Emerphed

• This is a premixed formulation. Do not dilute prior to use.
• Discard any unused portion of EMERPHED.
• Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
• The single-dose prefilled syringe is intended for use in one patient during one surgical procedure.

EMERPHED is a clear, colorless solution. Do not use if the solution is not clear or if particulate matter is present.

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).

The proper method of administration of EMERPHED-PFS injection is described in the following instructions.

For each single-dose prefilled syringe:

1. Remove syringe from tray and check that it is not damaged or leaking.
2. Inspect drug product in glass syringe for any visible particulate matter or discoloration prior to use. Discard if particulate matter or discoloration is present.
3. Do not remove the tamper evident seal. Push plunger rod slightly in to break the stopper loose while tip cap is still on.
4. Hold the syringe upright on the syringe barrel (C). With the other hand, take hold of the cap (A) and twist off cap counterclockwise from syringe tip (see Figure 1).Figure 1
5. Once cap (A) is off, DO NOT TOUCH THE STERILE SYRINGE TIP (Luer-Lok) (B) (see Figure 2).Figure 2
6. Discard the tip cap.
7. Expel air bubble.
8. Adjust dose into sterile material (if applicable).
9. Connect the syringe to an appropriate intravenous connection.
   • Before injection, ensure that the syringe is securely attached to the needle or needleless luer access device (NLAD).
10. Depress plunger rod to deliver medication. Ensure that pressure is maintained on the plunger rod during the entire administration.
11. Remove syringe from NLAD (if applicable) and discard into appropriate receptacle.
    • To prevent needle stick injuries, do not recap needle when needle is connected to syringe.

    NOTE: All steps must be done sequentially

    • Do not re-sterilize syringe
    • Do not use this product on a sterile field
    • Do not introduce any other fluid into the syringe at any time
    • This product is for single dose only

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.

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.

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

Safety and effectiveness of EMERPHED and EMERPHED-PFS in pediatric patients have not been established.

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.

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.

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.

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 ].

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].