Naturetin

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

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

Naturetin tablets are indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.

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. 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: Nonteratogenic Effects 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 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.

Thiazides 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.

Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.

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

Lithium generally should not be given with diuretics; diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such concomitant therapy.

Gastrointestinal: nausea, vomiting, cramping and anorexia are not uncommon; diarrhea, constipation, gastric irritation, abdominal bloating, jaundice (intrahepatic cholestatic jaundice), hepatitis, and sialadenitis occasionally occur; and pancreatitis has been reported.

Central Nervous System: dizziness, vertigo, paresthesia, headache, and xanthopsia occasionally occur.

Hematologic: leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, and aplastic anemia have been reported.

Dermatologic-Hypersensitivity: purpura, exfoliative dermatitis, pruritus, ecchymosis, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), respiratory distress including pneumonitis, fever, and anaphylactic reactions occasionally occur; photosensitivity and rash have been reported.

Cardiovascular: orthostatic hypotension may occur and may be potentiated by coadministration with certain other drugs (e.g., alcohol, barbiturates, narcotics, other antihypertensive medications, etc. (See PRECAUTIONS: Drug Interactions.)

Other: muscle spasm, weakness, or restlessness is not uncommon; hyperglycemia, glycosuria, metabolic acidosis in diabetic patients, hyperuricemia, allergic glomerulonephritis, and transient blurred vision occasionally occur.

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

Symptoms of overdosage may be manifested in several ways: temporary elevation of BUN; gastrointestinal irritation; and lethargy progressing to coma with minimal depression of respiration and cardiovascular function and without significant serum electrolyte changes or dehydration. Serum electrolyte changes may occur, especially in patients with impaired renal function. The mechanism of thiazide-induced central nervous system depression is unknown.

Treatment is essentially supportive. Evacuation of gastric contents may be useful provided aspiration is avoided in unconscious patients. In conscious patients, induced vomiting using Ipecac Syrup USP is helpful in removing the drug from the stomach. Cathartics should be avoided since they tend to enhance the loss of fluid and electrolytes. Electrolyte levels and renal function should be monitored, and supportive measures instituted to maintain hydration, electrolyte balance, respiration, and cardiovascular-renal function as required. Gastrointestinal irritation is usually of short duration and may be treated symptomatically.

Naturetin® (Bendroflumethiazide Tablets USP)

5 mg/tablet: bottles of 100 (NDC 0003-0606-50).

Each green, round, biconvex tablet with bisect bar is imprinted with identification number 606.

10 mg/tablet: bottles of 100 (NDC 0003-0618-50).

Each orange, round, biconvex tablet with bisect bar is imprinted with identification number 618.

Storage

Dispense in tight containers. Store at room temperature; avoid excessive heat.

APOTHECON®

A Bristol-Myers Squibb Company

Princeton, NJ 08540 USA

1017988A1
Revised August 2000

Thiazide diuretics are excreted into human milk in low concentrations. While a rare case of thrombocytopenia has been reported in one nursing infant whose mother was taking a related drug, chlorothiazide, adverse effects in the nursing infant are unlikely. The manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.