EPHEDRINE SULFATE

Ephedrine is an alpha- and beta-adrenergic agonist and a norepinephrine-releasing agent. Ephedrine Sulfate Injection, 5 mg/mL is a clear, colorless, sterile, ready-to-use solution for intravenous injection. The chemical name of ephedrine sulfate is (1 R ,2S)-(-)-2-methylamine-1-phenylpropan-1-ol sulfate, and the molecular weight is 428.5 g/mol. Its molecular formula is (C 10 H 15 NO) 2 · H 2 SO 4 and its structural formula is depicted below: Ephedrine sulfate is freely soluble in water and ethanol, very slightly soluble in chloroform, and practically insoluble in ether. Each mL contains ephedrine sulfate 5 mg (equivalent to 3.8 mg ephedrine base), sodium chloride 9 mg, and sodium hydroxide and/or acetic acid for pH adjustment, if necessary. The pH range is 4.5 to 7.0. Chemical Structure

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

Bolus intravenous injection: 5 mg to 10 mg (equivalent to 3.8 to 7.6 mg ephedrine base) as needed, not to exceed 50 mg. ( 2 ) Ready-to-Use formulation. Do not dilute. 2.1 General Dosage and Administration Instructions Ready to Use formulation. Do not dilute. Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Ephedrine Sulfate Injection is a clear, colorless solution. Do not use if discolored. 2.2 Dosing for the Treatment of Clinically Important Hypotension in the Setting of Anesthesia The recommended dosages for the treatment of clinically important hypotension in the setting of anesthesia is an initial dose of 5 mg 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 Instructions for Use of Single-Dose Prefilled Syringe Important Administration Information Ephedrine Sulfate Injection is administered undiluted by slow intravenous injection. The syringe should be administered with clean gloved hands. Check the compatibility of Ephedrine Sulfate Injection with all other medications and any intravenous fluids the patient is currently receiving This product is for single dose only; discard unused portion FIGURE A. PREFILLED SYRINGE Figure A Step 1 Examine syringe for damage or cracks and ensure the Luer cap is intact. DO NOT USE if the Luer cap is missing, loose or damaged. Inspect and ensure the EPHEDRINE liquid in the prefilled syringe is clear and colorless. DO NOT USE if the liquid looks discolored, cloudy, or if the liquid contains any particulate matter. Check the expiration date on the syringe and confirm product has not expired. DO NOT USE if the expiration date has passed. Step 2 Check the intravenous site for signs of infiltration from fluid or medications leaking into surrounding tissue. If signs of infiltration are observed, existing IV administration should be discontinued. A new IV administration site should be established. Step 3 Thoroughly cleanse the injection port closest to the patient with alcohol prep pad. Step 4 Twist the tip cap to open. See Figure B. Figure B Step 5 Remove air from the syringe if necessary. With the tip of the syringe pointing up, tap the syringe barrel to make air bubbles rise to the top. Expel air and excess medication by pushing the plunger up until the edge of the plunger is at the graduation mark that corresponds to volume of the prescribed dose. See Figure C Figure C Step 6 Connect the syringe to the injection port. Step 7 If the intravenous line does not have backflow protection, pinch/clamp the intravenous tubing between intravenous bag and injection port. Step 8 Press down on the plunger of the prefilled syringe to administer the medication by intravenous bolus. Inject 5 mg to 10 mg by intravenous bolus at a time. Adjust dosage according to the blood pressure goal (i.e., titrate to effect). DO NOT exceed a total dosage of 50 mg. Step 9 Remove the syringe from injection port. Step 10 If necessary, release the pinched intravenous tubing ensuring continuous flow of intravenous fluid. Alternatively, manually flush the line after administration of Ephedrine Sulfate Injection so there is no residual drug in the intravenous tubing. Step 11 Dispose of used syringe. Safely throw away syringe(s) immediately after use into an appropriate medical waste container. Figure A Figure B This is an image of Figure C.

None None ( 4 )

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 Most common adverse reactions during treatment: nausea, vomiting, and tachycardia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Endo at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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: α-adrenergic antagonists, β-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. Interactions that Augment 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. 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. 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. 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. 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.