PROPRANOLOL HYDROCHLORIDE
Clinical safety rating: caution
Other drugs that lower heart rate or blood pressure can have additive effects Abrupt withdrawal may exacerbate angina pectoris or cause myocardial infarction.
Non-selective beta-adrenergic receptor antagonist that blocks catecholamine effects at beta-1 and beta-2 receptors, reducing heart rate, myocardial contractility, and blood pressure; also suppresses renin release and decreases sympathetic outflow.
| Metabolism | Primarily hepatic via CYP2D6 and CYP1A2; also glucuronidation. |
| Excretion | Hepatic metabolism (extensive first-pass) to inactive metabolites; <1% excreted unchanged in urine; renal elimination of metabolites (~90% as glucuronide and sulfate conjugates); biliary/fecal elimination minimal. |
| Half-life | 3-6 hours (terminal half-life), prolonged in hepatic impairment (up to 10-12 hours) and in elderly; half-life ~1-2 hours after IV administration; clinically, twice-daily dosing is sufficient due to sustained pharmacodynamic effect despite short half-life. |
| Protein binding | 90-95% bound to albumin; binding is saturable at high doses. |
| Volume of Distribution | 3-4 L/kg; distributes extensively into tissues, crosses blood-brain barrier and placenta. |
| Bioavailability | Oral: 30% (due to high first-pass metabolism; range 25-50%); IV: 100%; bioavailability increased in hepatic disease and with food. |
| Onset of Action | Oral: 30-60 minutes; IV: 2-3 minutes; peak effect oral: 1-2 hours. |
| Duration of Action | Oral: 6-12 hours (antihypertensive effect may persist up to 24 hours with chronic therapy); IV: 3-4 hours; sustained-release formulations: 24 hours. |
Adults: 40 mg orally twice daily, increased gradually to 160-320 mg/day divided into 2-3 doses; maximum 640 mg/day. For hypertension: 80 mg orally twice daily, titrated to 120-240 mg/day. For migraine prophylaxis: 80 mg orally daily in divided doses, up to 160-240 mg/day. For angina: 80-320 mg orally divided into 2-4 doses. For essential tremor: 40 mg orally twice daily, up to 320 mg/day. For thyrotoxicosis: 10-40 mg orally every 6 hours. For IV use: 1-3 mg slow IV bolus (1 mg/min), repeated every 2-5 minutes up to total of 5 mg under continuous monitoring.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For GFR <10 mL/min: use with caution; reduce dose by 50% and monitor for bradycardia and hypotension. For hemodialysis: not significantly removed; administer after dialysis if needed. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 40-50% and titrate slowly. Child-Pugh Class C: contraindicated or use with extreme caution; consider alternative agent. Hepatic impairment increases bioavailability due to reduced first-pass metabolism. |
| Pediatric use | Hypertension: initial 0.5-1 mg/kg/day orally divided every 6-12 hours; maximum 16 mg/kg/day. Arrhythmias: 0.5-1 mg/kg/day in divided doses every 6-8 hours; maximum 60 mg/day. Migraine prophylaxis (≥10 years): 10-20 mg orally 3 times daily, up to 60 mg/day. IV: 0.01-0.15 mg/kg slow IV over 10 minutes, not to exceed 1 mg/dose for infants; repeat every 6-8 hours as needed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that lower heart rate or blood pressure can have additive effects Abrupt withdrawal may exacerbate angina pectoris or cause myocardial infarction.
| FDA category | Animal |
| Breastfeeding | Propranolol is excreted into breast milk with an estimated milk-to-plasma (M/P) ratio of approximately 0.5. Infant doses are low (less than 1% of maternal weight-adjusted dose). Use is generally considered compatible with breastfeeding, but monitor infant for signs of bradycardia or hypotension if mother is on high doses. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | angina |
| Serious Effects |
["Cardiogenic shock","Sinus bradycardia","Heart block greater than first degree","Uncompensated heart failure","Bronchial asthma","Hypersensitivity to propranolol"]
| Precautions | ["Abrupt discontinuation may exacerbate angina or MI","May mask signs of hypoglycemia in diabetics","May precipitate heart failure in patients with poor cardiac reserve","Bronchospasm in patients with asthma or COPD","Peripheral vascular disease exacerbation","May mask thyrotoxicosis symptoms","Hypotension and bradycardia","Use with calcium channel blockers may cause AV block","Impaired hepatic or renal function"] |
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| Geriatric use | Start at lowest effective dose, typically 10-20 mg orally twice daily for hypertension; titrate slowly. Increased sensitivity to bradycardia and hypotension; monitor heart rate and blood pressure closely. Avoid doses >160 mg/day unless carefully titrated. Consider reduced renal function and potential for drug interactions. |
| First trimester: Population-based studies have not consistently demonstrated a major increase in congenital malformations with propranolol use. However, beta-blockers as a class have been associated with fetal bradycardia and hypoglycemia. Second and third trimesters: Risks include intrauterine growth restriction (IUGR), preterm birth, and neonatal bradycardia, hypotension, and hypoglycemia. Avoid use in the third trimester if possible or monitor neonate closely. |
| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and glucose levels regularly. Fetal monitoring includes serial ultrasound for growth (due to risk of IUGR), fetal heart rate monitoring, and biophysical profile in third trimester. Neonatal monitoring for bradycardia, hypoglycemia, and respiratory depression for 24-48 hours after delivery. |
| Fertility Effects | Propranolol has no known direct effects on fertility. However, underlying conditions treated with propranolol (e.g., hypertension, migraines) may affect fertility. Limited data suggest no significant impairment of reproductive function. |