Diucardin (hydroflumethiazide) is an oral thiazide (benzothiadiazide) diuretic-antihypertensive agent.

Diucardin is available as 50 mg tablets for oral administration.

Chemical name:  3,4-Dihydro-6-(trifluoromethyl)-2H-1,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide.

Structural formula:


Hydroflumethiazide is an odorless white to cream-colored, finely divided, crystalline powder. It has a melting point between 270° and 275° C. Hydroflumethiazide is freely soluble in acetone, soluble in alcohol, and very slightly soluble in water.

The inactive ingredients contained in Diucardin tablets are: lactose, magnesium stearate, microcrystalline cellulose, povidone, and starch.

Hydroflumethiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. It appears to have a biphasic biological half-life with an estimated alpha-phase of about 2 hours and an estimated beta-phase of about 17 hours; it has a metabolite with a longer half-life, which is extensively bound to the red blood cells. Hydroflumethiazide is excreted in the urine; its metabolite has also been detected in the urine.

The mechanism of action results in an interference with the renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage, all thiazides are approximately equal in their diuretic potency. The mechanism whereby thiazides function in the control of hypertension is unknown.

Diucardin is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.

Diucardin has also been found useful in edema due to various forms of renal dysfunction such as: nephrotic syndrome; acute glomerulonephritis; and chronic renal failure.

Diucardin is indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.


The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.

Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Thiazides are indicated in pregnancy when edema is due to pathologic causes just as they are in the absence of pregnancy (however, see " PRECAUTIONS --PREGNANCY" below).

Dependent edema in pregnancy, resulting from restriction of venous return by the expanded uterus, is properly treated through elevation of the lower extremities and use of support hose. Use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in absence of cardiovascular disease), but which is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of diuretics may provide relief and may be appropriate.



Hypersensitivity to this or other sulfonamide-derived drugs.

Diucardin should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Thiazides may add to or potentiate the action of other antihypertensive drugs. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs.

Sensitivity reactions may occur in patients with a history of allergy or bronchial asthma.

The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.



All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance; namely, hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Medication such as digitalis may also influence serum electrolytes. Warning signs, irrespective of cause, are: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Hypokalemia may develop with thiazides as with any other potent diuretic, especially with brisk diuresis, when severe cirrhosis is present, or during concomitant use of corticosteroids or ACTH.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially with reference to myocardial activity.

Any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Insulin requirements in diabetic patients may be increased, decreased, or unchanged. Latent diabetes mellitus may become manifested during thiazide administration.

The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient.

If progressive renal impairment becomes evident, as indicated by a rising creatinine or blood urea nitrogen, a careful reappraisal of therapy is necessary with consideration given to withholding or discontinuing diuretic therapy.

Thiazides may decrease serum PBI levels without signs of thyroid disturbance.

Lithium generally should not be given with diuretics because they reduce its renal clearance and increase the risk of lithium toxicity. Read circulars for lithium preparations before use of such concomitant therapy with Diucardin.

Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Calcium excretion is decreased by thiazides. Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. The common complications of hyperparathyroidism, such as renal lithiasis, bone resorption, and peptic ulceration, have not been seen.


Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.


Anticoagulants, oral

(Effects may be decreased when used concurrently with thiazide diuretics; dosage adjustments may be necessary.)

Antigout medications

(Thiazide diuretics may raise the level of blood uric acid; dosage adjustment of antigout medications may be necessary to control hyperuricemia and gout.)

Antihypertensive medications, other, especially diazoxide, or preanesthetic and anesthetic agents used in surgery or skeletal-muscle relaxants, nondepolarizing, used in surgery

(Effects may be potentiated when used concurrently with thiazide diuretics; dosage adjustments may be necessary.)

Amphotericin B or Corticosteroids or Corticotropin (ACTH)

(Concurrent use with thiazide diuretics may intensify electrolyte imbalance, particularly hypokalemia.)

