Hikma will be marketing this product under the name IMMPHENTIV and is introducing the first FDA approved 1,000mcg/10mL presentation to the US market, broadening the choice of medicines available to hospitals.

Hikma is a top three supplier of generic injectable medicines by volume in the US, with a growing portfolio of more than 150 products. We are continuously expanding our portfolio of essential medicines and introducing new dosage forms that enhance patient care.

Source: IQVIA MAT October 2023, generic injectable volumes by eaches, excluding branded generics and Becton Dickinson

This product has been approved for marketing in the United States by the US FDA. This product approval does not confer the right on Hikma, or any other party, to market this product outside the United States. 

Important Safety Information for Phenylephrine HCl Injection, USP, in 500mcg/5mL and 1,000mcg/10mL:

CONTRAINDICATIONS

The use of IMMPHENTIV 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL is contraindicated in patients with:

• Hypersensitivity to the products or any of their components

WARNINGS & PRECAUTIONS

• 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.
• Bradycardia – IMMPHENTIV 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL can cause severe bradycardia and decreased cardiac output.
• 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.
• Skin and Subcutaneous Necrosis – Extravasation of phenylephrine can cause necrosis or sloughing of tissue.
• Pressor Effect with Concomitant Oxytocic Drugs – Oxytocic drugs potentiate the pressor effect of sympathomimetic pressor amines including IMMPHENTIV 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL, with the potential for hemorrhagic stroke.
• Allergic Reactions – Phenylephrine Hydrochloride Injection 10 mg/mL 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.
• Peripheral and Visceral Ischemia – IMMPHENTIV 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs, particularly in patients with extensive peripheral vascular disease.
• Renal Toxicity – IMMPHENTIV 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL can increase the need for renal replacement therapy in patients with septic shock. Monitor renal function.

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

DRUG INTERACTIONS

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

Antagonists

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

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

In animal reproductive and developmental studies, decreased fetal body weights were noted at 0.4 times the human daily dose (HDD) of 10 mg. No malformations were reported, however, an increased incidence of agenesis of the intermediate lobe of the lung, a visceral variation, was reported at levels as low as 0.08 times the HDD.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

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.

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.

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.

DOSAGE AND ADMINISTRATION

General Administration Instructions

There are TWO formulations of this product:

• IMMPHENTIV injection 100 mcg/mL Ready-To-Use formulation (500 mcg/5 mL, 1,000 mcg/10 mL) do NOT dilute prior to administration.
• Phenylephrine Hydrochloride Injection 10 mg/mL formulation (10 mg/mL, 50 mg/5mL, and 100 mg/10 mL) MUST BE DILUTED before administration as an intravenous bolus or for continuous intravenous infusion. The diluted solution should not be held for more than 4 hours at room temperature or for more than 24 hours under refrigerated conditions (2°C – 8°C).

Parenteral drug products should be inspected for particulate matter and discoloration prior to administration. Discard any unused portion. During IMMPHENTIV 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL administration:

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

Preparation of Phenylephrine Hydrochloride Injection

Preparing a 100 mcg/mL Solution for Intravenous Bolus Administration

For intravenous bolus administration, withdraw 10 mg (1 mL of a 10 mg/mL concentration) of Phenylephrine Hydrochloride Injection 10 mg/mL 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 intravenous bolus administration.

Preparing a 20 mcg/mL Solution for Continuous Intravenous Infusion

For continuous intravenous infusion, withdraw 10 mg (1 mL of 10 mg/mL concentration) of phenylephrine hydrochloride injection 10 mg/mL 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).

Directions for Dispensing from Phenylephrine Hydrochloride Injection 10 mg/mL Pharmacy Bulk Vial

The Pharmacy Bulk Vial is intended for dispensing of single doses to multiple patients in a pharmacy admixture program and is restricted to the preparation of admixtures for infusion. Each closure shall be penetrated only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. The Pharmacy Bulk Vial is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). Dispensing from a pharmacy bulk vial should be completed within 4 hours after the vial is penetrated.

Dosing for Perioperative Setting

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

• IMMPHENTIV Injection 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL (diluted to 100 mcg/mL): 50 mcg to 250 mcg by intravenous bolus administration. The most frequently reported initial bolus dose is 50 mcg or 100 mcg.
• Phenylephrine Hydrochloride Injection 10 mg/mL (diluted to 20 mcg/mL): 0.5 mcg/kg/min to 1.4 mcg/kg/min by intravenous continuous infusion, titrated to blood pressure goal.

Dosing for Septic or Other Vasodilatory Shock (Phenylephrine Hydrochloride Injection 10 mg/mL only)

In adult patients with septic or other vasodilatory shock:

• No bolus.
• 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.

OVERDOSAGE

Overdose of IMMPHENTIV 100 mcg/mL and phenylephrine hydrochloride injection 10 mg/mL 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.

INDICATIONS AND USAGE

IMMPHENTIV injection 100 mcg/mL is indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia.

Phenylephrine Hydrochloride Injection 10 mg/mL is indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation in the settings of anesthesia and septic shock.

HOW SUPPLIED/STORAGE AND HANDLING

IMMPHENTIV® Injection, USP, 100 mcg/mL Ready-to-Use vials is supplied as follows:

• NDC 0641-6245-10: 500 mcg in 5 mL (100 mcg/mL) single-dose vials packaged in cartons containing 10 vials per carton
• NDC 0641-6246-10: 1,000 mcg in 10 mL (100 mcg/mL) single-dose vials packaged in cartons containing 10 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. Discard any unused portion.

Phenylephrine Hydrochloride injection, USP, 10 mg/mL, is supplied as follows:

• NDC 0641-6142-25: 10 mg in 1 mL fill (10 mg/mL) in 2 mL single-dose vials packaged in cartons containing 25 vials per carton
• NDC 0641-6188-10: 50 mg in 5 mL (10 mg/mL) Pharmacy Bulk Package vials packed in cartons containing 10 vials per carton
• NDC 0641-6189-10: 100 mg in 10 mL (10 mg/mL) Pharmacy Bulk Package vials packed in cartons containing 10 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.

The 1 mL vials are for single-dose only. Discard any unused portion. The 5 mL and 10 mL vials are pharmacy bulk packages. The diluted solution should not be held for more than 4 hours at room temperature or for more than 24 hours under refrigerated conditions (2°C – 8°C). Discard any unused portion.

ENDING INFORMATION

Patient Counseling Information should be shared with the patient prior to administration.

For additional information, please refer to the Package Insert for full prescribing information, available on hikma.com.

To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800 FDA-1088 or fda.gov

Manufactured by:

Hikma Pharmaceuticals USA Inc.

Berkeley Heights, NJ 07922 USA