Chlorothiazide

Drug Interactions When given concurrently the following drugs may interact with thiazide diuretics. Alcohol, Barbiturates, or Narcotics - potentiation of orthostatic hypotension may occur. Antidiabetic Drugs (Oral Agents and Insulin) - dosage adjustment of the antidiabetic drug may be required. Other Antihypertensive Drugs - additive effect or potentiation. Cholestyramine and Colestipol Resins - Both cholestyramine and colestipol resins have the potential of binding thiazide diuretics and reducing diuretic absorption from the gastrointestinal tract. Corticosteroids, ACTH - intensified electrolyte depletion, particularly hypokalemia.

Pressor Amines (e.g., Norepinephrine) - possible decreased response to pressor amines but not sufficient to preclude their use. Skeletal Muscle Relaxants, Nondepolarizing (e.g., Tubocurarine) - possible increased responsiveness to the muscle relaxant. 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 preparations with DIURIL.

Non-steroidal Anti-inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 (COX-2) Inhibitors - In some patients, the administration of a non-steroidal anti-inflammatory agent including a selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when DIURIL and non-steroidal anti-inflammatory agents or selective COX-2 inhibitors are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with NSAIDs, including selective COX-2 inhibitors, the co-administration of angiotensin II receptor antagonists or ACE inhibitors may result in a further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. These interactions should be considered in patients taking NSAIDs including selective COX-2 inhibitors concomitantly with diuretics and angiotensin II antagonists or ACE inhibitors.

Therefore, the combination should be administered with caution, especially in the elderly.

Pregnancy Teratogenic Effects - Although reproduction studies performed with chlorothiazide doses of 50 mg/kg/day in rabbits, 60 mg/kg/day in rats and 500 mg/kg/day in mice revealed no external abnormalities of the fetus or impairment of growth and survival of the fetus due to chlorothiazide, such studies did not include complete examinations for visceral and skeletal abnormalities. It is not known whether chlorothiazide can cause fetal harm when administered to a pregnant woman; however, thiazides cross the placental barrier and appear in cord blood. DIURIL should be used during pregnancy only if clearly needed (see INDICATIONS AND USAGE ).

Nonteratogenic Effects - Chlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult.

Nursing Mothers Because of the potential for serious adverse reactions in nursing infants from DIURIL, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.