Aldoment (Methyldopa HCl)

ALDOMET® Injection ALDOMET® Tablets

MSD

Methyldopa HCl

Methyldopa

Antihypertensive

Indications And Clinical Uses: The treatment of arterial hypertension. May be employed in a general treatment program in conjunction with a diuretic and/or other antihypertensive drugs as needed for proper response in patients with hypertension of various severity.

May be employed as the initial agent in the treatment of hypertension in those patients for which treatment should not be started with a diuretic.

The treatment of hypertensive crises may be initiated with methyldopa injection.

Contra-Indications: Active hepatic disease, such as acute hepatitis and active cirrhosis. If previous methyldopa therapy has been associated with liver disorders or hemolytic anemia (see Precautions). Hypersensitivity to methyldopa.

Precautions: With prolonged methyldopa therapy, 10 to 20% of patients develop a positive direct Coombs’ test which usually occurs between 6 and 12 months of methyldopa therapy. Lowest incidence is at a 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. If a positive Coombs’ test develops during methyldopa therapy, the physician should determine whether 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.

At the start of methyldopa therapy, 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 hemolytic anemia occurs, 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 lgG (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 on his blood. 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 (AST, ALT), bilirubin, cephalin cholesterol flocculation, prothrombin time and bromsulphalein retention. 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.

Rarely, fatal hepatic necrosis has been reported after use of methyldopa. These hepatic changes may represent hypersensitivity reactions. Periodic determination 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. Methyldopa should be used with caution in patients with a history of previous liver disease or dysfunction.

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.

When methyldopa is used with other antihypertensive drugs, potentiation of antihypertensive effect may occur. Patients should be followed carefully to detect adverse effects or unusual manifestations of drug idiosyncrasy. A paradoxical pressor response has been reported with i.v. methyldopate HCl.

When methyldopa and lithium are given concomitantly, the patient should be carefully observed for symptoms of lithium toxicity.

Pregnancy and Lactation: Methyldopa has been used for treatment of hypertension during pregnancy. Such use requires close medical and obstetrical supervision. No unusual adverse reactions have been reported in association with the use of methyldopa during pregnancy. Although no obvious teratogenic effects have been reported, the possibility of fetal injury cannot be excluded and the use of the drug in women who are or may become pregnant or who are nursing their newborn infant requires that anticipated benefits be weighed against possible risks.

Methyldopa does cross the placental barrier and appears in cord blood and breast milk.

Methyldopa should be used with caution in patients with a history of previous liver disease or dysfunction.

Methyldopa may interfere with measurement of urinary uric acid by the phosphotungstate method, serum creatinine by the alkaline picrate method, and AST by colorimetric methods. Interference with spectrophotometric methods for AST analysis has not been reported.

Since methyldopa causes fluorescence in urine samples at the same wave lengths as catecholamines, falsely high concentrations of urinary catecholamines may be reported. This will interfere with the diagnosis of pheochromocytoma. It is important to recognize this phenomenon before a patient with a possible pheochromocytoma is subjected to surgery. Methyldopa does not interfere with measurement of VMA (vanillylmandelic acid), a test for pheochromocytoma, by those methods which convert VMA to vanillin. Methyldopa is not recommended for the treatment of patients with pheochromocytoma. Rarely, when urine is exposed to air after voiding, it may darken because of breakdown of methyldopa or its metabolites.

Rarely, involuntary choreoathetotic movements have been observed during therapy with methyldopa in patients with severe bilateral cerebrovascular disease. Should these movements occur, stop therapy.

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.

Patients may require reduced doses of anesthetics when on methyldopa. If hypotension does occur during anesthesia, it usually can be controlled by vasopressors. The adrenergic receptors remain sensitive during treatment with methyldopa.

Hypertension has recurred occasionally after dialysis in patients given methyldopa because the drug is removed by this procedure.

Sulfites have been reported to cause severe allergic reactions in certain susceptible individuals, particularly patients with asthma. Aldomet injection contains sodium bisulfite. Aldomet tablets contain no sulfites.

Adverse Reactions: 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.

CNS: sedation, headache, asthenia or weakness, dizziness, lightheadedness, symptoms of cerebrovascular insufficiency (may be due to lowering of blood pressure), paresthesias, parkinsonism, Bell’s palsy, decreased mental acuity, involuntary choreoathetotic movements. Psychic disturbances including nightmares and reversible mild psychoses or depression. Toxic encephalopathy.

Cardiovascular: bradycardia, prolonged carotid sinus hypersensitivity, aggravation of angina pectoris. Orthostatic hypotension (decrease daily dosage). Edema (and weight gain) usually relieved by use of a diuretic. (Discontinue methyldopa if edema progresses or signs of heart failure appear.)

