PHENYLEPHRINE AGUETTANT

1 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. IMMPHENTIV injection 100 mcg/mL is an alpha-1 adrenergic receptor agonist 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 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.

2 DOSAGE AND ADMINISTRATION IMMPHENTIV Injection 100 mcg/mL: Do NOT dilute prior to administration ( 2.1 ) Dosing for Perioperative Hypotension - Intravenous bolus administration: 50 mcg to 250 mcg ( 2.2 ) Phenylephrine Hydrochloride Injection 10 mg/mL: MUST BE DILUTED before administration. ( 2.1 ) Dosing for Perioperative Hypotension Intravenous bolus administration: 50 mcg to 250 mcg ( 2.2 ) Intravenous continuous infusion: 0.5 mcg/kg/minute to 1.4 mcg/kg/minute titrated to effect ( 2.2 ) Dosing for Patients with Vasodilatory Shock Intravenous continuous infusion: 0.5 mcg/kg/minute to 6 mcg/kg/minute titrated to effect ( 2.2 ) 2.1 General Administration Instructions Phenylephrine Hydrochloride Injection is injected by bolus intravenous infusion or in dilute solution as a continuous intravenous infusion. 2.2 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. 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.

5 WARNINGS AND PRECAUTIONS Severe 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 ) Allergic-type reactions with Phenylephrine Hydrochloride Injection 10 mg/mL : Sulfite ( 5.6 ) 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 IMMPHENTIV 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL 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 IMMPHENTIV 100 mcg/mL and Phenylephrine Hydrochloride Injection 10 mg/mL [see Drug Interactions (7.1) ] , with the potential for hemorrhagic stroke. 5.6 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. 5.7 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. 5.8 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.

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 Most common adverse reactions: nausea and vomiting, headache, nervousness ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .