EPHEDRINE SULFATE injection, solution

1. No Title 1572551341
2. No Title 1572555809
3. Highlights Of Prescribing Information
4. Indications And Usage
5. Dosage And Administration
6. Dosage Forms And Strengths
7. Contraindications
8. Warnings And Precautions
9. Adverse Reactions
10. Drug Interactions
11. 1 Indications And Usage
12. 2 Dosage And Administration
13. 3 Dosage Forms And Strengths
14. 4 Contraindications
15. 5 Warnings And Precautions
16. 6 Adverse Reactions
17. 7 Drug Interactions
18. 8 Use In Specific Populations
19. 10 Overdosage
20. 11 Description
21. 12 Clinical Pharmacology
22. 13 Nonclinical Toxicology
23. 14 Clinical Studies
24. 16 How Supplied
25. No Title 1572449039
26. Principal Display Panel - Vial Label
27. Full Prescribing Information: Contents*
28. 1 Indications & Usage
29. 2 Dosage & Administration
30. 3 Dosage Forms & Strengths
31. 4 Contraindications
32. 6 Adverse Reactions
33. 10 Overdosage
34. 11 Description
35. 13 Nonclinical Toxicology
36. 14 Clinical Studies
37. 16 How Supplied
38. Spl Unclassified
39. Principal Display Panel, Vial Label
40. Principal Display Panel, Serialized Label
41. No Title 1572455697
42. Ephedrine Sulfate Injection Usp, 50 Mg/ml
43. Description
44. Clinical Pharmacology
45. Indications And Usage
46. Contraindications
47. Precautions
48. Adverse Reactions
49. Drug Abuse And Dependence
50. Overdosage
51. Dosage And Administration
52. How Supplied
53. Principal Display Panel - Carton Label

No Title 1572551341 ⮝

Distributed by:

Par Pharmaceutical

Chestnut Ridge, NY 10977

R1/17

No Title 1572555809 ⮝

Distributed by:

Par Pharmaceutical

Chestnut Ridge, NY 10977

PREMIERProRx

PREMIERProRx is a registered trademark of Premier Healthcare Alliance, L.P., used under license.

I04/18

OS216P-01-95-01

3003824

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 (5.1)

Tachyphylaxis and Tolerance: Repeated administration of ephedrine may cause tachyphylaxis (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 -adrenergic antagonists, -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

1 Indications And Usage ⮝

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

2 Dosage And Administration ⮝

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

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 And 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.

7 Drug Interactions ⮝

Interactions that Augment the Pressor Effect
Oxytocin and oxytocic drugs
Clinical Impact:	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). Some of these patients experienced a stroke.
Intervention:	Carefully monitor the blood pressure of individuals who have received both ephedrine and an oxytocic.
Clonidine, propofol, monoamine oxidase inhibitors (MAOIs), atropine
Clinical Impact:	These drugs augment the pressor effect of ephedrine.
Intervention:	Carefully monitor the blood pressure of individuals who have received both ephedrine and any of these drugs.
Interactions that Antagonize the Pressor Effect
Clinical Impact:	These drugs antagonize the pressor effect of ephedrine.
Intervention:	Carefully monitor the blood pressure of individuals who have received both ephedrine and any of these drugs.
Examples:	-adrenergic antagonists, -adrenergic receptor antagonists, reserpine, quinidine, mephentermine
Other Drug Interactions
Guanethidine
Clinical Impact:	Ephedrine may inhibit the neuron blockage produced by guanethidine, resulting in loss of antihypertensive effectiveness.
Intervention:	Clinician should monitor patient for blood pressor response and adjust the dosage or choice of pressor accordingly.
Rocuronium
Clinical Impact:	Ephedrine may reduce the onset time of neuromuscular blockade when used for intubation with rocuronium if administered simultaneously with anesthetic induction.
Intervention:	Be aware of this potential interaction. No treatment or other interventions are needed.
Epidural anesthesia
Clinical Impact:	Ephedrine may decrease the efficacy of epidural blockade by hastening the regression of sensory analgesia.
Intervention:	Monitor and treat the patient according to clinical practice.
Theophylline
Clinical Impact:	Concomitant use of ephedrine may increase the frequency of nausea, nervousness, and insomnia.
Intervention:	Monitor patient for worsening symptoms and manage symptoms according to clinical practice.
Cardiac glycosides
Clinical Impact:	Giving ephedrine with a cardiac glycoside, such as digitalis, may increase the possibility of arrhythmias.
Intervention:	Carefully monitor patients on cardiac glycosides who are also administered ephedrine.

