Levophed 1mg/ml Inj, 4ml

Manufacturer HOSPIRA Active Ingredient Norepinephrine(nor ep i NEF rin) Pronunciation nor-ep-i-NEF-rin
It is used to treat low blood pressure.
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Drug Class
Vasopressor
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Pharmacologic Class
Alpha- and Beta-adrenergic Agonist
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Pregnancy Category
Category C
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FDA Approved
Jun 1950
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DEA Schedule
Not Controlled

Overview

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What is this medicine?

Norepinephrine is a strong medicine given through a vein to help raise your blood pressure when it is dangerously low, such as during severe shock. It helps your heart pump blood more effectively and tightens your blood vessels.
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How to Use This Medicine

Taking Your Medication

To use this medication correctly, follow your doctor's instructions and read all the information provided to you. It is essential to follow the instructions carefully. This medication is administered as an infusion into a vein over a specified period.

Storing and Disposing of Your Medication

If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.

Missing a Dose

This medication will be administered on an as-needed basis in a healthcare setting, so you will not need to take it at home. If you have any concerns about your treatment schedule, be sure to discuss them with your healthcare provider.
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Lifestyle & Tips

  • Not applicable as this is an acute, hospital-administered medication.
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Available Forms & Alternatives

Available Strengths:

Dosing & Administration

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Adult Dosing

Standard Dose: Initial rate of 0.5 to 1 mcg/min (base) by intravenous infusion, titrated to desired hemodynamic response.
Dose Range: 0.01 - 30 mg

Condition-Specific Dosing:

septicShock: Initial: 0.01-3 mcg/kg/min (base), titrate to mean arterial pressure (MAP) target, typically 65 mmHg. Usual maintenance: 0.01-0.5 mcg/kg/min.
cardiogenicShock: Initial: 0.01-0.3 mcg/kg/min (base), titrate to MAP and cardiac output.
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Pediatric Dosing

Neonatal: Initial: 0.05-0.1 mcg/kg/min (base) by continuous IV infusion, titrate to effect. Max: 2 mcg/kg/min.
Infant: Initial: 0.05-0.1 mcg/kg/min (base) by continuous IV infusion, titrate to effect. Max: 2 mcg/kg/min.
Child: Initial: 0.05-0.1 mcg/kg/min (base) by continuous IV infusion, titrate to effect. Max: 2 mcg/kg/min.
Adolescent: Initial: 0.05-0.1 mcg/kg/min (base) by continuous IV infusion, titrate to effect. Max: 2 mcg/kg/min.
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Dose Adjustments

Renal Impairment:

Mild: No specific dose adjustment recommended; monitor hemodynamic response.
Moderate: No specific dose adjustment recommended; monitor hemodynamic response.
Severe: No specific dose adjustment recommended; monitor hemodynamic response.
Dialysis: Not significantly removed by dialysis; monitor hemodynamic response.

Hepatic Impairment:

Mild: No specific dose adjustment recommended; monitor hemodynamic response.
Moderate: No specific dose adjustment recommended; monitor hemodynamic response.
Severe: No specific dose adjustment recommended; monitor hemodynamic response.

Pharmacology

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Mechanism of Action

Norepinephrine is a potent alpha-adrenergic receptor agonist with some beta-1 adrenergic receptor agonist activity. It causes peripheral vasoconstriction (alpha-1 effect) leading to increased systemic vascular resistance (SVR) and mean arterial pressure (MAP). It also has positive inotropic effects (beta-1 effect) on the heart, increasing cardiac contractility and heart rate, though reflex bradycardia may occur due to increased blood pressure.
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Pharmacokinetics

Absorption:

Bioavailability: Not available (poor oral absorption, administered intravenously)
Tmax: Not applicable (continuous IV infusion)
FoodEffect: Not applicable

Distribution:

Vd: Not available (rapidly distributed)
ProteinBinding: Not available (low)
CnssPenetration: Limited

Elimination:

HalfLife: Approximately 1-2 minutes
Clearance: Not available (rapid)
ExcretionRoute: Renal (as inactive metabolites)
Unchanged: Less than 1%
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Pharmacodynamics

OnsetOfAction: Immediate (within seconds)
PeakEffect: Within 1-2 minutes
DurationOfAction: 1-2 minutes after discontinuation of infusion

Safety & Warnings

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Side Effects

Urgent Side Effects: Seek Medical Help Right Away

While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure, including:
+ Severe headache
+ Dizziness
+ Fainting
+ Changes in eyesight
Abnormal heart rhythms, such as:
+ Slow heartbeat
+ Irregular heartbeat
Anxiety
Shortness of breath
Sudden weight gain
Swelling in the arms or legs

If you experience any of these symptoms, do not hesitate to seek medical help.

