carbidopa-levodopa-entacapone

carbidopa-levodopa-entacapone

Stalevo

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. Entacapone increases levodopa blood level by more than 30% and prolongs levodopa's effects.

Availability

Tablets: 12.5 mg carbidopa/50 mg levodopa/200 mg entacapone; 25 mg carbidopa/100 mg levodopa/200 mg entacapone; 37.5 mg carbidopa/150 mg levodopa/200 mg entacapone

⊘Indications and dosages

➣ Idiopathic Parkinson's disease; postencephalitic parkinsonism; symptomatic parkinsonism resulting from carbon monoxide or manganese intoxication

Adults: Optimal daily dosage determined by careful individual titration. Target carbidopa dosage is 70 mg to 100 mg P.O. daily, not to exceed 200 mg; maximum entacapone dosage is 1,600 mg P.O. daily. Patients should receive no more than eight tablets daily.

Contraindications

• Hypersensitivity to drug
• Malignant melanoma (or history of this disease)
• MAO inhibitor use within 14 days
• Angle-closure glaucoma
• Undiagnosed skin lesions
• Breastfeeding

Precautions

Use cautiously in:
• biliary obstruction, renal disease, cerebrovascular disease, endocrine disorders, hepatic impairment, psychiatric disorders
• history of cardiac disease or GI ulcers
• pregnant patients
• children younger than age 18 (safety not established).

Administration

• Give with meals if GI upset occurs.
• Don't crush or break tablets.

Route	Onset	Peak	Duration
P.O.	Unknown	2-3 hr	12 hr

Adverse reactions

CNS: involuntary movements, bradykinesia, anxiety, dizziness, hallucinations, memory loss, psychiatric problems, trismus, increased hand tremor, headache, numbness, weakness, confusion, insomnia, nightmares, delusions, psychotic changes, depression, dementia

CV: cardiac irregularities, palpitations, orthostatic hypotension, arrhythmias

EENT: blurred vision, blepharospasm, mydriasis, diplopia

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dysphagia, burning sensation, flatulence, anorexia, upper GI hemorrhage

GU: urinary retention, urinary incontinence, dark urine

Hematologic: hemolytic anemia, leukopenia

Hepatic: hepatotoxicity

Musculoskeletal: muscle twitching

Respiratory: hiccups, hyperventilation, pulmonary infiltrates

Skin: melanoma, rash, flushing, abnormally dark sweat

Other: sialorrhea, weight changes, hot flashes

Interactions

Drug-drug. Ampicillin, chloramphenicol, cholestyramine, erythromycin, probenecid, rifampin: interference with biliary excretion, additive increase in entacapone blood level

Anticholinergics: decreased levodopa absorption

Antihypertensives: additive hypotension

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

Inhalation hydrocarbon anesthetics: increased risk of arrhythmias

MAO inhibitors: severe hypertension

Methyldopa: altered levodopa efficacy, increased risk of adverse CNS effects

Pyridoxine: antagonism of levodopa's beneficial effects

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

Coombs' test: false-positive result

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

Urine glucose and ketone tests: test interference

Drug-food. Foods high in protein: reduced absorption of carbidopa-levodopa-entacapone

Foods high in pyridoxine: reversal of levodopa effects

Drug-herbs. Kava: decreased levodopa efficacy

Octacosanol: worsening of dyskinesia

Patient monitoring

☞ Monitor patient closely for mental changes, especially psychosis and depression. Report suicidal ideation immediately.
• Assess neurologic status closely to evaluate drug efficacy and identify adverse effects.
• Monitor CBC with white cell differential; also monitor liver function test results.
• Evaluate vital signs. Watch for arrhythmias, orthostatic hypotension, and respiratory problems.
• Assess fluid intake and output. Check for urinary problems.

Patient teaching

• Inform patient or caregiver that drug may cause significant neurologic effects. Instruct him to report anxiety, dizziness, hallucinations, memory loss, increased hand tremor, headache, confusion, nightmares, and depression.
• Tell patient or caregiver to report breathing problems.
• Teach patient or caregiver about recommended home modifications and other safety measures to reduce risk of injury.
• Advise patient to rise slowly and carefully. Drug may cause blood pressure to drop if he sits up or stands suddenly.
• Caution patient to avoid hazardous activities until disease is well controlled and he knows how drug affects concentration, alertness, vision, and motor function.
• Advise patient to minimize GI upset by eating small, frequent servings of healthy food and ensuring adequate fluid intake.
• Tell patient he'll undergo regular blood testing while taking this drug.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.