Mode of action of Levodopa/carbidopa combination: Levodopa is an amino acid precursor of dopamine, which acts mainly by replenishing depleted striatal dopamine. Carbidopa is an extracerebral dopa decarboxylase inhibitor, which prevents the peripheral degradation of levodopa to dopamine. It does not cross the blood-brain barrier hence higher concentrations of dopamine are attained in the brain.

Dosing: Adult

Parkinson's disease:

Oral:

Immediate release tablet, orally-disintegrating tablet:

Initial: Carbidopa 25 mg/levodopa 100 mg 3 times/day

Dosage adjustment: Alternate tablet strengths may be substituted according to individual carbidopa/levodopa requirements. Increase by 1 tablet every 1-2 days as necessary, except when using the carbidopa 25 mg/levodopa 250 mg tablets where increases should be made using 1/2-1 tablet every 1-2 days. Use of more than 1 dosage strength or dosing 4 times/day may be required (maximum: 8 tablets of any strength/day or 200 mg of carbidopa and 2000 mg of levodopa)

Controlled release tablet:

Patients not currently receiving levodopa: Initial: Carbidopa 50 mg/levodopa 200 mg 2 times/day, at intervals not <6 hours

Patients converting from immediate release formulation to controlled release: Initial: Dosage should be substituted at an amount that provides ~10% more of levodopa/day; total calculated dosage is administered in divided doses 2-3 times/day (or ≥3 times/day for patients maintained on levodopa ≥700 mg). Intervals between doses should be 4-8 hours while awake; when divided doses are not equal, smaller doses should be given toward the end of the day. Depending on clinical response, dosage may need to be increased to provide up to 30% more levodopa/day.

Dosage adjustment: May adjust every 3 days; intervals should be between 4-8 hours during the waking day (maximum dose: 8 tablets/day)

Intestinal infusion via PEG tube: Intestinal gel (Canadian labeling; not available in U.S.): Note: Conversion to/from oral levodopa tablet formulations and the intestinal gel formulation can be done on a 1:1 ratio. Total daily dose (expressed in terms of levodopa) consists of a morning bolus dose, a continuous maintenance dose, and additional bolus doses when necessary. Nighttime dosing may be necessary in certain rare situations (eg, nocturnal akinesia). Dosage adjustments should be carried out over a period of a few weeks.

Morning bolus dose (based on previous morning levodopa intake and volume to fill intestinal tubing): Usual: Levodopa 100-200 mg (5-10 mL); Maximum: Levodopa 300 mg (15 mL)

Continuous maintenance dose: Adjustable in increments of 2 mg/hour (0.1 mL/hour) and based on previous daily intake of levodopa: Usual: Levodopa 40-120 mg/hour (2-6 mL/hour) infused up to 16 hours; Range: Levodopa 20-200 mg/hour (1-10 mL/hour)

Additional bolus doses: Usual: Levodopa: 10-40 mg (0.5-2 mL), if needed for daytime hypokinesia; in patients requiring >5 additional boluses/day, the maintenance dose should be increased

Restless leg syndrome (RLS) (unlabeled use; Silber, 2004): Oral:

Immediate release tablet: Carbidopa 25 mg/levodopa 100 mg (0.5-1 tablet) given in the evening, at bedtime, or upon waking during the night with RLS symptoms

Controlled release tablet: Carbidopa 25 mg/levodopa 100 mg (1 tablet) before bedtime for RLS symptoms that awaken patient during the night

Dosing: Geriatric

Refer to adult dosing