PHENYLEPHRINE HCI

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 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.

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 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.

7 DRUG INTERACTIONS 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.

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

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Animal 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.