INDERAL LA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INDERAL LA (INDERAL LA).

How it works

Propranolol is a non-selective beta-adrenergic receptor antagonist that competitively blocks beta-1 and beta-2 receptors, decreasing heart rate, myocardial contractility, and blood pressure; also inhibits renin release and reduces sympathetic outflow.

What the body does with it

Metabolism	Primarily hepatic via CYP2D6 (major) and CYP1A2, CYP2C19; extensive first-pass metabolism; metabolites include 4-hydroxypropranolol (active).
Excretion	Primarily hepatic metabolism with renal elimination of metabolites. Less than 1% excreted unchanged in urine. Biliary/fecal excretion of metabolites accounts for approximately 20% of eliminated dose.
Half-life	Terminal elimination half-life is 8-11 hours (range 4-16 hours) after oral administration. The extended-release formulation (INDERAL LA) results in a prolonged half-life of approximately 10 hours, allowing once-daily dosing.
Protein binding	Approximately 90% bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein.
Volume of Distribution	Vd is 4 L/kg (range 3-6 L/kg) in adults. This large Vd indicates extensive distribution into tissues, including brain and lungs, consistent with its lipophilicity.
Bioavailability	Oral bioavailability is 30% (range 20-40%) due to extensive first-pass hepatic metabolism. INDERAL LA has similar bioavailability to immediate-release but with reduced peak-to-trough fluctuations.
Onset of Action	Oral: 1-2 hours for beta-blockade (reduction in heart rate/contractility). Peak effect at 4-6 hours. Intravenous: immediate onset within minutes.
Duration of Action	Oral immediate-release: 6-12 hours. INDERAL LA: 24 hours due to sustained-release formulation, providing stable plasma concentrations over 24 hours once steady state is achieved.

Classification & Brands

Action Class	Beta blocker- Non selective
Brand Substitutes	Proparise 80mg Tablet, Ciplar-LA 80 Tablet

Dosing & administration

Initial: 80 mg orally once daily; titrate to 120-160 mg once daily; maximum 640 mg/day.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: reduce dose by 50%; CrCl <10 mL/min: reduce dose by 75%.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduce dose by 75%.
Pediatric use	Hypertension: initial 0.5-1 mg/kg/day orally once daily; maximum 4 mg/kg/day up to 640 mg/day.
Geriatric use	Start at 80 mg once daily; titrate cautiously; monitor for bradycardia, hypotension, and bronchospasm.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for INDERAL LA (INDERAL LA).

Breastfeeding	Limited human data; propranolol is excreted in breast milk with an M/P ratio of approximately 0.2. It is considered compatible with breastfeeding, but monitor infant for bradycardia and hypoglycemia.
Teratogenic Risk	First trimester: limited data; associated with intrauterine growth restriction (IUGR) if used in second/third trimester. Avoid use if possible; use only if benefit outweighs risk.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

DO NOT abruptly discontinue therapy as it may precipitate myocardial infarction, ventricular arrhythmias, or severe hypertension; taper dose gradually over 1-2 weeks.

Side Effect Profile

Serious Effects

Absolute Contraindications

Cardiogenic shock, sinus bradycardia, heart block greater than first degree, severe asthma or bronchospastic disease, sick sinus syndrome, decompensated heart failure, known hypersensitivity to propranolol.

Clinical Precautions

Precautions

May mask signs of hypoglycemia in diabetic patients; use with caution in patients with bronchospastic diseases (e.g., asthma), heart failure, or peripheral vascular disease; may cause bradycardia, hypotension, or Raynaud's phenomenon; may worsen AV conduction disturbances.

Clinical Tips & Counseling

Drug interactions

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INDERAL LA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INDERAL LA (INDERAL LA).

How it works

What the body does with it

Metabolism	Primarily hepatic via CYP2D6 (major) and CYP1A2, CYP2C19; extensive first-pass metabolism; metabolites include 4-hydroxypropranolol (active).
Excretion	Primarily hepatic metabolism with renal elimination of metabolites. Less than 1% excreted unchanged in urine. Biliary/fecal excretion of metabolites accounts for approximately 20% of eliminated dose.
Half-life	Terminal elimination half-life is 8-11 hours (range 4-16 hours) after oral administration. The extended-release formulation (INDERAL LA) results in a prolonged half-life of approximately 10 hours, allowing once-daily dosing.
Protein binding	Approximately 90% bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein.
Volume of Distribution	Vd is 4 L/kg (range 3-6 L/kg) in adults. This large Vd indicates extensive distribution into tissues, including brain and lungs, consistent with its lipophilicity.
Bioavailability	Oral bioavailability is 30% (range 20-40%) due to extensive first-pass hepatic metabolism. INDERAL LA has similar bioavailability to immediate-release but with reduced peak-to-trough fluctuations.
Onset of Action	Oral: 1-2 hours for beta-blockade (reduction in heart rate/contractility). Peak effect at 4-6 hours. Intravenous: immediate onset within minutes.
Duration of Action	Oral immediate-release: 6-12 hours. INDERAL LA: 24 hours due to sustained-release formulation, providing stable plasma concentrations over 24 hours once steady state is achieved.

Classification & Brands

Action Class	Beta blocker- Non selective
Brand Substitutes	Proparise 80mg Tablet, Ciplar-LA 80 Tablet

Dosing & administration

Initial: 80 mg orally once daily; titrate to 120-160 mg once daily; maximum 640 mg/day.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: reduce dose by 50%; CrCl <10 mL/min: reduce dose by 75%.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduce dose by 75%.
Pediatric use	Hypertension: initial 0.5-1 mg/kg/day orally once daily; maximum 4 mg/kg/day up to 640 mg/day.
Geriatric use	Start at 80 mg once daily; titrate cautiously; monitor for bradycardia, hypotension, and bronchospasm.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for INDERAL LA (INDERAL LA).

Breastfeeding	Limited human data; propranolol is excreted in breast milk with an M/P ratio of approximately 0.2. It is considered compatible with breastfeeding, but monitor infant for bradycardia and hypoglycemia.
Teratogenic Risk	First trimester: limited data; associated with intrauterine growth restriction (IUGR) if used in second/third trimester. Avoid use if possible; use only if benefit outweighs risk.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

DO NOT abruptly discontinue therapy as it may precipitate myocardial infarction, ventricular arrhythmias, or severe hypertension; taper dose gradually over 1-2 weeks.