8 Use In Specific Populations ⮝

8.1 Pregnancy

Risk Summary

Limited published data on the use of ephedrine sulfate are insufficient to determine a drug associated risk of major birth defects or miscarriage. However, there are clinical considerations [see Clinical Considerations]. Animal reproduction studies have not been conducted with ephedrine sulfate.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Fetal/Neonatal adverse reactions

Cases of potential metabolic acidosis in newborns at delivery with maternal ephedrine exposure have been reported in the literature. These reports describe umbilical artery pH of 7.2 at the time of delivery [see Clinical Pharmacology 12.3]. Monitoring of the newborn for signs and symptoms of metabolic acidosis may be required. Monitoring of infant s acid-base status is warranted to ensure that an episode of acidosis is acute and reversible.

8.2 Lactation

Risk Summary

Limited published literature reports that ephedrine is present in human milk. However, no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ephedrine sulfate injection and any potential adverse effects on the breastfed child from ephedrine sulfate injection or from the underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of ephedrine 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. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Renal Impairment

Ephedrine and its metabolite are excreted in urine. In patients with renal impairment, excretion of ephedrine is likely to be affected with a corresponding increase in elimination half-life, which will lead to slow elimination of ephedrine and consequently prolonged pharmacological effect and potentially adverse reactions. Monitor patients with renal impairment carefully after the initial bolus dose for adverse events.

10 Overdosage ⮝

Overdose of ephedrine can cause a rapid rise in blood pressure. In the case of an overdose, careful monitoring of blood pressure is recommended. If blood pressure continues to rise to an unacceptable level, parenteral antihypertensive agents can be administered at the discretion of the clinician.

11 Description ⮝

Ephedrine sulfate is an alpha- and beta-adrenergic agonist and a norepinephrine-releasing agent. Ephedrine sulfate injection, USP is a clear, colorless, sterile solution for intravenous injection. Each mL contains ephedrine sulfate 50 mg in water for injection as a single-dose product. The pH range is 4.5 to 7.0. The drug product must be diluted before intravenous administration. The chemical name of ephedrine sulfate is (1R,2S)-(-)-2-methylamine-1-phenylpropan-1-ol sulfate (2:1) (salt). Its molecular weight is 428.54.

The structural formula is:

image 1

Ephedrine sulfate darkens on exposure to light. It is freely soluble in water and ethanol, very slightly soluble in chloroform, and practically insoluble in ether.

12 Clinical Pharmacology ⮝

12.1 Mechanism of Action

Ephedrine sulfate is a sympathomimetic amine that directly acts as an agonist at - and adrenergic receptors and indirectly causes the release of norepinephrine from sympathetic neurons. Pressor effects by direct alpha- and beta-adrenergic receptor activation are mediated by increases in arterial pressures, cardiac output, and peripheral resistance. Indirect adrenergic stimulation is caused by norepinephrine release from sympathetic nerves.

12.2 Pharmacodynamics

Ephedrine stimulates heart rate and cardiac output and variably increases peripheral resistance; as a result, ephedrine usually increases blood pressure. Stimulation of the -adrenergic receptors of smooth muscle cells in the bladder base may increase the resistance to the outflow of urine. Activation of -adrenergic receptors in the lungs promotes bronchodilation.

The overall cardiovascular effect from ephedrine is the result of a balance among -1 adrenoceptor-mediated vasoconstriction, -2 adrenoceptor-mediated vasoconstriction, and -2 adrenoceptor-mediated vasodilatation. Stimulation of the -1 adrenoceptors results in positive inotrope and chronotrope action.

Tachyphylaxis to the pressor effects of ephedrine may occur with repeated administration [see Warnings and Precautions 5.3].

