Methyldopa

INDICATION AND USAGE Hypertension.

has yet to be conclusively demonstrated, the antihypertensive effect of methyldopa probably is due to its metabolism to alpha-methylnorepinephrine, which then lowers arterial pressure by stimulation of central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. Methyldopa has been shown to cause a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine. Only methyldopa, the L -isomer of alpha-methyldopa, has the ability to inhibit dopa decarboxylase and to deplete animal tissues of norepinephrine. In man the antihypertensive activity appears to be due solely to the L -isomer. About twice the dose of the racemate ( DL -alpha-methyldopa) is required for equal antihypertensive effect.

ADULTS Initiation of Therapy The usual starting dosage of Methyldopa is 250 mg two or three times a day in the first 48 hours. The daily dosage then may be increased or decreased, preferably at intervals of not less than two days, until an adequate response is achieved. To minimize the sedation, start dosage increases in the evening. By adjustment of dosage, morning hypotension may be prevented without sacrificing control of afternoon blood pressure. When methyldopa is given to patients on other antihypertensives, the dose of these agents may need to be adjusted to effect a smooth transition. When Methyldopa is given with antihypertensives other than thiazides, the initial dosage of Methyldopa should be limited to 500 mg daily in divided doses, when Methyldopa is added to a thiazide, the dosage of thiazide need not be changed.

Methyldopa is contraindicated in patients: — with active hepatic disease, such as acute hepatitis and active cirrhosis — with liver disorders previously associated with methyldopa therapy — with hypersensitivity to any component of these products. — on therapy with monoamine oxidase (MAO) inhibitors.

It is important to recognize that a positive Coombs test, hemolytic anemia, and liver disorders may occur with methyldopa therapy. The rare occurrences of hemolytic anemia or liver disorders could lead to potentially fatal complications unless properly recognized and managed. Read this section carefully to understand these reactions. With prolonged methyldopa therapy, 10 to 20 percent of patients develop a positive direct Coombs test which usually occurs between 6 and 12 months of methyldopa therapy. Lowest incidence is at daily dosage of 1 g or less. This on rare occasions may be associated with hemolytic anemia, which could lead to potentially fatal complications. One cannot predict which patients with a positive direct Coombs test may develop hemolytic anemia. Prior existence or development of a positive direct Coombs test is not in itself a contraindication to use of methyldopa.

Sedation, usually transient, may occur during the initial period of therapy or whenever the dose is increased. Headache, asthenia, or weakness may be noted as early and transient symptoms. However, significant adverse effects due to Methyldopa have been infrequent and this agent usually is well tolerated. The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity. Cardiovascular: Aggravation of angina pectoris, congestive heart failure, prolonged carotid sinus hypersensitivity, orthostatic hypotension (decrease daily dosage), edema or weight gain, bradycardia. Digestive: Pancreatitis, colitis, vomiting, diarrhea, sialadenitis, sore or “black” tongue, nausea, constipation, distension, flatus, dryness of mouth. Endocrine: Hyperprolactinemia.

Storage Store Methyldopa Tablets at controlled room temperature 20° to 25°C (68° to 77°F).