Methyldopa

Methyldopa tablets can be taken with or without food.

Methyldopa may cause a positive direct Coombs' test (see Warnings and Precautions). False positive urinary catecholamine testing may occur due to the presence of methyldopa in the urine. Methyldopa may interfere with AST measurement by colorimetry and creatinine using the alkaline picrate method.

Tolerance to methyldopa may occur, usually between the second and third month. Increasing the dose or adding a diuretic may help.

It is recommended to give a supplement dose of methyldopa 250 mg following hemodialysis.

acute pancreatitis, colitis, constipation, diarrhea, distention, dry mouth, flatulence, nausea, sore or black tongue, vomiting.

positive Coombs' test (10–20%), hemolytic anemia (0.1–0.2% of patients who develop a positive Coombs' test), leukopenia (rare, primarily granulocytopenia), immune thrombocytopenia (rare), bone marrow depression, positive lupus and rheumatoid factor tests, hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

drug related fever, myocarditis, pericarditis, lupus-like syndrome.

Common (occurs early in therapy): asthenia, drowsiness, vertigo, weakness, headache. Rare: Bell's palsy, depression, impaired concentration, involuntary choreoathetoid movements (indicates a need to discontinue methyldopa), memory impairment, nightmares, paresthesia, parkinsonism, reversible mild psychosis.

nasal congestion (common), decreased libido (frequent), impotence (16%). Rare: amenorrhea, breast enlargement, gynecomastia, hyperprolactinemia, lactation, increased BUN and serum amylase, blurred vision, nocturia.

eczema, hyperkeratosis, lichenoid eruptions, rash, toxic epidermal necrolysis, ulceration of the soles of the feet, urticaria.

aggravation of angina pectoris, bradycardia (occasional), heart failure, hypertension (rare, following abrupt discontinuation of oral dose), orthostatic hypotension (indicates a need to reduce dosage), prolonged carotid sinus hypersensitivity, sodium and fluid retention (can be controlled with diuretics).

Rare: abnormal liver function tests, cholestasis, jaundice, hepatitis, hepatic necrosis.

Methyldopa is rarely indicated in the elderly as there are better alternatives for treating hypertension in this age group. If methyldopa is used, start with lower doses since a higher incidence of CNS side effects, postural hypertension and syncope are reported in the elderly.

Lower doses may be required in patients with renal dysfunction. Methyldopa is removed during hemodialysis resulting in loss of blood pressure control. A supplement dose is recommended after hemodialysis (see Dosage and Administration).

It is recommended to perform a complete blood count and direct Coombs' test prior to and periodically while on methyldopa therapy. Ten to 20% of patients on prolonged methyldopa therapy develop a positive direct Coombs' test, usually 6 to 12 months after starting therapy. Patients with positive Coombs' test should be evaluated for hemolytic anemia. If hemolytic anemia exists, methyldopa must be discontinued and therapy should not be restarted. The anemia should resolve within several weeks after discontinuation of methyldopa. If not, corticosteroid therapy may be indicated. The positive Coombs' test may take weeks to months to return to normal after stopping methyldopa therapy.

Obtain a complete blood count, direct Coombs' test and liver function tests prior to initiating therapy and periodically while on therapy (see Warnings and Precautions).

There are no well-controlled trials in pediatric patients. Recommended dosages are based on published literature reports of methyldopa therapy in hypertensive pediatric patients (see Dosage and Administration).

Methyldopa may cause sedation, especially in the first 2 to 3 days of initiating therapy. Advise patients to avoid activities that require mental alertness until they know how methyldopa affects them.

Methyldopa is the most extensively used antihypertensive in pregnancy and is the initial drug of choice for the treatment of chronic hypertension in pregnant women. Neonates born to women on methyldopa therapy may have decreased systolic blood pressure for the first 2 to 3 days. There have also been reports of tremors. No substantial adverse effects have been detected in long-term follow up of children exposed in utero.

Methyldopa is excreted in the breast milk. However; the amount is not clinically significant. The American Academy of Pediatrics considers methyldopa to be compatible with breast-feeding.

Use methyldopa with caution in patients with a history of liver disease. Fever, sometimes associated with eosinophilia or abnormal liver function tests has occurred within 3 weeks of initiating therapy. Jaundice with or without fever has also occurred, usually after 2 to 3 months of therapy. Hepatic necrosis has been reported rarely. It is recommended to check liver function tests prior to and periodically while on methyldopa therapy, especially during the first 6 to 12 weeks or if the patient develops an unexplained fever. Discontinue methyldopa if unexplained fever or jaundice occurs, or if liver function tests are abnormal.

There is minimal protein binding of methyldopa. The drug crosses the blood-brain barrier and the placenta and is found in breast milk.

The extent of methyldopa absorption following an oral dose is variable, but is approximately 50%. Peak plasma concentrations occur 3 to 6 hours after a dose.

Methyldopa is metabolized to alpha-methylnoradrenaline in the central nervous system. It is thought that this metabolite is responsible for the antihypertensive properties of methyldopa by stimulating α-adrenergic receptors. This stimulation results in a reduction in sympathetic tone and total peripheral resistance. Other properties that may contribute to its therapeutic activity are an ability to reduce plasma renin activity and the inhibition of both central and peripheral norepinephrine and serotonin production .

Methyldopa is primarily excreted in the urine as unchanged drug and as the mono-O-sulphate conjugate. Removal from plasma is biphasic. In patients with normal renal function the first phase plasma half life is 1.8 hours. The half life for the second phase is longer, but undefined. Renal impairment will slow excretion of methyldopa and its metabolites.

The metabolism of methyldopa is extensive and occurs in the liver and GI tract. The main route is by conjugation to methyldopa mono-O-sulphate. This metabolite may be therapeutically active. Other metabolites have been identified.