NOREPINEPHRINE BITARTRATE IN 0.9% SODIUM CHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Norepinephrine is a direct-acting sympathomimetic amine that stimulates alpha-1 and alpha-2 adrenergic receptors, causing vasoconstriction and increased blood pressure. It also has weak beta-1 adrenergic receptor activity, resulting in positive inotropic and chronotropic effects on the heart.
| Metabolism | Primarily metabolized in the liver via catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Also metabolized in peripheral tissues by the same enzymes. |
| Excretion | Primarily renal (90-95% as inactive metabolites, including normetanephrine, vanillylmandelic acid, 4-hydroxy-3-methoxymandelic acid); less than 5% excreted unchanged. Minor biliary/fecal elimination (<5%). |
| Half-life | Terminal elimination half-life is approximately 2-3 minutes. Due to rapid clearance, continuous intravenous infusion is required to maintain therapeutic effect. Context: Short half-life allows rapid titration and quick reversal of effect upon discontinuation. |
| Protein binding | Approximately 25% bound to plasma proteins, primarily albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Vd is approximately 0.1-0.2 L/kg (8-15 L in 70 kg adult), indicating limited distribution primarily in the extracellular fluid and blood volume. Small Vd reflects poor tissue penetration, with norepinephrine acting mainly on vascular smooth muscle via alpha-1 receptors. |
| Bioavailability | Intravenous: 100% (intended route). Oral: negligible (<2%) due to extensive first-pass metabolism in the gut wall and liver. Subcutaneous/intramuscular: erratic and unpredictable; not used clinically. |
| Onset of Action | Intravenous: immediate (within 1-2 minutes). |
| Duration of Action | Duration of action is 1-2 minutes after infusion cessation due to rapid reuptake and metabolism. Continuous infusion is needed for sustained pressor effect. |
IV infusion: 0.1-0.5 mcg/kg/min, titrate to effect (max 2 mcg/kg/min).
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for any GFR level. |
| Liver impairment | No formal Child-Pugh based dose adjustments; severe hepatic impairment may require lower doses due to reduced clearance. |
| Pediatric use | IV infusion: 0.05-0.1 mcg/kg/min initial, titrate to effect (max 1-2 mcg/kg/min). |
| Geriatric use | Initial doses at lower end of range (0.1-0.3 mcg/kg/min) due to increased sensitivity and reduced compensatory responses. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Can cause hypernatremia and fluid overload.
| Breastfeeding | Norepinephrine is not orally bioavailable and is rapidly metabolized; minimal amounts are expected to enter breast milk. No data on M/P ratio. Use with caution in breastfeeding women due to potential for local vasoconstriction and theoretical risk to infant. |
| Teratogenic Risk | Norepinephrine is a catecholamine that may reduce placental blood flow via α-adrenergic vasoconstriction. Use in pregnancy, especially near term, may cause fetal hypoxia and bradycardia. There are no adequate and well-controlled studies in pregnant women; potential benefits must be weighed against risks. Category C according to former FDA classification. |
■ FDA Black Box Warning
None.
| Common Effects | fluid replacement |
| Serious Effects |
["Hypersensitivity to norepinephrine or any component of the formulation","Hypotension from hypovolemia (should be corrected first)","Hypertension or hyperthyroidism may require caution, but not absolute contraindications","Peripheral or mesenteric vascular thrombosis (may increase ischemia)"]
| Precautions | ["Extravasation: Risk of tissue necrosis; administer into large vein and monitor site.","Cardiovascular effects: May cause bradycardia, arrhythmias, or myocardial ischemia; use caution in patients with coronary insufficiency or hypertension.","Renal and mesenteric vasoconstriction: May decrease renal and splanchnic blood flow.","Hypovolemia: Correct volume depletion before or during administration.","Abrupt discontinuation: May cause rebound hypotension."] |
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| Fetal Monitoring | Continuous maternal heart rate, blood pressure, and oxygen saturation; fetal heart rate monitoring if viable gestation; assess uterine perfusion and signs of fetal distress. Monitor for extravasation at infusion site. |
| Fertility Effects | No specific human data. Animal studies have not reported adverse effects on fertility. Theoretical impairment due to vasoconstriction of reproductive organs is not clinically relevant at therapeutic doses. |