carbidopa/levodopa

kar-bi-doe-pa/lee-voe-doe-pa

Trade Name(s): (Apo-Levocarb , Dhivy, Duopa, Rytary, Sinemet)

Do not confuse Sinemet with Serevent.

FIXED-COMBINATION(S)

Stalevo: carbidopa/levodopa/entacapone (antiparkinson agent): 12.5 mg/50 mg/200 mg, 18.75 mg/75 mg/200 mg, 25 mg/100 mg/200 mg, 31.25 mg/125 mg/200 mg, 37.5 mg/150 mg/200 mg, 50 mg/200 mg/200 mg.

• PHARMACOTHERAPEUTIC: DOPa-mine precursor. Decarboxylase inhibitor. CLINICAL: Antiparkinson agent.

Parkinson's disease: Treatment of Parkinson's disease, postencephalitic parkinsonism, symptomatic parkinsonism following CNS injury by carbon monoxide poisoning, manganese intoxication. Duopa: Treatment of motor fluctuations in advanced Parkinson's disease. OFF-LABEL: Restless legs syndrome.

Contraindications: Hypersensitivity to carbidopa/levodopa. Concurrent use with MAOIs or use within 14 days. (Tablets only): Narrow-angle glaucoma. Cautions: History of MI, arrhythmias, bronchial asthma, emphysema, severe cardiac, pulmonary, renal/hepatic impairment; active peptic ulcer, treated open-angle glaucoma, seizure disorder, pts at risk for hypotension; elderly.

Levodopa is converted to DOPamine in basal ganglia, increasing DOPamine concentration in brain, inhibiting hyperactive cholinergic activity. Carbidopa prevents peripheral breakdown of levodopa, making more levodopa available for transport into brain. Therapeutic Effect: Treats symptoms (e.g., stiffness, tremors) associated with Parkinson's disease.

Widely distributed. Excreted primarily in urine. Levodopa is converted to DOPamine. Excreted primarily in urine. Half-life: 1–2 hrs (carbidopa); 1–3 hrs (levodopa).

Pregnancy/Lactation: Unknown if drug crosses placenta or is distributed in breast milk. May inhibit lactation. Breastfeeding not recommended. Children: Safety and efficacy not established. Elderly: More sensitive to effects of levodopa. Anxiety, confusion, nervousness more common when receiving anticholinergics.

DRUG: Antipsychotics, pyridoxine may decrease therapeutic effect. May increase adverse effects of MAOIs (e.g., phenelzine, selegiline). HERBAL: None significant. FOOD: High-protein diets may cause decreased or erratic response to levodopa. LAB VALUES: May increase serum BUN, LDH, alkaline phosphatase, bilirubin, ALT, AST. May decrease Hgb, Hct, WBC.

Enteral Suspension: (Duopa): 100-mL cassette containing 4.63 mg carbidopa and 20 mg levodopa per mL. Tablets: (Immediate-Release [Sinemet]): 10 mg carbidopa/100 mg levodopa, 25 mg carbidopa/100 mg levodopa, 25 mg carbidopa/250 mg levodopa. [Dhivy]: 25 mg/100 mg (each tablet with 3 functional scores with each segment 6.25 mg/25 mg. Tablets: (Orally Disintegrating Immediate-Release): 10 mg carbidopa/100 mg levodopa, 25 mg carbidopa/100 mg levodopa, 25 mg carbidopa/250 mg levodopa.

Capsules: (Extended-Release [Rytary]): carbidopa/levodopa: 23.75 mg/95 mg, 36.25 mg/145 mg, 48.75 mg/195 mg, 61.25 mg/245 mg. Tablets: (Extended-Release): 25 mg carbidopa/100 mg levodopa, 50 mg carbidopa/200 mg levodopa.

Note: Space doses evenly over waking hours.

Enteral Suspension

• Refrigerate. Remove 20 min prior to administration.

PO

Extended-release capsule:

• Scored tablets may be crushed.
• Give May give without regard to food. Administer whole (do not crush, divide, or allowing chewing).
• May be opened, sprinkled on applesauce, and given immediately. Oral tablets: Administer with meals to decrease GI upset. · Con-trolled-release tablet should not be chewed, crushed. Dhivy tablets may be broken at score lines. · (Orally Disintegrating Tablet): Place orally disintegrating tablet on top of tongue. Tablet will dissolve in seconds; pt to swallow with saliva. Not necessary to administer with liquid.

Parkinsonism

PO: ADULTS, ELDERLY: (Immediate-Release Orally Disintegrating Tablet): Initially, 10 mg carbidopa/100 mg levodopa PO 3–4 times daily or 25/100 mg 3 times/day. May increase daily or every other day by 1 tablet (25/100 mg) up to 200/2,000 mg daily divided in 4 or more doses/day. (Extended-Release): Initially, 50/200 mg 2 times/day at least 6 hrs apart. May adjust dose no faster than 3 days up to a maximum of 2,400 mg levodopa/day. (Rytary): Initially, 23.75/95 mg 3 times/day for 3 days, then to 36.25/145 mg 3 times/day. Frequency may be increased to maximum of 5 times/day if needed and tolerated. Maximum daily dose: 612.5/2,450 mg/day. (Enteral Suspension): Maximum: 2,000 mg (1 container) over 16 hrs through NJ or PEG tube via infusion pump. Also take oral immediate-release in evening after disconnecting pump. Refer to manufacturer's guidelines for morning dose, continuous dose escalation, titration instructions.

Dosage in Renal/Hepatic Impairment

Use caution.

Frequent (80%–50%): Involuntary movements of face, tongue, arms, upper body; nausea/vomiting; anorexia. Occasional: Depression, anxiety, confusion, nervousness, urinary retention, palpitations, dizziness, light-headedness, decreased appetite, blurred vision, constipation, dry mouth, flushed skin, headache, insomnia, diarrhea, unusual fatigue, darkening of urine and sweat. Rare: Hypertension, ulcer, hemolytic anemia (marked by fatigue).

High incidence of involuntary choreiform, dystonic, dyskinetic movements may occur in pts on long-term therapy. Numerous mild to severe CNS and psychiatric disturbances may occur (reduced attention span, anxiety, nightmares, daytime drowsiness, euphoria, fatigue, paranoia, psychotic episodes, depression, hallucinations).

• BASELINE ASSESSMENTAssess symptoms of Parkinson's disease (e.g., muscular rigidity, pen rolling motion, gait disturbance, tremors), emotional state. Receive full medication history and screen for interactions.INTERVENTION/EVALUATIONBe alert to neurologic effects (headache, lethargy, mental confusion, agitation). Monitor for evidence of dyskinesia (difficulty with movement). Assess for clinical reversal of symptoms (improvement of tremor of head and hands at rest, mask-like facial expression, shuffling gait, muscular rigidity). Monitor B/P (standing, sitting, supine).PATIENT/FAMILY TEACHING
• Avoid tasks that require alertness, motor skills until response to drug is established.
• Take with food to minimize GI upset.
• Effects may be delayed from several wks to mos.
• May cause darkening of urine or sweat (not harmful).
• Report any uncontrolled movement of face, eyelids, mouth, tongue, arms, hands, legs; mental changes; palpitations; severe or persistent nausea/vomiting; difficulty urinating.
• Report exacerbations of asthma, underlying depression, psychosis.