PHENYLEPHRINE HYDROCHLORIDE injection

Phenylephrine Hydrochloride by

Drug Labeling and Warnings

Phenylephrine Hydrochloride by is a Prescription medication manufactured, distributed, or labeled by Fresenius Kabi USA, LLC , Fresenius Kabi USA, LLC. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    Phenylephrine Hydrochloride is an alpha-1 adrenergic receptor agonist indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation, in such settings as septic shock or anesthesia.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 General Administration Instructions

    Phenylephrine hydrochloride must be diluted before administration as bolus intravenous infusion or continuous intravenous infusion.

    Inspect the solution for particulate matter and discoloration prior to administration. The diluted solution should not be held for more than 4 hours at room temperature or for more than 24 hours under refrigerated conditions. Discard any unused portion.

    During phenylephrine hydrochloride administration:

    • Correct intravascular volume depletion.
    • Correct acidosis. Acidosis may reduce the effectiveness of phenylephrine.

    2.2 Preparing a 100 mcg/mL Solution for Bolus Intravenous Administration

    For bolus intravenous administration, withdraw 10 mg (1 mL of a 10 mg/mL concentration) of phenylephrine injection and dilute with 99 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP. This will yield a final concentration of 100 mcg/mL. Withdraw an appropriate dose from the 100 mcg/mL solution prior to bolus intravenous administration.

    2.3 Preparing a Solution for Continuous Intravenous Infusion

    For continuous intravenous infusion, withdraw 10 mg (1 mL of 10 mg/mL concentration) of phenylephrine hydrochloride injection and add to 500 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (providing a final concentration of 20 mcg/mL).

    2.4 Dosing for Perioperative Setting

    In adult patients undergoing surgical procedures with either neuraxial anesthesia or general anesthesia:

    • 50 mcg to 250 mcg by intravenous bolus administration. The most frequently reported initial bolus dose is 50 mcg or 100 mcg.
    • 0.5 mcg/kg/min to 1.4 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal.

    2.5 Dosing for Septic or Other Vasodilatory Shock

    In adult patients with septic or other vasodilatory shock:

    • No bolus.
    • 0.5 mcg/kg/min to 6 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal. Doses above 6 mcg/kg/min do not show significant incremental increase in blood pressure.
  • 3 DOSAGE FORMS AND STRENGTHS

    Injection: 10 mg per mL phenylephrine hydrochloride is supplied as a 1 mL single dose vial.

  • 4 CONTRAINDICATIONS

    The use of phenylephrine hydrochloride is contraindicated in patients with:

    • Hypersensitivity to it or any of its components
  • 5 WARNINGS AND PRECAUTIONS

    5.1 Exacerbation of Angina, Heart Failure, or Pulmonary Arterial Hypertension

    Because of its pressor effects, phenylephrine hydrochloride can precipitate angina in patients with severe arteriosclerosis or history of angina, exacerbate underlying heart failure, and increase pulmonary arterial pressure.

    5.2 Bradycardia

    Phenylephrine hydrochloride can cause severe bradycardia and decreased cardiac output.

    5.3 Risk in Patients with Autonomic Dysfunction

    The pressor response to adrenergic drugs, including phenylephrine, can be increased in patients with autonomic dysfunction, as may occur with spinal cord injuries.

    5.4 Skin and Subcutaneous Necrosis

    Extravasation of phenylephrine can cause necrosis or sloughing of tissue.

    5.5 Pressor Effect with Concomitant Oxytocic Drugs

    Oxytocic drugs potentiate the pressor effect of sympathomimetic pressor amines including phenylephrine hydrochloride [see Drug Interactions (7.1)], with the potential for hemorrhagic stroke.

    5.7 Peripheral and Visceral Ischemia

    Phenylephrine hydrochloride can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs, particularly in patients with extensive peripheral vascular disease.

    5.8 Renal Toxicity

    Phenylephrine hydrochloride can increase the need for renal replacement therapy in patients with septic shock. Monitor renal function.

