carbidopa-levodopa

carbidopa-levodopa

Co-carledopa (UK), Half Sinemet (UK), Sinemet, Sinemet CR, Tilolec (UK)

Pharmacologic class: Dopamine agonist

Therapeutic class: Antiparkinsonian

Pregnancy risk category C

Action

After conversion to dopamine in CNS, levodopa acts as a neurotransmitter, relieving symptoms of Parkinson's disease. Carbidopa prevents destruction of levodopa, making more levodopa available to be decarboxylated to dopamine in brain.

Availability

Tablets: 10 mg carbidopa/100 mg levodopa, 25 mg carbidopa/100 mg levodopa, 25 mg carbidopa/250 mg levodopa

Tablets (extended-release): 25 mg carbidopa/100 mg levodopa, 50 mg carbidopa/200 mg levodopa

⊘Indications and dosages

➣ Idiopathic Parkinson's disease; parkinsonism; symptomatic parkinsonism Conventional tablets -

Adults not currently receiving levodopa: Initially, 10 mg carbidopa/100 mg levodopa P.O. three to four times daily or 25 mg carbidopa/100 mg levodopa t.i.d.; may be increased q 1 to 2 days until desired effect occurs

Adults converting from levodopa alone (less than 1.5 g/day): Initially, 25 mg carbidopa/100 mg levodopa three to four times daily; may be increased q 1 to 2 days until desired effect occurs

Adults converting from levodopa alone (more than 1.5 g/day): Initially, 25 mg carbidopa/250 mg levodopa three to four times daily; may be increased q 1 to 2 days until desired effect occurs

Extended-release tablets -

Adults not currently receiving levodopa: Initially, 50 mg carbidopa/200 mg levodopa P.O. b.i.d., with doses spaced at least 6 hours apart

Adults converting from standard carbidopa-levodopa: Initiate therapy with at least 10% more levodopa content/day (may need up to 30% more) given at 4- to 8-hour intervals while awake; wait 3 days between dosage changes. Some patients may need higher dosages and shorter dosing intervals.

Contraindications

• Hypersensitivity to drug or tartrazine
• Angle-closure glaucoma
• MAO inhibitor use within past 14 days
• Malignant melanoma
• Breastfeeding

Precautions

Use cautiously in:
• cerebrovascular, renal, hepatic, or endocrine disease
• history of cardiac, psychiatric, or ulcer disease
• abrupt drug discontinuation or dosage
• pregnant patients
• children ages 18 and under (safety not established).

Administration

• Give dose as close as possible to time ordered to ensure stable drug blood level.
• Know that giving extended-release form with food increases drug bioavailability.
• If patient needs general anesthesia, continue drug therapy as appropriate (if he's allowed to have oral fluids and drugs).
☞ Be aware that drug shouldn't be withdrawn abruptly.

Route	Onset	Peak	Duration
P.O.	Unknown	40-120 min	Unknown

Adverse reactions

CNS: anxiety, dizziness, hallucinations, memory loss, headache, numbness, confusion, insomnia, nightmares, delusions, psychotic changes, depression, dementia, poor coordination, worsening hand tremor

CV: cardiac irregularities, palpitations, orthostatic hypotension

EENT: blurred vision, diplopia, mydriasis, eyelid twitching, difficulty swallowing

GI: nausea, vomiting, diarrhea, constipation, abdominal pain or discomfort, flatulence, excessive salivation, dry mouth, anorexia, upper GI hemorrhage (with history of peptic ulcer)

GU: urinary retention, urinary incontinence, dark urine

Hematologic: hemolytic anemia, leukopenia

Hepatic: hepatotoxicity

Musculoskeletal: muscle twitching, involuntary or spasmodic movements

Respiratory: hyperventilation

Skin: melanoma, flushing, rash, abnormally dark sweat

Other: altered or bitter taste, burning sensation of tongue, tooth grinding (especially at night), weight changes, hot flashes, hiccups

Interactions

Drug-drug. Anticholinergics: decreased carbidopa-levodopa absorption

Antihypertensives: additive hypotension

Haloperidol, papaverine, phenothiazines, phenytoin, reserpine: reversal of carbidopa-levodopa effects

Inhalation hydrocarbon anesthetics: increased risk of arrhythmias

MAO inhibitors: hypertensive reactions

Methyldopa: altered efficacy of carbidopa-levodopa, increased risk of adverse CNS reactions

Pyridoxine: antagonism of carbidopa-levodopa effects

Selegiline: increased risk of adverse reactions

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, blood urea nitrogen, lactate dehydrogenase, low-density lipoproteins, protein-bound iodine, uric acid: increased levels

Coombs' test: false-positive result

Granulocytes, hemoglobin, platelets, white blood cells: decreased values

Urine glucose, urine ketones: test interference

Drug-food. Foods rich in pyridoxine (liver, yeast, cereals): reversal of carbidopa-levodopa effects

Drug-herbs. Kava: decreased carbidopa-levodopa efficacy

Octacosanol: worsening of dyskinesia

Drug-behaviors. Cocaine use: increased risk of adverse reactions to carbidopa-levodopa

Patient monitoring

• Monitor patient for orthostatic hypotension.
• Assess patient's need for drug "holiday" if his response to drug decreases.

Patient teaching

☞ Inform patient that muscle and eyelid twitching may indicate toxicity. Tell him to report these symptoms immediately.
☞ Caution patient not to stop taking drug abruptly.
• Instruct patient to swallow extended-release tablets whole without crushing or chewing them.
• Advise patient to move slowly when sitting up or standing, to avoid dizziness or light-headedness caused by sudden blood pressure drop.
• Tell patient that drug may darken or discolor his urine and sweat.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.