EPHEDRINE SULFATE

EPHEDRINE SULFATE- ephedrine sulfate injection, solution
HF Acquisition Co LLC, DBA HealthFirst

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use EPHEDRINE SULFATE INJECTION safely and effectively. See full prescribing information for EPHEDRINE SULFATE INJECTION.
EPHEDRINE SULFATE injection, USP, for intravenous use
Initial U.S. Approval: 2016

INDICATIONS AND USAGE

Ephedrine Sulfate Injection, USP is an alpha- and beta- adrenergic agonist and a norepinephrine-releasing agent indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia. ( 1)

DOSAGE AND ADMINISTRATION

Treatment of hypotension developing during anesthesia: Bolus intravenous injection: 5 to 10 mg as needed, not to exceed 50 mg. Dilute before use. See Full Prescribing Information for instructions on administration and preparation for injection. ( 2)

DOSAGE FORMS AND STRENGTHS

Injection: 50 mg/mL ephedrine sulfate in single-dose vial ( 3)

CONTRAINDICATIONS

None ( 4)

WARNINGS AND PRECAUTIONS

• Pressor Effect with Concomitant Oxytocic Drugs: Pressor effect of sympathomimetic pressor amines is potentiated ( 5-5.1)

• Tachyphylaxis and Tolerance: Repeated administration of ephedrine may cause tachyphylaxis ( 5-5.2)

ADVERSE REACTIONS

Most common adverse reactions during treatment: nausea, vomiting, and tachycardia.( 6)

To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Interactions that Augment the Pressor Effect: clonidine, oxytocin and oxytocic drugs, propofol, monoamine oxidase inhibitors (MAOIs), and atropine. Monitor blood pressure. ( 7)

• Interactions that Antagonize the Pressor Effect: Antagonistic effects with α-adrenergic antagonists, β-adrenergic antagonists, reserpine, quinidine, mephentermine. Monitor blood pressure. ( 7)

• Guanethidine: Ephedrine may inhibit the neuron blockage produced by guanethidine, resulting in loss of antihypertensive effectiveness. Monitor blood pressure and adjust the dosage of pressor accordingly. ( 7)

• Rocuronium: Ephedrine may reduce the onset time of neuromuscular blockade when used for intubation with rocuronium if administered simultaneously with anesthetic induction. Be aware of this potential interaction. No treatment or other interventions are needed. ( 7)

• Epidural anesthesia: Ephedrine may decrease the efficacy of epidural blockade by hastening the regression of sensory analgesia. Monitor and treat the patient according to clinical practice. ( 7)

• Theophylline: Concomitant use of ephedrine may increase the frequency of nausea, nervousness, and insomnia. Monitor patient for worsening symptoms and manage symptoms according to clinical practice. ( 7)

• Cardiac glycosides: Giving ephedrine with a cardiac glycoside, such as digitalis, may increase the possibility of arrhythmias. Carefully monitor patients on cardiac glycosides who are also administered ephedrine. ( 7)

Revised: 1/2017

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 General Dosage and Administration Instructions
2.2 Dosing for the Treatment of Clinically Important Hypotension in the Setting of Anesthesia
2.3 Preparation of a 5 mg/mL Solution for Bolus Intravenous Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Pressor Effect with Concomitant Oxytocic Drugs
5.2 Tolerance and Tachyphylaxis
5.3 Risk of Hypertension When Used Prophylactically
6 ADVERSE REACTIONS
7 DRUG INTERACTIONS
88 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED

* Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS & USAGE

Ephedrine sulfate injection is indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia.

2 DOSAGE & ADMINISTRATION

2.1 General Dosage and Administration Instructions

Ephedrine sulfate injection must be diluted before administration to achieve the desired concentration as an intravenous bolus or intravenous infusion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the solution is colored or cloudy, or if it contains particulate matter.

2.2 Dosing for the Treatment of Clinically Important Hypotension in the Setting of Anesthesia

The recommended dosage for the treatment of clinically important hypotension in the setting of anesthesia is an initial dose of 5 to 10 mg administered by intravenous bolus. Administer additional boluses as needed, not to exceed a total dosage of 50 mg.

Adjust dosage according to the blood pressure goal (i.e., titrate to effect).

2.3 Preparation of a 5 mg/mL Solution for Bolus Intravenous Administration

For bolus intravenous administration, prepare a solution containing a final concentration of 5 mg/mL of ephedrine sulfate injection.

Withdraw 50 mg (1 mL of 50 mg/mL) of ephedrine sulfate injection and dilute with 9 mL of 5% Dextrose Injection or Sodium Chloride Injection.

Withdraw an appropriate dose of the 5 mg/mL solution prior to bolus intravenous administration.

3 DOSAGE FORMS & STRENGTHS

Ephedrine sulfate injection is available as a single-dose 1 mL vial that contains 50 mg/mL ephedrine sulfate, equivalent to 38 mg ephedrine base.

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

5.1 Pressor Effect with Concomitant Oxytocic Drugs

Serious postpartum hypertension has been described in patients who received both a vasopressor (i.e., methoxamine, phenylephrine, ephedrine) and an oxytocic (i.e., methylergonovine, ergonovine) [see Drug Interactions ( 7)]. Some of these patients experienced a stroke. Carefully monitor the blood pressure of individuals who have received both ephedrine and an oxytocic.

5.2 Tolerance and Tachyphylaxis

Data indicate that repeated administration of ephedrine can result in tachyphylaxis. Clinicians treating anesthesia-induced hypotension with ephedrine sulfate injection should be aware of the possibility of tachyphylaxis and should be prepared with an alternative pressor to mitigate unacceptable responsiveness.

5.3 Risk of Hypertension When Used Prophylactically

When used to prevent hypotension, ephedrine has been associated with an increased incidence of hypertension compared with when ephedrine is used to treat hypotension.

6 ADVERSE REACTIONS

The following adverse reactions associated with the use of ephedrine sulfate 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.

Gastrointestinal disorders: Nausea, vomiting

Cardiac disorders: Tachycardia, palpitations (thumping heart), reactive hypertension, bradycardia, ventricular ectopics, R-R variability

Nervous system disorders: Dizziness

Psychiatric disorders: Restlessness

For medical advice about adverse reactions, contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.