NDC 51662-1576 Phenylephrine Hydrochloride

Phenylephrine Hydrochloride

NDC Product Code 51662-1576

NDC 51662-1576-1

Package Description: 1 mL in 1 VIAL, SINGLE-DOSE

NDC Product Information

Phenylephrine Hydrochloride with NDC 51662-1576 is a a human prescription drug product labeled by Hf Acquisition Co Llc, Dba Healthfirst. The generic name of Phenylephrine Hydrochloride is phenylephrine hydrochloride. The product's dosage form is injection and is administered via intravenous form. The RxNorm Crosswalk for this NDC code indicates a single RxCUI concept is associated to this product: 1666372.

Dosage Form: Injection - A sterile preparation intended for parenteral use; five distinct classes of injections exist as defined by the USP.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Phenylephrine Hydrochloride Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • TRISODIUM CITRATE DIHYDRATE (UNII: B22547B95K)
  • WATER (UNII: 059QF0KO0R)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)
  • NITROGEN (UNII: N762921K75)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • alpha-1 Adrenergic Agonist - [EPC] (Established Pharmacologic Class)
  • Adrenergic alpha1-Agonists - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Hf Acquisition Co Llc, Dba Healthfirst
Labeler Code: 51662
FDA Application Number: ANDA210665 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 06-30-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Phenylephrine Hydrochloride Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Highlights Of Prescribing Information

These highlights do not include all the information needed to use PHENYLEPHRINE HYDROCHLORIDE safely and effectively. See full prescribing information for PHENYLEPHRINE HYDROCHLORIDE.

PHENYLEPHRINE HYDROCHLORIDE injection, for intravenous use

Initial U.S. Approval: 2012
INDICATIONS AND USAGEPhenylephrine 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. (
1)
DOSAGE AND ADMINISTRATIONDilute before administration. (
2.1)
Dosing for Perioperative HypotensionIntravenous bolus administration: 50 mcg to 250 mcg
(2.4)

Intravenous continuous infusion: 0.5 mcg/kg/minute to 1.4 mcg/kg/minute titrated to effect (
2.4)
Dosing for Patients with Vasodilatory ShockIntravenous continuous infusion: 0.5 mcg/kg/minute to 6 mcg/kg/minute titrated to effect (
2.5)
DOSAGE FORMS AND STRENGTHSInjection: 10 mg per mL supplied as a 1 mL single dose vial (
3,
11,
16)
CONTRAINDICATIONSHypersensitivity to it or any of its components (
4)
WARNINGS AND PRECAUTIONSSevere bradycardia and decreased cardiac output (
5.2)

Extravasation: during intravenous administration may cause necrosis or sloughing of tissue (
5.4)

Concomitant use with oxytocic drugs: pressor effect of sympathomimetic pressor amines is potentiated (
5.5)
ADVERSE REACTIONSMost common adverse reactions: nausea and vomiting, headache, nervousness (
6)
To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.DRUG INTERACTIONSAgonistic effects with monoamine oxidase inhibitors (MAOI), β-adrenergic blocking agents, α-2 adrenergic agonists, steroids, tricyclic antidepressants, norepinephrine transport inhibitors, ergot alkaloids, centrally-acting sympatholytic agents and atropine sulfate (
7.1)

Antagonistic effects on and by α-adrenergic blocking agents (
7.2)
See 17 for PATIENT COUNSELING INFORMATION.Revised: 3/2019

Table Of Contents

FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION

2.1 General Administration Instructions

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

2.3 Preparing a Solution for Continuous Intravenous Infusion

2.4 Dosing for Perioperative Setting

2.5 Dosing for Septic or Other Vasodilatory Shock
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS

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

5.2 Bradycardia

5.3 Risk in Patients with Autonomic Dysfunction

5.4 Skin and Subcutaneous Necrosis

5.5 Pressor Effect with Concomitant Oxytocic Drugs

5.7 Peripheral and Visceral Ischemia

5.8 Renal Toxicity
6 ADVERSE REACTIONS
7 DRUG INTERACTIONS

7.1 Agonists

7.2 Antagonists
8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

8.7 Renal Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*

Sections or subsections omitted from the full prescribing information are not listed.

1 Indications & 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 & Administration

2.1 General Administration InstructionsPhenylephrine 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 AdministrationFor 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 InfusionFor 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 SettingIn 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 ShockIn 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 & 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 HypertensionBecause 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 BradycardiaPhenylephrine hydrochloride can cause severe bradycardia and decreased cardiac output.5.3 Risk in Patients with Autonomic DysfunctionThe 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 NecrosisExtravasation of phenylephrine can cause necrosis or sloughing of tissue.5.5 Pressor Effect with Concomitant Oxytocic DrugsOxytocic 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 IschemiaPhenylephrine hydrochloride can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs, particularly in patients with extensive peripheral vascular disease.5.8 Renal ToxicityPhenylephrine 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 AgonistsThe 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 Antagonistsα-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 PregnancyPregnancy Category CAnimal 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 canaffect reproduction capacity. Phenylephrine hydrochloride should be given to a pregnant woman only if clearly needed.8.2 Labor and DeliveryThe 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 MothersIt is not known whether this drug is excreted in human milk.8.4 Pediatric UseSafety and effectiveness in pediatric patients have not been established.8.5 Geriatric UseClinical 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 ImpairmentIn 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 ImpairmentIn 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: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 ActionPhenylephrine hydrochloride is an α-1 adrenergic receptor agonist.12.2 PharmacodynamicsPhenylephrine 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 PharmacokineticsFollowing 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: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 produceheart 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
Lake Zurich, IL 60047www.fresenius-kabi.com/us451579Issued: March 2019

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