LEVOPHED
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVOPHED (LEVOPHED).
Norepinephrine acts predominantly on alpha-1 adrenergic receptors to cause vasoconstriction and increase blood pressure. It also has beta-1 adrenergic receptor agonist activity, resulting in positive inotropic effects on the heart.
| Metabolism | Primarily metabolized in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). |
| Excretion | Norepinephrine is primarily metabolized in the liver and other tissues by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Less than 5% is excreted unchanged in urine. Metabolites are excreted renally (approximately 80-95% as normetanephrine, vanillylmandelic acid, and other conjugates). |
| Half-life | The terminal elimination half-life is approximately 2 minutes. The clinical effect is short-lived due to rapid reuptake and metabolism; continuous intravenous infusion is required for sustained effect. |
| Protein binding | Approximately 25-30% bound to albumin and other plasma proteins. |
| Volume of Distribution | Approximately 0.7-1.0 L/kg. This indicates moderate distribution into tissues and plasma, consistent with a hydrophilic catecholamine. |
| Bioavailability | Bioavailability is 100% via intravenous administration. Oral bioavailability is negligible due to extensive first-pass metabolism; not administered orally. Intramuscular or subcutaneous administration results in erratic absorption and significant vasoconstriction leading to poor bioavailability; thus, intravenous infusion is the only reliable route. |
| Onset of Action | Intravenous: Immediate (within 1-2 minutes). |
| Duration of Action | Intravenous: 1-2 minutes after infusion is discontinued; effect wanes rapidly as the drug is cleared. |
Initial dose: 8-12 mcg/min intravenously, titrate to desired blood pressure; typical maintenance: 2-4 mcg/min IV continuous infusion.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for renal impairment; titrate to clinical response. |
| Liver impairment | No specific dose adjustment required for hepatic impairment; titrate to clinical response. |
| Pediatric use | Initial: 0.05-0.1 mcg/kg/min IV continuous infusion, titrate to effect; maximum dose not established. |
| Geriatric use | Start at lower end of dosing range (2-4 mcg/min IV) due to increased sensitivity and comorbidities; titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVOPHED (LEVOPHED).
| Breastfeeding | Norepinephrine is not expected to be excreted into breast milk in clinically significant amounts due to its short half-life and rapid metabolism. M/P ratio not established. Use with caution in breastfeeding women, as effects on the infant are unknown. |
| Teratogenic Risk | Norepinephrine is a catecholamine that does not cross the placenta extensively. Animal studies have not shown teratogenicity, but human data are limited. Inadequate uteroplacental blood flow due to maternal vasoconstriction may cause fetal hypoxia and bradycardia. Use only if clearly needed, and monitor fetal heart rate. FDA Pregnancy Category C. |
■ FDA Black Box Warning
No FDA boxed warning exists for LEVOPHED.
| Serious Effects |
["Hypersensitivity to norepinephrine or any component of the formulation","Hypovolemia (should be corrected before or during therapy)","Use with cyclopropane or halothane anesthesia (increases risk of ventricular arrhythmias)","Severe peripheral vascular disease with risk of gangrene"]
| Precautions | ["Risk of extravasation leading to tissue necrosis; ensure proper IV access and avoid infiltration","Monitor blood pressure, heart rate, and cardiac output continuously","May cause ischemia to limbs, kidneys, and splanchnic organs due to vasoconstriction","Use with caution in patients with hypertension, hyperthyroidism, or myocardial ischemia","Abrupt discontinuation may cause rebound hypotension"] |
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| Fetal Monitoring | Continuous maternal blood pressure, heart rate, and ECG monitoring; assess uterine activity and fetal heart rate if pregnant; monitor for signs of extravasation; assess peripheral perfusion and urine output. |
| Fertility Effects | No specific studies on human fertility. Animal studies have not shown impairment of fertility. However, severe vasoconstriction may affect reproductive organ perfusion, potentially impacting fertility. |