Cardiac glycosides

(Concurrent use with thiazide diuretics may enhance the possibility of digitalis toxicity associated with hypokalemia.)


(May inhibit gastrointestinal absorption of the thiazide diuretics; administration 1 hour before or 4 hours after colestipol is recommended.)


(Thiazide diuretics may raise blood glucose levels; for adult-onset diabetics, dosage adjustment of hypoglycemic medications may be necessary during and after thiazide diuretic therapy; insulin requirements may be increased, decreased, or unchanged.)

Lithium salts

(Concurrent use with thiazide diuretics is not recommended, as they may provoke lithium toxicity because of reduced renal clearance.)


(Effectiveness may be decreased when used concurrently with thiazide diuretics because of alkalinization of the urine.)

Nonsteroidal anti-inflammatory agents

(In some patients, the steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium sparing, and thiazide diuretics. Therefore, when hydroflumethiazide and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.)


(Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.)


(Thiazide drugs may increase the responsiveness to tubocurarine.)

DIAGNOSTIC INTERFERENCE--With expected physiologic effects:

Blood and urine glucose levels (usually only in patients with a predisposition for glucose intolerance) and

Serum bilirubin levels (by displacement from albumin binding) and

Serum calcium levels (thiazide diuretics should be discontinued before parathyroid-function tests are carried out) and

Serum uric acid levels (may be increased)

Serum magnesium, potassium, and sodium levels (may be decreased; serum magnesium levels may increase in uremic patients)

Serum protein-bound iodine (PBI) levels (may be decreased)

Thiazides should be discontinued before carrying out tests for parathyroid function (see " PRECAUTIONS --GENERAL, Calcium excretion").


No studies have been performed to evaluate carcinogenic or mutagenic potential of Diucardin or the potential of Diucardin to impair fertility.


Teratogenic Effects--Pregnancy Category C

Animal reproduction studies have not been conducted with Diucardin. It is also not known whether Diucardin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Diucardin should be given to a pregnant woman only if clearly needed.

Nonteratogenic Effects

Fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult.


Thiazides appear in breast milk. If use of the drug is deemed essential, the patient may consider stopping nursing.


Safety and effectiveness in children have not been established.


The following adverse reactions have been observed, but there is not enough systematic collection of data to support an estimate of their frequency.


Anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialadenitis.


Dizziness, vertigo, paresthesias, headache, xanthopsia.


Leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia.


Orthostatic hypotension (may be aggravated by alcohol, barbiturates, or narcotics).


Purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), fever, respiratory distress including pneumonitis, anaphylactic reactions.


Hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, transient blurred vision.

Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.



Diuresis, lethargy progressing to coma, with minimal cardiorespiratory depression and with or without significant serum electrolyte changes or dehydration; GI irritation; hypermotility; transient elevation in BUN level.


Empty stomach by gastric lavage, taking care to avoid aspiration. Monitor serum electrolyte levels and renal function, and institute supportive measures, as required to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function. Treat GI effects symptomatically.


The average adult diuretic dose is 25 to 200 mg per day. The average adult antihypertensive dose is 50 to 100 mg per day.

Therapy should be individualized according to patient response. This therapy should be titrated to gain maximal response as well as the minimal dose possible to maintain that therapeutic response.


Diucardin®--Each scored, white oval compressed tablet, inscribed "DIUCARDIN 50," contains 50 mg hydroflumethiazide, in bottles of 100 (NDC 0046-0702-81).

Store at room temperature (approximately 25° C)

Dispense in a well-closed container as defined in the USP

Caution:  Federal law prohibits dispensing without prescription.

Manufactured by:

Ayerst Laboratories Inc.

A Wyeth-Ayerst Company

Philadelphia, PA 19101

CI 4104-4  Revised July 27, 1995


NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer and reproduced in full color by PDR as a quick-reference identification aid. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug' identity should be verified by chemical analysis.