methyldopa
Aldomet, Apo-Methyldopa ◆, Dopamet ◆, Novomedopa ◆, Nu-Medopa

Available forms
Available by prescription only
Tablets: 125 mg, 250 mg, 500 mg
Oral suspension: 50 mg/ml ◆
Injection (as methyldopate hydrochloride): 50 mg/ ml in 5-ml vials

Indications and dosages
 Moderate to severe hypertension. Adults: Initially, 250 mg P.O. b.i.d. or t.i.d. in first 48 hours; then increased or decreased, p.r.n., q 2 days. Or, 250 to 500 mg I.V. q 6 hours (maximum dose, 1 g q 6 hours). Adjust dosage if other antihypertensives are added to or deleted from therapy.
 Maintenance dosage is 500 mg to 2 g P.O. daily in two to four divided doses. Maximum recommended daily dose is 3 g. I.V. infusion dose is 250 to 500 mg given over 30 to 60 minutes q 6 hours. Maximum I.V. dose, 1 g q 6 hours.
Children: Initially, 10 mg/kg P.O. daily or 300 mg/m² P.O. daily in two to four divided doses. Or, 20 to 40 mg/kg I.V. daily or 0.6 to 1.2 g/m² I.V. daily in four divided doses. Increase dosage at least q 2 days until desired response occurs. Maximum daily dose is 65 mg/kg, 2 g/m², or 3 g, whichever is least.

Pharmacodynamics
Antihypertensive action: Exact mechanism of antihypertensive effect is unknown; it’s thought to be caused by a metabolite of methyldopa, alpha-methylnorepinephrine, which stimulates central inhibitory alpha-adrenergic receptors, decreasing total peripheral resistance; drug may act as a false neurotransmitter. Drug may also reduce plasma renin activity.

Pharmacokinetics
Absorption: Absorbed partially from the GI tract. Absorption varies, but usually about 50% of an oral dose is absorbed. No correlation exists between plasma level and antihypertensive effect. After I.V. administration, blood pressure usually begins to decrease in 4 to 6 hours.
Distribution: Distributed throughout the body and is bound weakly to plasma proteins. Crosses the blood-brain barrier.
Metabolism: Metabolized extensively in the liver and intestinal cells.
Excretion: Drug and its metabolites are excreted in urine; unabsorbed drug is excreted unchanged in feces. Elimination half-life is about 2 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with active hepatic disease (such as acute hepatitis and active cirrhosis) and in those taking MAO inhibitors. Also contraindicated if previous methyldopa therapy has been linked to liver disorders. Use cautiously in patients with impaired hepatic function, and in breast-feeding women.

Interactions
Drug-drug. Anesthetics: Increases effects. Patient undergoing surgery may require reduced dosage of anesthetic.
Antihypertensives: Potentiates antihypertensive effects. Use together cautiously.
Diuretics: May increase hypotensive effect of methyldopa. Use together cautiously.
Haloperidol: May produce dementia and sedation. Use together cautiously.
Levodopa: Increases hypotensive effects. Monitor blood pressure.
Lithium: May increase risk of lithium toxicity. Monitor lithium levels.
MAO inhibitors: May cause severe hypertension. Avoid use together.
Oral iron therapy: May decrease hypotensive effects and increase serum levels of levodopa. Use together cautiously.
Phenothiazines: Increases risk of hypertension. Use together cautiously.
Phenoxybenzamine: May cause reversible urinary incontinence. Avoid use together.
Sulfonylureas (glipizide, glyburide, tolbutamide): May impair sulfonylurea metabolism. Monitor serum glucose levels.
Sympathomimetic amines (dopamine, norepinephrine, pseudoephedrine): Potentiates pressor effects. Use together cautiously.
Tricyclic antidepressants: May reduce antihypertensive effects. Monitor patient’s blood pressure.
Drug-herb. Capsicum: May reduce antihypertensive effects. Discourage use together.

