 |
DESCRIPCION
Description: Triamterene is a potassium-sparing, distal tubule diuretic. It is similar in action to amiloride, but triamterene increases the urinary excretion of magnesium while amiloride does not. Triamterene is a relatively weak diuretic and antihypertensive and is most often used in the management of hypokalemia, especially in patients who cannot tolerate or have been unresponsive to potassium supplements. The diuretic activity of triamterene was originally described in 1961 and it was approved by the FDA in 1964. Mechanism of Action: Triamterene, like amiloride, inhibits the sodium-potassium ion exchange mechanism in the distal renal tubule independently of aldosterone. Triamterene appears to interfere with sodium reabsorption in the distal tubule by inhibiting sodium transport mechanisms directly, thereby setting up an electrical-potential difference across the membrane that blocks the passive distal tubular secretion of potassium. In conditions in which potassium loss is minimal, triamterene modifies distal tubule handling of potassium only slightly. If potassium renal clearance is increased by loop diuretics or mineralocorticoids, however, triamterene causes a significant drop in potassium excretion. Increased urinary excretion of sodium, bicarbonate, calcium, magnesium, chloride, and water lead to a slight diuresis. In addition, triamterene does not inhibit carbonic anhydrase activity. In general, diuretics worsen LVH and glucose tolerance, and exert detrimental effects on the lipid profile. Pharmacokinetics: Triamterene is rapidly but incompletely absorbed from the GI tract following oral administration; bioavailability is roughly 30—70%. The onset of action is 2—4 hours, with peak effects at 6—8 hours and a 12—16 hour duration of action. Triamterene is approximately 67% bound to plasma proteins. Triamterene crosses the placenta, but it is not known whether it distributes into breast milk. However, animal studies have demonstrated small amounts in breast milk. Triamterene is metabolized to at least one active metabolite (p-hydroxytriamterene ester). Slightly less than 50% of triamterene and its metabolite are excreted in the urine. Roughly 21% of triamterene is eliminated unchanged. The remainder of the drug is eliminated via biliary/fecal routes. The half-life of triamterene is 1—2 hours in patients with normal renal function. The active metabolite has a half-life of approximately 3 hours in patients with normal renal function. •Special Populations: In patients with chronic renal disease, the half-life of triamterene (10 hours) and the active metabolite is significantly increased, along with the risk of drug-induced hyperkalemia. Cirrhosis is associated with a prolonged half-life of triamterene, by approximately four-fold. Drug accumulation of triamterene and its active metabolite has been reported in older patients; however, one report showed no change in drug disposition or pharmacodynamics of triamterene in the elderly.[1604]
Indications...Dosage For the treatment of peripheral edema states (e.g., heart failure, idiopathic edema, nephrotic syndrome, ascites due to hepatic cirrhosis, secondary hyperaldosteronism), hypertension†, or hypokalemia: Oral dosage: Adults and adolescents: Initially, 50—100 mg PO twice daily. Use lower initial doses when used in combination with another diuretic or antihypertensive agent. Maximum dosage is 300 mg/day PO. Elderly: See adult dosage. Elderly patients may be more sensitive to the diuretic effects of the drug and are more likely to have an increased risk of hyperkalemia. Children: Doses of 2—4 mg/kg/day PO in 1—2 divided doses have been used in children†. Maximum dosage is 6 mg/kg/day PO or 300 mg/day, whichever is less. For the treatment of symptoms of bloating and weight gain associated with premenstrual syndrome (PMS)†: Oral dosage: Adults: 50—100 mg PO given once daily or twice daily. Diuretic use should be limited to patients who demonstrate a premenstrual weight gain of > 1.4 kg. Dosage should be titrated to achieve desired diuresis and to minimize weight gain.[734] Maximum Dosage Limits: •Adults: 300 mg/day PO. •Elderly: 300 mg/day PO. •Adolescents: 300 mg/day PO. •Children: 6 mg/kg/day PO or 300 mg/day PO, whichever is less. Patients with hepatic impairment: Dose reduction may be warranted; cirrhosis is associated with a prolonged half-life of triamterene (by approximately four-fold). Patients with renal impairment: CrCl >= 10 ml/min: no dosage adjustment needed. CrCl < 10 ml/min: avoid use of drug due to the potential for hyperkalemia. Intermittent hemodialysis: Triamterene is contraindicated in patients with renal failure (CrCl < 10 m/min) or anuria. †non-FDA-approved indication
Administration Oral Administration •Generally administer after meals to minimize GI adverse effects.
