No

Anti-Parkinson's Agent (Dopamine Agonist)

Idiopathic Parkinson's disease; postencephalitic parkinsonism; symptomatic parkinsonism

C

Known hypersensitivity to levodopa, carbidopa, or any component; narrow-angle glaucoma; use of MAO inhibitors 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); history of melanoma or undiagnosed skin lesions

Use with caution in patients with history of cardiovascular disease (including myocardial infarction and arrhythmias); pulmonary diseases such as asthma, psychosis, wide-angle glaucoma, peptic ulcer disease; as well as in renal, hepatic, or endocrine disease. Sudden discontinuation of levodopa may cause a worsening of Parkinson's disease. Elderly may be more sensitive to CNS effects of levodopa. May cause or exacerbate dyskinesias. May cause orthostatic hypotension; Parkinson's disease patients appear to have an impaired capacity to respond to a postural challenge; use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Observe patients closely for development of depression with concomitant suicidal tendencies. Some products may contain tartrazine. Has been associated with a syndrome resembling neuroleptic malignant syndrome on withdrawal or significant dosage reduction after long-term use. Toxic reactions have occurred with dextromethorphan. Protein in the diet should be distributed throughout the day to avoid fluctuations in levodopa absorption.

Cardiovascular: Orthostatic hypotension, arrhythmias, chest pain, hypertension, syncope, palpitations, phlebitis

Central nervous system: Dizziness, anxiety, confusion, nightmares, headache, hallucinations, on-off phenomenon, decreased mental acuity, memory impairment, disorientation, delusions, euphoria, agitation, somnolence, insomnia, gait abnormalities, nervousness, ataxia, EPS, falling

Gastrointestinal: Anorexia, nausea, vomiting, constipation, GI bleeding, duodenal ulcer, diarrhea, dyspepsia, taste alterations, sialorrhea, heartburn

Genitourinary: Discoloration of urine, urinary frequency

Hematologic: Hemolytic anemia, agranulocytosis, thrombocytopenia, leukopenia, decreased hemoglobin and hematocrit, abnormalities in AST and ALT, LDH, bilirubin, BUN, Coombs' test

Neuromuscular & skeletal: Choreiform and involuntary movements, paresthesia, bone pain, shoulder pain, muscle cramps, weakness

Ocular: Blepharospasm

Renal: Difficult urination

Respiratory: Dyspnea, cough

Miscellaneous: Hiccups, discoloration of sweat

Symptoms of overdose include palpitations, arrhythmias, spasms, hypotension; may cause hypertension or hypotension

Treatment is supportive; initiate gastric lavage, administer I.V. fluids judiciously and monitor EKG; use fluids judiciously to maintain pressures; may precipitate a variety of arrhythmias

Benzodiazepines may inhibit the antiparkinsonian effects of levodopa; monitor for reduced effect

Antipsychotics may inhibit the antiparkinsonian effects of levodopa via dopamine receptor blockade; use antipsychotics with low dopamine blockade (clozapine, olanzapine, quetiapine)

High-protein diets may inhibit levodopa's efficacy; avoid high protein foods

Iron binds levodopa and reduces its bioavailability; separate doses of iron and levodopa

Concurrent use of levodopa with nonselective MAOIs may result in hypertensive reactions via an increased storage and release of dopamine, norepinephrine, or both. Use with carbidopa to minimize reactions if combination is necessary; otherwise avoid combination.

L-methionine, phenytoin, pyridoxine, and spiramycin may inhibit levodopa's antiparkinsonian effects

Tacrine may inhibit the effects of levodopa via enhanced cholinergic activity; monitor

Parkinson's symptoms are due to a lack of striatal dopamine; levodopa circulates in the plasma to the blood-brain-barrier (BBB), where it crosses, to be converted by striatal enzymes to dopamine; carbidopa inhibits the peripheral plasma breakdown of levodopa by inhibiting its decarboxylation, and thereby increases available levodopa at the BBB

Duration: Variable, 6-12 hours; longer with CR dosage forms

Carbidopa:

Absorption: Oral: 40% to 70%

Protein binding: 36%

Half-life: 1-2 hours

Elimination: Excreted unchanged

Levodopa:

Absorption: May be decreased if given with a high protein meal

Half-life: 1.2-2.3 hours

Elimination: Primarily in urine (80%) as dopamine, norepinephrine, and homovanillic acid

Oral:

Elderly: Initial: 25/100 twice daily, increase as necessary

Conversion from Sinemet® to Sinemet® CR (50/200): (Sinemet®[total daily dose of levodopa] / Sinemet® CR)

300-400 mg / 1 tablet twice daily

500-600 mg / 11/2 tablets twice daily or one 3 times/day

700-800 mg / 4 tablets in 3 or more divided doses

900-1000 mg / 5 tablets in 3 or more divided doses

Intervals between doses of Sinemet® CR should be 4-8 hours while awake

Avoid vitamin products containing vitamin B₆ (pyridoxine), which reduces the effectiveness of this medication.

Blood pressure, standing and sitting/supine; symptoms of parkinsonism, dyskinesias, mental status

False-positive reaction for urinary glucose with Clinitest®; false-negative reaction using Clinistix®; false-positive urine ketones with Acetest®, Ketostix®, Labstix®

No information available to require special precautions

Dopaminergic therapy in Parkinson's disease (ie, treatment with levodopa and carbidopa combination) is associated with orthostatic hypotension. Patients medicated with this drug combination should be carefully assisted from the chair and observed for signs of orthostatic hypotension.

Take exactly as directed; do not change dosage or discontinue without consulting prescriber. Therapeutic effects may take several weeks or months to achieve and you may need frequent monitoring during first weeks of therapy. Take with meals if GI upset occurs, before meals if dry mouth occurs, after eating if drooling or if nausea occurs. Take at the same time each day. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake); void before taking medication. Do not use alcohol and prescription or OTC sedatives or CNS depressants without consulting prescriber. Urine or perspiration may appear darker. You may experience drowsiness, dizziness, confusion, or vision changes (use caution when driving, climbing stairs, or engaging in tasks requiring alertness until response to drug is known); orthostatic hypotension (use caution when changing position - rising to standing from sitting or lying); increased susceptibility to heat stroke, decreased perspiration (use caution in hot weather - maintain adequate fluids and reduce exercise activity); constipation (increased exercise, fluids, or dietary fruit and fiber may help); dry skin or nasal passages (consult prescriber for appropriate relief); nausea, vomiting, loss of appetite, or stomach discomfort (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report unresolved constipation or vomiting; chest pain or irregular heartbeat; difficulty breathing; acute headache or dizziness; CNS changes (hallucination, loss of memory, nervousness, etc); painful or difficult urination; abdominal pain or blood in stool; increased muscle spasticity or rigidity; skin rash; or significant worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Space doses evenly over the waking hours; sustained release product should not be crushed

Tablet:

25/100: Carbidopa 25 mg and levodopa 100 mg

25/250: Carbidopa 25 mg and levodopa 250 mg

Sustained release: Carbidopa 25 mg and levodopa 100 mg; carbidopa 50 mg and levodopa 200 mg

Koller WC, Silver DE, and Lieberman A, "An Algorithm for the Management of Parkinson's Disease," Neurology, 1994, 44(12 Suppl 10):S1-52.

Stern MB, "Contemporary Approaches to the Pharmacotherapeutic Management of Parkinson's Disease: An Overview," Neurology, 1997, 49(1 Suppl 1):S2-9.

Walker SW, Fina A, and Kryger MH, "L-Dopa/Carbidopa for Nocturnal Movement Disorders in Uremia," Sleep, 1996, 19(3):214-8.