ephedrine (Rx)

Brand and Other Names:Akovaz, Corphedra, more...Emerphed, Rezipres
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injectable solution, as sulfate

  • 50mg/mL (Akovaz, Corphedra, generics)
  • 50mg/10mL (5mg/mL) (Emerphed); equivalent to ephedrine base 3.8mg/mL

injectable solution, as hydrochloride (Rezipres)

  • 47mg/mL; equivalent to ephedrine base 38mg/mL
  • 47mg/5mL (9.4mg/mL); equivalent to ephedrine base 7.7mg/mL
  • 23.5mg/5mL (4.7mg/mL); equivalent to ephedrine base 3.8mg/mL

Hypotension

Indicated for treatment of clinically important hypotension occurring in the setting of anesthesia

Akovaz, Corphedra, Emerphed, generics

  • Initial dose: 5-10 mg IV bolus
  • Administer additional boluses as needed, not to exceed a total cumulative dosage of 50 mg
  • Titrate dosage according to blood pressure (BP) goal

Rezipres

  • Initial dose: 4.7-9.4 mg IV bolus
  • Administer additional boluses as needed, not to exceed a total cumulative dosage of 47 mg
  • Titrate dosage according to blood pressure goal

Dosage Modifications

Renal impairment

  • Ephedrine and its metabolite are excreted in urine
  • Patients with renal impairment may have an increase in elimination half-life, which may slow the elimination, prolong the effects, and increase the risk of adverse reactions of ephedrine
  • Carefully monitor these patients after initial bolus dose for adverse reactions

Dosing Considerations

Premixed formulations (Emerphed, Rezipres 4.7 mg/mL)

  • Do NOT dilute before use

Safety and efficacy not established

Start 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

Drug is substantially excreted by the kidney, and the risk of adverse reactions may be greater with impaired renal function

Because elderly patients are more likely to have decreased renal function, carefully select dose and consider monitoring renal function

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Interactions

Interaction Checker

and ephedrine

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            Adverse Effects

            Frequency Not Defined

            Gastrointestinal disorders: Nausea, vomiting

            Cardiac disorders: Tachycardia, palpitations (thumping heart), reactive hypertension, bradycardia, ventricular ectopics, heart rhythm/rate variability

            Nervous system disorders: Dizziness

            Psychiatric disorders: Restlessness

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            Warnings

            Contraindications

            None

            Cautions

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

            Repeated administration may cause tachyphylaxis; an alternative vasopressor may be needed to mitigate unresponsiveness to treatment

            An increased incidence of hypertension has occurred when used for prevention compared with treatment of hypotension

            Drug interaction overview

            • Oxytocin and oxytocic drugs
              • Carefully monitor BP
              • Coadministration of a vasopressor and an oxytocic cause serious postpartum hypertension; some patients experienced a stroke
            • Drugs that augment vasopressor effects of ephedrine
              • Carefully monitor BP
              • Clonidine, propofol, monoamine oxidase inhibitors (MAOIs), atropine may augment the vasopressor effects of ephedrine
            • Drugs that antagonize vasopressor effects of ephedrine
              • Carefully monitor BP
              • Alpha-adrenergic antagonists, beta-adrenergic receptor antagonists, reserpine, or quinidine may antagonize the vasopressor effects of ephedrine
            • Rocuronium
              • Be aware of interaction
              • Ephedrine may reduce onset time of neuromuscular blockade when used for intubation with rocuronium if administered simultaneously with anesthetic induction
            • Epidural anesthesia
              • Monitor and treat according to clinical practice
              • Ephedrine may decrease the efficacy of epidural blockage by hastening the regression of sensory analgesia
            • Theophylline
              • Monitor for worsening symptoms and manage symptoms according to clinical practice
              • Ephedrine may increase the frequency of nausea, nervousness, and insomnia
            • Cardiac glycosides
              • Carefully monitor
              • Coadministration with a cardiac glycoside (eg, digoxin) may increase the risk of arrhythmias
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            Pregnancy & Lactation

            Pregnancy

            Available data of use in pregnant females have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Animal data

