Indications
Parkinson’s disease. Not useful for drug-induced extrapyramidal
reactions.
Action
Levodopa is converted to dopamine in the CNS, where it
serves as a neurotransmitter. Carbidopa, a decarboxylase
inhibitor, prevents peripheral destruction of levodopa.
Therapeutic Effects: Relief of tremor and rigidity
in Parkinson’s syndrome.
Pharmacokinetics
Absorption: Well absorbed following oral administration.
Distribution: Widely distributed. Levodopa—enters
the CNS in small concentrations. Carbidopa—
does not cross the blood-brain barrier but does cross
the placenta. Both enter breast milk.
Metabolism and Excretion: Levodopa—mostly
metabolized by the GI tract and liver. Carbidopa—
30% excreted unchanged by the kidneys.
Half-life: Levodopa—1 hr; carbidopa—1–2 hr.
TIME/ACTION PROFILE (antiparkinson effects)
ROUTE ONSET PEAK DURATION
Carbidopa unknown unknown 5–24 hr
Levodopa 10–15 min unknown 5–24 hr or
more
Carbidopa/levodopa
sustained
release
unknown 2 hr 12 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Angle-closure
glaucoma; Nonselective MAO inhibitor therapy; Malignant
melanoma; Undiagnosed skin lesions; Some products
contain tartrazine, phenylalanine, or aspartame and should be avoided in patients with known hypersensitivity.
Use Cautiously in: History of cardiac, psychiatric,
or ulcer disease; OB, Pedi: Safety not established; Lactation:
Maypserum prolactin; levodopa enters breast
milk.
Adverse Reactions/Side Effects
CNS: depression, involuntary movements, anxiety,
confusion, dizziness, drowsiness, hallucinations, memory
loss, psychiatric problems, sudden sleep onset,
urges (gambling, sexual). CV: orthostatic hypotension.
EENT: blurred vision, mydriasis. GI: GI HEMORRHAGE
(enteral suspension), GI ISCHEMIA (enteral suspension),
GI OBSTRUCTION (enteral suspension), GI PERFORATION
(enteral suspension), HEPATOTOXICITY, INTUSSUSCEPTION
(enteral suspension), PANCREATITIS (enteral
suspension), PERITONITIS (enteral suspension), constipation,
nausea, vomiting, anorexia, bezoar (enteral suspension),
dry mouth. Derm: melanoma. Hemat: hemolytic
anemia, leukopenia. MS: dyskinesias. Neuro:
neuropathy. Misc: MELANOMA, darkening of urine or
sweat.
Interactions
Drug-Drug: Use with nonselective MAO inhibitors
may result in hypertensive reactions; concurrent
use contraindicated (MAO inhibitor must be discontinued
2 wk before initiating carbidopa/levodopa).q
risk of arrhythmias with inhalation hydrocarbon anesthetics
(especially halothane; if possible discontinue
6–8 hr before anesthesia). Phenothiazines,
haloperidol, papaverine, phenytoin, and reserpine
maypeffect of levodopa. Large doses of pyridoxine
maypbeneficial effects of levodopa. Concurrent
use with methyldopa may alter the effectiveness of levodopa
andqrisk of CNS side effects.qhypotension
may result with concurrent antihypertensives. Anticholinergics
maypabsorption of levodopa.qrisk of
adverse reactions with selegiline or cocaine.
Drug-Natural Products: Kava-kava mayplevodopa
effectiveness.
Drug-Food: Ingestion of foods containing large
amounts of pyridoxine maypeffect of levodopa.
Route/Dosage
Carbidopa/Levodopa
PO (Adults): 25 mg carbidopa/100 mg levodopa 3
times daily; may beqevery 1–2 days until desired effect
is achieved (max8 tablets of 25 mg carbidopa/
100 mg levodopa/day).
Enteral (Adults): Patients must be converted to and be
on stable dose of PO immediate-release carbidopa/levodopa
tablets before initiation enteral suspension therapy.
