognitive status and severity of the disease and adjusted according to requirement, clinical response and tolerance. Each conventional tab or ODT contains carbidopa (mg)/levodopa (mg): 10/100; 12.5/50 (conventional tab only): Initial: 1 tab 3-4 times/day; increased by 1 tab every day or every other day, as required. Max: 8 tabs/day. Maintenance: At least 70-100 mg of carbidopa daily. 25/100: Initial: 1 tab tid; increased by 1 tab every day or every other day, as required. Max: 8 tabs/day. Patients on current levodopa monotherapy (<1,500 mg): 1 tab 3-4 times/day. Discontinue levodopa at least 12 hours before initiation of combination therapy. Maintenance: At least 70-100 mg of carbidopa/day. 25/250: Patients on current levodopa monotherapy (>1,500 mg): 1 tab 3-4 times/day. Max: 8 tabs/day. Discontinue levodopa at least 12 hours before initiation of combination therapy. Maintenance: At least 70-100 mg of carbidopa/day. Each ER tab contains carbidopa (mg)/levodopa (mg): 25/100; 50/200: Initial: 50 mg/200 mg bid; increased or decreased based on therapeutic response. Each ER cap contains carbidopa (mg)/levodopa (mg): 23.75/95; 36.25/145; 48.75/195; 61.25/245: Initial: 23.75 mg/95 mg tid for 3 days; increased to 36.25 mg/145 mg tid on day 4. Max: 97.5 mg/390 mg tid. Maintenance: Lowest dosage required to achieve symptomatic control. Max: 612.5 mg/2,450 mg/day. Gastroenteral Each mL contains carbidopa 4.63 mg and levodopa 20 mg: Administer into the jejunum through a percutaneous endoscopic gastrostomy with jejunal tube with an appropriate portable infusion pump. Titrate total daily dose according to therapeutic response. Max: 2,000 mg of levodopa/day.
Dosage Details
Gastroenteral
Parkinson's disease
Adult: Available preparation:
Carbidopa 4.63 mg and levodopa 20 mg per mL susp
Administer into the jejunum through a percutaneous endoscopic gastrostomy with jejunal tube with an appropriate portable infusion pump. Titrate total daily dose according to therapeutic response. Max: 2,000 mg of levodopa daily.

Oral
Parkinson's disease
Adult: Dosage is individualised based on patient’s age, cognitive status and severity of the disease and adjusted according to requirement, clinical response and tolerance.

Conventional tab:

Carbidopa 10 mg and levodopa 100 mg
Carbidopa 12.5 mg and levodopa 50 mg
Initially, 1 tab 3-4 times daily; may be increased by 1 tab every day or every other day, as required. Max: 8 tabs daily. Maintenance: At least 70-100 mg of carbidopa daily.

Carbidopa 25 mg and levodopa 100 mg
Initially, 1 tab tid; may be increased by 1 tab every day or every other day, as required. Max: 8 tabs daily. Patients on current levodopa monotherapy (<1,500 mg): 1 tab 3-4 times daily. Discontinue levodopa at least 12 hours before initiation of combination therapy. Maintenance: At least 70-100 mg of carbidopa daily.

Carbidopa 25 mg and levodopa 250 mg
Patients on current levodopa monotherapy (>1,500 mg): 1 tab 3-4 times daily. Max: 8 tabs daily. Discontinue levodopa at least 12 hours before initiation of combination therapy. Maintenance: At least 70-100 mg of carbidopa daily.

Orally-disintegrating tab (ODT):
Carbidopa 10 mg and levodopa 100 mg
1 tab 3-4 times daily; may be increased by 1 tab every day or every other day. Max: 8 tabs daily. Maintenance: At least 70-100 mg of carbidopa daily.

Carbidopa 25 mg and levodopa 100 mg
1 tab tid; may be increased by 1 tab every day or every other day. Max: 8 tabs daily. Patients on current levodopa monotherapy (<1,500 mg): 1 tab 3-4 times daily. Discontinue levodopa at least 12 hours before initiation of combination therapy. Maintenance: At least 70-100 mg of carbidopa daily.

