Adult Dosing
Hypertension
- Start dose: 15 mg/250 mg PO bid-tid or 25 mg/250 mg PO bid
- Alt: 30 mg/500 mg PO qd or 50 mg/500 mg PO daily
Note: Avoid hydrochlorothiazide doses >50 mg/day
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
- Positive coombs test, hemolytic anemia, and liver disorders are associated with methyldopa component of this combination drug therapy. Unless properly recognized and managed the rare occurrences of hemolytic anemia or liver disorders may lead to potentially fatal complications. Positive direct Coombs test usually occurs between 6-12 months of methyldopa therapy. Development of hemolytic anemia may lead to potentially fatal complications. Determine whether hemolytic anemia exists and whether the positive Coombs test may be a problem if a positive Coombs test develops during therapy. Before initiation of therapy it is desirable to obtain a blood count (hematocrit, hemoglobin, or red cell count) for a baseline or to establish whether there is anemia. Periodically determine blood counts during therapy for detection of hemolytic anemia. It is recommended to do a direct Coombs test before therapy and at 6 and 12 months after initiation of therapy. Discontinue the drug if Coombs-positive hemolytic anemia occurs and avoid reinstitution of therapy if the hemolytic anemia is related to methyldopa. The positive Coombs test does not revert to normal until weeks to months after cessation of therapy. Perform both a direct and indirect Coombs test if the need for transfusion arises in a patient receiving methyldopa. Problems may arise in the major cross match and the assistance of a hematologist or transfusion expert will be needed if the indirect Coombs test is also positive
- Fever may occur within the first 3wks of therapy associated in some cases with eosinophilia or abnormalities in one or more LFTs such as serum alkaline phosphatase, serum transaminases (SGOT, SGPT), bilirubin, and prothrombin time. Jaundice, with or without fever can occur with onset usually within the first 2-3 months of therapy. Findings are consistent with those of cholestasis, hepatitis and hepatocellular injury. Rare occasions of fatal hepatic necrosis may occur. Periodically determine hepatic function particularly during the first 6-12 wks of therapy or whenever an unexplained fever occurs. On development of fever, abnormalities in LFTs or jaundice cease therapy with this drug
- Reversible reduction of the WBC count with a primary effect on the granulocytes may occur. Rare cases of granulocytopenia, reversible thrombocytopenia may occur
- Cumulative effects of the drug may occur in patients with impaired renal function
- Minor alterations of fluid and electrolyte balance may precipitate hepatic coma
- Thiazide component is associated with addition to or potentiating the action of other antihypertensive drugs
- Sensitivity reactions has occurred in patients with or without a history of allergy or bronchial asthma
- The possibility of exacerbation or activation of systemic lupus erythematosus may occur
- Avoid concurrent administration of lithium
- Discontinue therapy if edema progresses or signs of heart failure appear
- Hypertension may recurred occasionally following dialysis
- Rare occasions of involuntary choreoathetotic movements may occur during therapy with methyldopa in patients with severe bilateral cerebrovascular disease; on occurrence of these movements stop therapy
- At appropriate intervals periodically determine serum electrolytes to detect possible electrolyte imbalance. Observe patients receiving thiazide therapy for clinical signs of fluid or electrolyte imbalance. Determine serum and urine electrolyte when the patient is vomiting excessively or receiving parenteral fluids. Hypokalemia with brisk diuresis have occurred in presence of severe cirrhosis, during concurrent use of corticosteroids or adrenocorticotropic hormone (ACTH) or after long term therapy. Cardiac arrhythmia has occurred in association with hypokalemia resulting in sensitization or exaggeration of the response of the heart to the toxic effects of digitalis. Chloride replacement may be essential for treatment of metabolic alkalosis. Dilutional hyponatremia have occurred in edematous patients in hot weather; Impose water restriction rather than administration of salt except in rare occasions when the hyponatremia is fatal. In actual salt depletion provide appropriate replacement therapy. Thiazide component is associated with hyperuricemia or precipitation of acute gout in certain patients
- Manifestations of latent diabetes mellitus may occur and diabetic patients given thiazides may require adjustment of their insulin dose
- Antihypertensive effects of the drug may be enhanced in the postsympathectomy patients
- Consider withholding or discontinuing therapy if progressive renal impairment becomes evident
- Hypomagnesemia is associated with thiazide component of this drug
- Intermittent and slight elevation of serum calcium may occur. Discontinue therapy before carrying out tests for parathyroid function
- Increases in cholesterol and triglyceride levels are associated with this drug
Cautions: Use cautiously in
- Severe renal impairment
- Hepatic impairment
- Progressive liver disease
- History of previous liver disease or dysfunction
- Bradycardia
- Concurrent levodopa therapy
- Concurrent use with other antihypertensives
- Elderly patients
Pregnancy Category:C
Breastfeeding: Methyldopa is excreted in breastmilk in small amounts and thus would not be expected to cause any adverse events in breastfed infants. Hydrochlorothiazide doses of 
50 mg/day are acceptable during lactation. Intense diuresis with higher doses may decrease breastmilk production. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 27 May 2011). According to manufacturer's data a decision should be made for discontinuing nursing or the drug taking into account the importance of the drug to the mother.
US Trade Name(s)
US Availability
hydrochlorothiazide/methyldopa (generic)
Canadian Trade Name(s)
- Methazide 15
- Methazide 25
- Dopazide 15
- Dopazide 25
Canadian Availability
Methazide 15 (hydrochlorothiazide/methyldopa)
Methazide 25 (hydrochlorothiazide/methyldopa)
Dopazide 15 (hydrochlorothiazide/methyldopa)
Dopazide 25 (hydrochlorothiazide/methyldopa)
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability
[Outline]