Methyldopa is indicated for the treatment of hypertension.

Methyldopa, also known as α-methyldopa, is a centrally acting sympatholytic and antihypertensive agent. It is an analog of DOPA (3,4-dihydroxyphenylalanine) and acts as a prodrug, requiring conversion in the body to its active metabolite to produce therapeutic effects. Methyldopa stimulates alpha-2 adrenergic receptors in the central nervous system, which leads to reduced sympathetic outflow and decreased vasoconstrictor signals. Methyldopa exists in two isomeric forms: D-α-methyldopa and L-α-methyldopa, with the L-form being pharmacologically active.

Introduced in 1960 as an antihypertensive agent, Methyldopa has been widely used, particularly in specific populations such as pregnant women and patients with renal impairment. Although newer antihypertensive agents have largely replaced it due to better tolerability, it is still used either alone or in combination with other drugs such as hydrochlorothiazide. Methyldopa is also available in intravenous form for use when oral administration is not feasible or in the management of hypertensive crises.

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. 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 to be changed.
• Maintenance Therapy: The usual daily dosage of Methyldopa is 500 mg to 2 g in two to four doses. Although occasional patients have responded to higher doses, the maximum recommended daily dosage is 3 gm. Occasionally tolerance may occur, usually between the second and third month of therapy. Adding a diuretic or increasing the dosage of Methyldopa frequently will restore effective control of blood pressure. A thiazide may be added at any time during Methyldopa therapy and is recommended if therapy has not been started with a thiazide or if effective control of blood pressure cannot be maintained on 2 gm of Methyldopa daily. Methyldopa is largely excreted by the kidney and patients with impaired renal function may respond to smaller doses. Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses.

Pediatric Use: Initial dosage is based on 10 mg/kg of body weight daily in two to four doses. The daily dosage then is increased or decreased until an adequate response is achieved. The maximum dosage is 65 mg/kg or 3 gm daily, whichever is less.

When Methyldopa is used together with other antihypertensive agents, an additive effect on lowering blood pressure may occur. Patients receiving Methyldopa may require reduced doses of anesthetics. Concomitant use of Methyldopa with lithium requires careful monitoring for signs of lithium toxicity. The combined use of Methyldopa with ferrous sulfate or ferrous gluconate is not recommended.

Methyldopa is contraindicated in patients:

• With active liver disease such as acute hepatitis or active cirrhosis
• With a history of liver disorders associated with previous Methyldopa therapy
• With hypersensitivity to Methyldopa or any component of the formulation
• Receiving monoamine oxidase (MAO) inhibitors

Sedation, usually temporary, may occur at the beginning of therapy or with dose increase. Early transient symptoms may include headache, weakness, or fatigue. Rare systemic adverse effects include angina pectoris, congestive heart failure, orthostatic hypotension, edema or weight gain, bradycardia, pancreatitis, colitis, nausea, vomiting, diarrhea, constipation, dry mouth, hyperprolactinemia, bone marrow suppression, leukopenia, granulocytopenia, thrombocytopenia, hemolytic anemia, hepatitis, jaundice, myocarditis, pericarditis, vasculitis, eosinophilia, parkinsonism, Bell’s palsy, nightmares, mild reversible psychosis or depression, dizziness, paresthesia, joint and muscle pain, nasal congestion, rash, amenorrhea, gynecomastia, lactation, and impotence. However, serious adverse effects are uncommon and Methyldopa is generally well tolerated.

Pregnancy Category B. Methyldopa is excreted in breast milk; therefore, caution should be exercised when administered to breastfeeding mothers.

Methyldopa should be used cautiously in patients with a history of liver disease or dysfunction. Some patients may develop edema or weight gain, which can often be controlled with diuretics. If edema worsens or signs of heart failure appear, the drug should be discontinued. Blood pressure may rise again after dialysis since Methyldopa is removed during the procedure. Rare involuntary movements (choreoathetosis) have been reported in patients with severe cerebrovascular disease; therapy should be discontinued if such symptoms occur.

Pediatric Use: Adequate and well-controlled clinical studies in pediatric patients are lacking. Dosing recommendations are based on published clinical experience in treating hypertension in children.

Acute overdose may cause hypotension along with symptoms related to central nervous system and gastrointestinal disturbances such as excessive sedation, weakness, bradycardia, dizziness, constipation, abdominal distension, diarrhea, nausea, and vomiting. Management includes symptomatic and supportive care. If ingestion is recent, gastric lavage or induced vomiting may reduce absorption; in later stages, fluid therapy may help enhance elimination.

Centrally acting antihypertensive drugs (central sympatholytic)

Store below 30°C. Keep out of the reach of children.