CARBIDOPA-LEVODOPA

CARBIDOPA-LEVODOPA
(kar-bi-doe'pa)
Sinemet, Sinemet-CR, Parcopa
CARBIDOPA
Lodosyn
Classifications: anticholinergic; antiparkinson agent;
Therapeutic: antiparkinson agent
Pregnancy Category: C

Availability

Carbidopa: 25 mg tablet

Carbidopa/Levodopa: 10 mg/100 mg, 25 mg/100 mg, 25 mg/250 mg tablets; 25 mg/100 mg, 50 mg/200 mg sustained-release tablets and orally disintegrating tablets

Action

When levodopa is given alone, large doses must be administered. Carbidopa prevents peripheral metabolism (decarboxylation) of levodopa and thereby makes more levodopa available for transport to the brain. Carbidopa does not cross blood–brain barrier and therefore does not affect metabolism of levodopa within the brain. Carbidopa also prevents the inhibitory effect of pyridoxine (vitamin B₆) on levodopa.

Therapeutic Effect

Effective in management of symptoms of Parkinson's disease and parkinsonism of secondary origin and improving life expectancy and quality of life.

Uses

Symptomatic treatment of idiopathic Parkinson's disease (paralysis agitans), postencephalitic parkinsonism, and parkinsonism following carbon dioxide and manganese intoxication. Carbidopa is available alone from manufacturer, on request by physician, for use with levodopa when separate titration of each agent is indicated, and for investigational purposes.

Contraindications

Hypersensitivity to carbidopa or levodopa; narrow-angle glaucoma; history of or suspected melanoma; pregnancy (category C), lactation. Safe use in women of childbearing potential and in children <18 y not established.

Cautious Use

Cardiovascular, hepatic, pulmonary, or renal disorders; history of MI; urinary retention; history of peptic ulcer; psychiatric states; endocrine disease; chronic wide-angle glaucoma; seizure disorders.

Route & Dosage

Parkinson's Disease in Patients Not Currently Receiving Levodopa
Adult: PO 1 tablet containing 10 mg carbidopa/100 mg levodopa or 25 mg carbidopa/100 mg levodopa t.i.d., increased by 1 tablet q.d. or q.o.d. up to 6 tablets/d

Patients Receiving Levodopa
Adult: PO 1 tablet of the 25/250 mixture t.i.d. or q.i.d., adjusted by ?–1 tablet as needed up to 8 tablets/d (start at 20–25% of initial dose of levodopa)

Administration

Oral

Ensure that sustained-release form of drug (Sinemet CR) is not chewed or crushed. It may be broken in half but otherwise swallowed whole.
Give consistently with respect to food. High protein meals may interfere with absorption of levodopa.
When patient has been taking levodopa alone, carbidopa-levodopa is usually initiated with a morning dose after patient has been without levodopa for at least 8 h.
Store in tight, light-resistant containers.

Adverse Effects (≥1%)

Body as a Whole: Hoarseness, unusual breathing patterns, neuroleptic malignant syndrome. CV: Orthostatic hypotension, irregular heartbeat, palpitation, arrhythmias, phlebitis, edema. GI: Nausea, anorexia, dry mouth, bruxism, vomiting, excess salivation. Hematologic: Hemolytic and nonhemolytic anemia, thrombocytopenia, agranulocytosis. Metabolic: Abnormal liver function tests, abnormal BUN. CNS: Involuntary movements (dyskinetic, dystonic, choreiform), ataxia, muscle twitching, increase in hand tremor, numbness, headache, dizziness, euphoria, fatigue, confusion, insomnia, nightmares, mental disturbances, anxiety, depression with suicidal tendencies, delirium, seizures. Skin: Body odor, skin rash, dark sweat, loss of hair. Special Senses: Blepharospasm, mydriasis, miosis, blurred vision, diplopia, oculogyric crisis. Urogenital: Dark urine, priapism, urinary frequency, retention, incontinence.