Additional Side Effects:

Most people taking this medication will not experience side effects, or they will be mild. However, if you notice any of the following side effects, contact your doctor for advice:

Headache

Reporting Side Effects:

If you have concerns about side effects or experience any symptoms that bother you or do not go away, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Important Note:

If you receive this medication through a vein, monitor the injection site for signs of tissue damage, such as redness, burning, pain, swelling, blisters, skin sores, or fluid leakage. Inform your nurse immediately if you notice any of these symptoms.
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Seek Immediate Medical Attention If You Experience:

  • Patients receiving norepinephrine are typically critically ill and closely monitored by healthcare professionals. Self-monitoring for specific symptoms is not applicable.
  • However, if the patient is conscious and able to communicate, they should report any new or worsening chest pain, difficulty breathing, or pain/swelling at the IV site.
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Before Using This Medicine

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
If you have low blood volume (hypovolemia).
* If you have a history of blood clots (thrombosis).

This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your existing health conditions and other medications.

Remember, do not start, stop, or adjust the dosage of any medication without first consulting your doctor to ensure your safety.
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Precautions & Cautions

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor will closely monitor your blood pressure, heart rate, and oxygen levels while you are on this drug, so be sure to discuss any concerns with them. If you have a known allergy to sulfites, consult with your doctor, as some formulations of this medication may contain sulfites. Additionally, if you are pregnant, planning to become pregnant, or are currently breast-feeding, you must discuss this with your doctor to carefully weigh the benefits and risks of this medication to both you and your baby.
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Overdose Information

Overdose Symptoms:

  • Severe hypertension (dangerously high blood pressure)
  • Reflex bradycardia (slow heart rate due to high blood pressure)
  • Arrhythmias (irregular heartbeats)
  • Headache
  • Photophobia (sensitivity to light)
  • Stabbing retrosternal pain
  • Pallor (pale skin)
  • Sweating
  • Vomiting
  • Cerebral hemorrhage (bleeding in the brain)
  • Pulmonary edema (fluid in the lungs)

What to Do:

Overdose is managed by discontinuing the infusion or reducing the rate of infusion. In severe cases, an alpha-adrenergic blocking agent (e.g., phentolamine) may be administered to counteract the pressor effects. Call 1-800-222-1222 (Poison Control) for further guidance if needed, though this is typically managed in an acute care setting.

Drug Interactions

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Major Interactions

  • Monoamine Oxidase Inhibitors (MAOIs): Potentiation of pressor effect, severe hypertension, hyperpyrexia, headache, arrhythmias.
  • Tricyclic Antidepressants (TCAs): Potentiation of pressor effect.
  • General Anesthetics (e.g., Halothane, Cyclopropane): May sensitize the myocardium to the effects of catecholamines, increasing risk of ventricular arrhythmias.
  • Ergot Alkaloids (e.g., Ergotamine, Methylergonovine): Increased vasoconstriction, severe hypertension, peripheral ischemia.
  • Linezolid: MAOI activity, risk of hypertensive crisis.
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Moderate Interactions

  • Alpha-adrenergic Blockers (e.g., Phentolamine, Phenoxybenzamine): May antagonize the pressor effect of norepinephrine.
  • Beta-adrenergic Blockers (e.g., Propranolol, Labetalol): May result in unopposed alpha-adrenergic effects, leading to severe hypertension and reflex bradycardia.
  • Cardiac Glycosides (e.g., Digoxin): Increased risk of arrhythmias.
  • Diuretics: May reduce vascular responsiveness to vasopressors.
  • Oxytocin: May enhance pressor effects.

Monitoring

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Baseline Monitoring

Blood Pressure (MAP)

Rationale: To establish target and initial response.

Timing: Prior to initiation and continuously thereafter.

Heart Rate (HR)

Rationale: To assess cardiac response and detect arrhythmias.

Timing: Prior to initiation and continuously thereafter.

Electrocardiogram (ECG)

Rationale: To monitor for arrhythmias and myocardial ischemia.

Timing: Prior to initiation and continuously thereafter.

Central Venous Pressure (CVP) or Pulmonary Artery Pressure (PAP)

Rationale: To assess fluid status and cardiac preload, guiding fluid resuscitation.

Timing: Prior to initiation if central access available.

Urine Output

Rationale: Indicator of renal perfusion and overall organ perfusion.

Timing: Prior to initiation and hourly thereafter.

Lactate

Rationale: Indicator of tissue hypoperfusion and anaerobic metabolism.

Timing: Prior to initiation and serially as indicated by clinical status.

Peripheral Perfusion (Capillary refill, skin temperature, mental status)

Rationale: Clinical indicators of systemic perfusion.

Timing: Prior to initiation and frequently thereafter.

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Routine Monitoring

Mean Arterial Pressure (MAP)

Frequency: Continuously (arterial line preferred)

Target: Typically 65-75 mmHg (individualized based on patient condition)

Action Threshold: Below target: Increase infusion rate; Above target: Decrease infusion rate or consider other agents.

Heart Rate (HR)

Frequency: Continuously

Target: Individualized, generally within physiological limits

Action Threshold: Significant bradycardia/tachycardia: Investigate cause, adjust dose or consider antiarrhythmics.

