LEVOPHED
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 169.18 |
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 | Norepinephrine is generally avoided in the first trimester due to potential for reduced uterine blood flow and risk of fetal hypoxia, with some teratogenicity concerns in animal studies. |
| 2nd trimester | Use with caution during the second trimester; may be used if clearly indicated, as the risk of placental insufficiency must be weighed against maternal benefit. |
| 3rd trimester | Use in the third trimester is reserved for severe hypotension. May cause uterine vasoconstriction and fetal distress; monitor fetal heart rate closely. |
Clinical note
Comprehensive clinical and safety monograph for LEVOPHED (LEVOPHED).
| Placental transfer | Norepinephrine crosses the placenta to a limited extent; however, placental transfer is variable and may increase under conditions of maternal stress or high doses. It can cause placental vasoconstriction, potentially reducing fetal oxygen delivery. |
| Breastfeeding | Norepinephrine has very low oral bioavailability and is rapidly metabolized, making significant transfer into breast milk unlikely. However, intravenous administration to the mother may produce high maternal levels; caution is advised. Monitor infant for signs of sympathetic stimulation (e.g., tachycardia, hypertension) if used in lactating women. |
| Lactation Rating | L3 - Moderately Safe |
| 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. |
| 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. |
■ FDA Black Box Warning
No FDA boxed warning exists for LEVOPHED.
| Serious Effects |
Hypersensitivity to norepinephrine or any component of the formulationPre-existing severe hypertensionPeripheral or mesenteric vascular thrombosis (risk of ischemia and gangrene)Hypovolemia (should be corrected prior to administration)Use with halogenated hydrocarbon anesthetics (e.g., cyclopropane, halothane) due to risk of severe ventricular arrhythmias
| 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 |
| Food/Dietary | No clinically significant food interactions. Monitor for hyperglycemia in diabetic patients due to alpha-adrenergic effects. |
| Clinical Pearls | LEVOPHED (norepinephrine) is a first-line vasopressor for septic shock. Administer via central line to avoid extravasation injury; if extravasation occurs, treat with phentolamine 5-10 mg in 10 mL saline infiltrated locally. Titrate to mean arterial pressure (MAP) ≥ 65 mmHg. Taper gradually to avoid rebound hypotension. |
| Patient Advice | This medication is used to treat dangerously low blood pressure. · It will be given intravenously (IV) in a hospital setting by healthcare professionals. · You may feel anxiety, headache, or heart palpitations as the medication works. · Report any pain, redness, or swelling at the IV site immediately. · Do not stop the medication abruptly; it must be tapered under medical supervision. |
Loading safety data…