INDERIDE-40/25
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INDERIDE-40/25 (INDERIDE-40/25).
Inderide-40/25 is a combination of propranolol (non-cardioselective beta-blocker) and hydrochlorothiazide (thiazide diuretic). Propranolol reduces heart rate, myocardial contractility, and renin secretion via beta-adrenergic receptor blockade. Hydrochlorothiazide inhibits Na+/Cl- cotransporter in distal convoluted tubule, increasing excretion of Na+, Cl-, and water; also reduces peripheral vascular resistance.
| Metabolism | Propranolol: extensively metabolized by CYP2D6 and CYP1A2 to active metabolite 4-hydroxypropranolol; also undergoes glucuronidation. Hydrochlorothiazide: not metabolized, excreted unchanged by kidneys. |
| Excretion | Propranolol: extensively metabolized in liver via CYP2D6 and glucuronidation; <1% excreted unchanged in urine. Hydrochlorothiazide: ~70% excreted unchanged in urine via tubular secretion. |
| Half-life | Propranolol: 3-6 hours (terminal); clinical context: dosing 2-3 times daily due to short half-life; may accumulate in hepatic impairment. Hydrochlorothiazide: 6-15 hours (terminal); clinical context: longer in renal impairment. |
| Protein binding | Propranolol: 90% bound primarily to albumin; hydrochlorothiazide: 40-68% bound to plasma proteins. |
| Volume of Distribution | Propranolol: 3.0-4.7 L/kg (extensive tissue distribution; crosses blood-brain barrier). Hydrochlorothiazide: 0.8-1.2 L/kg (confined to extracellular fluid). |
| Bioavailability | Propranolol: absolute oral bioavailability ~30% due to extensive first-pass metabolism; range 20-70% interindividual. Hydrochlorothiazide: oral bioavailability ~60-80% (50-80% in some sources). |
| Onset of Action | Oral: propranolol antihypertensive effect within 2-4 hours; hydrochlorothiazide diuresis within 2 hours. Peak effect at 1-3 days for blood pressure reduction. |
| Duration of Action | Propranolol: 6-12 hours (antihypertensive effect); dosing every 6-12 hours. Hydrochlorothiazide: 6-12 hours (diuresis); antihypertensive effect persists up to 24 hours. |
| Molecular Weight | Propranolol HCl: 295.81 Da; Hydrochlorothiazide: 297.75 Da. Combined product: Inderide-40/25 is a combination, but individual components have these weights. |
One tablet (40 mg propranolol HCl/25 mg hydrochlorothiazide) orally twice daily; may increase to maximum of 160 mg propranolol/100 mg hydrochlorothiazide per day in divided doses.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-50 mL/min: reduce dose by 50% or use alternative. For GFR <30 mL/min: contraindicated due to hydrochlorothiazide component. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce propranolol dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for use in children; safety and efficacy not established. |
| Geriatric use | Initiate at lowest dose (one tablet once daily) and titrate slowly; monitor for hypotension, bradycardia, and electrolyte disturbances. |
| 1st trimester | Risk of fetal bradycardia, hypotension, and hypoglycemia. Use only if maternal benefit outweighs risk. |
| 2nd trimester | May cause intrauterine growth restriction. Monitor fetal growth. |
| 3rd trimester | Risk of neonatal bradycardia, hypotension, and hypoglycemia. Avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for INDERIDE-40/25 (INDERIDE-40/25).
| Placental transfer | Propranolol crosses the placenta (fetal concentrations ~40-50% maternal). Hydrochlorothiazide crosses the placenta. |
| Breastfeeding | Propranolol and hydrochlorothiazide are excreted into breast milk. Monitor infant for bradycardia, hypotension, and diuretic effects. Use with caution, especially in premature infants. |
| Lactation Rating |
■ FDA Black Box Warning
Exacerbation of angina and myocardial infarction upon abrupt discontinuation: Beta-blocker withdrawal may precipitate angina and, in patients with coronary artery disease, myocardial infarction. Taper dose gradually over 1-2 weeks.
| Serious Effects |
Bronchial asthmaSinus bradycardiaHeart block greater than first degreeCardiogenic shockOvert cardiac failureAnuriaHypersensitivity to hydrochlorothiazide or sulfonamide-derived drugs
| Precautions | Abrupt discontinuation, bronchospasm in asthmatics, masking of hypoglycemia in diabetics, bradycardia/heart block, worsening heart failure, hypotension, electrolyte disturbances (hypokalemia, hyponatremia), hyperuricemia, acute angle-closure glaucoma, exacerbation of peripheral vascular disease. |
| Food/Dietary | Avoid excessive salt intake; potassium-rich foods (bananas, oranges) may be beneficial but monitor potassium levels if on other potassium-altering drugs. Grapefruit juice may increase propranolol levels; avoid concurrent use. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Avoid use due to possible association with congenital malformations (e.g., cardiovascular defects) based on limited studies. Second and third trimesters: Associated with fetal bradycardia, intrauterine growth restriction, oligohydramnios, and neonatal hypoglycemia. Risk of hypoperfusion and hypoxia in fetus if maternal hypotension occurs. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, serum electrolytes, renal function, fetal growth, amniotic fluid index, fetal heart rate (bradycardia risk). Neonatal: Monitor for hypoglycemia, bradycardia, and respiratory depression after delivery. |
| Fertility Effects | No established direct effects on fertility. Beta-blockers may impair male libido and erectile function; thiazide diuretics may alter menstrual cycle or cause gynecomastia. |
| Clinical Pearls | Inderide 40/25 (propranolol 40mg/hydrochlorothiazide 25mg) is a fixed-dose combination for hypertension. Propranolol is a non-selective beta-blocker; avoid in asthma, COPD, and heart block. Hydrochlorothiazide may cause hypokalemia; monitor electrolytes. Use with caution in diabetes (masks hypoglycemia) and peripheral vascular disease. Taper beta-blockers slowly to avoid rebound hypertension. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · May cause dizziness or fatigue; avoid driving until effects known. · Avoid sudden discontinuation; can cause rapid heart rate or hypertension. · Limit alcohol and NSAIDs; they may increase blood pressure or reduce effect. · Report shortness of breath, unusual weight gain, or swelling of extremities. · Monitor blood pressure regularly and keep appointments for lab tests (potassium, renal function). · May increase sensitivity to cold; dress warmly. |