TRIAMTERENE
Clinical safety rating: safe
Animal studies have demonstrated safety
Triamterene is a potassium-sparing diuretic that inhibits epithelial sodium channels (ENaC) in the distal convoluted tubule and collecting duct of the nephron, reducing sodium reabsorption and potassium excretion.
| Metabolism | Triamterene is metabolized in the liver via hydroxylation and conjugation, primarily by cytochrome P450 enzymes (CYP1A2 and CYP3A4). Its active metabolite is hydroxytriamterene sulfate. |
| Excretion | Approximately 50% of an oral dose is excreted unchanged in urine; about 20% is excreted as metabolites (mainly hydroxytriamterene sulfate conjugate) in urine; biliary/fecal excretion accounts for less than 10%. |
| Half-life | Terminal elimination half-life is approximately 1.5 to 2 hours. However, in patients with hepatic cirrhosis, half-life may be prolonged up to 4 hours; in renal impairment, half-life can extend significantly (up to 10 hours) due to reduced renal clearance. |
| Protein binding | Approximately 67% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 2.5 to 3.0 L/kg, indicating extensive tissue distribution including binding to renal tubules. |
| Bioavailability | Oral: approximately 30-70% due to first-pass metabolism; bioavailability is variable and reduced in patients with hepatic impairment. |
| Onset of Action | Oral: diuresis begins within 2 to 4 hours after administration. |
| Duration of Action | Oral: diuretic effect lasts approximately 7 to 9 hours; antihypertensive effect may persist for 12 to 24 hours with chronic dosing. |
| Molecular Weight | 253.26 |
100-300 mg orally once daily; maximum 300 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%; GFR <30 mL/min: contraindicated. |
| Liver impairment | No dosage adjustment recommended; use with caution in severe hepatic impairment. |
| Pediatric use | 2-4 mg/kg/day orally in divided doses; maximum 300 mg/day. |
| Geriatric use | Start at 100 mg orally once daily; titrate based on renal function and electrolyte monitoring. |
| 1st trimester | Avoid; associated with folate antagonism and potential neural tube defects. Use only if no alternative. |
| 2nd trimester | Use with caution; may cause electrolyte disturbances and decrease placental perfusion. |
| 3rd trimester | Avoid; may cause neonatal thrombocytopenia and electrolyte abnormalities. |
Clinical note
ACE inhibitors and ARBs may increase risk of hyperkalemia Can cause hyperkalemia and kidney stones.
| Placental transfer | Present; crosses placenta based on animal studies and clinical observation of fetal effects. |
| Breastfeeding | Excreted into breast milk in low amounts; not recommended due to potential adverse effects (e.g., electrolyte imbalances) in the infant. Consider alternative diuretics. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Common Effects | edema |
| Serious Effects |
AnuriaSevere renal impairment (eGFR < 30 mL/min)HyperkalemiaConcomitant use with potassium supplements or potassium-sparing agentsHypersensitivity to triamterene or any component
| Precautions | Hyperkalemia risk, especially in patients with renal impairment, diabetes, or using other potassium-sparing agents or potassium supplements; monitor serum potassium regularly. May cause electrolyte imbalances (hyponatremia, hypomagnesemia). Caution in patients with hepatic cirrhosis due to risk of folate deficiency and megaloblastic anemia. May cause photosensitivity. |
| Food/Dietary | Avoid foods high in potassium such as bananas, oranges, tomatoes, spinach, potatoes, avocados, and salt substitutes containing potassium chloride. Excessive intake can lead to hyperkalemia. No other significant food interactions. |
Loading safety data…
| L3 - Limited data, potential risk |
| Teratogenic Risk | Pregnancy Category C. First trimester: Potential risk based on animal studies showing teratogenic effects (cleft palate, skeletal abnormalities) at high doses. Second and third trimesters: Risk of electrolyte imbalances (hyponatremia, hyperkalemia) in mother and fetus; may cause fetal thrombocytopenia. Avoid use during pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal serum electrolytes (potassium, sodium, magnesium, calcium), renal function, and blood pressure. Fetal monitoring for growth restriction and amniotic fluid volume. Assess for signs of fetal thrombocytopenia (e.g., petechiae). |
| Fertility Effects | No specific studies on human fertility. In animal studies, high doses caused impaired spermatogenesis and reduced fertility. Clinical relevance in humans is unknown. |
| Clinical Pearls | Triamterene is a potassium-sparing diuretic that inhibits epithelial sodium channels in the distal nephron. It is often combined with thiazides (e.g., HCTZ) to reduce potassium loss. Avoid in patients with hyperkalemia, renal impairment (CrCl < 30 mL/min), or severe hepatic disease. Monitor serum potassium and renal function frequently. Can cause megaloblastic anemia in patients with folate deficiency (triamterene is a weak folic acid antagonist). |
| Patient Advice | Take triamterene exactly as prescribed, usually in the morning to avoid nighttime urination. · Do not take additional potassium supplements or salt substitutes containing potassium without consulting your doctor. · Avoid prolonged sun exposure and use sunscreen; triamterene may increase sensitivity to sunlight. · Report symptoms of hyperkalemia such as muscle weakness, irregular heartbeat, or fatigue. · Stay hydrated unless advised otherwise, but avoid excessive water intake if on fluid restriction. · Keep regular appointments for blood tests to monitor potassium levels and kidney function. |