carbidopa/levodopa

KAR-bi-doe-pa/LEE-voe-doe-pa

Therapeutic Classification: antiparkinson agents

Pharmacologic Classification: dopamine agonists

REMS

Parkinson's disease, postencephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

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.

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.

Metabolism/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.

(antiparkinson effects)

ROUTE	ONSET	PEAK	DURATION
Carbidopa	unknown	unknown	5–24 hr
Levodopa	10–15 min	unknown	5–24 hr or more
Carbidopa/levodopa extended release	unknown	2 hr	12 hr

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: Safety not established in pregnancy;
Lactation: May ↓ serum prolactin; levodopa enters breast milk; use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children.

CV: orthostatic hypotension

Derm: melanoma

EENT: blurred vision, mydriasis

GI: constipation, nausea, vomiting, anorexia, bezoar (enteral suspension), dry mouth, 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)

Hemat: hemolytic anemia, leukopenia

MS: dyskinesias

Neuro: depression, involuntary movements, anxiety, confusion, dizziness, drowsiness, hallucinations, memory loss, neuropathy, psychiatric problems, sudden sleep onset, urges (gambling, sexual)

Resp: aspiration pneumonia (enteral suspension)

Misc: darkening of urine or sweat, MELANOMA, SEPSIS (ENTERAL SUSPENSION)

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).
↑risk of arrhythmias with inhalation hydrocarbon anesthetics, especially halothane; if possible, discontinue 6–8 hr before anesthesia.
Phenothiazines, haloperidol, papaverine, and phenytoin may ↓ effect of levodopa.
Large doses of pyridoxine may ↓ beneficial effects of levodopa.
↑hypotension may result with concurrent antihypertensives.
Anticholinergics may ↓ absorption of levodopa.
↑risk of adverse reactions with selegiline or cocaine.

Drug-Natural Products:

Kava-kava may ↓ levodopa effectiveness.

Drug-Food:

Ingestion of foods containing large amounts of pyridoxine may ↓ effect of levodopa.

Carbidopa/Levodopa

PO (Adults ): Immediate-release (IR) or orally disintegrating tablets: 25 mg carbidopa/100 mg levodopa 3 times daily; may be ↑ every 1–2 days until desired effect is achieved (max = 8 tablets of 25 mg carbidopa/100 mg levodopa/day).
Enteral(Adults ): Patients must be converted to and be on stable dose of PO IR carbidopa/levodopa tablets before initiation of 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 IR carbidopa/levodopa taken by patient on previous day * 0.8); Continuous dose for Day 1 (mL) (to be administered over 16 hr) = Determine amount of levodopa (in mg) patient received from IR carbidopa/levodopa doses throughout 16 waking hr of previous day (do not include doses of IR 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-hr infusion, patients will disconnect the pump from feeding tube and take their nighttime dose of oral IR carbidopa/levodopa tablets. Total daily dose can be titrated after Day 1 based on patient response and tolerability.

Carbidopa/Levodopa Extended-Release (ER) (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 for 3 days; then 36.25 mg carbidopa/145 mg levodopa 3 times daily. May continue to ↑ dose as needed (max dose = 97.5 mg carbidopa/390 mg levodopa 3 times daily). May also ↑ frequency of administration up to 5 times daily (max dose = 612.5 mg carbidopa/2450 mg levodopa/day). Patients not currently receiving levodopa (Crexont): 35 mg carbidopa/140 mg levodopa twice daily for 3 days. May then gradually ↑ dose as needed to max dose of 525 mg carbidopa/2100 mg levodopa/day in up to 4 divided doses.Conversion from 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 dose = 612.5 mg carbidopa/2450 mg levodopa). Conversion from IR carbidopa/levodopa to Crexont: If taking <500 mg/day of IR levodopa and most frequent single dose of IR levodopa is 100 mg, give Crexont 70 mg carbidopa/280 mg levodopa twice daily. If taking <500 mg/day of IR levodopa and most frequent single dose of IR levodopa is 150 mg, give 2 capsules of Crexont 52.5 mg carbidopa/210 mg levodopa twice daily. If taking <500 mg/day of IR levodopa and most frequent single dose of IR levodopa is 200 mg, give 2 capsules of Crexont 70 mg carbidopa/280 mg levodopa twice daily. If taking ≥500 mg/day of IR levodopa and most frequent single dose of IR levodopa is 100 mg, give Crexont 70 mg carbidopa/280 mg levodopa 3 times daily. If taking ≥500 mg/day of IR levodopa and most frequent single dose of IR levodopa is 150 mg, give 2 capsules of Crexont 52.5 mg carbidopa/210 mg levodopa 3 times daily. If taking ≥500 mg/day of IR levodopa and most frequent single dose of IR levodopa is 200 mg, give 2 capsules of Crexont 70 mg carbidopa/280 mg levodopa 3 times daily. If taking ≥500 mg/day of IR levodopa and most frequent single dose of IR levodopa is >200 mg, give 2 capsules of Crexont 87.5 mg carbidopa/350 mg levodopa 3 times daily. Conversion from Rytary to Crexont: Initiate Crexont on an approximately 1:1 mg basis using the levodopa component for conversion.