  • 6 ADVERSE REACTIONS

    The following adverse reactions associated with the use of phenylephrine hydrochloride were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

    •   Cardiac disorders: Bradycardia, AV block, ventricular extrasystoles, myocardial ischemia
    •   Gastrointestinal disorders: Nausea, vomiting
    •   General disorders and administrative site conditions: Chest pain, extravasation
    •   Immune system disorders: Sulfite sensitivity
    •   Nervous system disorders: Headache, nervousness, paresthesia, tremor
    •   Psychiatric disorders: Excitability
    •   Respiratory: Pulmonary edema, rales
    •   Skin and subcutaneous tissue disorders: Diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation
    •   Vascular disorders: Hypertensive crisis
  • 7 DRUG INTERACTIONS

    7.1 Agonists

    The pressor effect of phenylephrine hydrochloride is increased in patients receiving:

    • Monoamine oxidase inhibitors (MAOI), such as selegiline.
    • β-adrenergic blockers
    • α-2 adrenergic agonists, such as clonidine
    • Steroids
    • Tricyclic antidepressants
    • Norepinephrine transport inhibitors, such as atomoxetine
    • Ergot alkaloids, such as methylergonovine maleate
    • Centrally-acting sympatholytic agents, such as guanfacine or reserpine
    • Atropine sulfate

    7.2 Antagonists

    α-adrenergic blocking agents, including phenothiazines (e.g., chlorpromazine) and amiodarone block phenylephrine and are in turn blocked by phenylephrine.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Pregnancy Category C

    Animal reproduction studies have not been conducted with intravenous phenylephrine. It is also not known whether phenylephrine can cause fetal harm when administered to a pregnant woman or can

    affect reproduction capacity. Phenylephrine hydrochloride should be given to a pregnant woman only if clearly needed.

    8.2 Labor and Delivery

    The most common maternal adverse reactions reported in studies of phenylephrine use during neuraxial anesthesia during cesarean delivery include nausea and vomiting, which are commonly associated with hypotension, bradycardia, reactive hypertension, and transient arrhythmias. Phenylephrine does not appear to cause a decrease in placental perfusion sufficient to alter either the neonate Apgar scores or blood-gas status.

    8.3 Nursing Mothers

    It is not known whether this drug is excreted in human milk.

    8.4 Pediatric Use

    Safety and effectiveness in pediatric patients have not been established.

    8.5 Geriatric Use

    Clinical studies of phenylephrine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    8.6 Hepatic Impairment

    In patients with liver cirrhosis [Child Pugh Class A (n=3), Class B (n=5) and Class C (n=1)], dose-response data indicate decreased responsiveness to phenylephrine. Consider using larger doses than usual in hepatic impaired subjects.

    8.7 Renal Impairment

    In patients with end stage renal disease (ESRD) undergoing hemodialysis, dose-response data indicates increased responsiveness to phenylephrine. Consider using lower doses of phenylephrine hydrochloride in ESRD patients.

  • 10 OVERDOSAGE

    Overdose of phenylephrine hydrochloride can cause a rapid rise in blood pressure. Symptoms of overdose include headache, vomiting, hypertension, reflex bradycardia, and cardiac arrhythmias including ventricular extrasystoles and ventricular tachycardia, and may cause a sensation of fullness in the head and tingling of the extremities.

    Consider using an α-adrenergic antagonist.

  • 11 DESCRIPTION

    Phenylephrine hydrochloride is a synthetic sympathomimetic agent in sterile form for parenteral injection. Chemically, phenylephrine hydrochloride is (-)-m-Hydroxy-α-[(methylamino)methyl]benzyl alcohol hydrochloride and has the following structural formula:

    Structural Formula

    Phenylephrine hydrochloride is very soluble in water, freely soluble in ethanol, and insoluble in chloroform and ethyl ether. Phenylephrine hydrochloride is sensitive to light.

    Phenylephrine Hydrochloride Injection, USP is a clear, colorless, aqueous solution that is essentially free of visible foreign matter. Each mL contains: Phenylephrine Hydrochloride 10 mg; Sodium Chloride 3.5 mg; Sodium Citrate Dihydrate 4 mg; and Citric Acid Monohydrate 1 mg in water for injection. The pH may be adjusted in the range of 3.5 to 5.5 with Sodium Hydroxide and/or Hydrochloric Acid, if necessary.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Phenylephrine hydrochloride is an α-1 adrenergic receptor agonist.

    12.2 Pharmacodynamics

    Phenylephrine is the active moiety. Metabolites are inactive at both the α-1and α-2 adrenergic receptors. Following parenteral administration of phenylephrine hydrochloride, increases in systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and total peripheral vascular resistance are observed. The onset of blood pressure increase following an intravenous bolus phenylephrine hydrochloride administration is rapid and the effect may persist for up to 20 minutes. As mean arterial pressure increases following parenteral doses, vagal activity also increases, resulting in reflex bradycardia.

    Most vascular beds are constricted, including renal, splanchnic, and hepatic.