Contraindications Hyperkalemia can cause life-threatening cardiac arrhythmias and is more likely to occur in patients with impaired renal function, diabetes mellitus, or in elderly patients. Triamterene should be prescribed cautiously to these patients. Elderly patients also may be more sensitive to the hypotensive and diuretic effects of triamterene. Triamterene is contraindicated in patients with hyperkalemia (potassium levels greater than 5.5 mEq/L ) or in those receiving other potassium-sparing agents. Patients receiving triamterene should not receive potassium supplementation or increase their dietary intake of potassium unless they have refractory hypokalemia. Serum potassium, creatinine, and BUN levels should be monitored. Clinicians should note that the precaution for triamterene in patients with diabetes mellitus is due to the risk of hyperkalemia and not the risk of inducing hyperglycemia, a problem seen more with thiazide diuretics. Triamterene is contraindicated in patients with anuria, diabetic nephropathy or any renal disease associated with chronic, severe renal impairment (i.e., CrCl < 10 ml/min) or renal failure. Triamterene should be used with caution in patients with preexisting hyponatremia. Triamterene may worsen this condition. Close monitoring of the acid-base status of patients with cardiac disease or uncontrolled diabetes mellitus is required. These patients are at a higher risk for developing sudden metabolic acidosis or respiratory acidosis, with resultant rapid increases in serum potassium concentrations that could be exacerbated by triamterene therapy. The safety of triamterene administration during pregnancy has not been established, so the drug should be administered to pregnant women only when the potential benefits to the mother outweigh the potential risk to the fetus. Triamterene is classified as pregnancy category D. Triamterene crosses the placenta, but it is not known whether it is distributed into the breast milk of humans. In addition, triamterene is a weak folic acid antagonist and can contribute to the development of megaloblastic anemia in patients with depleted stores of folic acid. In addition, maternal folic acid deficiency has been associated with spinal column defects in the fetus. Therefore, triamterene should be used cautiously in pregnant women and during breast-feeding. In general, diuretics are contraindicated in pregnant women with mild edema not associated with more severe disease. Triamterene-induced fluctuations in serum electrolyte concentration (including potassium loss in patients with hepatic cirrhosis) can occur and precipitate hepatic encephalopathy in susceptible patients. In addition, triamterene is a weak folic acid antagonist and can contribute to the development of megaloblastic anemia in patients with depleted stores of folic acid such as occur in hepatic cirrhosis. In addition, the use of triamterene in patients with ascites due to cirrhotic liver disease has been occasionally associated with adverse effects such as renal insufficiency and bone marrow megaloblastosis. Therefore, the drug should be used with caution in patients with hepatic disease. Triamterene has been reported to be a constituent of renal stones in patients receiving the drug and therefore must be used with caution in patients predisposed to nephrolithiasis. Thiazide diuretics have been reported to reduce the clearance of uric acid. Caution should also be used when triamterene is administered to patients with gout or hyperuricemia.