Carbidopa 25 mg and levodopa 250 mg
Patients on current levodopa monotherapy (>1,500 mg): 1 tab 3-4 times daily. Max: 8 tabs daily. Discontinue levodopa at least 12 hours before initiation of combination therapy. Maintenance: At least 70-100 mg of carbidopa daily.

Extended-release (ER) tab:
Carbidopa 25 mg and levodopa 100 mg
Carbidopa 50 mg and levodopa 200 mg
Initially, 50 mg/200 mg bid; may be increased or decreased based on therapeutic response.

Extended-release (ER) cap:
Carbidopa 23.75 mg and levodopa 95 mg
Carbidopa 36.25 mg and levodopa 145 mg
Carbidopa 48.75 mg and levodopa 195 mg
Carbidopa 61.25 mg and levodopa 245 mg
Initially, 23.75 mg/95 mg tid for the 1st 3 days; may be increased to 36.25 mg/145 mg tid on day 4. Max: 97.5 mg/390 mg tid. Maintenance: Lowest dosage required to achieve symptomatic control. Max: 612.5 mg/2,450 mg daily.
Administration
Should be taken on an empty stomach. May be taken w/ meals if GI discomfort occurs.
Contraindications
Major psychotic disorder, narrow-angle glaucoma, and history of melanoma. Concurrent use of or within 14 days of discontinuing MAOIs.
Special Precautions
Patient with severe CV disease (e.g. history of MI who have residual atrial, nodal or ventricular arrhythmias), psychotic disorder, pulmonary or endocrine disease, wide-angle glaucoma, history of or risk factors for neuropathy (e.g. diabetes mellitus, hypothyroidism), history of peptic ulcer. Avoid abrupt withdrawal or dose reduction. Hepatic and renal impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Dyskinesia, neuroleptic malignant syndrome, somnolence, orthostatic hypotension, impulse control disorders (e.g. urge to gamble, increased sexual urges), abnormal thinking, behavioural changes, hallucinations, melanoma, peripheral neuropathy.
Blood and lymphatic system disorders: Leucopenia, haemolytic and non-haemolytic anaemia, thrombocytopenia, agranulocytosis.
Cardiac disorders: Palpitations.
Eye disorders: Blurred vision, diplopia, dilated pupils, blepharospasm, oculogyric crises.
Gastrointestinal disorders: Nausea, vomiting, constipation, diarrhoea, sialorrhoea, dysphagia, flatulence, dyspepsia, gastrointestinal pain and bleeding, dry mouth, dysgeusia, discoloured saliva, bruxism, hiccups.
General disorders and administration site conditions: Asthenia, fatigue, weakness, malaise.
Metabolism and nutrition disorders: Anorexia, weight gain or loss.
Musculoskeletal and connective tissue disorders: Muscle spasms, shoulder and back pain.
Nervous system disorders: Headache, numbness, convulsions, dizziness.
Psychiatric disorders: Confusion, nightmares, insomnia, depression (with or without suicidal ideation), euphoria, dementia, agitation, fear, disorientation, dysphonia.
Renal and urinary disorders: Dark urine, urinary retention, urinary incontinence.
Reproductive system and breast disorders: Priapism.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, upper respiratory tract infection.
Skin and subcutaneous tissue disorders: Angioedema, alopecia, urticaria, pruritus, hair loss, rash, discoloured sweat, Henoch-Schonlein purpura.
Vascular disorders: Hypertension, hypotension, syncope, phlebitis, hot flushes.
Gastroenteral/PO: C
Patient Counseling Information
This drug may cause dark discolouration of the saliva, urine or sweat. May also cause dizziness and somnolence, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor hepatic, haematopoietic, renal and cardiac function; standing and sitting blood pressure; intra-ocular pressure in patients with glaucoma. Perform routine dermatologic tests. Monitor for signs and symptoms of neuroleptic malignant syndrome, peripheral neuropathy, depression, somnolence.
Overdosage
Symptoms: Initially, hypertension then hypotension for a few hours, sinus tachycardia, orthostatic hypotension, marked confusion, agitation, insomnia, restlessness, severe anorexia. Management: Symptomatic and supportive treatment. Immediately perform gastric lavage. Maintain adequate airways and administer IV fluids. Monitor for ECG changes and observe for the possible development of cardiac arrhythmias. Administer proper antiarrhythmic therapy when necessary.
Drug Interactions
Levodopa: Decreased levodopa absorption and increased risk of postural hypotension with TCA (e.g. imipramine). Diminished therapeutic effect with concomitant use of antipsychotic agent (e.g. risperidone). Anticholinergic agents (e.g. atropine) decrease the absorption of levodopa and may diminish its therapeutic effect. Concomitant use with antihypertensives may cause postural hypotension. Decreased therapeutic response is observed with papaverine, phenytoin, and isoniazid. Decreased bioavailability with concurrent Fe salt use. Increased parkinsonian symptoms with metoclopramide.
Potentially Fatal: Hypertensive crisis may result when used concomitantly or within 14 days of stopping MAOI (e.g. phenelzine).
Food Interaction
High protein diet may impair the absorption of levodopa.
Lab Interference
False-negative reaction in glucose-oxidase test for glucosuria. False-positive reaction is observed in tests for urinary glucose and urine ketones. Rarely, false diagnosis for phaeochromocytoma occurs when based on plasma and urine levels of catecholamines.
Action
Description: Levodopa is a precursor of dopamine. It crosses the blood-brain barrier to be converted to dopamine in the brain.
Carbidopa is a dopa-decarboxylase inhibitor that prevents the peripheral breakdown of levodopa, thereby increasing the available levodopa at the blood-brain barrier. It is used only in conjunction with levodopa as it does not exhibit therapeutic effect when given alone.
Pharmacokinetics:
Absorption: Carbidopa: Rapidly but incompletely absorbed from the gastrointestinal tract.
Levodopa: Rapidly and well absorbed from the gastrointestinal tract. Time to peak plasma concentration: Within 2 hours.
Distribution: Carbidopa: Widely distributed into most body tissues. Crosses the placenta and enters breast milk. Plasma protein binding: Approx 36%.
Levodopa: Crosses placenta, enters the breast milk, and passes the blood-brain barrier. Volume of distribution: 0.9-1.6L/kg (in the presence of carbidopa). Plasma protein binding: Approx 10-30%.
Metabolism: Levodopa: Extensively metabolised to form dopamine and, to a lesser extent, epinephrine and norepinephrine which are further metabolised to dopacetic acid, homovanillic acid and vanillylmandelic acid.
Excretion: Carbidopa: Via urine, as unchanged drug and metabolites. Elimination half-life: 1-2 hours.
Levodopa: Mainly via urine (80%); faeces (small amounts). Elimination half-life: Approx 30-60 minutes.
Chemical Structure

