Corphedra

Contraindications

None

Cautions

Serious postpartum hypertension and stroke have been described with coadministration of a vasopressor (ie, methoxamine, phenylephrine, ephedrine) and an oxytocic (ie, methylergonovine, ergonovine); monitor blood pressure if patient has received both ephedrine and an oxytocic

Repeated administration can result in tolerance and tachyphylaxis; an alternative vasopressor may be needed to mitigate unresponsiveness to treatment

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

This section provides information on the proper use of a number of products that contain ephedrine. It may not be specific to Corphedra. Please read with care.

A doctor or other trained health professional will give you this medicine. This medicine is given through a needle placed in your veins.

Corphedra is indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia.

General Dosage and Administration Instructions

Corphedra 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.

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).

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.

Mechanism of Action

Ephedrine sulfate is a sympathomimetic amine that directly acts as an agonist at α- and ß­ 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.

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 ß-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, ß-2 adrenoceptor-mediated vasoconstriction, and ß-2 adrenoceptor-mediated vasodilatation. Stimulation of the ß-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].

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].

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.

NDC 42023-196-01

Corphedra (ephedrine Sulfate Injection, USP)

50 mg/mL, 1 mL Single-Dose Vial

Image 2

Applies to ephedrine: intravenous solution

Along with its needed effects, ephedrine (the active ingredient contained in Corphedra) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking ephedrine:

• Blurred vision
• dizziness
• fast, pounding, or irregular heartbeat or pulse
• headache
• nervousness
• pounding in the ears
• slow or fast heartbeat

Some side effects of ephedrine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Nausea or vomiting
• restlessness