Electrocardiogram (ECG)

Frequency: Continuously

Target: Normal sinus rhythm, no ischemia

Action Threshold: Arrhythmias, ST-T changes: Investigate, manage appropriately.

Urine Output

Frequency: Hourly

Target: >0.5 mL/kg/hr

Action Threshold: <0.5 mL/kg/hr: Assess fluid status, consider increasing MAP target, or renal support.

Peripheral Perfusion

Frequency: Every 1-4 hours or as needed

Target: Warm extremities, brisk capillary refill, alert mental status

Action Threshold: Signs of poor perfusion: Re-evaluate dose, fluid status, consider other vasopressors/inotropes.

Infusion Site

Frequency: Hourly or more frequently

Target: No signs of extravasation

Action Threshold: Redness, swelling, pallor, coldness: Stop infusion, infiltrate with phentolamine.

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Symptom Monitoring

  • Signs of extravasation (pain, burning, swelling, pallor, coldness at infusion site)
  • Signs of excessive vasoconstriction (e.g., mottled skin, cyanosis, peripheral ischemia, decreased urine output despite adequate MAP)
  • Signs of myocardial ischemia (chest pain, ECG changes)
  • Arrhythmias (palpitations, irregular pulse)
  • Headache, anxiety, tremor (signs of excessive adrenergic stimulation)

Special Patient Groups

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Pregnancy

Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Norepinephrine can cause uterine contractions and fetal anoxia.

Trimester-Specific Risks:

First Trimester: Potential for adverse effects, but data limited.
Second Trimester: Potential for adverse effects, but data limited.
Third Trimester: May cause uterine contractions and reduce placental blood flow, leading to fetal anoxia or bradycardia. Use with extreme caution.
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Lactation

Norepinephrine is rapidly metabolized and has a very short half-life, making systemic exposure to the infant unlikely. However, caution should be exercised. The decision to breastfeed should consider the clinical need for norepinephrine, the potential risks to the infant, and the underlying maternal condition.

Infant Risk: L3 (Moderate risk - limited data, potential for minor adverse effects or no data available to assess risk).
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Pediatric Use

Norepinephrine is used in pediatric patients for shock states. Dosing is weight-based and requires careful titration and continuous hemodynamic monitoring. Pediatric patients may be more sensitive to the effects of vasopressors.

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Geriatric Use

No specific dose adjustment is generally required, but elderly patients may be more sensitive to the effects of norepinephrine and may have underlying cardiovascular disease. Close monitoring of hemodynamic parameters and organ perfusion is essential. Start with lower doses and titrate carefully.

Clinical Information

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Clinical Pearls

  • Norepinephrine is the first-line vasopressor for most forms of shock, particularly septic shock, due to its potent alpha-adrenergic effects and favorable safety profile compared to dopamine.
  • Administer via a central venous catheter whenever possible to minimize the risk of extravasation and tissue necrosis. If peripheral administration is necessary in an emergency, use a large vein and switch to central access as soon as possible.
  • In case of extravasation, immediately stop the infusion, aspirate any remaining drug from the catheter, and infiltrate the affected area with 5-10 mg of phentolamine mesylate diluted in 10-15 mL of normal saline. This should be done as soon as possible.
  • Ensure adequate fluid resuscitation prior to or concurrently with norepinephrine administration to optimize cardiac output and prevent excessive vasoconstriction.
  • Titrate the infusion rate slowly and carefully to achieve the desired mean arterial pressure (MAP) target, typically 65 mmHg, while monitoring for signs of excessive vasoconstriction or arrhythmias.
  • Norepinephrine is light-sensitive; protect the solution from light during storage and administration.
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Alternative Therapies

  • Dopamine (less potent, more arrhythmogenic, not first-line for septic shock)
  • Phenylephrine (pure alpha-agonist, may cause reflex bradycardia, less effective in some shock states)
  • Vasopressin (non-adrenergic vasopressor, often used as an add-on in refractory shock)
  • Epinephrine (alpha and beta agonist, used in anaphylactic shock, cardiac arrest, or refractory shock)
  • Dobutamine (primarily inotropic, used for cardiogenic shock with low cardiac output)
  • Angiotensin II (vasoconstrictor, approved for vasodilatory shock)
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Cost & Coverage

Average Cost: Not readily available for hospital-use injectables per vial
Generic Available: Yes
Insurance Coverage: Typically covered by hospital formulary and medical insurance for inpatient use.
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General Drug Facts

If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others, and do not take medication prescribed for someone else. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Dispose of unused or expired medications properly. Unless instructed otherwise, avoid flushing medications down the toilet or pouring them down the drain. If you are unsure about the correct disposal method, consult your pharmacist for guidance. Many communities offer drug take-back programs, which your pharmacist can help you locate. Some medications may come with an additional patient information leaflet; check with your pharmacist to see if this applies to your prescription. If you have any questions or concerns about your medication, discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it was taken to ensure prompt and effective treatment.