Chemical Structure Image
Carbidopa

Source: National Center for Biotechnology Information. PubChem Database. Carbidopa, CID=34359, https://pubchem.ncbi.nlm.nih.gov/compound/Carbidopa (accessed on Jan. 21, 2020)


Chemical Structure Image
Levodopa

Source: National Center for Biotechnology Information. PubChem Database. Levodopa, CID=6047, https://pubchem.ncbi.nlm.nih.gov/compound/Levodopa (accessed on Jan. 21, 2020)

Storage
Tab/Cap: Store below 30°C. Protect from light and moisture. Enteral susp: Store at -20°C. Protect from light.
ATC Classification
N04BA02 - levodopa and decarboxylase inhibitor ; Belongs to the class of dopa and dopa derivative dopaminergic agents. Used in the management of Parkinson's disease.
References
Anon. Carbidopa and Levodopa. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 13/05/2020.

Anon. Levodopa/Carbidopa. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 13/05/2020.

Buckingham R (ed). Carbidopa. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/05/2020.

Buckingham R (ed). Levodopa. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/05/2020.

Carbidopa and Levodopa Tablet (Actavis Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 13/05/2020.

Carbidopa and Levodopa Tablet, Extended-release (Alembic Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/05/2019.

Co-careldopa 10mg/100mg Tablets. MHRA. https://products.mhra.gov.uk/. Accessed 22/05/2019.

Duopa Suspension (AbbVie Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/05/2019.

Parcopa Tablet, Orally disintegrating (Schwarz Pharma). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/05/2019.

Rytary Capsule, Extended-release (Amneal Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/05/2019.

Sinemet Tablet (Mylan Pharmaceuticals Inc.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 13/05/2020.

Disclaimer: This information is independently developed by MIMS based on Carbidopa + Levodopa from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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