INDERIDE-80/25
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INDERIDE-80/25 (INDERIDE-80/25).
INDERIDE-80/25 is a combination of propranolol (a non-selective beta-adrenergic receptor antagonist) and hydrochlorothiazide (a thiazide diuretic). Propranolol blocks beta-1 and beta-2 adrenergic receptors, reducing heart rate, myocardial contractility, and renin release, thereby lowering blood pressure. Hydrochlorothiazide inhibits the sodium-chloride symporter in the distal convoluted tubule of the kidney, increasing excretion of sodium, chloride, and water, reducing plasma volume.
| Metabolism | Propranolol is extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP2D6 and CYP1A2, forming active metabolites (e.g., 4-hydroxypropranolol). Hydrochlorothiazide is not metabolized and is excreted unchanged in urine. |
| Excretion | Renal: 40% unchanged propranolol; 60% as metabolites. Biliary/fecal: minimal (less than 1%). Hydrochlorothiazide: renal 95% unchanged. |
| Half-life | Propranolol: 3-6 hours (single dose), prolonged with chronic dosing (up to 12 hours). Hydrochlorothiazide: 6-15 hours; prolonged in renal impairment. |
| Protein binding | Propranolol: 90-95% bound to albumin; hydrochlorothiazide: 68% bound to albumin. |
| Volume of Distribution | Propranolol: 4 L/kg (large Vd due to lipophilicity); hydrochlorothiazide: 0.8 L/kg (restricted to extracellular fluid). |
| Bioavailability | Propranolol: 30% (oral) due to extensive first-pass metabolism; bioavailability increased with food or chronic dosing. Hydrochlorothiazide: 65-70% (oral). |
| Onset of Action | Oral: propranolol antihypertensive effect in 1-2 hours; hydrochlorothiazide diuresis in 2 hours. Max effect: 1-2 weeks for BP. |
| Duration of Action | Propranolol: 6-12 hours (BP control). Hydrochlorothiazide: 6-12 hours (diuresis). Dose-dependent: once-daily dosing effective. |
One tablet (80 mg propranolol/25 mg hydrochlorothiazide) orally twice daily.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: reduce dose or extend interval; GFR <30 mL/min: contraindicated due to hydrochlorothiazide component. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for children; safety and efficacy not established. |
| Geriatric use | Initiate at lowest dose; monitor renal function and orthostatic hypotension; adjust based on response and tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INDERIDE-80/25 (INDERIDE-80/25).
| Breastfeeding | Propranolol is excreted into breast milk in small amounts; the M/P ratio is approximately 0.3-0.5. Infant dose is less than 1% of maternal weight-adjusted dose, considered compatible with breastfeeding. Hydrochlorothiazide is also excreted into breast milk, but levels are low; M/P ratio unknown. However, thiazides may suppress lactation and cause neonatal electrolyte disturbances. Use with caution, especially in newborns with impaired renal function. |
| Teratogenic Risk | INDERIDE-80/25 contains propranolol (a beta-blocker) and hydrochlorothiazide (a thiazide diuretic). Propranolol: First trimester: limited human data, no clear increased risk of major malformations, but possible fetal bradycardia and growth restriction; Second and third trimesters: risk of intrauterine growth restriction, neonatal hypoglycemia, bradycardia, and respiratory depression at delivery. Hydrochlorothiazide: First trimester: based on limited data, no major teratogenic risk; Second and third trimesters: may cause fetal or neonatal jaundice, thrombocytopenia, electrolyte disturbances, and potential placental hypoperfusion. |
■ FDA Black Box Warning
Exacerbation of angina pectoris and myocardial infarction upon abrupt discontinuation of beta-blockade; taper dose gradually.
| Serious Effects |
Bronchial asthma, sinus bradycardia, heart block (greater than first degree), cardiogenic shock, decompensated heart failure, anuria (for hydrochlorothiazide component), hypersensitivity to any component.
| Precautions | May exacerbate heart failure, bronchospasm, and mask hypoglycemia in diabetic patients. Use caution in patients with renal impairment (monitor electrolytes and renal function). Hydrochlorothiazide can cause electrolyte imbalances, hyperglycemia, and hyperuricemia. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of bronchospasm or heart failure. In pregnancy, assess fetal growth via ultrasound every 4-6 weeks due to risk of intrauterine growth restriction. Fetal heart rate monitoring may detect bradycardia. Neonates should be observed for hypoglycemia, bradycardia, and respiratory depression. In mothers, monitor serum electrolytes, uric acid, and renal function due to hydrochlorothiazide. |
| Fertility Effects | Propranolol may rarely cause decreased libido or erectile dysfunction in males, but no significant effects on female fertility. Hydrochlorothiazide has no known direct impact on fertility. Overall, INDERIDE-80/25 is not expected to impair fertility but caution in patients with underlying conditions. |