Morning dose for Day 1 (mL) (to be administered
over 10–30 min)(Amount of levodopa (in
mg) in first dose of immediate-release carbidopa/levodopa
taken by patient on previous day * 0.8)/20; Continuous
dose for Day 1 (mL) (to be administered
over 16 hr)Determine amount of levodopa (in mg)
patient received from immediate-release carbidopa/levodopa
doses throughout 16 waking hours of previous
day (do not include doses of immediate-release carbidopa/
levodopa taken at night when calculating the levodopa
amount). Then, subtract amount of first levodopa
dose (in mg) taken by patient on previous day. Divide
result by 20 to obtain the # of mL to be administered
over 16 hr. Do not exceed dose of 2000 mg. At end of
daily 16-hour infusion, patients will disconnect the
pump from feeding tube and take their night-time dose
of oral immediate-release carbidopa/levodopa tablets.
Total daily dose can be titrated after Day 1 based on patient
response and tolerability.
Carbidopa/Levodopa Extended-Release
(doses of all other dosage forms of carbidopa/
levodopa and Rytary are not interchangeable)
PO (Adults): Patients not currently receiving levodopa
(Sinemet CR)—50 mg carbidopa/200 mg levodopa
twice daily (minimum of 6 hr apart) initially. Patients
not currently receiving levodopa (Rytary)—
23.75 mg carbidopa/95 mg levodopa 3 times daily x 3
days, then 36.25 mg carbidopa/145 mg levodopa 3
times daily. May continue toqdose as needed (max
dose97.5 mg carbidopa/390 mg levodopa 3 times
daily) May alsoqfrequency of administration up to 5
times daily (max dose612.5 mg carbidopa/2450 mg
levodopa/day). Conversion from immediate—release
(IR) carbidopa/levodopa to Sinemet CR—initiate
therapy with at least 10% more levodopa content/
day (may need up to 30% more) given at 4–8 hr intervals
while awake. Allow 3 days between dosage
changes; some patients may require larger doses and
shorter dosing intervals. Conversion from IR carbidopa/
levodopa to Rytary—If taking 400–549 mg/day
of IR levodopa, give 3 capsules of Rytary 23.75 mg carbidopa/
95 mg levodopa 3 times daily. If taking 550–
749 mg/day of IR levodopa, give 4 capsules of Rytary
23.75 mg carbidopa/95 mg levodopa 3 times daily. If
taking 750–949 mg/day of IR levodopa, give 3 capsules
of Rytary 36.25 mg carbidopa/145 mg levodopa 3 times
daily. If taking 950–1249 mg/day of IR levodopa, give
3 capsules of Rytary 48.75 mg carbidopa/195 mg levodopa
3 times daily. If taking 1250 mg/day of IR levodopa,
give 4 capsules of Rytary 48.75 mg carbidopa/
195 mg levodopa 3 times daily or 3 capsules of Rytary
61.25 mg carbidopa/245 mg levodopa 3 times daily;
may then titrate as needed (max daily dose612.5 mg
carbidopa/2450 mg levodopa).
Availability (generic available)
Tablets: 10 mg carbidopa/100 mg levodopa, 25 mg
carbidopa/100 mg levodopa, 25 mg carbidopa/250 mg
levodopa. Cost: Generic—10 mg/100 mg $25.28/
100, 25 mg/100 mg $28.91/100, 25 mg/250 mg
$19.22/100. Orally disintegrating tablets (mint):
10 mg carbidopa/100 mg levodopa, 25 mg carbidopa/100 mg levodopa, 25 mg carbidopa/250 mg levodopa.
Cost: Generic—10 mg/100 mg $121.48/100, 25 mg/
100 mg $137.18/100, 25 mg/250 mg $174.76/100.
Extended-release tablets (Sinemet CR): 25 mg
carbidopa/100 mg levodopa, 50 mg carbidopa/200 mg
levodopa. Cost: Generic—25 mg/100 mg $93.90/
100, 50 mg/200 mg $180.50/100. Extended-release
capsules (Rytary): 23.75 mg carbidopa/95 mg levodopa,
36.25 mg carbidopa/145 mg levodopa, 48.75 mg
carbidopa/195 mg levodopa, 61.25 mg carbidopa/245
mg levodopa. Enteral suspension (Duopa): 4.63 mg
carbidopa/20 mg levodopa/mL in 100–mL single-use
cassettes, 5 mg carbidopa/20 mg levodopa/mL in
100–mL single-use cassettes. In combination with:
entacapone (Stalevo); see Appendix B.
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