NOREPINEPHRINE BITARTRATE
Clinical safety rating: safe
MAOIs can cause severe hypertension Extravasation can cause tissue necrosis and sloughing.
Norepinephrine is a sympathomimetic amine that acts as an agonist at alpha-1 and alpha-2 adrenergic receptors, and to a lesser extent at beta-1 receptors. Its primary effects include vasoconstriction (alpha-1) and increased cardiac contractility and heart rate (beta-1), leading to elevated blood pressure.
| Metabolism | Primarily metabolized in the liver via catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Also metabolized in the kidneys and other tissues. Major metabolites include normetanephrine and vanillylmandelic acid. |
| Excretion | Renal: 80-90% as inactive metabolites (vanillylmandelic acid, normetanephrine) and unchanged drug. Biliary/fecal: minimal (<5%). |
| Half-life | 2-3 minutes (terminal half-life). Clinically, steady state is achieved within 5-10 minutes of continuous IV infusion; effects dissipate rapidly after discontinuation. |
| Protein binding | 25-30% bound, primarily to serum albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | 0.2-0.4 L/kg; indicates limited distribution primarily in plasma and extracellular fluid. |
| Bioavailability | Oral: <1% (extensive first-pass metabolism). IV: 100%. |
| Onset of Action | IV: 1-2 minutes; intraosseous: similar to IV. |
| Duration of Action | 1-2 minutes after IV infusion cessation; effect duration is short due to rapid metabolism and reuptake, necessitating continuous infusion. |
IV continuous infusion: initial 0.5-1 mcg/min, titrate to target blood pressure; typical range 2-20 mcg/min; max 30 mcg/min.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required; titrate to clinical effect; monitor for extravasation and renal perfusion. |
| Liver impairment | No specific Child-Pugh based dose adjustments; consider reduced clearance in severe hepatic impairment; titrate cautiously. |
| Pediatric use | IV continuous infusion: 0.05-0.1 mcg/kg/min, titrate to effect; typical range up to 2 mcg/kg/min. |
| Geriatric use | Start at low end of adult dosing (0.5 mcg/min); titrate slowly due to increased vascular reactivity and risk of organ hypoperfusion. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause severe hypertension Extravasation can cause tissue necrosis and sloughing.
| FDA category | Animal |
| Breastfeeding | Norepinephrine is poorly excreted into breast milk due to its short half-life and rapid metabolism. The milk-to-plasma (M/P) ratio is likely very low (<0.1), but specific data are unavailable. Intravenous infusion results in minimal oral bioavailability in infants. The American Academy of Pediatrics considers it compatible with breastfeeding. However, caution is advised in mothers with compromised circulation or if the infant has cardiovascular instability. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | hypotension |
| Serious Effects |
["Hypersensitivity to norepinephrine or any component of the formulation","Hypotension due to hypovolemia unless volume resuscitation is underway","Patients with mesenteric or peripheral vascular thrombosis (risk of ischemia)","Use with cyclopropane or halothane anesthesia (risk of ventricular arrhythmias)"]
| Precautions | ["Extravasation: Risk of tissue necrosis; administer via central line if possible","Cardiovascular effects: May cause hypertension, bradycardia, arrhythmias, especially in patients with cardiac disease","Use with caution in patients with hypotension due to blood volume deficits (hypovolemia), as vasoconstriction may worsen tissue perfusion","May exacerbate hyperthyroidism, diabetes, or glaucoma","Abrupt discontinuation may cause rebound hypotension"] |
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| Norepinephrine bitartrate is a catecholamine that, when used at standard vasopressor doses, is not expected to increase the risk of congenital anomalies. However, maternal hypotension or hypoperfusion from inadequate treatment can cause fetal hypoxia and adverse outcomes. In the first trimester, limited animal studies show no teratogenicity at clinically relevant doses. In the second and third trimesters, the drug may reduce uteroplacental blood flow; however, maintaining maternal blood pressure is critical. There are no well-controlled human studies; risk is considered low when used for approved indications. |
| Fetal Monitoring | Continuous maternal heart rate, blood pressure, and ECG monitoring are required during infusion. Fetal heart rate monitoring is recommended if gestational age allows, especially when used for prolonged periods or at high doses. Assess maternal cardiac function (e.g., signs of ischemia, arrhythmias) and monitor extravasation at the infusion site. Intrauterine growth restriction surveillance may be warranted if vasopressor use is extended. |
| Fertility Effects | Norepinephrine is not known to directly impair human fertility. Animal studies have not shown adverse effects on fertility at doses that do not cause systemic toxicity. However, severe hypotension or shock requiring vasopressors can compromise ovarian perfusion and potentially affect ovulation or implantation. No specific data exist on long-term fertility outcomes in women treated with norepinephrine. |