Adverse reactions
CNS: sedation, headache, weakness, dizziness, decreased mental acuity, paresthesia, parkinsonism, involuntary choreoathetoid movements, psychic disturbances, depression, nightmares.
CV: bradycardia, orthostatic hypotension, aggravated angina, myocarditis, edema.
EENT: nasal congestion.
GI: nausea, vomiting, diarrhea, pancreatitis, dry mouth, constipation.
GU: amenorrhea, impotence.
Hematologic: hemolytic anemia, thrombocytopenia, leukopenia, bone marrow depression.
Hepatic: hepatic necrosis, hepatitis.
Musculoskeletal: arthralgia.
Skin: rash.
Other: gynecomastia, galactorrhea, drug-induced fever, decreased libido.

Effects on lab test results
• May increase AST, ALT, alkaline phosphatase, bilirubin, and creatinine levels.
• May decrease hemoglobin and platelet and WBC counts.

Overdose and treatment
Evidence of overdose includes sedation, hypotension, impaired AV conduction, and coma.
 After recent (within 4 hours) ingestion, empty stomach by induced emesis or gastric lavage. Give activated charcoal to reduce absorption; then treat symptomatically and supportively. In severe cases, hemodialysis may be considered.

Special considerations
• Patients with impaired renal function may require smaller maintenance dosage.
• Multiple dosing may decrease patient compliance, but twice-daily dosing may provide adequate control with decreased cost.
• Drug fever usually occurs within the first 3 months on therapy and may be accompanied by eosinophilia or hepatic function test changes.
• Methyldopate hydrochloride is administered I.V. Administration by I.M. or S.C. route isn’t recommended because of unpredictable absorption.
• Patients receiving methyldopa may become hypertensive after dialysis because drug is dialyzable.
• Sedation and drowsiness usually disappear with continued therapy; bedtime dosage will minimize this effect. Orthostatic hypotension may indicate a need for dosage reduction. Some patients tolerate entire daily dose in the evening or at bedtime.
• Tolerance may develop after 2 to 3 months.
• Signs of hepatotoxicity may occur 2 to 4 weeks after therapy begins.
• For I.V. use, add required dose of drug to 100 ml of 5% dextrose injection. Or, a concentration of 100 mg/ml may be used. ADD-Vantage vials contain 50 mg/ml and should be reconstituted per manufacturer direction. Administer I.V. infusion over 30 to 60 minutes.
• Methyldopa may cause falsely high levels of urine catecholamines, interfering with the diagnosis of pheochromocytoma. A positive direct antiglobulin (Coombs’) test may also occur.
• At the start of therapy and periodically throughout, monitor hemoglobin, hematocrit, and RBC count for hemolytic anemia; also monitor liver function tests, especially during the first 6 to 12 weeks of treatment.
• Take blood pressure in supine, sitting, and standing positions during dosage adjustment; take blood pressure at least every 30 minutes during I.V. infusion until patient is stable.
• Monitor intake, output, and daily weights to detect sodium and water retention; voided urine exposed to air may darken because of the breakdown of methyldopa or its metabolites.
• Monitor patient for signs and symptoms of drug-induced depression.
Pregnant patients
• Methyldopa is the most extensively used hypotensive agent in pregnant women.
Breast-feeding patients
• Drug appears in breast milk. The American Academy of Pediatrics considers methyldopa to be compatible with breast-feeding.
Pediatric patients
• Safety and efficacy in children haven’t been established. Use only if potential benefits outweigh risks.
Geriatric patients
• Dosage reductions may be needed in geriatric patients because they’re more sensitive to sedation and hypotension.

Patient education
• Teach patient signs and symptoms of adverse effects, such as jerky movements, and about the need to report them; he should also report excessive weight gain (5 lb weekly), signs of infection, or fever.
• Teach patient to minimize adverse effects by taking drug at bedtime until tolerance develops to sedation, drowsiness, and other CNS effects; by avoiding sudden position changes to minimize orthostatic hypotension; and by using ice chips or sugarless hard candy or gum to relieve dry mouth.
• Warn patient to avoid hazardous activities that require mental alertness until sedative effects subside.
• Instruct patient to call for instructions before taking OTC cold preparations.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use