TRIAMTERENE AND HYDROCHLOROTHIAZIDE

Drug Interactions: Thiazides may add to or potentiate the action of other antihypertensive drugs. The thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use. Thiazides have also been shown to increase the responsiveness to tubocurarine. Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Refer to the package insert on lithium before use of such concomitant therapy. Acute renal failure has been reported in a few patients receiving indomethacin and formulations containing triamterene and hydrochlorothiazide. Caution is therefore advised when administering non-steroidal anti-inflammatory agents with triamterene and hydrochlorothiazide. Potassium-sparing agents should be used very cautiously, if at all, in conjunction with angiotensin-converting enzyme (ACE) inhibitors due to a greatly increased risk of hyperkalemia. Serum potassium should be monitored frequently.

INDICATIONS AND USAGE This fixed combination drug is not indicated for the initial therapy of edema or hypertension except in individuals in whom the development of hypokalemia cannot be risked. Triamterene and hydrochlorothiazide capsules are indicated for the treatment of hypertension or edema in patients who develop hypokalemia on hydrochlorothiazide alone. Triamterene and hydrochlorothiazide capsules are also indicated for those patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked. Triamterene and hydrochlorothiazide capsules may be used alone or as an adjunct to other antihypertensive drugs, such as beta-blockers. Since triamterene and hydrochlorothiazide capsules may enhance the action of these agents, dosage adjustments may be necessary. 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.

DOSAGE AND ADMINISTRATION: The usual dose of triamterene and hydrochlorothiazide tablets 37.5mg/25mg is one or two tablets daily, given as a single dose, with appropriate monitoring of serum potassium (see WARNINGS ). The usual dose of triamterene and hydrochlorothiazide tablets 75mg/ 50 mg is one tablet daily, with appropriate monitoring of serum potassium (see WARNINGS ). There is no experience with the use of more than one triamterene and hydrochlorothiazide tablet 75mg/50mg daily or more than two triamterene and hydrochlorothiazide tablets 37.5mg/25mg daily. Clinical experience with the administration of two triamterene and hydrochlorothiazide tablets 37.5mg/25mg daily in divided doses (rather than as a single dose) suggests an increased risk of electrolyte imbalance and renal dysfunction. Patients receiving 50 mg of hydrochlorothiazide who become hypokalemic may be transferred to triamterene and hydrochlorothiazide tablets 75mg/50mg directly. Patients receiving 25 mg hydrochlorothiazide who become hypokalemic may be transferred to triamterene and hydrochlorothiazide tablets 37.5mg/25mg directly. In patients requiring hydrochlorothiazide therapy and in whom hypokalemia cannot be risked therapy may be initiated with triamterene and hydrochlorothiazide tablets 37.5mg/25mg. If an optimal blood pressure response is not obtained with triamterene and hydrochlorothiazide tablets 37.5mg/25mg, the dose should be increased to two triamterene and hydrochlorothiazide tablets 37.5mg/25mg daily as a single dose, or one triamterene and hydrochlorothiazide tablet 75mg/25mg daily. If blood pressure still is not controlled, another antihypertensive agent may be added (see PRECAUTIONS: Drug Interactions ). Clinical studies have shown that patients taking less bioavailable formulations of triamterene and hydrochlorothiazide in daily doses of 25 mg to 50 mg hydrochlorothiazide and 50 mg to 100 mg triamterene may be safely changed to one triamterene and hydrochlorothiazide tablets 37.5mg/25mg daily. All patients changed from less bioavailable formulations to triamterene and hydrochlorothiazide tablets 75mg/50mg should be monitored clinically and for serum potassium after the transfer.

ADVERSE REACTIONS Adverse effects are listed in decreasing order of severity. 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: Non-Melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.