yperkalemia, and is not recommended. Triamterene should not be used concomitantly with amiloride or spironolactone because of the increased risk of developing hyperkalemia. In addition, ACE inhibitors, angiotensin II receptor antagonists, heparin, potassium supplements, potassium-containing medications (e.g., penicillin G potassium), and any substance containing potassium salts (e.g., blood, salt substitutes, low-salt milk) can increase the risk of hyperkalemia developing in patients receiving triamterene, especially in the presence of renal impairment. These agents should be used with caution and serum potassium levels monitored when the substances are concurrently administered with triamterene. Triamterene can have additive effects when administered with antihypertensive agents or other diuretics. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary. Lithium clearance can be decreased in patients receiving triamterene, and concomitant administration of these two drugs could result in lithium toxicity. Triamterene can reduce the renal clearance of amantadine, with subsequent increased serum concentrations and possible toxicity. This interaction has been reported with a combination product of hydrochlorothiazide and triamterene. Since it is unclear which component was responsible for the interaction, caution should be exercised when administering either drug concurrently with amantadine. Triamterene can interfere with the hypoglycemic effects of antidiabetic agents. This can lead to a loss of diabetic control, so diabetic patients should be monitored closely. Triameterene, when used concomitantly with metformin, may increase the risk of lactic acidosis. Triamterene may decrease metformin elimination by competing for common renal tubular transport systems. Careful patient monitoring while on concurrent therapy with metformin is recommended. Significant renal impairment has occurred when triamterene and indomethacin were used together. NSAIDs, especially indomethacin, can reduce the diuretic effects of triamterene. Indomethacin inhibits renal prostaglandin synthesis, which can cause fluid retention. Concomitant administration of NSAIDs with diuretics, particularly triamterene, also can increase the risk for renal failure due to the decrease in renal blood flow caused by inhibition of renal prostaglandin synthesis. Limited data suggest that other potassium-sparing diuretics may be less likely than triamterene to interact with indomethacin. NSAIDs can reduce the effectiveness of all diuretics and can independently cause renal impairment. NSAIDs are also associated with increased serum potassium levels, and concurrent administration with potassium-sparing agents such as triamterene can lead to hyperkalemia. Hawthorn, Crataegus laevigata may lower peripheral vascular resistance. Hawthorn use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients receiving hawthorn concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Drugs that are actively secreted via cationic tubular secretion (e.g., triamterene, metformin and amiloride) should be co-administered with caution with dofetilide since they could increase dofetilide plasma concentrations via potential competition for renal cationic secretion. Increased dofetilide plasma concentrations may be associated with proarrhythmias. Escin, an active saponin in the horse chestnut seed, appears to have weak diuretic activity, but the exact mechanism is not clear. The effect appears to be dose-dependent and may be additive with traditional diuretics. Triamterene-induced electrolyte disturbances can potentiate the cardiac toxicity of arsenic trioxide. Salicylates can increase the risk of renal toxicity in patients receiving diuretics secondary salicylate inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Concomitant use of salicylates and triamterene may cause hyperkalemia.
Adverse Reactions Triamterene-induced hyperkalemia can cause life-threatening cardiac arrhythmias, and it is more likely to occur in patients with renal insufficiency, diabetes mellitus, or in geriatric patients. Signs and symptoms of hyperkalemia include muscular weakness, paresthesia, fatigue, flaccid paralysis of the extremities, bradycardia, shock, and ECG changes. Geriatric patients, severely ill patients, or patients with impaired renal function who are receiving triamterene therapy are particularly at risk for developing hyperkalemia, and periodic serum electrolyte, creatinine, and BUN determinations should be made. If hyperkalemia occurs, triamterene should be discontinued immediately, and specific measures should be taken to reduce serum potassium levels. Concomitant use of triamterene with thiazide diuretics can deplete magnesium stores (hypomagnesemia), and triamterene can markedly reduce serum sodium concentration, causing hyponatremia in edematous patients whose intake of sodium chloride has been restricted. Patients with alcoholic cirrhosis who received triamterene therapy have developed megaloblastic anemia. Rarely, agranulocytosis and thrombocytopenia have occurred during triamterene therapy. Adverse GI effects reported during triamterene therapy include jaundice, liver enzyme abnormalities, nausea/vomiting, and diarrhea. Nausea/vomiting can be prevented by administering the drug after meals but can also indicate electrolyte imbalance. Adverse nervous system effects reported in patients receiving triamterene therapy include headache, weakness, fatigue, dizziness, and xerostomia (dry mouth). Adverse renal effects reported with triamterene include azotemia, acute interstitial nephritis, nephrolithiasis, and elevated creatinine concentrations. Muscle cramps, photosensitivity, and rash also have been reported during triamterene therapy. Due to the diuretic action of triamterene, polyuria can be troublesome for some patients during therapy.
|
