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Trade Names:
Methyldopa
- Tablets 250 mg methyldopa
- Tablets 500 mg methyldopa

Trade Names:
Methyldopate Hydrochloride
- Injection 50 mg/mL

Mechanism of Action

Pharmacology

Causes central alpha-adrenergic stimulation, which inhibits sympathetic cardioaccelerator and vasoconstrictor centers; reduces plasma renin activity; reduces standing and supine BP.

Pharmacokinetics

Absorption

Absorption is variable and incompletely absorbed. Mean bioavailability is approximately 50%.

Distribution

Methyldopa and methyldopate cross the blood-brain and placental barriers, appear in cord blood and breast milk, and are approximately 8% protein bound.

Metabolism

Methyldopa and methyldopate are extensively metabolized. Approximately 17% appears in plasma as free methyldopa; active metabolite is alpha-methylnorepinephrine.

Elimination

Approximately 70% (oral) and approximately 49% (IV) is excreted in urine as methyldopa Mono-0-sulfate conjugate; excretion is complete in 36 h after oral dose. The t _½ is 1.8 h and the renal clearance is approximately 130 mL/min (oral) and 156 mL/min (IV).

Onset

Onset is 4 to 6 h.

Peak

Time to peak effect is 12 to 24 h.

Duration

Duration for methyldopa is 24 to 48 h and 10 to 16 h for methyldopate.

Special Populations

Methyldopa is largely excreted by the kidneys. Patients with renal impairment may respond to smaller doses.

Indications and Usage

Treatment of hypertension.

Contraindications

Active hepatic disease or previous hepatic disease associated with methyldopa therapy; coadministration with MAOIs.

Dosage and Administration

PO 250 mg bid to tid in the first 48 h initially, then 500 mg to 2 g/day in 2 to 4 divided doses. Adjust doses at intervals of not less than 2 days until adequate response is achieved.

IV 250 to 500 mg every 6 h as needed (max, 1 g every 6 h).

PO 10 mg/kg/day in 2 to 4 doses (max, 65 mg/kg/day or 3 g/day, whichever is less).

IV 20 to 40 mg/kg/day in divided doses every 6 h (max, 65 mg/kg/day or 3 g/day, whichever is less).

Storage/Stability

Store at controlled room temperature (59° to 86°F).

Drug Interactions

May require reduced doses of anesthetics.

Actions of methyldopa may be reduced.

May cause paradoxical hypertension (rare).

May decrease methyldopa absorption.

May result in dementia or sedation.

BP lowering effects of methyldopa may be potentiated. Central effects of levodopa in Parkinson disease may be potentiated.

May precipitate lithium toxicity.

May lead to excessive sympathetic stimulation.

Serious elevations in BP may occur.

May potentiate pressor effects of sympathomimetics and lead to hypertension.

Enhanced hypoglycemic effects may occur.

Reversal or attenuation of the hypotensive effects of methyldopa.

Laboratory Test Interactions

May interfere with tests for urinary uric acid, serum creatinine, AST; may give falsely high levels of urinary catecholamines, abnormal LFT results, positive Coombs test, or rise in BUN.

Adverse Reactions

Cardiovascular

Bradycardia; prolonged carotid sinus hyperactivity; aggravation of angina pectoris; CHF; paradoxical pressor response with IV use; pericarditis; myocarditis; orthostatic hypotension; edema.

CNS

Dizziness; sedation; nightmares; headache; asthenia or weakness; paresthesias; lightheadedness; symptoms of cerebrovascular insufficiency; parkinsonism; Bell palsy; decreased mental acuity; involuntary choreoathetotic movements.

Dermatologic

Rash; toxic epidermal necrolysis.

EENT

Sore or “black” tongue; nasal stuffiness.

GI

Constipation; dry mouth; nausea; vomiting; distention; flatus; diarrhea; sialadentis.

Genitourinary

Impotence; decreased libido; rise in BUN.

Hematologic

Hemolytic anemia; bone marrow depression; leukopenia; granulocytopenia; thrombocytopenia; reduced WBC count; positive tests for anti-nuclear antibody, lupus erythematosus cells and rheumatoid factor.

Hepatic

Abnormal LFTs; jaundice; hepatitis or liver disorders.

Metabolic

Breast enlargement; gynecomastia; lactation; amenorrhea.

Miscellaneous

Fever; lupus-like syndrome; mild arthralgia or myalgia.

Precautions

Pregnancy

Category B (methyldopa); Category C (methyldopate HCl).

Lactation

Excreted in breast milk.

Children

Individualize dosage.

Elderly

Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. May be avoided by lower doses.

Renal Function

Use with caution in patients with hepatic or renal function impairment.

Hepatic Function

Use with caution in patients with hepatic or renal function impairment.

IV use

Paradoxical pressor response has been reported.

Liver disorders

Jaundice, with or without fever, may occur. Fatal hepatic necrosis has been reported rarely. If symptoms or tests indicate liver effects, the drugs may need to be discontinued.

Positive Coombs test, hemolytic anemia, and liver disorders

May occur; monitor patient closely because of potentially fatal complications.

Blood transfusions

Perform both a direct and an indirect Coombs test. A positive direct Coombs test alone will not interfere with typing or cross matching. If the indirect Coombs test is also positive, problems may arise in the major cross-match and assistance from a hematologist or transfusion expert will be needed.

Overdosage

Symptoms

Sedation, coma, acute hypotension, weakness, bradycardia, dizziness, lightheadedness, constipation, distention, flatus, diarrhea, nausea, vomiting, impaired atrioventricular conduction.

Patient Information

• Encourage patient's compliance with health care provider recommendations of weight reduction, sodium and alcohol restriction, cessation of smoking, regular exercise, stress reduction, and other methods of BP control.
• Teach patient or family proper technique for BP monitoring at home.
• Prepare schedule for return visits to health care provider for additional monitoring of BP and hepatic function. Emphasize importance of return visits.
• Caution patient not to stop taking drug abruptly.
• Warn patient that dizziness may occur and that hot baths or showers may aggravate dizziness.
• Inform patient that nausea, vomiting, or diarrhea may cause increase in hypotensive effect because of dehydration. If this occurs, the patient should contact health care provider for dosage adjustment.
• Advise patient that urine may darken when exposed to air after voiding and assure patient that this is not a problem.
• Instruct patient to report the following symptoms to health care provider: fever, muscle aches, jaundice, flu-like symptoms.
• Advise patient to take sips of water frequently, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs. Dry mouth usually does not continue for more than 2 wk; if it does, patient should report to health care provider.
• Caution patient to avoid sudden position changes to avoid orthostatic hypotension.
• Instruct patient to avoid intake of alcoholic beverages.
• Advise patient that drug may cause drowsiness, especially during first days of therapy or when dose is increased, and to use care while driving or performing other activities requiring mental alertness.
• Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.