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Note: Optimal daily dosage determined by careful titration; generally if carbidopa is ≥70 mg/day, a 1:10 proportion of carbidopa:levodopa provides the most patient response. Carbidopa augmentation in patients receiving carbidopa-levodopa: Patients receiving Sinemet® 10/100: 25 mg carbidopa daily with first daily dose of Sinemet® 10/100; if necessary, 12.5-25 carbidopa mg may be given with each subsequent dose of Sinemet® 10/100; maximum: 200 mg carbidopa/day (including carbidopa from Sinemet®) Patients receiving Sinemet® 25/250 or Sinemet® 25/100: 25 mg carbidopa with any dose of Sinemet® 25/250 or Sinemet® 25/100 throughout the day; maximum: 200 mg carbidopa/day (including carbidopa from Sinemet®) Individual titration of carbidopa and levodopa: Initial: 25 mg carbidopa 3-4 times/day; administer at the same time as levodopa, initial dose of levodopa should be 20% to 25% of the previous levodopa dose in carbidopa-naive patients; first dose of carbidopa should be taken ≥12 hours after the last dose of levodopa in carbidopa-naive patients; increase or decrease dose by 1 / 2 or 1 tablet/day Dosing: Geriatric Refer to adult dosing. Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Tablet, oral: Lodosyn®: 25 mg [scored] Generic Equivalent Available: U.S. No Administration Administer with meals to decrease GI upset. Use Given with carbidopa-levodopa in the treatment of parkinsonism to enable a lower dosage of levodopa to be used and a more rapid response to be obtained and to decrease side effects; use with carbidopa-levodopa in patients requiring additional carbidopa; has no effect without levodopa Medication Safety Issues International issues: Lodosyn [U.S.] may be confused with Lidosen brand name for lidocaine [Italy] Adverse Reactions Significant Adverse reactions are associated with concomitant administration with levodopa. Cardiovascular: Arrhythmia, chest pain, edema, flushing, hypotension, hypertension, MI, orthostatic hypotension, palpitation, phlebitis, syncope

Lodosyn [U.S.] may be confused with Lidosen brand name for lidocaine [Italy] Adverse Reactions Significant Adverse reactions are associated with concomitant administration with levodopa. Cardiovascular: Arrhythmia, chest pain, edema, flushing, hypotension, hypertension, MI, orthostatic hypotension, palpitation, phlebitis, syncope Central nervous system: Agitation, anxiety, ataxia, confusion, delusions, dementia, depression (with or without suicidal tendencies), disorientation, dizziness, dreams abnormal, EPS, euphoria, faintness, falling, fatigue, gait abnormalities, headache, hallucinations, impulse control symptoms, insomnia, malaise, memory impairment, mental acuity decreased, nervousness, neuroleptic malignant syndrome, nightmares, on-off phenomena, paranoid ideation, pathological gambling, psychosis, seizure (causal relationship not established), somnolence Dermatologic: Alopecia, malignant melanoma, rash Endocrine & metabolic: Hot flashes, hyperglycemia, hypokalemia, libido increased (including hypersexuality), uric acid increased Gastrointestinal: Abdominal pain, abdominal distress, anorexia, bruxism, constipation, diarrhea, discoloration of saliva, duodenal ulcer, dyspepsia, dysphagia, flatulence, GI bleeding, heartburn, nausea, sialorrhea, taste alterations, tongue burning sensation, weight gain/loss, vomiting, xerostomia Genitourinary: Discoloration of urine, glycosuria, urinary frequency, priapism, proteinuria, urinary incontinence, urinary retention, urinary tract infection Hematologic: Agranulocytosis, anemia, Coombs’ test abnormal, hematocrit decreased, hemoglobin decreased, hemolytic anemia, leukopenia, thrombocytopenia Hepatic: Alkaline phosphatase abnormal, ALT abnormal, AST abnormal, bilirubin abnormal, LDH abnormal Neuromuscular & skeletal: Back pain, dyskinesias (including choreiform, dystonic and other involuntary movements), leg pain, muscle cramps, muscle twitching, numbness, paresthesia, peripheral neuropathy, shoulder pain, tremor increased, trismus, weakness Ocular: Blepharospasm, blurred vision, diplopia, Horner’s syndrome reactivation, mydriasis, oculogyric crises (may be associated with acute dystonic reactions) Renal: BUN increased, serum creatinine increased Respiratory: Cough, dyspnea, hoarseness, pharyngeal pain, upper respiratory infection