Diagnostic Test Interference

Urine glucose: False-negative tests may result with use of glucose oxidase methods (e.g., Clinistix, TesTape) and false-positive results with copper reduction methods (e.g., Benedict's, Clinitest), especially in patients receiving large doses. It is reported that Clinistix and TesTape may be used if reading is taken at margin of wet and dry tape. There is also the possibility of false-positive tests for urinary ketones by dipstick tests [e.g., Acetest (equivocal), Ketostix, Labstix] false elevation of serum and urinary uric acid levels by colorimetric methods (not with uricase); and interference with urine PKU test results.

Interactions

Drug: mao inhibitors may precipitate hypertensive crisis; tricyclic antidepressants potentiate postural hypotension; anticholinergic agents may enhance levodopa effects but can exacerbate involuntary movements; methyldopa, guanethidine increase hypotensive and CNS effects; phenothiazines, haloperidol, phenytoin, papaverine may interfere with levodopa effects.

Pharmacokinetics

Absorption: 40–70% of carbidopa absorbed after PO dose; carbidopa may enhance absorption of levodopa. Distribution: Widely distributed in most body tissues except CNS; crosses placenta; excreted in breast milk. Elimination: In urine. Half-Life: 2 h.

Nursing Implications

Assessment & Drug Effects

Make accurate observations and report promptly adverse reactions and therapeutic effects. Rate of dosage increase is determined primarily by patient's tolerance and response to levodopa.
Monitor vital signs, particularly during period of dosage adjustment. Report alterations in BP, pulse, and respiratory rate and rhythm.
Monitor all patients closely for behavior changes. Patients in depression should be closely observed for suicidal tendencies.
Monitor for changes in intraocular pressure in patients with chronic wide-angle glaucoma.
Monitor patients with diabetes carefully for alterations in diabetes control. Frequent monitoring of blood sugar is advised.
Lab tests: Periodic blood glucose, hepatic and renal function tests, CBC with differential, Hgb and Hct.
Report promptly abnormal involuntary movement such as facial grimacing, exaggerated chewing, protrusion of tongue, rhythmic opening and closing of mouth, bobbing of head, jerky arm and leg movements, and exaggerated respiration.
Assess for "on-off" phenomenon: sudden, unpredictable loss of drug effectiveness ("off" effect), which lasts 1 min–1 h. This is followed by an equally abrupt return of function ("on" effect). Sometimes symptoms can be controlled by increasing number of doses per day.
Monitor therapeutic effects. Some patients manifest increase in bradykinesia ("leg freezing" or slow body movement). The patient is unable to start walking and frequently falls. Reduction of dosage may be indicated in these patients.
Patients who require more frequent drug administration are most likely to manifest gradual return of parkinsonian symptoms toward the end of a dose period.

Patient & Family Education

Follow physician's directions regarding continuation or discontinuation of levodopa. Both adverse reactions and therapeutic effects occur more rapidly with carbidopa-levodopa combination than with levodopa alone.
Make positional changes slowly and in stages, particularly from recumbent to upright position, dangle your legs a few minutes before standing, and walk in place before ambulating, as some patients experience weakness, dizziness, and faintness. Tolerance to this effect usually develops within a few months of therapy. Support stockings may help. Consult physician.
Report muscle twitching and spasmodic winking promptly, as these may be early signs of overdosage.
You may notice elevation of mood and sense of well-being before any objective improvement. Resume activities gradually and observe safety precautions to avoid injury.
Maintain your prescribed drug regimen. Abrupt withdrawal can lead to parkinsonian crisis with return of marked muscle rigidity, akinesia, tremor, hyperpyrexia, mental changes.
Avoid driving or other hazardous activities until reaction to drug is determined.
Levodopa may cause urine to darken on standing and may also cause sweat to be dark-colored. This effect is not clinically significant.
Wear medical identification. Inform all health care providers that you are taking carbidopa-levodopa.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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