LEVODOPA (L-DOPA)

(lee-voe-doe'pa)

Classifications: anticholinergic; antiparkinson agent;
Therapeutic:antiparkinson agent
Pregnancy Category: C

Availability

100 mg, 250 mg, 500 mg tablets and capsules

Action

Drug is a metabolic precursor of dopamine, a catecholamine neurotransmitter. Unlike dopamine, levodopa readily crosses the blood–brain barrier. Precise mechanism of action unknown.

Therapeutic Effect

Levodopa restores dopamine levels in extrapyramidal centers (believed to be depleted in parkinsonism).

Uses

Idiopathic Parkinson's disease, postencephalitic and arteriosclerotic parkinsonism, and parkinsonism symptoms associated with manganese and carbon monoxide poisoning.

Unlabeled Uses

To relieve pain of herpes zoster (shingles), liver coma (caused by cirrhosis or fulminating hepatitis), bone pain in metastatic breast carcinoma, adjunctive therapy in CHF.

Contraindications

Known hypersensitivity to levodopa; narrow-angle glaucoma patients with suspicious pigmented lesion or history of melanoma; acute psychoses, severe psychoneurosis, within 2 wk of use of MAO INHIBITORS; pregnancy (category C), lactation. Safe use in children <2 y is not established.

Cautious Use

Cardiovascular, kidney, liver, or endocrine disease, history of MI with residual arrhythmias; peptic ulcer; convulsions: psychiatric disorders; chronic wide-angle glaucoma; diabetes; pulmonary diseases, bronchial asthma; patients receiving antihypertensive drugs.

Route & Dosage

Parkinson's Disease
Adult: PO 500 mg to 1 g daily in 2 or more equally divided doses, may be increased by 100–750 mg q3–7d (max: 8 g/d); used in combination with carbidopa, decrease levodopa dose by 75–80%

Administration

Oral

Give with food to reduce nausea. Absorption is decreased with high-protein meals.
Crush tablets or empty capsule content into fruit juice as needed.
Store in tight, light-resistant containers.

Adverse Effects (≥1%)

CNS: Choreiform and involuntary movements, increased hand tremor, bradykinetic episodes (on–off phenomena), trismus, grinding of teeth (bruxism), ataxia, muscle twitching, numbness, weakness, fatigue, headache, opisthotonos, confusion, agitation, anxiety, euphoria, insomnia, nightmares; psychotic episodes with paranoid delusions or hallucinations, severe depression, including suicidal tendencies, hypomania. CV: Orthostatic hypotension; palpitations, tachycardia, hypertension. Special Senses: Blepharospasm, diplopia, blurred vision, dilated pupils. GI: Anorexia, nausea, vomiting, abdominal distress, flatulence, dry mouth, dysphagia, sialorrhea; burning sensation of tongue, bitter taste, diarrhea or constipation; GI bleeding, hepatotoxicity. Body as a Whole: Flushing, increased sweating, weight gain or loss, edema, dark sweat or urine. Urogenital: Urinary retention or incontinence, increased sexual drive, priapism, postmenopausal bleeding. Skin: Skin rashes, loss of hair. Respiratory: Rhinorrhea, bizarre breathing patterns.

Diagnostic Test Interference

Altered laboratory values: Elevated BUN, AST, ALT, alkaline phosphatase, LDH, bilirubin, protein-bound iodine, serum level of growth hormone; decreased glucose tolerance; hypokalemia, decreased WBC, Hgb, Hct. Urine glucose: False-negative tests may result with use of glucose oxidase methods (e.g., Clinistix, TesTape) and false-positive results with the copper reduction method (e.g., 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. Urinary ketones: There is possibility of false-positive tests by dipsticks [e.g., Acetest (equivocal), Ketostix, Labstix]; Serum and urinary uric acid: False elevations by colorimetric methods, but not with uricase; Urinary protein: False increases by Lowry method; Urinary VMA: False decreases by Pisano method; Urinary catecholamine: False increases by Hingerty method. PKU urine test: Interference.

Interactions

Drug: mao inhibitors may precipitate hypertensive crisis; tricyclic antidepressants augment postural hypotension; phenothiazines, haloperidol may antagonize the therapeutic effects of levodopa; pyridoxine can reverse effects of levodopa; anticholinergics may exacerbate abnormal involuntary movements; methyldopa may increase toxic CNS effects; halogenated general anesthetics increase risk of arrhythmias. Food: Food decreases the rate and extent of levodopa absorption. Herbal: Kava may worsen parkinsonian symptoms.

Pharmacokinetics

Absorption: Rapidly and well absorbed from GI tract; lower absorption if taken with food. Peak: 1–3 h. Distribution: Widely distributed in body. Metabolism: Most of drug is decarboxylated to dopamine in lumen of GI tract, liver, and serum. Elimination: 80–85% of dose excreted in urine in 24 h. Half-Life: 1 h.

Nursing Implications

Assessment & Drug Effects

Monitor vital signs, particularly during period of dosage adjustment. Report alterations in BP, pulse, and respiratory rate and rhythm.
Supervise ambulation as indicated. Orthostatic hypotension is usually asymptomatic, but some patients experience dizziness and syncope. Tolerance to this effect usually develops within a few months of therapy.
Make accurate observations and report adverse reactions and therapeutic effects promptly. Rate of dosage increase is determined primarily by patient's tolerance and response to drug.
Monitor all patients closely for behavior changes.
Monitor patients with chronic wide-angle glaucoma for changes in intraocular pressure.
Monitor diabetics for loss of glycemic control.
Lab tests: Monitor blood glucose & HbA_1C, CBC, Hgb and Hct, serum potassium, and liver & kidney function periodically.
Report promptly muscle twitching and spasmodic winking (blepharospasm); these are early signs of overdosage. Patients on full therapeutic doses for >1 y may develop such abnormal involuntary movements as well as jerky arm and leg movements. Symptoms tend to increase if dosage is not reduced.
Report to physician any S&S of the on–off phenomenon sometimes associated with chronic management: Rapid unpredictable swings in intensity of motor symptoms of parkinsonism evidenced by increase in bradykinesia (attacks of "leg freezing" or slow body movement).
Monitor mental status for S&S of drug-induced neuropsychiatric adverse reactions.

Patient & Family Education

Do not take with high-protein foods. Also avoid high consumption of food sources of pyridoxine, including wheat germ, green vegetables, banana, whole-grain cereals, muscular and glandular meats (especially liver), legumes. Learn good dietary practices.
Do not take OTC preparations or fortified cereals unless approved by physician. Multivitamins, antinauseants, and fortified cereals usually contain vitamin B₆.
Make positional changes slowly, particularly from lying to upright position, and dangle legs a few minutes before standing.
Resume activities gradually, observing safety precautions to avoid injury. Elevation of mood and sense of well-being may precede objective improvement. Significant improvement usually occurs during second or third wk of therapy, but may not occur for 6 mo or more in some patients.
Follow prescribed drug regimen. Sudden withdrawal of medication can lead to parkinsonism crisis (with return of marked rigidity, akinesia, tremor, hyperpyrexia) or neuroleptic malignant syndrome (NMS).
A metabolite of levodopa may cause urine to darken and sweat to be dark-colored.

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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