NDC 0641-6189 Phenylephrine Hydrochloride

Phenylephrine Hydrochloride

NDC Product Code 0641-6189

NDC 0641-6189-10

Package Description: 10 VIAL, PHARMACY BULK PACKAGE in 1 CARTON > 10 mL in 1 VIAL, PHARMACY BULK PACKAGE (0641-6189-01)

NDC Product Information

Phenylephrine Hydrochloride with NDC 0641-6189 is a a human prescription drug product labeled by Hikma Pharmaceuticals Usa Inc.. The generic name of Phenylephrine Hydrochloride is phenylephrine hydrochloride. The product's dosage form is injection and is administered via intravenous form.

Labeler Name: Hikma Pharmaceuticals Usa Inc.

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.


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: Hikma Pharmaceuticals Usa Inc.
Labeler Code: 0641
FDA Application Number: NDA203826 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: NDA - A product marketed under an approved 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: 06-19-2019 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: 12-31-2020 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 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. Values = ‘Y’ or ‘N’.

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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

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.

2.1 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 Of 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/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

5.1 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.

5.6 Allergic Reactions

This product contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.  The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

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 ischemiaGastrointestinal disorders: Nausea, vomitingGeneral disorders and administrative site conditions: Chest pain, extravasationImmune system disorders: Sulfite sensitivityNervous system disorders: Headache, nervousness, paresthesia, tremorPsychiatric disorders: ExcitabilityRespiratory: Pulmonary edema, ralesSkin and subcutaneous tissue disorders: Diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasationVascular disorders: Hypertensive crisis

7.1 Agonists

  • The pressor effect of phenylephrine hydrochloride is increased in patients receiving:Monoamine oxidase inhibitors (MAOI), such as selegiline.β-adrenergic blockersα-2 adrenergic agonists, such as clonidineSteroidsTricyclic antidepressantsNorepinephrine transport inhibitors, such as atomoxetineErgot alkaloids, such as methylergonovine maleateCentrally-acting sympatholytic agents, such as guanfacine or reserpineAtropine sulfate

7.2 Antagonists

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

8.1 Pregnancy

Pregnancy 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 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 a-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; Citric Acid Monohydrate 1 mg; and Sodium Metabisulfite 2 mg in water for injection. The pH  may be adjusted in the range of 3.0 to 6.5 with Sodium Hydroxide and/or Hydrochloric Acid, if necessary.

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:NDC 0641-6142-25: 1 mL single dose vials packaged in cartons containing 25 vials per carton.Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F 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 painskin or tissue damage if the drug leaks out of the venous catheter into the surrounding tissueheadache, nervousness, tremor, numbness/tingling (paresthesias) in hands or feetnausea, vomitingexcitability, dizziness, sweating, flushing

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