What are the side effects of Triamterene (potassium-sparing diuretic)?

Triamterene Side Effects

Triamterene is generally well-tolerated but carries specific risks including hyperkalemia (especially when combined with ACE inhibitors or ARBs), metabolic acidosis, elevated uric acid levels, renal stones, and acute renal failure particularly when combined with NSAIDs. 1

Common Electrolyte and Metabolic Effects

Hyperkalemia Risk

• Hyperkalemia is the most clinically significant adverse effect, particularly dangerous in patients with renal insufficiency or those taking concurrent medications that affect potassium homeostasis 2, 1
• The risk increases substantially when triamterene is combined with ACE inhibitors, ARBs, or aldosterone antagonists 2, 1
• Elderly patients face higher hyperkalemia risk, especially when combining triamterene with ACE inhibitors or NSAIDs 2
• Serum potassium should be monitored within 5-7 days after initiation and every 5-7 days until values stabilize 3

Metabolic Acidosis

• Triamterene may cause decreasing alkali reserve with the possibility of metabolic acidosis 1
• This effect is related to its mechanism as a potassium-sparing diuretic that affects renal tubular ion exchange 1

Hyperuricemia

• Triamterene elevates uric acid levels, especially in persons predisposed to gouty arthritis 1
• Serum uric acid should be monitored bi-weekly during initial therapy 4

Renal Complications

Nephrolithiasis

• Triamterene has been reported in renal stones in association with other calculus components and should be used with caution in patients with histories of renal stones 1, 5
• This represents a unique adverse effect among potassium-sparing diuretics 5

Acute Renal Failure

• A critical drug interaction exists between triamterene and NSAIDs that can result in acute renal failure 1, 5
• This interaction is particularly concerning given the increased availability of over-the-counter NSAIDs 5
• Indomethacin specifically has been reported to cause acute renal failure when combined with triamterene 1

Other Renal Effects

• Mild nitrogen retention may occur, which is reversible upon drug withdrawal and seldom observed with intermittent (every-other-day) therapy 1
• Abnormalities in urinary sediment and interstitial nephritis have been reported 5

Hematologic Effects

Megaloblastic Anemia

• Triamterene is a weak folic acid antagonist and may contribute to megaloblastosis in cases where folic acid stores have been depleted 1
• Periodic blood studies are recommended, particularly in patients with cirrhosis and splenomegaly who may have marked variations in blood counts 1

Hepatic Considerations

• Patients with underlying liver disease should be observed for exacerbations during triamterene therapy 1
• Cirrhotic patients require particularly careful monitoring due to their baseline metabolic derangements 1

Drug Interactions and Potentiation Effects

Lithium Toxicity

• Diuretic-induced sodium loss may reduce renal clearance of lithium and increase serum lithium levels with risk of toxicity 1
• Patients receiving combined therapy should have serum lithium levels monitored closely and lithium dosage adjusted if necessary 1

Potentiation of Other Medications

• Triamterene may potentiate the effects of antihypertensive medications, other diuretics, preanesthetic and anesthetic agents, and skeletal muscle relaxants (non-depolarizing) 1

Blood Glucose Effects

• Triamterene may raise blood glucose levels, requiring dosage adjustments of hypoglycemic agents in adult-onset diabetes 1
• Concurrent use with chlorpropamide may increase the risk of severe hyponatremia 1

Rebound Effects

Kaliuresis Upon Withdrawal

• In patients receiving intensive therapy or prolonged treatment, a rebound kaliuresis could occur upon abrupt withdrawal 1
• Withdrawal of triamterene should be gradual in such patients 1
• Studies demonstrate that within the first 2 days of triamterene discontinuation, all retained potassium eliminates from the body 6

Tolerance and Efficacy Considerations

• The potassium-retaining action of triamterene may be inhibited by day 2-3 of daily treatment 6
• No drug tolerance develops with long-term therapy when used appropriately 7
• Clinical studies over 2.5 years showed no significant undesirable side effects in heart failure patients 4

Laboratory Test Interference

• Triamterene interferes with fluorescent measurement of quinidine due to similar fluorescence spectra 1

Critical Monitoring Parameters

• Serum potassium and renal function should be checked within 5-7 days after initiation 3
• Continue monitoring every 5-7 days until potassium values stabilize 3
• Bi-weekly monitoring of serum sodium, potassium, chloride, uric acid, and SGOT is recommended during initial therapy 4
• The normal adult range of serum potassium is 3.5 to 5.0 mEq/L, with potassium levels persistently above 6 mEq/L requiring careful observation and treatment 1