NORMODYNE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORMODYNE (NORMODYNE).
Competitive antagonist at beta-1 adrenergic receptors with additional alpha-1 adrenergic receptor blocking activity, resulting in vasodilation and decreased heart rate, contractility, and cardiac output.
| Metabolism | Primarily hepatic via glucuronidation and sulfation; first-pass effect; CYP2D6 minor role. |
| Excretion | Renal: 55-65% as unchanged drug and metabolites; Fecal: ~20% via bile; Hepatic metabolism: ~25% |
| Half-life | 8-12 hours; extended in hepatic impairment (up to 20 hours) and renal impairment (up to 15 hours) |
| Protein binding | Labetalol: ~50% bound to albumin |
| Volume of Distribution | 11 L/kg (extensive tissue distribution, including placenta and breast milk) |
| Bioavailability | Oral: 25-40% due to extensive first-pass metabolism; IV: 100% |
| Onset of Action | Oral: 30-60 minutes; IV: 5-10 minutes |
| Duration of Action | Oral: 8-12 hours; IV: 4-6 hours; duration may be prolonged in elderly or hepatic impairment |
Oral: Initial 100 mg twice daily, increase by 100 mg/day every 2 weeks; maintenance 200-400 mg twice daily. Max 1200 mg/day. IV: 20 mg (1 mL) over 2 minutes, repeat if needed at 10 min intervals up to total 300 mg.
| Dosage form | INJECTABLE |
| Renal impairment | GFR > 50 mL/min: No adjustment. GFR 10-50 mL/min: Reduce dose by 50% or prolong interval. GFR < 10 mL/min: Use with caution; consider 50% dose reduction. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Use with caution; reduce dose by 50%. Child-Pugh C: Contraindicated. |
| Pediatric use | Oral: 0.25-1 mg/kg/dose twice daily; increase gradually. Max 2 mg/kg/day (up to 120 mg/day). IV: 0.1-0.2 mg/kg over 2 minutes; may repeat every 10 min up to 1 mg/kg total. |
| Geriatric use | Start at lowest dose (100 mg twice daily oral); titrate slowly. Monitor orthostatic hypotension and bradycardia. IV use with caution; reduce initial dose to 10 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORMODYNE (NORMODYNE).
| Breastfeeding | Excreted in breast milk in low concentrations (M/P ratio ~1.3). Considered compatible with breastfeeding; monitor infant for bradycardia and hypotension. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Use may cause fetal hypotension, bradycardia, and growth restriction; risk of neonatal hypotension, bradycardia, and hypoglycemia if used near term. Avoid in preeclampsia due to risk of fetal distress. |
■ FDA Black Box Warning
Exacerbation of angina pectoris and myocardial infarction may occur following abrupt discontinuation of beta-blocker therapy.
| Serious Effects |
["Bronchial asthma","Sinus bradycardia","Heart block greater than first degree","Cardiogenic shock","Overt cardiac failure","Hypersensitivity to labetalol or any component"]
| Precautions | ["Congestive heart failure","Bronchospasm in patients with asthma/COPD","Hepatic injury","Hypotension/syncope","Masking of hypoglycemia in diabetics","Thyrotoxicosis symptoms masked","Abrupt discontinuation leading to rebound hypertension/angina"] |
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| Fetal Monitoring |
| Monitor maternal blood pressure and heart rate; fetal heart rate and growth; neonatal monitoring for hypotension, bradycardia, and hypoglycemia after delivery. |
| Fertility Effects | No known adverse effects on fertility in animal or human studies. |