PHENYLEPHRINE HYDROCHLORIDE

Phenylephrine Hydrochloride Injection, USP contains active pharmaceutical ingredient phenylephrine in the form of hydrochloride salt. Phenylephrine is a synthetic sympathomimetic agent in sterile form for parenteral injection. Phenylephrine hydrochloride chemical name 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, 10 mg per mL Phenylephrine Hydrochloride Injection, USP is a clear, colorless, aqueous solution that is essentially free of visible foreign matter. It MUST BE DILUTED before administration as bolus intravenous infusion or continuous intravenous infusion. Each mL contains: 10 mg of Phenylephrine Hydrochloride (equivalent to 8.2 mg of phenylephrine base); 3.5 mg of Sodium Chloride USP as tonicity agent; 1 mg of Citric Acid Monohydrate USP and 4 mg of Sodium Citrate Dihydrate USP, as buffering agents; 2 mg of Sodium Metabisulfite NF, as antioxidant, and Sodium Hydroxide NF and Hydrochloric Acid NF, as pH adjusters in Water for Injection. Phenylephrine Hydrochloride Injection, USP pH range is 3.0 to 6.5. structural formula

Phenylephrine Hydrochloride Injection 10 mg per 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. Phenylephrine Hydrochloride Injection 10 mg per mL is alpha-1 adrenergic receptor agonist indicated for increasing blood pressure in adults with clinically important hypotension resulting primarily from vasodilation in the settings of anesthesia and septic shock. ( 1 )

Phenylephrine Hydrochloride Injection 10 mg per mL: MUST BE DILUTED before administration. ( 2.1 ) Dosing for Perioperative Hypotension – Intravenous 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 Shock – Intravenous continuous infusion: 0.5 mcg/kg/minute to 6 mcg/kg/minute titrated to effect ( 2.5 ) 2.1 General Administration Instructions Phenylephrine hydrochloride injection 10 mg per mL formulation (10 mg per 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° to 8°C). Parenteral drug products should be inspected for particulate matter and discoloration prior to administration. Discard any unused portion. During phenylephrine hydrochloride injection 10 mg per mL administration: Correct intravascular volume depletion. Correct acidosis. Acidosis may reduce the effectiveness of phenylephrine. 2.2 Preparation of Phenylephrine Hydrochloride Injection Preparing a 100 mcg per mL Solution for Intravenous Bolus Administration For intravenous bolus administration, withdraw 10 mg (1 mL of a 10 mg per mL concentration) of phenylephrine hydrochloride injection 10 mg per 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 per mL. Withdraw an appropriate dose from the 100 mcg per mL solution prior to intravenous bolus administration. Preparing a 20 mcg per mL Solution for Continuous Intravenous Infusion For continuous intravenous infusion, withdraw 10 mg (1 mL of 10 mg per mL concentration) of phenylephrine hydrochloride injection 10 mg per 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 per mL). Dosing for Perioperative Setting In adult patients undergoing surgical procedures with either neuraxial anesthesia or general anesthesia: Phenylephrine hydrochloride injection 10 mg per mL (diluted to 100 mcg per 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 per mL (diluted to 20 mcg per 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 per mL only) 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.

The use of phenylephrine hydrochloride injection 10 mg per mL is contraindicated in patients with: Hypersensitivity to the products or any of their components Hypersensitivity to the products or any of their components ( 4 )

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 Most common adverse reactions: nausea and vomiting, headache, nervousness ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc. at 1-844-824-8426 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Agonistic 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 ) 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.