Phenylephrine Hydrochloride

PHENYLEPHRINE HYDROCHLORIDE — phenylephrine hydrochloride injection
AuroMedics Pharma LLC

1 INDICATIONS AND USAGE

Phenylephrine hydrochloride injection 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 AND ADMINISTRATION

2.1 General Administration Instructions

Phenylephrine hydrochloride injection 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 injection administration:

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

2.2 Preparing a 100 mcg/mL Solution for Bolus Intravenous Administration

For bolus intravenous administration, withdraw 10 mg (1 mL of a 10 mg/mL concentration) of phenylephrine hydrochloride 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 injection, USP is supplied as a 1 mL single-dose vial (10 mg of phenylephrine hydrochloride per vial).

4 CONTRAINDICATIONS

The use of phenylephrine hydrochloride injection 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.

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

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.

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.