    12.3 Pharmacokinetics

    Following an intravenous infusion of phenylephrine hydrochloride, the effective half-life was approximately 5 minutes. The steady-state volume of distribution (340 L) exceeded the body volume by a factor of 5, suggesting a high distribution into certain organ compartments. The average total serum clearance (2095 mL/min) was close to one-third of the cardiac output.

    A mass balance study showed that phenylephrine is extensively metabolized by the liver with only 12% of the dose excreted unchanged in the urine. Deamination by monoamino oxidase is the primary metabolic pathway resulting in the formation of the major metabolite (m-hydroxymandelic acid) which accounts for 57% of the total administered dose.

  • 14 CLINICAL STUDIES

    Increases in systolic and mean blood pressure following administration of phenylephrine were observed in 42 literature-based studies in the perioperative setting, including 26 studies where phenylephrine was used in low-risk (ASA 1 and 2) pregnant women undergoing neuraxial anesthesia during cesarean delivery, 3 studies in non-obstetric surgery under neuraxial anesthesia, and 13 studies in patients undergoing surgery under general anesthesia. Mean arterial blood pressure increases were also observed in two double-blind, active-controlled studies in patients with septic shock.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    Phenylephrine Hydrochloride Injection, USP, is supplied as follows:

    Product
    Code
    Unit of Sale
    Strength
    Each
    751101 NDC: 63323-751-01
    Unit of 25
    		10 mg per mL NDC: 63323-751-00
    1 mL Single Dose Vial

    Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. Keep covered in carton until time of use. For single use only. Discard unused portion.

  • 17 PATIENT COUNSELING INFORMATION

    Inform patients, families, or caregivers that the primary side effect of phenylephrine is hypertension and rarely, hypertensive crisis. Patients may experience bradycardia (slow heart rate), which in some cases may produce

    heart block or other cardiac arrhythmias, extra ventricular beats, myocardial ischemia in patients with underlying cardiac disease, and pulmonary edema (fluid in the lungs) or rales. Common, less serious symptoms include the following:

    • chest pain
    • skin or tissue damage if the drug leaks out of the venous catheter into the surrounding tissue
    • headache, nervousness, tremor, numbness/tingling (paresthesias) in hands or feet
    • nausea, vomiting
    • excitability, dizziness, sweating, flushing

    Fresenius Kabi Logo

    Lake Zurich, IL 60047

    www.fresenius-kabi.com/us

    451579

    Issued: March 2019

  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL- PRINCIPAL DISPLAY – Phenylephrine 1 mL Vial Label

    NDC: 63323-751-00          751101

    Phenylephrine

    Hydrochloride

    Injection, USP

    10 mg per mL

    For Intravenous Use

    Dilute Before Use

    DISCARD UNUSED PORTION

    PROTECT FROM LIGHT

    1 mL Single Dose Vial Rx only

    PACKAGE LABEL- PRINCIPAL DISPLAY – Phenylephrine 1 mL Vial Label
  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL- PRINCIPAL DISPLAY – Phenylephrine 1 mL Vial Carton Label

    NDC: 63323-751-01          751101

    Phenylephrine Hydrochloride

    Injection, USP

    10 mg per mL

    For Intravenous Use

    Dilute Before Use

    DISCARD UNUSED PORTION

    Rx only

    25 x 1 mL Single Dose Vials

    PACKAGE LABEL- PRINCIPAL DISPLAY – Phenylephrine 1 mL Vial Carton Label
  • INGREDIENTS AND APPEARANCE
    PHENYLEPHRINE HYDROCHLORIDE 
    phenylephrine hydrochloride injection
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 63323-751
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    Phenylephrine Hydrochloride (UNII: 04JA59TNSJ) (Phenylephrine - UNII:1WS297W6MV) Phenylephrine Hydrochloride10 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    Sodium Chloride (UNII: 451W47IQ8X)  
    Trisodium Citrate Dihydrate (UNII: B22547B95K)  
    Citric Acid Monohydrate (UNII: 2968PHW8QP)  
    Water (UNII: 059QF0KO0R)  
    Sodium Hydroxide (UNII: 55X04QC32I)  
    Hydrochloric Acid (UNII: QTT17582CB)  
    Nitrogen (UNII: N762921K75)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 63323-751-0125 in 1 CARTON05/25/2019
    1NDC: 63323-751-001 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA21066505/25/2019
    Labeler - Fresenius Kabi USA, LLC (608775388)
    Establishment
    NameAddressID/FEIBusiness Operations
    Fresenius Kabi USA, LLC784336252ANALYSIS(63323-751)
    Establishment
    NameAddressID/FEIBusiness Operations
    Fresenius Kabi USA, LLC023648251MANUFACTURE(63323-751)
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