Neuromuscular & skeletal: Back pain, dyskinesias (including choreiform, dystonic and other involuntary movements), leg pain, muscle cramps, muscle twitching, numbness, paresthesia, peripheral neuropathy, shoulder pain, tremor increased, trismus, weakness Ocular: Blepharospasm, blurred vision, diplopia, Horner’s syndrome reactivation, mydriasis, oculogyric crises (may be associated with acute dystonic reactions) Renal: BUN increased, serum creatinine increased Respiratory: Cough, dyspnea, hoarseness, pharyngeal pain, upper respiratory infection Miscellaneous: Discoloration of sweat, diaphoresis increased, hiccups, hypersensitivity reactions (including angioedema, pruritus, urticaria, bullous lesions [including pemphigus-like reactions], Henoch-Schönlein purpura) Contraindications Hypersensitivity to carbidopa or any component of the formulation; use of nonselective MAO inhibitor therapy with or within prior 14 days (however, may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B); narrow-angle glaucoma; history of melanoma or undiagnosed skin lesions Warnings/Precautions

Concerns related to adverse effects: • Dyskinesias: May occur at lower levodopa dosages than with monotherapy (levodopa dosage may need to be reduced). • Impulse control disorders: Dopamine agonists used for Parkinson’s disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases. • Melanoma: Risk for melanoma development is increased in Parkinson’s disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed.

Disease-related concerns: • Cardiovascular disease: Use with caution in patients with cardiovascular disease, including a history of myocardial infarction and arrhythmias. • Endocrine disease: Use with caution in patients with endocrine disease. • Glaucoma: Use with caution in patients with wide-angle glaucoma; monitor IOP carefully. • Hepatic impairment: Use with caution in patients with hepatic impairment. • Peptic ulcer disease: Use with caution in patients with peptic ulcer disease. • Psychotic disorders: Use with extreme caution in patients with psychotic disorders; observe patients closely for development of depression with concomitant suicidal tendencies. • Renal impairment: Use with caution in patients with renal impairment. • Respiratory disease: Use with caution in patients with respiratory disease (such as asthma).

Other warnings/precautions: • Antiparkinsonian activity: Has no antiparkinsonian activity when administered alone. • Discontinuation of therapy: Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on abrupt withdrawal or significant dosage reduction after long-term use. Metabolism/Transport Effects None known. Drug Interactions (For additional information: Launch Lexi-Interact™ Drug Interactions Program ) There are no known significant interactions. Pregnancy Risk Factor C ( show table ) Pregnancy Implications Adverse events have not been observed in animal reproduction studies. Carbidopa has been found to cross the human placenta; absorption in fetal tissue was minimal. Lactation Excretion in breast milk unknown/not recommended Dietary Considerations May be taken with meals to decrease GI upset. Pricing: U.S. (Medi-Span®)

Tablets (Lodosyn Oral) 25 mg (100): $454.45 Monitoring Parameters Signs and symptoms of Parkinson's disease; CBC, liver function tests, renal function; blood pressure, mental status; signs and symptoms of neuroleptic malignant syndrome if abrupt discontinuation required (as with surgery); periodic intraocular pressure (in patients with wide-angle glaucoma) International Brand Names Duellin [+ Levodopa] (PL); Nakom [+ Levodopa] (PL); Pardopa [+ Levidopa] (PL); Poldomet [+ Levidopa] (PL); Sinemet [+ Levodopa] (PL) Mechanism of Action Carbidopa is a peripheral decarboxylase inhibitor with little or no pharmacological activity when given alone in usual doses. It inhibits the peripheral decarboxylation of levodopa to dopamine; and as it does not cross the blood-brain barrier, unlike levodopa, effective brain concentrations of dopamine are produced with lower doses of levodopa. At the same time, reduced peripheral formation of dopamine reduces peripheral side-effects, notably nausea and vomiting, and cardiac arrhythmias, although the dyskinesias and adverse mental effects associated with levodopa therapy tend to develop earlier. Pharmacodynamics/Kinetics Distribution: Does not cross the blood-brain barrier Use of UpToDate is subject to the Subscription and License Agreement . Topic 9200 Version 32.0 © 2013 UpToDate, Inc. All rights reserved. | Subscription and License Agreement | Release: 21.6- C21.56 Licensed to: AsanBook Dig. Med. Lib. | Support Tag: [0604-58.240.98.179-9F9DC17642-S244013.14]