Thiazide+Triamterene

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. 1. It (trIamterene and hydrochlorothIazIde) Is IndIcated for the treatment of hypertensIon or edema In patIents who develop hypokalemIa on hydrochlorothIazIde alone. 2. It Is also IndIcated for those patIents who requIre a thIazIde dIuretIc and In whom the development of hypokalemIa cannot be rIsked (e.g., patIents on concomItant dIgItalIs preparatIons, or wIth a hIstory of cardIac arrhythmIas, etc.). It may be used alone or In combInatIon wIth other antIhypertensIve drugs, such as beta-blockers. SInce It (trIamterene and hydrochlorothIazIde) may enhance the actIons of these drugs, dosage adjustments may be necessary

Potassium-Sparing and Thiazide

Triamterene directly inhibits the exchange of Na for K and hydrogen in the distal renal tubule. Hydrochlorothiazide increases the excretion of Na and Cl ions, and consequently of water, by reducing electrolyte reabsorption from the renal tubules. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of anangiotensin converting enzyme (ACE) inhibitor tends to reverse the potassium loss associated with these diuretics. Triamterene directly inhibits the exchange of Na for K and hydrogen in the distal renal tubule. Hydrochlorothiazide increases the excretion of Na and Cl ions, and consequently of water, by reducing electrolyte reabsorption from the renal tubules. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of anangiotensin converting enzyme (ACE) inhibitor tends to reverse the potassium loss associated with these diuretics.

The usual dose of it-25 MG is one or two tablets daily, given as a single dose, with appropriate monitoring of serum potassium . The usual dose of it is one tablet daily, with appropriate monitoring of serum potassium . There is no experience with the use of more than one it tablet daily or more than two its daily. Clinical experience with the administration of two its 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 it (triamterene and hydrochlorothiazide) directly. Patients receiving 25 mg hydrochlorothiazide who become hypokalemic may be transferred to(37.5 mg triamterene/25 mg hydrochlorothiazide) directly. In patients requiring hydrochlorothiazide therapy and in whom hypokalemia cannot be risked therapy may be initiated with 25 MG. If an optimal blood pressure response is not obtained with 25 MG, the dose should be increased to two its daily as a single dose, or one it tablet daily. If blood pressure still is not controlled, another antihypertensive agent may be added 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 it daily. All patients changed from less bioavailable formulations to it should be monitored clinically and for serum potassium after the transfer

May reduce the renal clearance of lithium. May antagonise diuretic effect with NSAIDs, corticosteroids, oestrogens, combined OCs. Enhanced effect with other hypotensive agents, baclofen, tizanidine. May decrease arterial responsiveness to norepinephrine. Increases responsiveness to tubocurarine. Risk of acute renal failure with indometacin. Increased risk of hyperkalaemia with reboxetine, tacrolimus. Increased risk of ototoxicity and nephrotoxicity with platinum compounds (e.g. cisplatin).

Hyperkalemia: it (triamterene and hydrochlorothiazide) should not be used in the presence of elevated serum potassium levels (greater than or equal to 5.5 mEq/liter). If hyperkalemia develops, this drug should be discontinued and a thiazide alone should be substituted. Antikaliuretic Therapy or Potassium Supplementation: it should not be given to patients receiving other potassium-conserving agents such as spironolactone, amiloride hydrochloride or other formulations containing triamterene. Concomitant potassium supplementation in the form of medication, potassium-containing salt substitute or potassium-enriched diets should also not be used. Impaired Renal Function: is contraindicated in patients with anuria, acute and chronic renal insufficiency or significant renal impairment. Hypersensitivity: it should not be used in patients who are hypersensitive to triamterene or hydrochlorothiazide or other sulfonamide-derived drugs.

Gastrointestinal: jaundice (intrahepatic cholestatic jaundice), pancreatitis, nausea, appetite disturbance, taste alteration, vomiting, diarrhea, constipation, anorexia, gastric irritation, cramping. Central Nervous System: drowsiness and fatigue, insomnia, headache, dizziness, dry mouth, depression, anxiety, vertigo, restlessness, paresthesias. Cardiovascular: tachycardia, shortness of breath and chest pain, orthostatic hypotension (may be aggravated by alcohol, barbiturates or narcotics). Renal: acute renal failure, acute interstitial nephritis, renal stones composed of triamterene in association with other calculus materials, urine discoloration. Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia and megaloblastosis. Ophthalmic: xanthopsia, transient blurred vision. Hypersensitivity: anaphylaxis, photosensitivity, rash, urticaria, purpura, necrotizing angiitis (vasculitis, cutaneous vasculitis), fever, respiratory distress including pneumonitis. Other: muscle cramps and weakness, decreased sexual performance and sialadenitis.

Nursing Mothers: Thiazides and triamterene in combination have not been studied in nursing mothers. Triamterene appears in animal milk and 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.Pregnancy: Teratogenic Effects. Category C: it: Animal reproduction studies to determine the potential for fetal harm by it have not been conducted. Nevertheless, a One Generation Study in the rat approximated it’s composition by Reference ID: 2920651 17 using a 1:1 ratio of triamterene to hydrochlorothiazide (30:30 mg/kg/day). There was no evidence of teratogenicity at those doses that were, on a body-weight basis, 15 and 30 times, respectively, the MRHD, and, on the basis of body-surface area, 3.1 and 6.2 times, respectively, the MRHD. The safe use of it in pregnancy has not been established since there are no adequate and well controlled studies with it in pregnant women. it should be used during pregnancy only if the potential benefit justifies the risk to the fetus. Triamterene: Reproduction studies have been performed in rats at doses as high as 20 times the Maximum Recommended Human Dose (MRHD) on the basis of body-weight, and 6 times the MRHD on the basis of body-surface area without evidence of harm to the fetus due to triamterene. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Hydrochlorothiazide: Hydrochlorothiazide was orally administered to pregnant mice and rats during respective periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively. At these doses, which are multiples of the MRHD equal to 3000 for mice and 1000 for rats, based on body-weight, and equal to 282 for mice and 206 for rats, based on body-surface area, there was no evidence of harm to the fetus. There are, however, no adequate and well controlled studies in pregnant women. Because animal Reference ID: 2920651 18 reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nonteratogenic Effects: Thiazides and triamterene have been shown to cross the placental barrier and appear in cord blood. The use of thiazides and triamterene in pregnant women requires that the anticipated benefits be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and possibly other adverse reactions that have occurred in the adult.

Store at controlled room temperature 20° to 25°C; excursions permitted to 15° to 30°C. Protect from light. Dispense in a tight, light-resistant container.