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. |
| Molecular Weight | Hydrochlorothiazide: 297.74 Da; Triamterene: 253.27 Da |
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 | Avoid. Teratogenic risk (neural tube defects) and reduced placental perfusion. Contraindicated in pregnancy. |
| 2nd trimester | Avoid. Risk of fetal/neonatal jaundice, thrombocytopenia, and electrolyte disturbances. |
| 3rd trimester | Avoid. May cause fetal/neonatal electrolyte abnormalities, hypotension, and oligohydramnios. |
Clinical note
ACE inhibitors and ARBs may increase risk of hyperkalemia Can cause hyperkalemia and kidney stones.
| FDA category | Animal |
| Placental transfer | Both components cross the placenta. Hydrochlorothiazide demonstrates significant transfer; triamterene transfer is limited but present. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | edema |
| Serious Effects |
AnuriaAcute or chronic renal insufficiency (eGFR <30 mL/min)Hyperkalemia (serum potassium >5.5 mEq/L)Hypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide) or triamtereneConcurrent use with other potassium-sparing agents (e.g., amiloride, spironolactone)Pregnancy (contraindicated)
| 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 |
| Food/Dietary |
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| Hydrochlorothiazide passes into breast milk; may suppress lactation. Triamterene excretion unknown. Use with caution in breastfeeding only if clearly needed. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | 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. |
| Avoid high-potassium foods (bananas, oranges, spinach, avocados, tomatoes) and potassium-rich salt substitutes. Limit alcohol as it may enhance hypotension. Grapefruit juice may alter drug metabolism; avoid excessive consumption. |
| Clinical Pearls | Monitor serum potassium closely; triamterene spares potassium while HCTZ causes loss, but net effect can be hyperkalemia in elderly or renal impairment. Avoid in severe renal disease (CrCl <30 mL/min) or hyperkalemia. Can cause photosensitivity; advise sun protection. Onset of action is 2-4 hours for both components. May increase serum uric acid and glucose. Use with caution in sulfonamide allergy (HCTZ is a sulfonamide derivative). |
| Patient Advice | Take medication as prescribed, usually once daily in the morning with food to reduce stomach upset. · Avoid potassium supplements or salt substitutes containing potassium unless directed by your doctor. · Minimize sun exposure and use sunscreen; this medication can increase sensitivity to sunlight. · Monitor for signs of hyperkalemia (muscle weakness, irregular heartbeat) or hypokalemia (cramps, fatigue). · Report symptoms of gout (joint pain, swelling) or high blood sugar (increased thirst, urination). |