            • Decreased fetal body weights were observed when pregnant rats were administered IV bolus doses of 60 mg/kg ephedrine sulfate (12 times the maximum recommended human dose (MRHD) based on body surface area [BSA]) from gestation day (GD) 6-17; dose was associated with evidence of maternal toxicity (decreased body weight of dams and abnormal head movements)
            • Decreased fetal survival and fetal body weights were observed in presence of maternal toxicity after normotensive pregnant rats were administered 60 mg/kg IV ephedrine sulfate (12x the MRHD of 50 mg/day based on BSA) from GD 6 through Lactation Day 20

            Clinical considerations

            • Untreated hypotension associated with spinal anesthesia for cesarean section is associated with increase in maternal nausea and vomiting
            • Decreased uterine blood flow due to maternal hypotension may result in fetal bradycardia and acidosis
            • 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
              • Monitor newborn for signs and symptoms of metabolic acidosis
              • Monitoring of infant’s acid-base status is warranted to ensure that an episode of acidosis is acute and reversible

            Lactation

            A single published case report indicates that ephedrine is present in human milk

            No information is available on its effects on breastfed infants or on milk production

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Sympathomimetic amine that directly acts as an agonist at alpha- and beta­adrenergic receptors and indirectly causes the release of norepinephrine from sympathetic neurons

            Resulting pharmacodynamic effects include increased heart rate, BP, cardiac output, and variable increases in peripheral resistance

            Stimulates alpha-adrenergic receptors of smooth muscle cells in the bladder (increases resistance to urinary outflow)

            Activation of beta-adrenergic receptors in the lungs promotes bronchodilation

            Distribution

            Crosses the placental barrier

            Metabolism

            Publications studying pharmacokinetics of oral (-)-ephedrine support that (-)-ephedrine is metabolized into norephedrine; however, metabolic pathway is unknown

            Elimination

            Half-life: 6 hr (oral)

            Excretion: Urine (ephedrine and its metabolites)

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            Administration

            IV Compatibilities

            0.9% NaCl

            D5W

            IV Preparation

            Visually inspect parenteral drug products for particulate matter and discoloration before preparation and administration

            Dilution requirements before administration

            • Products vary regarding requirement for dilution
            • Products requiring dilution
              • 50 mg/mL (Akovaz, Corphedra, generics)
              • 47 mg/mL (Rezipres)
              • 9.4 mg/mL (Rezipres): Can use as provided or may be diluted
            • Do not dilute
              • 5 mg/mL (Emerphed)
              • 4.7 mg/mL (Rezipres)
              • 9.4 mg/mL (Rezipres): Can use as provided or may be diluted

            Rezipres

            • 47 mg/mL
              • Withdraw 1 mL of 47 mg/mL ampule and dilute with 9 mL of D5W or 0.9% NaCl to yield 4.7 mg/mL
              • Withdraw an appropriate dose of the diluted 4.7-mg/mL solution prior to administration
            • 9.4 mg/mL
              • Withdraw 5 mL of 9.4-mg/mL ampule and dilute with 5 mL of D5W or 0.9% NaCl to yield 4.7 mg/mL
              • Withdraw an appropriate dose of the diluted 4.7-mg/mL solution prior to administration

            Akovaz, Corphedra, generics

            • Withdraw 1 mL of 50 mg/mL ampule and dilute with 9 mL of D5W or 0.9% NaCl to yield 5 mg/mL
            • Withdraw an appropriate dose of the diluted 5-mg/mL solution prior to administration

            IV Administration

            Administer prepared diluted solutions or undiluted drug as IV bolus

            Formulations for direct IV bolus administration

            • Emerphed (ephedrine sulfate 5 mg/mL)
            • Rezipres (ephedrine HCl 4.7 mg/mL and 9.7 mg/mL)

            Storage

            All formulations are single dose only; discard any unused portion

            Akovaz, Corphedra, Emerphed, generics

            • Vial stoppers are not manufactured with natural rubber latex
            • Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
            • Protect from light, store in carton until time of use

            Rezipres

            • Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
            • Diluted solutions: Discard after >4 hr at room temperature or >24 hr under refrigerated conditions
            • For single-dose only; discard any unused portion
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.