12.3 Pharmacokinetics

Publications studying pharmacokinetics of oral administration of (-)-ephedrine support that (-) -ephedrine is metabolized into norephedrine. However, the metabolism pathway is unknown. Both the parent drug and the metabolite are excreted in urine. Limited data after IV administration of ephedrine support similar observations of urinary excretion of drug and metabolite. The plasma elimination half-life of ephedrine following oral administration was about 6 hours.

Ephedrine crosses the placental barrier [see Use in Specific Populations 8.1].

13 Nonclinical Toxicology ⮝

13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility

Carcinogenesis: Two-year feeding studies in rats and mice conducted under the National Toxicology Program (NTP) demonstrated no evidence of carcinogenic potential with ephedrine sulfate at doses up to 10 mg/kg/day and 27 mg/kg/day (approximately 2 times and 3 times the maximum human recommended dose on a mg/m2 basis, respectively).

Mutagenesis: Ephedrine sulfate tested negative in the in vitro bacterial reverse mutation assay, the in vitro mouse lymphoma assay, the in vitro sister chromatid exchange, and the in vitro chromosomal aberration assay.

Impairment of Fertility: Studies to evaluate the effect of ephedrine on fertility have not been conducted.

14 Clinical Studies ⮝

The evidence for the efficacy of ephedrine injection is derived from the published literature. Increases in blood pressure following administration of ephedrine were observed in 14 studies, including 9 where ephedrine was used in pregnant women undergoing neuraxial anesthesia during Cesarean delivery, 1 study in non-obstetric surgery under neuraxial anesthesia, and 4 studies in patients undergoing surgery under general anesthesia. Ephedrine has been shown to raise systolic and mean blood pressure when administered as a bolus dose following the development of hypotension during anesthesia.

16 How Supplied ⮝

Ephedrine Sulfate Injection, USP, 50 mg/mL, is supplied as follows:

NDC	Strength	How Supplied
42023-216-83	50 mg/mL	1 mL clear glass vial; for single use (supplied in packages of 25)

Vial stoppers are not manufactured with natural rubber latex.

Store ephedrine sulfate injection, 50 mg/mL, at 20 to 25 C (68 to 77 F), with excursions permitted to 15 C to 30 C (59 F to 86 F) [See USP Controlled Room Temperature.] Protect from light. Store in carton until time of use. For single use only. Discard unused portion.

No Title 1572449039 ⮝

Distributed by:

Par Pharmaceutical

Chestnut Ridge, NY 10977

R1/17

Principal Display Panel - Vial Label ⮝

Ephedrine Sulfate Injection, USP

50 mg/mL, 1 mL Single-Dose Vial

Vial Label

EPHEDRINE SULFATE ephedrine sulfate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:42023-216 Route of Administration INTRAVENOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength EPHEDRINE SULFATE (UNII: U6X61U5ZEG) (EPHEDRINE - UNII:GN83C131XS) EPHEDRINE SULFATE 50 mg in 1 mL

Inactive Ingredients Ingredient Name Strength WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:42023-216-83 25 in 1 CARTON 06/26/2018 1 1 mL in 1 VIAL; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA208943 06/26/2018

Labeler - Par Pharmaceutical, Inc. (092733690)

Registrant - Par Pharmaceutical Inc. (092733690)

Revised: 1/2017 Document Id: 6df5e5f1-6375-45ff-9905-f19927e92ee2 34391-3 Set id: 3e43cc8e-bf4e-44ef-a07d-4336367b9bdb Version: 1 Effective Time: 20170101 Par Pharmaceutical, Inc.

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

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.

10 Overdosage ⮝

Overdose of ephedrine can cause a rapid rise in blood pressure. In the case of an overdose, careful monitoring of blood pressure is recommended. If blood pressure continues to rise to an unacceptable level, parenteral antihypertensive agents can be administered at the discretion of the clinician.

