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. |
| Molecular Weight | Propranolol: 259.34 Da; Hydrochlorothiazide: 297.74 Da; Fixed combination: 259.34 + 297.74 = 557.08 Da (not additive in formulation, but individual weights) |
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 | Propranolol crosses the placenta. Use in first trimester associated with risk of congenital anomalies (e.g., cardiovascular defects) in some studies. Avoid unless benefit outweighs risk. |
| 2nd trimester | Use only if clearly needed; may cause fetal bradycardia, growth restriction, or other adverse effects. Monitor fetal heart rate and growth. |
| 3rd trimester | Contraindicated near term due to risk of neonatal bradycardia, hypoglycemia, and respiratory depression. Discontinue prior to delivery if possible. |
Clinical note
Comprehensive clinical and safety monograph for INDERIDE-80/25 (INDERIDE-80/25).
| Placental transfer | Both propranolol (lipid-soluble) and hydrochlorothiazide cross the placenta. Propranolol achieves fetal serum concentrations similar to maternal. Hydrochlorothiazide crosses but to a lesser extent. |
| Breastfeeding | Propranolol and hydrochlorothiazide are excreted into breast milk in low amounts. Monitor infant for bradycardia, hypotension, and hypoglycemia. Hydrochlorothiazide may suppress lactation. Use with caution. |
■ FDA Black Box Warning
Exacerbation of angina pectoris and myocardial infarction upon abrupt discontinuation of beta-blockade; taper dose gradually.
| Serious Effects |
Bronchial asthma or COPD with bronchospasmSinus bradycardia or sick sinus syndrome (without pacemaker)Second- or third-degree atrioventricular blockCardiogenic shockDecompensated heart failure (unless controlled with digoxin and diuretics)AnuriaHypersensitivity to propranolol, hydrochlorothiazide, or sulfonamide derivatives
| 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. |
| Food/Dietary | Avoid high-sodium foods to prevent blunting of antihypertensive effect. Limit potassium-rich foods (bananas, oranges) due to hyperkalemia risk from HCTZ. Grapefruit juice may increase propranolol levels. Alcohol may potentiate hypotension. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Combination product of propranolol (80 mg) and hydrochlorothiazide (25 mg). Propranolol is a non-selective beta-blocker; contraindicated in asthma, bradycardia, and heart block. Monitor for bronchospasm, hypoglycemia (masks symptoms), and bradycardia. Hydrochlorothiazide (HCTZ) is a thiazide diuretic; check electrolytes, renal function, and for gout/hyperuricemia. Titrate doses separately before switching to combination. Avoid abrupt withdrawal of beta-blocker (risk of myocardial ischemia). |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning to avoid nocturia. · Do not stop abruptly; consult doctor before discontinuing (risk of chest pain or heart attack). · May cause dizziness or lightheadedness; avoid driving if affected. · Report slow heartbeat, fainting, difficulty breathing, or swelling. · Monitor for increased blood sugar if diabetic; beta-blockers may hide signs of low blood sugar. · Avoid excessive sweating or dehydration; stay well-hydrated. · Limit alcohol and caffeine intake as they may affect blood pressure. · Use sunscreen; medication may increase sensitivity to sunlight. |