Gastrointestinal: nausea, vomiting, distention, constipation, flatus, diarrhea, colitis, mild dryness of mouth, sore or “black” tongue, pancreatitis, sialadenitis.

Hepatic: abnormal liver function tests, jaundice, hepatocellular damage.

Hematologic: positive Coombs’ test, hemolytic anemia, bone marrow depression, leukopenia, granulocytopenia, thrombocytopenia. Positive tests for antinuclear antibody, LE cells and rheumatoid factor.

Allergic: drug related fever, myocarditis, pericarditis, lupus like syndrome.

Dermatologic: rash as in eczema or lichenoid eruption; toxic epidermal necrolysis.

Other: nasal stuffiness, rise in BUN, breast enlargement, gynecomastia, lactation, hyperprolactinemia, amenorrhea, impotence, decreased libido, dermatologic reactions including eczema and lichenoid eruptions, mild arthralgia, with or without joint swelling, myalgia.

Symptoms And Treatment Of Overdose: Symptoms: Acute overdosage may produce acute hypotension with other major responses attributable to brain and gastrointestinal malfunction (excessive sedation, weakness, bradycardia, dizziness, lightheadedness, constipation, distention, flatus, diarrhea, nausea, vomiting).

Potentiation of antihypertensive action may occur in combination therapy with other antihypertensives.

Chronic overdosage may produce hypotension and syncope, especially in the presence of advanced arteriosclerosis.

Treatment: Discontinue the drug. If ingestion is recent, gastric lavage or emesis may reduce absorption; when ingestion has been earlier, infusions may be helpful to promote urinary excretion. Otherwise, management includes symptomatic treatment with special attention to cardiac rate and output, blood volume, electrolyte balance, paralytic ileus, urinary function, and cerebral activity. Administration of sympathomimetic drugs may be indicated.

Dosage And Administration: Oral: Adults: The usual starting dosage is 250 mg 2 or 3 times a day in the first 48 hours. The daily dosage then may be increased or decreased, preferably at intervals of not less than 2 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.

The usual daily maintenance dosage of methyldopa is 500 mg to 2 g in 2 to 4 doses. Although occasional patients have responded to higher doses, the maximum recommended daily dosage is 3 g.

The 125 mg tablet is valuable when small increments of methyldopa are required for adjustment of antihypertensive response. This dosage form is not designed for use as initial therapy in previously untreated hypertensive patients.

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 added to a thiazide, the dosage of thiazide usually need not be changed. 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. When methyldopa is given with antihypertensives other than thiazides, its initial dosage should be limited to 500 mg daily in divided doses.

Studies suggest that once optimum dosage is ascertained, the antihypertensive effect can be maintained by giving the same total daily dose once every 24 hours.

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.

Smaller doses may be needed in patients with impaired renal function or in older patients with an increased sensitivity or an advanced arteriosclerotic vascular disease (see Precautions).

Children: Initial dosage is based on 10 mg/kg daily in 2 to 4 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.

Parenteral: Adults: This preparation has been given i.v. in single doses of 100 mg to 3 g. The usual adult dosage is 250 to 500 mg i.v. at 6 hour intervals as required; doses up to 1 g may be used in severe cases if necessary to obtain a beneficial effect, but at the present time the maximum recommended dose is 1 g every 6 hours. If renal function is impaired, the dose required for effective lowering of the blood pressure may be less than that for patients with little renal dysfunction.

The desired dose should be added to 100 mL of 5% Dextrose Injection USP. This i.v. infusion should be given slowly over a period of 30 to 60 minutes.

Methyldopa, when administered i.v. in effective doses, will produce a decline in blood pressure that may begin in 4 to 6 hours and extend 10 to 16 hours after injection.

When control has been obtained, oral therapy may be substituted for i.v. therapy, starting with the same dosage schedule being used for the parenteral route.

Availability And Storage: Ampuls: Each mL of clear, colorless solution contains: methyldopate HCl 50 mg, citric acid anhydrous 5 mg, sodium bisulfite 3.2 mg, disodium edetate 500 µg, monothioglycerol 2 mg, sodium hydroxide to adjust pH, with methylparaben 1.5 mg and propylparaben 200 µg and water for injection. Ampuls of 5 mL.

Tablets: Each yellow, film-coated, biconvex shaped tablet, engraved Aldomet on one side and MSD 401 on the other side, contains: methyldopa 250 mg. Gluten-, lactose-, sulfite- and tartrazine-free. Bottles of 100 and 500.

ALDOMET® Injection ALDOMET® Tablets MSD Methyldopa HCl Methyldopa Antihypertensive

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