^ Pharmacodynamics
Ephedrine stimulates heart rate and cardiac output and variably increases peripheral resistance; as a result, ephedrine usually increases blood pressure. Stimulation of the α-adrenergic receptors of smooth muscle cells in the bladder base may increase the resistance to the outflow of urine. Activation of β- adrenergic receptors in the lungs promotes bronchodilation.
The overall cardiovascular effect from ephedrine is the result of a balance among α-1 adrenoceptor- mediated vasoconstriction, β-2 adrenoceptor- mediated vasoconstriction, and β-2 adrenoceptor-mediated vasodilatation. Stimulation of the β-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 5.2 ].
^4. Contraindications
None
^ 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 EMERPHED and EMERPHED-PFS and an oxytocic.
^ . How Supplied/storage And Handling
EMERPHED (ephedrine sulfate injection) is a clear, colorless solution available as single-dose vials containing 5 mg/mL ephedrine sulfate, equivalent to 3.8 mg/mL ephedrine base and is supplied as follows:
EMERPHED-PFS (ephedrine sulfate injection) is a clear, colorless solution available as single-dose pre-filled syringes containing 5 mg/mL ephedrine sulfate, equivalent to 3.8 mg/mL ephedrine base and is supplied as follows:
The single-dose prefilled syringes, each fitted with a removable tip cap and plunger rods, are presented in a carton.
EMERPHED (ephedrine sulfate injection) 50 mg/10 mL (5 mg/mL) and EMERPHED-PFS (ephedrine sulfate injection) 50 mg/10 mL (5 mg/mL) and 25 mg/5 mL (5 mg/mL) are not made with natural rubber latex.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Store in carton until time of use. For single dose only. Discard unused portion.
The single-dose prefilled syringe is intended for use in one patient during one surgical procedure.
Patent, www.emerphed.com/patent
Manufactured in Italy for:
Nexus Pharmaceuticals, LLC
400 Knightsbridge Parkway
Lincolnshire, IL 60069
USA
EPFPI01ITR06
^ . Clinical Studies
The evidence for the efficacy of EMERPHED / EMERPHED-PFS (ephedrine sulfate 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.
^3. Dosage Forms And Strengths
EMERPHED (ephedrine sulfate injection) is a clear, colorless solution available as:
EMERPHED-PFS (ephedrine sulfate injection) is a clear, colorless solution available as:
^7. Drug Interactions
^ Tolerance And Tachyphylaxis
Data indicate that repeated administration of ephedrine can result in tachyphylaxis. Be aware of this possibility when treating anesthesia-induced hypotension with EMERPHED and EMERPHED-PFS and be prepared with an alternative pressor to mitigate unacceptable responsiveness.
^ 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.
^ General Dosage And Administration Instructions
EMERPHED is a clear, colorless solution. Do not use if the solution is not clear or if particulate matter is present.
^ Instructions For Use Of Prefilled Syringe
The proper method of administration of EMERPHED-PFS injection is described in the following instructions.
For each single-dose prefilled syringe:
^ 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.
^ 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.
^ . Overdosage
Overdose of EMERPHED and EMERPHED-PFS 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.
^ 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].
^ Pediatric Use
Safety and effectiveness of EMERPHED and EMERPHED-PFS in pediatric patients have not been established.
^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
^ . Description
EMERPHED / EMERPHED-PFS (ephedrine sulfate injection) is a clear, colorless, sterile solution for intravenous injection. The chemical name of ephedrine sulfate is benzenemethanol, α-[1-(methylamino)ethyl]-, [R-(R*,S*)]-, sulfate (2:1) (salt), and the molecular weight is 428.5 g/mol. 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, USP 5 mg (equivalent to 3.8 mg ephedrine base), 0.9% sodium chloride, USP in water for injection. The pH range is 4.5 to 7.0.
^1. Indications And Usage
EMERPHED and EMERPHED-PFS is indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia.
^ Mechanism Of Action
Ephedrine sulfate is a sympathomimetic amine that directly acts as an agonist at α- and β-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.
^ 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.