MODURETIC 5-50
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MODURETIC 5-50 (MODURETIC 5-50).
Combination diuretic: amiloride blocks epithelial sodium channels (ENaC) in distal tubule, inhibiting sodium reabsorption and potassium excretion; hydrochlorothiazide inhibits sodium-chloride symporter in distal convoluted tubule, increasing sodium, chloride, and water excretion.
| Metabolism | Hydrochlorothiazide is not significantly metabolized; amiloride is metabolized in the liver (minimal). |
| Excretion | Both components are primarily excreted renally: hydrochlorothiazide (HCTZ) ~70% unchanged in urine; amiloride ~50% unchanged in urine. Minor biliary/fecal elimination (<10% for each). |
| Half-life | HCTZ: 5.6-14.8 hours; amiloride: 6-9 hours. Both prolonged in renal impairment (e.g., creatinine clearance <30 mL/min). Terminal elimination half-life for HCTZ may extend to >20 hours in severe renal disease. |
| Protein binding | HCTZ: ~40-68% bound to albumin; amiloride: ~20-30% bound to plasma proteins. |
| Volume of Distribution | HCTZ: 3-4 L/kg; amiloride: 4-6 L/kg. Indicates extensive distribution into tissues. |
| Bioavailability | Oral: HCTZ ~65-75%; amiloride ~40-60%. Both absorbed within gastrointestinal tract; food may slightly alter absorption but not clinically significant. |
| Onset of Action | Oral: Diuresis begins within 2 hours; peak effect at 4-6 hours. |
| Duration of Action | Approximately 12-24 hours. Antihypertensive effect persists with once-daily dosing; diuretic effect declines over 24 hours. |
1 tablet (5 mg amiloride/50 mg hydrochlorothiazide) orally once daily, increased if needed to 2 tablets daily as a single dose or divided doses.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: reduce dose to 1 tablet every other day; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: use with caution, reduce dose; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for pediatric use due to lack of safety and efficacy data. |
| Geriatric use | Start at 0.5 tablet (2.5 mg amiloride/25 mg hydrochlorothiazide) once daily; monitor renal function and electrolytes closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MODURETIC 5-50 (MODURETIC 5-50).
| Breastfeeding | Hydrochlorothiazide is excreted in low levels in breast milk; amiloride concentration unknown. M/P ratio not established. Use only if essential; monitor infant for electrolyte disturbances and dehydration. |
| Teratogenic Risk | First trimester: Avoid due to possible association with neural tube defects. Second/third trimesters: Risk of oligohydramnios, fetal renal dysfunction, and neonatal hypotension. Amiloride component may cause fetal metabolic acidosis. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Anuria","Hyperkalemia","Concomitant use with potassium-sparing diuretics or potassium supplements","Renal failure (acute or chronic)","Severe hepatic cirrhosis with ascites","Hypersensitivity to amiloride, hydrochlorothiazide, or sulfonamides"]
| Precautions | ["Electrolyte imbalances (hyperkalemia, hyponatremia, hypomagnesemia, hypochloremia)","Hyperkalemia risk, especially in renal impairment or with K+ supplements","Hypotension","Renal function impairment","Sulfonamide allergy (hydrochlorothiazide)","Acute angle-closure glaucoma","Systemic lupus erythematosus exacerbation"] |
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| Monitor maternal blood pressure, serum electrolytes (especially potassium, sodium), renal function, and urine output. Fetal ultrasound for growth and amniotic fluid volume. Neonatal assessment for electrolyte imbalances and hypotension. |
| Fertility Effects | No direct evidence of impaired fertility. However, thiazides may occasionally cause reversible gynecomastia or sexual dysfunction in males. No specific impact on female fertility reported. |