11 Description ⮝

Ephedrine sulfate is an alpha- and beta-adrenergic agonist and a norepinephrine-releasing agent. Ephedrine sulfate injection, USP is a clear, colorless, sterile solution for intravenous injection. Each mL contains ephedrine sulfate 50 mg in water for injection as a single-dose product. The pH range is 4.5 to 7.0. The drug product must be diluted before intravenous administration. The chemical name of ephedrine sulfate is (1R,2S)-(-)-2-methylamine-1-phenylpropan-1-ol sulfate (2:1) (salt). Its molecular weight is 428.54.

The structural formula is:

Image 1

Ephedrine sulfate darkens on exposure to light. It is freely soluble in water and ethanol, very slightly soluble in chloroform, and practically insoluble in ether.

13 Nonclinical Toxicology ⮝

13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility

Carcinogenesis: Two-year feeding studies in rats and mice conducted under the National Toxicology Program (NTP) demonstrated no evidence of carcinogenic potential with ephedrine sulfate at doses up to 10 mg/kg/day and 27 mg/kg/day (approximately 2 times and 3 times the maximum human recommended dose on a mg/m2 basis, respectively).

Mutagenesis: Ephedrine sulfate tested negative in the in vitro bacterial reverse mutation assay, the in vitro mouse lymphoma assay, the in vitro sister chromatid exchange, and the in vitro chromosomal aberration assay.

Impairment of Fertility: Studies to evaluate the effect of ephedrine on fertility have not been conducted.

14 Clinical Studies ⮝

The evidence for the efficacy of ephedrine injection is derived from the published literature. Increases in blood pressure following administration of ephedrine were observed in 14 studies, including 9 where ephedrine was used in pregnant women undergoing neuraxial anesthesia during Cesarean delivery, 1 study in non-obstetric surgery under neuraxial anesthesia, and 4 studies in patients undergoing surgery under general anesthesia. Ephedrine has been shown to raise systolic and mean blood pressure when administered as a bolus dose following the development of hypotension during anesthesia.

16 How Supplied ⮝

Ephedrine Sulfate Injection, USP, 50 mg/mL, is supplied as follows:

Vial stoppers are not manufactured with natural rubber latex.

Store ephedrine sulfate injection, 50 mg/mL, at 20 to 25 C (68 to 77 F), with excursions permitted to 15 C to 30 C (59 F to 86 F) [See USP Controlled Room Temperature.] Protect from light. Store in carton until time of use. For single use only. Discard unused portion.

Spl Unclassified ⮝

Distributed by:

Par Pharmaceutical

Chestnut Ridge, NY 10977

R1/17

Principal Display Panel, Vial Label ⮝

Ephedrine Sulfate Injection, USP

50 mg/mL, 1 mL Single-Dose Vial

Principal Display Panel, Serialized Label ⮝

EPHEDRINE SULFATE ephedrine sulfate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51662-1325(NDC:42023-216) Route of Administration INTRAVENOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength EPHEDRINE SULFATE (UNII: U6X61U5ZEG) (EPHEDRINE - UNII:GN83C131XS) EPHEDRINE SULFATE 50 mg in 1 mL

Inactive Ingredients Ingredient Name Strength WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51662-1325-1 1 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product 10/21/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA208943 10/21/2018

Labeler - HF Acquisition Co LLC, DBA HealthFirst (045657305)

Registrant - HF Acquisition Co LLC, DBA HealthFirst (045657305)

Establishment
Name	Address	ID/FEI	Business Operations
HF Acquisition Co LLC, DBA HealthFirst		045657305	relabel(51662-1325)

Revised: 10/2018 Document Id: 78c1daef-6e1f-5f2c-e053-2a91aa0a0dba 34391-3 Set id: 78c1daef-6e1e-5f2c-e053-2a91aa0a0dba Version: 1 Effective Time: 20181021 HF Acquisition Co LLC, DBA HealthFirst

No Title 1572455697 ⮝

Distributed by:

Par Pharmaceutical

Chestnut Ridge, NY 10977

PREMIERProRx

PREMIERProRx is a registered trademark of Premier Healthcare Alliance, L.P., used under license.

