Methyldopa

 

Manufacturer	Pharmaniaga Manufacturing Berhad
Distributor	Pharmaniaga Logistics
Contents	Methyldopa
Indications	Mild to moderate HTN.
Dosage	Adult Initially 250 mg daily for 2 days. May increase by 250 mg at 2-day intervals. Max: 2 g/day. Childn Initially 10 mg/kg bd-tds. Max: 65 mg/kg/day.
Administration	May be taken with or without food.
Contraindications	Phaeochromocytoma, depression, active hepatitis, hepatic or renal insufficiency.
Special Precautions	In halothane narcosis, risk of hepatotoxicity & intensity of narcosis may be enhanced.
Adverse Drug Reactions	Sedation, headache, weakness, dizziness, parkinsonism, bradycardia, orthostatic hypotension, GI symptoms, hepatic impairment, impotence. View ADR Monitoring Website
Drug Interactions	Other antihypertensives, anaesth, lithium. View more drug interactions with Pharmaniaga Methyldopa
Pregnancy Category (US FDA)	Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).
MIMS Class	Other Antihypertensives
ATC Classification	C02AB01 - methyldopa (levorotatory) ; Belongs to the class of methyldopa, centrally-acting antiadrenergic agents. Used in the treatment of hypertension.
Poison Schedule	B

Presentation/Packing

Form Photo Packing/Price Pharmaniaga Methyldopa film-coated tab 250 mg 50 × 10's (RM180.00/box)

 

 

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-O-sulfate; 3-0-methyl-α-Methyldopa; 3,4-dihydroxyphenylacetone; α-Methyldopamine; 3-0-methyl-α-Methyldopamine and their conjugates.

Approximately 70 percent of the drug which is absorbed is excreted in the urine as Methyldopa and its mono-O-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.

Contraindications

Methyldopa is contraindicated in patients:

• with active hepatic disease, such as acute hepatitis and active cirrhosis.
• with liver disorders previously associated with Methyldopa therapy (see WARNINGS).
• with hypersensitivity to any component of this product.
• on therapy with monoamine oxidase (MAO) inhibitors.

Warnings

It is important to recognize that a positive Coombs test, hemolytic anemia, and liver disorders may occur with Methyldopa therapy.

With prolonged Methyldopa therapy, 10 to 20 percent of patients develop a positive direct Coombs test which usually occurs between 6 and 12 months of Methyldopa therapy.
Lowest incidence is at daily dosage of 1 g or less. This on rare occasions may be associated with hemolytic anemia, which could lead to potentially fatal complications.

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.

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.


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 three 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 two to three 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.

Precautions

General

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

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. Should these movements occur, stop therapy.

REF:
http://www.drugs.com/pro/methyldopa.html
http://www.mims.com/MALAYSIA/drug/info/Pharmaniaga%20Methyldopa/#Content