methyldopate hydrochloride

methyldopate hydrochloride

Pharmacologic class: Centrally acting antiadrenergic

Therapeutic class: Antihypertensive

Pregnancy risk category B

Action

Stimulates CNS alpha-adrenergic receptors, decreasing sympathetic stimulation to heart and blood vessels. Also reduces arterial pressure and plasma renin.

Availability

Injection: 50 mg/ml in 5- and 10-ml vials

Oral suspension (contains bisulfites): 250 mg/5 ml

Tablets: 125 mg, 250 mg, 500 mg

⊘Indications and dosages

➣ Hypertension

Adults: 250 mg P.O. two to three times daily for 2 days (not to exceed 500 mg/day in divided doses if used with other agents); may increase q 2 days as needed. Usual maintenance dosage is 500 mg to 2 g/day (not to exceed 3 g/day) P.O. in two to four divided doses or 250 to 500 mg I.V. q 6 hours (up to 1 g q 6 hours).

Children: 10 mg/kg/day (300 mg/m²/day) P.O. in two to four divided doses. May increase q 2 days up to 65 mg/kg/day (2 g/m²/day), or 3 g/day in divided doses (whichever is lower) or 5 to 10 mg/kg I.V. q 6 hours; up to 65 mg/kg/day (2 g/m²/day), or 3 g/day in divided doses (whichever is lower).

Contraindications

• Hypersensitivity to drug or its components
• Pheochromocytoma
• Active hepatic disease or history of methyldopa-associated hepatic disorders
• MAO inhibitor use within past 14 days

Precautions

Use cautiously in:
• heart failure, edema, hemolytic anemia, hypotension, severe bilateral cerebrovascular disease
• dialysis patients
• elderly patients
• pregnant or breastfeeding patients.

Administration

☞ Don't give within 14 days of MAO inhibitors.
• To prepare I.V. infusion, add prescribed dosage to 100 ml 5% dextrose injection. Or administer in 5% dextrose injection in a concentration of 100 mg/10 ml. Give each dose over 30 to 60 minutes.
• Dilute and administer ADD-Vantage vials containing 50 mg/ml according to manufacturer's instructions.
☞ Don't stop drug therapy abruptly.

Route	Onset	Peak	Duration
P.O.	Unknown	4-6 hr	24-48 hr
I.V.	Unknown	4-6 hr	10-16 hr

Adverse reactions

CNS: headache, asthenia, weakness, dizziness, sedation, decreased mental acuity, depression, paresthesia, parkinsonism, Bell's palsy, involuntary choreoathetotic movements

CV: bradycardia, edema, orthostatic hypotension, myocarditis

EENT: nasal congestion

GI: nausea, vomiting, diarrhea, constipation, abdominal distention, colitis, dry mouth, sialadenitis, sore or black tongue, pancreatitis GU: breast enlargement, gynecomastia, failure to ejaculate, erectile dysfunction

Hematologic: eosinophilia, hemolytic anemia

Hepatic: hepatitis

Other: fever

Interactions

Drug-drug. Adrenergics, MAO inhibitors: excessive sympathetic stimulation

Amphetamines, barbiturates, nonsteroidal anti-inflammatory drugs, phenothiazines, tricyclic antidepressants: decreased antihypertensive effect

Anesthestics, antihypertensives, nitrates: additive hypotension

Ferrous gluconate, ferrous sulfate: decreased methyldopa blood level

Haloperidol: increased haloperidol effects, increased risk of psychoses

Levodopa: additive hypotension and CNS toxicity

Lithium: increased risk of lithium toxicity

Nonselective beta-adrenergic blockers: paradoxical hypertension

Tolbutamide: increased tolbutamide effects

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, blood urea nitrogen, creatinine, potassium, prolactin, sodium, uric acid: increased levels

Direct Coombs' test: positive result

Liver function tests: abnormal results

Prothrombin time: prolonged

Drug-herbs. Capsicum: reduced antihypertensive effects

Drug-behaviors . Alcohol use: increased hypotension

Patient monitoring

• Obtain direct Coombs' test before therapy starts and 6 and 12 months later.
• Monitor periodic blood counts to detect adverse hematologic reactions.
• Monitor liver function tests and check for signs and symptoms of hepatic dysfunction (particularly during first 6 to 12 weeks of therapy).
• Check for edema or weight gain to help determine if diuretic should be added to regimen.
• Monitor blood pressure. Drug tolerance may occur during second and third months of therapy.

Patient teaching

• Tell patient that sedation usually occurs when therapy starts and during dosage titration. To lessen this effect, advise him to begin dosage titration in evening.
☞ Tell patient not to stop taking drug abruptly.
☞ Instruct patient to report fever, yellowing of skin or eyes, fatigue, abdominal pain, flulike symptoms, swelling, or significant weight gain.
• Inform patient that urine may darken after exposure to air.
• Advise patient to move slowly when changing position, to avoid dizziness from sudden blood pressure decrease.
• Caution patient to avoid driving and other hazardous activities until effects of drug are known or dosage titration is completed.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.