I04/18

OS216P-01-95-01

3003824

Ephedrine Sulfate Injection Usp, 50 Mg/ml  ⮝

Forr IM, IV or SC Use

Rx only

Description  ⮝

Ephedrine Sulfate Injection, USP is a sterile solutionn of 50 mg ephedrine sulfate in Water for Injection.

Ephedrine ooccurs as fine, white, oodorless crystals or powder and darkens on exposure to light. It is freely soluble in water and sparingly soluble in alcohol.

The chemical name of ephedrine sulfate is (C10H15NO)2 H2SO4 benzenemethanol -[l - (methylamino) ethyl] - sufate (2:1) (salt). Its molecular weight is 428 .54. The structural formula is:

Clinical Pharmacology  ⮝

Ephedrine sulfate is a potent sympathomimetic that stimulates both and receptors and has clinical uses related to both actions. Its peripheral actions, which it owes in part to the release of norepinephrine, simulate responses that are obtained when adrenegenic nerves are stimulated. These include an increase in blood pressure, stimulation of heart muscle, constriction of arterioles, relaxation of the smooth muscle of the bronchi and gastrointestinal tract, and dilation of the pupils. In the bladder, relaxation of the detrusor muscle is not prominent, but the tone of the trigone and vesicle sphincter is increased.

Ephedrine sulfate also has a potent effect on the CNS. It stimulates the cerebral cortex and sub-cortical centers, which accounts for its use in narcolepsy.

The cardiovascular responses reported in man include moderate tachycardia, unchanged or augmened stroke volume, enhanced cardiac output, variable alterations in peripheral resistance and usually a rise in blood pressure. The action of ephedrine is more prominent on the heart than on the blood vessels. Ephedrine sulfate increases the flow of coronary, cerebral and muscle blood.

In patients with myasthenia gravis, administration of Ephedrine Sulfate Injection, USP produces a real but modest increase in motor power. The exact mechanism by which ephedrine sulfate affects skeletal muscle contractions is unknown.

Indications And Usage  ⮝

Ephedrine Sulfate Injectionn, USP is indicated in the treatment of allergic disorders, such as bronchial asthma The drug has long been used as a pressor agent, particularly during spinal anesthesia when hypotensionn frequently ooccurs. In Stokes-Adams syndromeme with complete heart block, ephedrine has a value similar to that of epinephrine. It is indicated as a central nervous system stimulant in narcolepsy and depressive states. It is also used in myasthenia gravis.

Contraindications  ⮝

Allergic reactions to ephedrine sulfate are rare. The hypersensitivity, if known, is a specific contraindication. Patients hypersensitive to other sympathomimetics may also be hypersensitive to ephedrine sulfate.

Precautions  ⮝

GENERAL - Special care should be used when administering Ephedrine Sulfate Injection, USP to patients with heart disease, angina pectoris, diabetes, hyperthyroidism, prostatic hypertrophy or hypertension and to patients receiving digitalis. Prolonged use may produce a syndrome resembling an anxiety state. Tolerance to ephedrine sulfate may develop, but temporary discontinuance to the drug restores its original effectiveness.

DRUG INTERACTIONS - Concurrent use of ephedrine sulfate with general anesthetics, especially cyclopropane or halogenated hydrocarbons or digitalis glycosides may cause cardiac arrhythmias, since these medications may sensitize the myocardium to the effects of ephedrine sulfate.

Therapeutic doses of ephedrine sulfate can inhibit the hypotensive effect of guanethidine, bethanidine, and debrisoquin by displacing the adrenergic blockers from their site of action in the sympathetic neurons. The effect in man is seen as a relative or a complete blockade of the antihypertensive drug by a sudden rise in blood pressure. Concomitant use of Ephedrine Sulfate Injection, USP and oxytocics may cause severe hypotension.

Monoamine oxidase inhibitors may potentiate the pressor effect of ephedrine sulfate, possibly resulting in a hypertensive crisis. Ephedrine Sulfate Injection, USP should not be administered during or within 14 days following the administration of MAO inhibitors.

PREGNANCY CATEGORY C - Animal reproduction studies have not been conducted with Ephedrine Sulfate Injection, USP. Also, it is not known whether the drug can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Ephedrine Sulfate Injection, USP should be given to a pregnant woman only if clearly indicated.

