Methyldopa and Methyldopate HCl

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

 Indications Treatment of hypertension.

 Contraindications Active hepatic disease or previous hepatic disease associated with methyldopa therapy; coadministration with MAO inhibitors.

 Route/Dosage

Adults: PO 250 mg bid to tid in the first 48 hr 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 q 6 hr prn (max, 1 g q 6 hr). Children: 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 hr (max, 65 mg/kg/day or 3 g/day, whichever is less).

 Interactions

Anesthetics: May require reduced doses of anesthetics. Barbiturates: Actions of methyldopa may be reduced. Beta blockers: May cause paradoxical hypertension (rare). Ferrous sulfate or gluconate May decrease methyldopa absorption. Haloperidol: May result in dementia or sedation. Levodopa: BP lowering effects of methyldopa may be potentiated. Central effects of levodopa in Parkinson disease may be potentiated. Lithium: May precipitate lithium toxicity. MAO inhibitors: May lead to excessive sympathetic stimulation. Phenothiazines: Serious elevations in BP may occur. Sympathomimetics: May potentiate pressor effects of sympathomimetics and lead to hypertension. Tolbutamide: Enhanced hypoglycemic effects may occur. Tricyclic antidepressants: Reversal or attenuation of the hypotensive effects of methyldopa.

 Lab Test Interferences 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's 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. GU: Impotence; decreased libido; rise in BUN. HEPATIC: Abnormal LFTs; jaundice; hepatitis or liver disorders. HEMATOLOGIC: Hemolytic anemia; bone marrow depression; leukopenia; granulocytopenia; thrombocytopenia; reduced WBC count; positive tests for anti-nuclear antibody, lupus erythematosus cells and rheumatoid factor. METABOLIC: Breast enlargement; gynecomastia; lactation; amenorrhea. OTHER: 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. Hepatic/Renal function impairment: Use with caution in patients with hepatic or renal dysfunction. 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 Coomb's test. A positive direct Coomb's test alone will not interfere with typing or cross matching. If the indirect Coomb's test is also positive, problems may arise in the major cross-match and assistance from a hematologist or transfusion expert will be needed.

 Administration/Storage

• Add 100 mL of D5W to dose and infuse IV medication slowly over 30 to 60 min.
• Shake oral suspension well prior to administration.
• Make dosage increases with evening dose to avoid daytime drowsiness.

Methyldopa

• Protect oral suspension from light. Avoid freezing.

Methyldopate HCl

• Refrigerate. Do not freeze.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Determine whether patient has active hepatic or renal disease.
• Prior to therapy, perform baseline blood counts (hematocrit and hemoglobin or RBC count) and BP readings.
• During therapy monitor carefully for hemolytic anemia and liver disorders (eg, fever, jaundice).
• Monitor for paradoxical pressor response after IV administration of methyldopa or methyldopate HCl.
• Monitor I&O and weight.
• Monitor renal studies for BUN, creatinine, protein.
• If Coombs' test-positive hemolytic anemia occurs, discontinue methyldopa and notify health care provider.

 Patient/Family Education

• 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.
• Instruct patient not to take OTC medications without consulting health care provider.