(Generic available)

Immediate-release tablets: carbidopa 10 mg/levodopa 100 mg; carbidopa 25 mg/levodopa 100 mg; carbidopa 25 mg/levodopa 250 mg
Orally disintegrating tablet: carbidopa 10 mg/levodopa 100 mg; carbidopa 25 mg/levodopa 100 mg; carbidopa 25 mg/levodopa 250 mg
Extended-release capsules (Crexont): carbidopa 35 mg/levodopa 140 mg; carbidopa 52.5 mg/levodopa 210 mg; carbidopa 70 mg/levodopa 280 mg; carbidopa 87.5 mg/levodopa 350 mg
Extended-release capsules (Rytary): carbidopa 23.75 mg/levodopa 95 mg; carbidopa 36.25 mg/levodopa 145 mg; carbidopa 48.75 mg/levodopa 195 mg; carbidopa 61.25 mg/levodopa 245 mg
Extended-release tablets: carbidopa 25 mg/levodopa 100 mg; carbidopa 50 mg/levodopa 200 mg
Enteral suspension (Duopa): carbidopa 4.63 mg/levodopa 20 mg/mL; carbidopa 5 mg/levodopa 20 mg/mL
In combination with: entacapone (Stalevo); see Appendix [not included in this PDA edition].

Assess parkinsonian symptoms (akinesia, rigidity, tremors, pill rolling, shuffling gait, mask-like face, twisting motions, drooling) during therapy. On-off phenomenon may cause symptoms to appear or improve suddenly.
Assess BP and HR frequently during period of dose adjustment.
Duopa: Monitor for signs and symptoms of GI complications (abdominal pain, prolonged constipation, nausea, vomiting, fever, melanotic stool) during therapy.

Lab Test Considerations:

May cause false-positive test results in Coombs’ test.
- May ↑ serum glucose. Dipstick for urine ketones may reveal false-positive results.
- Monitor hepatic and renal function and CBC periodically in patients on long-term therapy. May ↑ AST, ALT, bilirubin, alkaline phosphatase, LDH, and serum protein-bound iodine concentrations.
- May ↓ hemoglobin, ↓ hematocrit, and ↑ WBC.
- May cause agranulocytosis, hemolytic and nonhemolytic anemia, thrombocytopenia, and leukopenia.

Toxicity and Overdose:

Assess for signs of toxicity (involuntary muscle twitching, facial grimacing, spasmodic eye winking, exaggerated protrusion of tongue, behavioral changes). Consult health care professional if symptoms occur.

Do not confuse Sinemet with Janumet.
In preoperative patients or patients who are NPO, confer with health care professional about continuing medication administration using oral disintegrating tablets.
PO: Administer on a regular schedule. Hospitalized patients should be continued on same schedule as at home. Administer while awake, not around the clock, to improve sleep and prevent side effects.
- DNC: Controlled-release tablets may be administered as whole or half tablets. Do not crush or chew.
- Each Dhivy tablet is scored in three segments with each segment containing 6.25 mg of carbidopa and 25 mg of levodopa to help with titration.
- For enteral administration, administer Duopa into the jejunum through a percutaneous endoscopic gastrostomy with jejunal tube (PEG-J) with CADD-Legacy 1400 portable infusion pump. Take suspension out of refrigerator 20 min prior to use; must be at room temperature for use. Administer over 16 hr. If extra dose is needed, set function at 1 mL (20 mg of levodopa) when starting; may be adjusted in 0.2 mL increments. Limit to one extra dose every 2 hr. Frequent extra doses may cause or worsen dyskinesias. Discontinue gradually; do not stop abruptly.
- For ER capsules, administer without regard to food. DNC: Swallow capsules whole; do not chew, divide, or crush. For patients with difficulty swallowing, open capsule and sprinkle entire contents on 1–2 tablespoons of applesauce; consume immediately. Do not store mixture for future use. Inform patients that first dose of day may be taken 1–2 hr before eating, as a high-fat, high-calorie meal may delay the absorption of levodopa and onset of action by 2–3 hr. Discontinue gradually; do not stop abruptly. When adjusting dose of ER capsules, keep dose of other Parkinson's medications stable; dose may need to be ↑ in patients taking COMT inhibitor. ER capsules may be administered 3–5 times daily if more frequent dosing is needed and tolerated.

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Instruct patient to take medication at regular intervals as directed. Do not change dose regimen or take additional antiparkinson drugs, including more carbidopa/levodopa, without consulting health care professional. Take missed doses as soon as remembered, unless next scheduled dose is within 2 hr; do not double doses. Advise patient therapeutic effects usually become evident after 2–3 wk of therapy but may require up to 6 mo. Patients who take this medication for several yr may experience a ↓ in the drug's effectiveness.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially cold remedies. Large amounts of vitamin B₆ (pyridoxine) and iron may interfere with the action of levodopa.
Explain that gastric irritation may be ↓ by eating food shortly after taking medications but that high-protein meals may impair levodopa’s effects. Dividing daily protein intake among all the meals may help ensure adequate protein intake and drug effectiveness. Do not drastically alter diet during therapy without consulting health care professional.
May cause sudden onset of sleep, drowsiness, or dizziness. Advise patient to avoid driving and other activities that require alertness until response to drug is known.
Caution patient to change positions slowly to minimize orthostatic hypotension. Notify health care professional if orthostatic hypotension occurs.
Instruct patient that frequent rinsing of mouth, good oral hygiene, and sugarless gum or candy may ↓ dry mouth.
Caution patient to monitor skin lesions for any changes. Notify health care professional promptly because of the risk for malignant melanoma.
Inform patient that harmless darkening of saliva, urine, or sweat may occur.
Advise patient to notify health care professional if signs and symptoms of GI complications; palpitations; urinary retention; involuntary movements; behavioral changes; severe nausea and vomiting; new skin lesions; or new or ↑ gambling, sexual, binge or compulsive eating, or other intense urges occur. Dose ↓ may be required.
Inform patient that sometimes a wearing-off effect may occur at end of dosing interval. Notify health care professional if this poses a problem to lifestyle.
Rep: Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding. May inhibit lactation.

Relief of tremors and rigidity in Parkinson’s syndrome.

Crexont, Dhivy, Duopa, Rytary, Sinemet, ~~Sinemet CR~~

Duodopa

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Action ⬆ ⬇

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