It is not known what effect Ephedrine Sulfate Injection, USP may have on the newborn or on the child's later growth and development when the drug is administered to the mother just before or during labor.

NURSING MOTHERS - Ephedrine sulfate is excreted in breast milk. Use by nursing mothers is not recommended because of the higher than usual risks for infants.

Adverse Reactions  ⮝

With large doses of ephedrine sulfate most patients will experience nervousness, insomnia, vertigo, headache, tachycardia, palpitation and sweating. Some patients have nausea, vomiting and anorexia. Vesical sphincter spasm may occur and result in difficult and painful urination. Urinary retention may develop in males with prostatism.

Primordial pain and cardiac arrhythmias may occur following administration of Ephedrine Sulfate Injection, USP

Drug Abuse And Dependence  ⮝

Prolonged abuse of Ephedrine Sulfate Injection, USP can lead to symptoms of paranoid schizophrenia. When this occurs, patients exhibit such physical signs as tachycardia, poor nutrition and hygiene, fever, cold sweat and dilated pupils.

Some measure of tolerance may develop with prolonged or excessive use but addiction does not occur. Temporary cessation of medication and subsequent readministration restores its effectiveness.

Overdosage  ⮝

SYMPTOMS - The principal manifestation of ephedrine sulfate poisoning is convulsions. In acute poisoning the following signs and symptoms may occur: nausea, vomiting, chills, cyanosis, irritability, nervousness, fever, suicidal behavior, tachycardia, dilated pupils, blurred vision, opisthotonos, spasms, convulsions, pulmonary edema, gasping respirations, coma and respiratory failure. Initially, the patient may have hypertension, followed later by hypotension accompanied by anuria.

TREATMENT - If respirations are shallow or cyanosis is present, artificial respiration should be administered. Vasopressors are contraindicated. In cardiovascular collapse blood pressure should be maintained.

ANTIDOTE - For hypertension, 5 mg phentolamine mesylate diluted in saline may be administered slowly intravenously, or 100 mg may be given orally. Convulsions may be controlled by diazepam or paraldehyde. Cool applications and dexamethasone 1 mg/kg, administered slowly intravenously, may control pyrexia.

Dosage And Administration  ⮝

ADULTS - T he usual parenteral dose is 25 to 50 mg given subcutaneously or intramuscularly. Intravenously, 5 to 25 mg may be administered slowly, repeated in 5 to 10 minutes, if necessary.

CHILDREN - The usual subcutaneous or intramuscular dose is 0.5 mg/kg of body weight or 16 .7 mg/square meter of body surface every 4 to 6 hours.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

How Supplied  ⮝

Ephedrine Sulfate Injection USP, 50 mg/mL

1 mL vial in packs of 10, NDC 14789-014-01

STORAGE: Store at 20 to 25 C (68 to 77 F) [see USP Controlled Room Temperature]. Protect from light.

Principal Display Panel - Carton Label  ⮝

NEXUS
PHARMACEUTICALS, INC.

10 x 2 mL Vials NDC 14789-014-01

Ephedrine Sulfate
Injection, USP

50 mg/mL

1 mL fill in a 2 mL Vial

Single Dose Vial

Preservative Free

For subcutaneous,
intramuscular or
intravenous use.

Rx only

EPHEDRINE SULFATE ephedrine sulfate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:14789-014 Route of Administration INTRAVENOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Ephedrine Sulfate (UNII: U6X61U5ZEG) (Ephedrine - UNII:GN83C131XS) Ephedrine Sulfate 50 mg in 1 mL

Inactive Ingredients Ingredient Name Strength Water (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:14789-014-01 10 in 1 CARTON 1 1 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved drug other 06/08/2015

Labeler - Nexus Pharmaceuticals Inc (620714787)

Revised: 6/2014 Document Id: d483665c-4eaf-495f-94ed-c155f5d45f1c 34391-3 Set id: 16f212c3-d504-4d3c-813e-cc23a04aaa88 Version: 2 Effective Time: 20140601 Nexus Pharmaceuticals Inc