TRIAMTERENE AND HYDROCHLOROTHIAZIDE
Clinical safety rating: safe
ACE inhibitors and ARBs may increase risk of hyperkalemia Can cause hyperkalemia and kidney stones.
Triamterene inhibits sodium reabsorption in the distal renal tubules by blocking epithelial sodium channels, reducing potassium excretion. Hydrochlorothiazide inhibits sodium and chloride reabsorption in the distal convoluted tubule by binding to the thiazide-sensitive sodium-chloride cotransporter, leading to increased diuresis and natriuresis.
| Metabolism | Triamterene is metabolized in the liver via hydroxylation and conjugation, with the major metabolite being hydroxytriamterene sulfate. Hydrochlorothiazide is minimally metabolized and primarily excreted unchanged in the urine. |
| Excretion | Triamterene: renal 21-50% (unchanged) and 40-54% (metabolites); Hydrochlorothiazide: renal >95% unchanged. |
| Half-life | Triamterene: 1.5-2.5 hours (terminal), prolonged in hepatic impairment; Hydrochlorothiazide: 6-15 hours (terminal), prolonged in renal impairment. |
| Protein binding | Triamterene: 67% bound to albumin; Hydrochlorothiazide: 40-68% bound to albumin. |
| Volume of Distribution | Triamterene: 2.5-3 L/kg; Hydrochlorothiazide: 0.8-1.1 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Triamterene: ~30-70% (oral), variable; Hydrochlorothiazide: ~70% (oral). |
| Onset of Action | Oral: 2-4 hours (diuresis). |
| Duration of Action | Triamterene: 7-9 hours; Hydrochlorothiazide: 6-12 hours; clinical effect may last up to 24 hours with chronic dosing. |
Adults: 1 capsule (triamterene 37.5 mg / hydrochlorothiazide 25 mg) orally once daily or twice daily; maximum triamterene 150 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR ≥30 mL/min: No adjustment; GFR 15-29 mL/min: Caution, consider alternative; GFR <15 mL/min: Contraindicated (hyperkalemia risk). |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Caution, use lowest effective dose; Child-Pugh C: Contraindicated (hepatic encephalopathy risk). |
| Pediatric use | Not recommended for use in children due to lack of safety and efficacy data; alternative agents preferred. |
| Geriatric use | Start at lowest dose (37.5 mg/25 mg once daily), titrate slowly; monitor electrolytes and renal function; avoid in patients with significant renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
ACE inhibitors and ARBs may increase risk of hyperkalemia Can cause hyperkalemia and kidney stones.
| FDA category | Animal |
| Breastfeeding | Hydrochlorothiazide is excreted into breast milk in low concentrations; triamterene is excreted in animal milk but human data are lacking. M/P ratio for hydrochlorothiazide is approximately 0.8. Use during lactation is not recommended due to potential for neonatal electrolyte imbalances and suppression of lactation. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | edema |
| Serious Effects |
["Anuria","Hyperkalemia (serum K+ >5.5 mEq/L)","Severe or progressive renal disease (creatinine clearance <10 mL/min)","Known hypersensitivity to triamterene, hydrochlorothiazide, or sulfonamide-derived drugs","Concurrent use with other potassium-sparing diuretics or potassium supplements (except in severe hypokalemia)","History of renal calculi (triamterene component)"]
| Precautions | ["Hyperkalemia: risk increased with renal impairment, diabetes, or K+ supplements","Electrolyte imbalances: hyponatremia, hypomagnesemia, hypochloremia","Metabolic acidosis","Azotemia: may precipitate in renal disease","Sulfonamide hypersensitivity: cross-sensitivity with thiazides","Acute angle-closure glaucoma: reported with sulfonamides","Photosensitivity","Lithium toxicity: decreased renal clearance"] |
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| Triamterene/hydrochlorothiazide is contraindicated in pregnancy. Hydrochlorothiazide crosses the placenta and may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Triamterene is a folate antagonist and may increase risk of neural tube defects if used in the first trimester. Second and third trimester use may cause fetal dehydration, hyponatremia, and placental hypoperfusion. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (sodium, potassium, chloride, bicarbonate), renal function, and uric acid. For the fetus, assess growth via ultrasound and amniotic fluid volume. In neonates, monitor for jaundice, thrombocytopenia, and electrolyte disturbances. |
| Fertility Effects | Limited data. Hydrochlorothiazide may cause sexual dysfunction in some patients; triamterene has no known direct effect on fertility. The combination is not associated with significant impairment of fertility in animal studies. |