ether hemolytic anemia exists and whether the positive coombs test may be a problem. for example, in addition to a positive direct coombs test there is less often a positive indirect coombs test which may interfere with cross matching of blood. before treatment is started, it is desirable to do a blood count (hematocrit, hemoglobin, or red cell count) for a baseline or to establish whether there is anemia. periodic blood counts should be done during therapy to detect hemolytic anemia. it may be useful to do a direct coombs test before therapy and at 6 and 12 months after the start of therapy. if coombs-positive hemolytic anemia occurs, the cause may be methyldopa and the drug should be discontinued. usually the anemia remits promptly. if not, corticosteroids may be given and other causes of anemia should be considered. if the hemolytic anemia is related to methyldopa, the drug should not be reinstituted. when methyldopa causes coombs positivity alone or with hemolytic anemia, the red cell is usually coated with gamma globulin of the igg (gamma g) class only. the positive coombs test may not revert to normal until weeks to months after methyldopa is stopped. should the need for transfusion arise in a patient receiving methyldopa, both a direct and an indirect coombs test should be performed. in the absence of hemolytic anemia, usually only the direct coombs test will be positive. a positive direct coombs test alone will not interfere with typing or cross matching. if the indirect coombs test is also positive, problems may arise in the major cross match and the assistance of a hematologist or transfusion expert will be needed. occasionally, fever has occurred within the first 3 weeks of methyldopa therapy, associated in some cases with eosinophilia or abnormalities in one or more liver function tests, such as serum alkaline phosphatase, serum transaminases (sgot, sgpt), bilirubin, and prothrombin time. jaundice, with or without fever, may occur with onset usually within the first 2 to 3 months of therapy. in some patients the findings are consistent with those of cholestasis. in others the findings are consistent with hepatitis and hepatocellular injury. rarely, fatal hepatic necrosis has been reported after use of methyldopa. these hepatic changes may represent hypersensitivity reactions. periodic determinations of hepatic function should be done particularly during the first 6 to 12 weeks of therapy or whenever an unexplained fever occurs. if fever, abnormalities in liver function tests, or jaundice appear, stop therapy with methyldopa. if caused by methyldopa, the temperature and abnormalities in liver function characteristically have reverted to normal when the drug was discontinued. methyldopa should not be reinstituted in such patients. rarely, a reversible reduction of the white blood cell count with a primary effect on the granulocytes has been seen. the granulocyte count returned promptly to normal on discontinuance of the drug. rare cases of granulocytopenia have been reported. in each instance, upon stopping the drug, the white cell count returned to normal. reversible thrombocytopenia has occurred rarely.

nded to higher doses, the maximum recommended daily dosage is 3 g. once an effective dosage range is attained, a smooth blood pressure response occurs in most patients in 12 to 24 hours. since methyldopa has a relatively short duration of action, withdrawal is followed by return of hypertension usually within 48 hours. this is not complicated by an overshoot of blood pressure. 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 g 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. ( see precautions, geriatric use ) pediatric patients 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 g daily, whichever is less. ( see precautions, pediatric use )

eumatoid factor, positive coombs test. hepatic: liver disorders including hepatitis, jaundice, abnormal liver function tests ( see warnings ). hypersensitivity: myocarditis, pericarditis, vasculitis, lupus-like syndrome, drug-related fever, eosinophilia. nervous system/psychiatric: parkinsonism, bell's palsy, decreased mental acuity, involuntary choreoathetotic movements, symptoms of cerebrovascular insufficiency, psychic disturbances including nightmares and reversible mild psychoses or depression, headache, sedation, asthenia or weakness, dizziness, lightheadedness, paresthesias. metabolic: rise in bun. musculoskeletal: arthralgia, with or without joint swelling; myalgia. respiratory: nasal stuffiness. skin: toxic epidermal necrolysis, rash. urogenital: amenorrhea, breast enlargement, gynecomastia, lactation, impotence, decreased libido.

reduce glomerular filtration rate, renal blood flow, or filtration fraction. cardiac output usually is maintained without cardiac acceleration. in some patients the heart rate is slowed. normal or elevated plasma renin activity may decrease in the course of methyldopa therapy. methyldopa reduces both supine and standing blood pressure. methyldopa usually produces highly effective lowering of the supine pressure with infrequent symptomatic postural hypotension. exercise hypotension and diurnal blood pressure variations rarely occur. pharmacokinetics and metabolism the maximum decrease in blood pressure occurs four to six hours after oral dosage. once an effective dosage level is attained, a smooth blood pressure response occurs in most patients in 12 to 24 hours. after withdrawal, blood pressure usually returns to pretreatment levels within 24-48 hours. methyldopa is extensively metabolized. the known urinary metabolites are: α-methyldopa mono-0-sulfate; 3-0-methyl-α-methyldopa; 3,4-dihydroxyphenylacetone; α-methyldopamine; 3-0-methyl-α-methyldopamine and their conjugates. approximately 70% of the drug which is absorbed is excreted in the urine as methyldopa and its mono-0-sulfate conjugate. the renal clearance is about 130 ml/min in normal subjects and is diminished in renal insufficiency. the plasma half-life of methyldopa is 105 minutes. after oral doses, excretion is essentially complete in 36 hours. methyldopa crosses the placental barrier, appears in cord blood, and appears in breast milk.