METOPROLOL SUCCINATE
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.
Selective beta-1 adrenergic receptor antagonist; reduces heart rate, myocardial contractility, and blood pressure by blocking catecholamine effects at beta-1 receptors. Also suppresses renin release.
| Metabolism | Primarily hepatic via CYP2D6; forms inactive metabolites (including O-demethylmetoprolol). |
| Excretion | Primarily renal (95% as metabolites, <5% unchanged). Three main metabolites: O-demethylated (active), α-hydroxylated (active), and O-demethylated and α-hydroxylated. Biliary/fecal excretion: <5%. |
| Half-life | Terminal elimination half-life: 3-7 hours. Twice-daily dosing (metoprolol succinate) provides stable beta-blockade over 24 hours due to extended-release formulation, not due to half-life. |
| Protein binding | Approximately 12% bound to albumin; low binding is clinically insignificant. |
| Volume of Distribution | Vd: 4.5 L/kg (range 3.2-5.6 L/kg). Large Vd indicates extensive tissue distribution, preferentially to heart, lungs, and kidneys. |
| Bioavailability | Oral: 50-70% (first-pass effect; interindividual variability). Immediate-release: 50%; extended-release: 50-60%. IV: 100%. |
| Onset of Action | Oral: Extended-release (succinate): 1-2 hours to initial beta-blockade; full effect in 1-2 weeks. IV (tartrate, not succinate): rapid, within 5 minutes. |
| Duration of Action | Oral: Extended-release (succinate): 24 hours; once-daily dosing. Immediate-release (tartrate): 6-12 hours. Clinical effect persists for duration of dosing interval. |
25 to 100 mg orally once daily, titrated at weekly intervals as tolerated; maximum 400 mg/day
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for GFR >30 mL/min; for GFR 10-30 mL/min, reduce dose by 50%; for GFR <10 mL/min, use with caution and 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 | 1 to 2 mg/kg orally once daily; maximum 200 mg/day; for hypertension: initial 0.5-1 mg/kg/day, titrate to response |
| Geriatric use | Start at lower end of dosing range (25 mg once daily); titrate slowly; monitor for bradycardia and hypotension |
| 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 | Metoprolol excreted into breast milk. M/P ratio 1.0-1.5. Infant dose approx 1.5% maternal weight-adjusted dose. Considered compatible with breastfeeding; monitor infant for bradycardia, hypotension, and sedation. |
| Teratogenic Risk | First trimester: Metoprolol crosses placenta. Human data limited but unlikely major malformations. Second/third trimesters: Risk of fetal bradycardia, intrauterine growth restriction, neonatal hypotension, hypoglycemia, and respiratory depression. Avoid use near term unless maternal benefit outweighs fetal risk. |
■ FDA Black Box Warning
No FDA black box warning for metoprolol succinate; however, abrupt discontinuation may exacerbate angina or precipitate myocardial infarction in patients with coronary artery disease.
| Common Effects | angina |
| Serious Effects |
["Sinus bradycardia","Second or third degree AV block","Cardiogenic shock","Decompensated heart failure","Sick sinus syndrome (unless pacemaker present)","Hypersensitivity to metoprolol or any component","Severe peripheral arterial disease","Pheochromocytoma (unless alpha-blocked)"]
| Precautions | ["Abrupt withdrawal may exacerbate angina or cause MI","Bradycardia and heart block","Mask symptoms of hypoglycemia in diabetics","Mask tachycardias due to hyperthyroidism","Exacerbation of peripheral vascular disease","May worsen heart failure if not titrated properly","Use with caution in patients with hepatic impairment","Anaphylaxis may be resistant to epinephrine","May potentiate anesthesia-induced bradycardia"] |
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| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and signs of heart failure. Fetal ultrasound for growth restriction. Neonatal monitoring for bradycardia, hypoglycemia, and respiratory depression after delivery. |
| Fertility Effects | No known adverse effects on fertility in humans. In animal studies, no impairment of fertility at doses up to 100 mg/kg/day. |