Usage in Pregnancy:

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. Diuretics are indicated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy. 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 the 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.

Antikaliuretic Therapy and Potassium Supplementation:

DYAZIDE should not be given to patients receiving other potassium-sparing agents such as spironolactone, amiloride, or other formulations containing triamterene. Concomitant potassium-containing salt substitutes should also not be used.

Potassium supplementation should not be used with DYAZIDE except in severe cases of hypokalemia. Such concomitant therapy can be associated with rapid increases in serum potassium levels. If potassium supplementation is used, careful monitoring of the serum potassium level is necessary.

Impaired Renal Function:

DYAZIDE is contraindicated in patients with anuria, acute and chronic renal insufficiency, or significant renal impairment.

Hypersensitivity:

Hypersensitivity to either drug in the preparation or to other sulfonamide-derived drugs is a contraindication.

Hyperkalemia:

DYAZIDE should not be used in patients with pre-existing elevated serum potassium.

If hyperkalemia is suspected (warning signs include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, and shock), an electrocardiogram (ECG) should be obtained. However, it is important to monitor serum potassium levels because hyperkalemia may not be associated with ECG changes.

If hyperkalemia is present, DYAZIDE should be discontinued immediately and a thiazide alone should be substituted. If the serum potassium exceeds 6.5 mEq/L, more vigorous therapy is required. The clinical situation dictates the procedures to be employed. These include the intravenous administration of calcium chloride solution, sodium bicarbonate solution, and/or the oral or parenteral administration of glucose with a rapid-acting insulin preparation. Cationic exchange resins such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia may require dialysis.

The development of hyperkalemia associated with potassium-sparing diuretics is accentuated in the presence of renal impairment (see CONTRAINDICATIONS). Patients with mild renal functional impairment should not receive this drug without frequent and continuing monitoring of serum electrolytes. Cumulative drug effects may be observed in patients with impaired renal function. The renal clearances of hydrochlorothiazide and the pharmacologically active metabolite of triamterene, the sulfate ester of hydroxytriamterene, have been shown to be reduced and the plasma levels increased following administration of DYAZIDE to elderly patients and patients with impaired renal function.

Hyperkalemia has been reported in diabetic patients with the use of potassium-sparing agents even in the absence of apparent renal impairment. Accordingly, serum electrolytes must be frequently monitored if DYAZIDE is used in diabetic patients.

Metabolic or Respiratory Acidosis:

Potassium-sparing therapy should also be avoided in severely ill patients in whom respiratory or metabolic acidosis may occur. Acidosis may be associated with rapid elevations in serum potassium levels. If DYAZIDE is employed, frequent evaluations of acid/base balance and serum electrolytes are necessary.

Acute Myopia and Secondary Angle-Closure Glaucoma:

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Diabetes:

Caution should be exercised when administering DYAZIDE to patients with diabetes, since thiazides may cause hyperglycemia, glycosuria, and alter insulin requirements in diabetes. Also, diabetes mellitus may become manifest during thiazide administration.

Impaired Hepatic Function:

Thiazides should be used with caution in patients with impaired hepatic function. They can precipitate hepatic coma in patients with severe liver disease. Potassium depletion induced by the thiazide may be important in this connection. Administer DYAZIDE cautiously and be alert for early signs of impending coma such as confusion, drowsiness, and tremor; if mental confusion increases, discontinue DYAZIDE for a few days. Attention must be given to other factors that may precipitate hepatic coma, such as blood in the gastrointestinal tract or pre-existing potassium depletion.

Hypokalemia:

Hypokalemia is uncommon with DYAZIDE; but, should it develop, corrective measures should be taken such as potassium supplementation or increased intake of potassium-rich foods. Institute such measures cautiously with frequent determinations of serum potassium levels, especially in patients receiving digitalis or with a history of cardiac arrhythmias. If serious hypokalemia (serum potassium less than 3.0 mEq/L) is demonstrated by repeat serum potassium determinations, DYAZIDE should be discontinued and potassium chloride supplementation initiated. Less serious hypokalemia should be evaluated with regard to other coexisting conditions and treated accordingly.

Electrolyte Imbalance:

Electrolyte imbalance, often encountered in conditions such as heart failure, renal disease, or cirrhosis of the liver, may also be aggravated by diuretics and should be considered during therapy with DYAZIDE when using high doses for prolonged periods or in patients on a salt-restricted diet. Serum determinations of electrolytes should be performed and are particularly important if the patient is vomiting excessively or receiving fluids parenterally. Possible fluid and electrolyte imbalance may be indicated by warning signs such as: dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal symptoms.

Hypochloremia:

Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis. 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.

Renal Stones:

Triamterene has been found in renal stones in association with the other usual calculus components. DYAZIDE should be used with caution in patients with a history of renal stones.

Laboratory Tests:

Drug Interactions:

Information for Patients:

Drug/Laboratory Test Interactions:

Triamterene and quinidine have similar fluorescence spectra; thus, DYAZIDE will interfere with the fluorescent measurement of quinidine.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Pregnancy:

Nursing Mothers:

Thiazides and triamterene in combination have not been studied in nursing mothers. Triamterene appears in animal milk; this may occur in humans. Thiazides are excreted in human breast milk. If use of the combination drug product is deemed essential, the patient should stop nursing.

Pediatric Use:

Safety and effectiveness in pediatric patients have not been established.

Hypersensitivity:

Anaphylaxis, rash, urticaria, subacute cutaneous lupus erythematosus-like reactions, photosensitivity.

Cardiovascular:

Arrhythmia, postural hypotension.

Metabolic:

Diabetes mellitus, hyperkalemia, hypokalemia, hyponatremia, acidosis, hypercalcemia, hyperglycemia, glycosuria, hyperuricemia, hypochloremia.

Gastrointestinal:

Jaundice and/or liver enzyme abnormalities, pancreatitis, nausea and vomiting, diarrhea, constipation, abdominal pain.

Renal:

Acute renal failure (one case of irreversible renal failure has been reported), interstitial nephritis, renal stones composed primarily of triamterene, elevated BUN and serum creatinine, abnormal urinary sediment.

Hematologic:

Leukopenia, thrombocytopenia and purpura, megaloblastic anemia.

Musculoskeletal:

Muscle cramps.

Central Nervous System:

Weakness, fatigue, dizziness, headache, dry mouth.

Miscellaneous:

Impotence, sialadenitis.

Thiazides alone have been shown to cause the following additional adverse reactions:

Central Nervous System:

Paresthesias, vertigo.

Ophthalmic:

Xanthopsia, transient blurred vision.

Respiratory:

Allergic pneumonitis, pulmonary edema, respiratory distress.

Other:

Necrotizing vasculitis, exacerbation of lupus.

Hematologic:

Aplastic anemia, agranulocytosis, hemolytic anemia.

Neonate and infancy:

Thrombocytopenia and pancreatitis−rarely, in newborns whose mothers have received thiazides during pregnancy.

Skin:

Erythema multiforme, including Stevens-Johnson syndrome; exfoliative dermatitis, including toxic epidermal necrolysis.

Postmarketing Experience: