Description

Methyldopa, or α-methyldopa, is a centrally acting sympatholytic agent and an antihypertensive agent. It is an analog of DOPA (3,4‐hydroxyphenylanine), and it is a prodrug, meaning that the drug requires biotransformation to an active metabolite for therapeutic effects. Methyldopa works by binding to alpha(α)-2 adrenergic receptors as an agonist, leading to the inhibition of adrenergic neuronal outflow and reduction of vasoconstrictor adrenergic signals. Methyldopa exists in two isomers D-α-methyldopa and L-α-methyldopa, which is the active form. First introduced in 1960 as an antihypertensive agent, methyldopa was considered to be useful in certain patient populations, such as pregnant women and patients with renal insufficiency. Since then, methyldopa was largely replaced by newer, better-tolerated antihypertensive agents; however, it is still used as monotherapy or in combination with hydrochlorothiazide. Methyldopa is also available as intravenous injection, which is used to manage hypertension when oral therapy is unfeasible and to treat hypertensive crisis.

When Methyldopa is used with other antihypertensive drugs, potentiation of antihypertensive effect may occur. Patients may require reduced doses of anesthetics when on Methyldopa. When Methyldopa and lithium are given concomitantly the patient should be carefully monitored for symptoms of lithium toxicity. Coadministration of Methyldopa with ferrous sulfate or ferrous gluconate is not recommended.

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.

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. The following systemic side effects may rarely occur with the use of Methyldopa- angina pectoris, congestive heart failure, orthostatic hypotension, edema or weight gain, bradycardia, pancreatitis, colitis, vomiting, diarrhea, nausea, constipation, dryness of mouth, hyperprolactinemia, bone marrow depression, leukopenia, granulocytopenia, thrombocytopenia, hemolytic anemia; rheumatoid factor, hepatitis, jaundice, myocarditis, pericarditis, vasculitis, eosinophilia, parkinsonism, bell's palsy, nightmares and reversible mild psychoses or depression, dizziness, lightheadedness, paresthesias, arthralgia, myalgia, nasal stuffiness, rash, amenorrhea, gynecomastia, lactation, impotence. However, significant adverse effects due to Methyldopa have been infrequent and this agent usually is well tolerated.

Pregnancy category B. Methyldopa appears in breast milk. Therefore, caution should be exercised when Methyldopa is given to a nursing woman.

Methyldopa should be used with caution in patients with a history of previous liver disease or dysfunction. Some patients taking Methyldopa experience clinical edema or weight gain, which may be controlled by use of a diuretic. Methyldopa should not be continued if edema progresses or signs of heart failure appear. Hypertension has recurred occasionally after dialysis in patients given Methyldopa because the drug is removed by this procedure. Rarely involuntary choreoathetotic movements have been observed during therapy with Methyldopa in patients with severe bilateral cerebrovascular disease. If these movements occur, stop therapy

Pediatric Use: There are no well-controlled clinical trials in pediatric patients. Information on dosing in pediatric patients is supported by evidence from published literature regarding the treatment of hypertension in pediatric patients.