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 (hydroflumethiazide) .
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.
(Effects may be decreased when used concurrently with thiazide diuretics; dosage adjustments may be necessary.)
(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.)
(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.)
(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").
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
No studies have been performed to evaluate carcinogenic or mutagenic potential of Diucardin (hydroflumethiazide) or the potential of Diucardin (hydroflumethiazide) to impair fertility.
Teratogenic Effects Pregnancy Category C
Animal reproduction studies have not been conducted with Diucardin (hydroflumethiazide) . It is also not known whether Diucardin (hydroflumethiazide) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Diucardin (hydroflumethiazide) should be given to a pregnant woman only if clearly needed.
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.