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Triamterene

Pronunciation

Pronunciation

(trye AM ter een)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Dyrenium: 50 mg [contains fd&c yellow #6 (sunset yellow)]

Dyrenium: 100 mg

Brand Names: U.S.

  • Dyrenium

Pharmacologic Category

  • Antihypertensive
  • Diuretic, Potassium-Sparing

Pharmacology

Blocks epithelial sodium channels in the late distal convoluted tubule (DCT) and collecting duct which inhibits sodium reabsorption from the lumen. This effectively reduces intracellular sodium, decreasing the function of Na+/K+ ATPase, leading to potassium retention and decreased calcium, magnesium, and hydrogen excretion. As sodium uptake capacity in the DCT/collecting duct is limited, the natriuretic, diuretic, and antihypertensive effects are generally considered weak.

Absorption

Rapid

Metabolism

Primarily metabolized to the sulfate conjugate of hydroxytriamterene

Excretion

Urine (21% to <50%; primarily as metabolites)

Onset of Action

Diuresis: 2 to 4 hours; Note: Maximum therapeutic effect may not occur until after several days of therapy

Time to Peak

Plasma: ~3 hours

Duration of Action

Diuresis: 7 to 9 hours

Use: Labeled Indications

Edema: For the treatment of edema associated with congestive heart failure, cirrhosis of the liver and the nephrotic syndrome; also in steroid-induced edema, idiopathic edema and edema due to secondary hyperaldosteronism.

Use: Unlabeled

Hypertension: For the treatment of hypertension in children >1 year and adolescents.

Prevention of antihypertensive diuretic-induced hypokalemia: In combination with other diuretics (eg, hydrochlorothiazide), triamterene may be used to prevent hypokalemia associated with diuretics used to manage hypertension.

Note: According to the Eighth Joint National Committee (JNC 8) guidelines, potassium-sparing diuretics are not recommended for the initial treatment of hypertension (James, 2013).

Contraindications

Anuria; severe or progressive kidney disease or dysfunction with the possible exception of nephrosis; severe hepatic disease; hypersensitivity to the drug or any of its components; preexisting elevated serum potassium, as is sometimes seen in patients with impaired renal function or azotemia, or in patients who develop hyperkalemia while on the drug; coadministration with other potassium-sparing agents, such as spironolactone, amiloride, or other formulations containing triamterene

Dosing: Adult

Edema: Oral: 100 to 300 mg daily in 1 to 2 divided doses; maximum dose: 300 mg daily

Prevention of antihypertensive diuretic-induced hypokalemia (off-label use): Oral: Usual dose (ASH/ISH [Weber, 2014]): 100 mg daily

Dosing: Geriatric

Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Aronow, 2011).

Dosing: Pediatric

Hypertension (off-label use): Oral: Initial: 1 to 2 mg/kg/day in 2 divided doses; maximum: 3 to 4 mg/kg/day, up to 300 mg daily (NHLBI, 2004)

Dosing: Renal Impairment

Manufacturer’s labeling:

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling.

Severe impairment or progressive kidney disease: Use is contraindicated.

Alternate recommendations: CrCl ≤50 mL/minute: Avoid use (Aronoff 2007). The Beers Criteria recommends avoiding use in older adults ≥65 years of age with a CrCl <30 mL/minute due to the risk of hyperkalemia and hyponatremia (Beers Criteria [AGS 2015]).

Dosing: Hepatic Impairment

Mild-to-moderate impairment: No dosage adjustment provided in manufacturer's labeling (has not been studied).

Severe hepatic disease: Use is contraindicated.

Administration

May be administered with food.

Dietary Considerations

May be taken after meals to decrease the risk of upset stomach.

Drug Interactions

ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Monitor therapy

Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Canagliflozin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Canagliflozin may enhance the hypotensive effect of Potassium-Sparing Diuretics. Monitor therapy

Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Monitor therapy

CycloSPORINE (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dofetilide: Triamterene may increase the serum concentration of Dofetilide. Monitor therapy

Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Consider therapy modification

Heparin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy

Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Indomethacin: May enhance the nephrotoxic effect of Triamterene. Management: Consider alternatives to concomitant treatment with triamterene and indomethacin. If the combination cannot be avoided, monitor for development of renal failure. Consider therapy modification

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Consider therapy modification

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification

Spironolactone: Triamterene may enhance the hyperkalemic effect of Spironolactone. Avoid combination

Tacrolimus (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus (Systemic). Avoid combination

Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Test Interactions

Interferes with fluorometric assay of quinidine

Adverse Reactions

Frequency not defined.

Central nervous system: Dizziness, fatigue, headache

Dermatologic: Skin photosensitivity, skin rash

Endocrine & metabolic: Hyperkalemia, hypokalemia, increased uric acid, metabolic acidosis

Gastrointestinal: Diarrhea, nausea, vomiting, xerostomia

Genitourinary: Azotemia

Hematologic & oncologic: Hematologic abnormality, megaloblastic anemia, thrombocytopenia

Hepatic: Jaundice, liver enzyme disorder

Hypersensitivity: Anaphylaxis

Neuromuscular & skeletal: Weakness

Renal: Acute interstitial nephritis (rare), acute renal failure (rare), increased blood urea nitrogen, increased serum creatinine, nephrolithiasis

ALERT: U.S. Boxed Warning

Hyperkalemia:

Abnormal elevation of serum potassium levels (at least 5.5 mEq/L) can occur with all potassium-sparing agents, including triamterene. Hyperkalemia is more likely to occur in patients with renal impairment and diabetes (even without evidence of renal impairment), and in elderly or severely ill patients. Because uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals especially in patients receiving triamterene, when dosages are changed, or with any illness that may influence renal function.

Warnings/Precautions

Concerns related to adverse effects:

• Fluid/electrolyte loss: Triamterene can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Patients with heart failure, renal disease, or cirrhosis may be particularly susceptible to fluid and electrolyte abnormalities. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration.

• Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction. . In patients who develop hyperkalemia or if hyperkalemia is suspected, obtain an electrocardiogram to rule out hyperkalemia-induced QRS prolongation or other cardiac arrhythmias. Discontinue triamterene and any potassium supplementation in patients who develop hyperkalemia; treat cardiac arrhythmias as clinically indicated.

• Hypersensitivity reactions: Isolated occurrences have been reported. Observe for blood dyscrasias, liver damage or idiosyncratic reactions

• Photosensitivity: Can cause photosensitivity.

Disease-related concerns:

• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may increase blood glucose concentrations and necessitate dosage adjustment of hypoglycemic agents.

• Gout: May cause elevation in uric acid.

• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.

• Kidney stones: Use with caution in patients with kidney stones.

Concurrent drug therapy issues:

• Potassium supplements: Avoid potassium supplements, potassium-containing salt substitutes, a diet rich in potassium, or other drugs that can cause hyperkalemia.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Abrupt discontinuation: In patients who have received triamterene for prolonged periods of time, a hypothetical risk of rebound kaliuresis may occur when abruptly discontinued; withdraw triamterene gradually in these patients.

Monitoring Parameters

Blood pressure; serum electrolytes (especially potassium), renal function; weight, I & O

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Triamterene crosses the placenta and is found in cord blood. Use of triamterene to treat edema during normal pregnancies is not appropriate; use may be considered when edema is due to pathologic causes (as in the nonpregnant patient); monitor.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, lack of appetite, nausea, or loss of strength and energy. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, nausea, or vomiting), bruising, bleeding, chills, pharyngitis, severe dizziness, passing out, severe diarrhea, or bradycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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