INDERIDE-40/25

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INDERIDE-40/25 (INDERIDE-40/25).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for INDERIDE-40/25 (INDERIDE-40/25).

Breastfeeding	Both propranolol and hydrochlorothiazide are excreted into breast milk. Propranolol milk-to-plasma ratio approximately 1.0. Hydrochlorothiazide M/P ratio 0.1–0.8. Use caution: potential for adverse effects in nursing infant (bradycardia, hypotension, electrolyte disturbances).
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Cardiogenic shock, sinus bradycardia, second- or third-degree AV block, severe asthma or COPD, hypersensitivity to sulfonamide-derived drugs (hydrochlorothiazide), anuria, concomitant treatment with MAOIs (except MAO-B inhibitors).

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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INDERIDE-40/25

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INDERIDE-40/25 (INDERIDE-40/25).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for INDERIDE-40/25 (INDERIDE-40/25).

Breastfeeding	Both propranolol and hydrochlorothiazide are excreted into breast milk. Propranolol milk-to-plasma ratio approximately 1.0. Hydrochlorothiazide M/P ratio 0.1–0.8. Use caution: potential for adverse effects in nursing infant (bradycardia, hypotension, electrolyte disturbances).
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.