Product Elements:
Ephedrine sulfate ephedrine sulfate ephedrine sulfate ephedrine acetic acid sodium hydroxide water
Drug Interactions:
7 drug interactions 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 ant
Read more...agonists, 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.
Indications and Usage:
1 indications and usage 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)
Warnings and Cautions:
5 warnings and precautions pressor effects with concomitant use with oxytocic drugs : pressor effect of sympathomimetic pressor amines is potentiated (5.1) tachyphylaxis and tolerance : repeated administration of ephedrine may cause tachyphylaxis (5.2) 5.1 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 ephedrine and an oxytocic. 5.2 tolerance and tachyphylaxis data indicate that repeated administration of ephedrine can result in tachyphylaxis. clinicians treating anesthesia-induced hypotension with ephedrine sulfate injection should be aware of the possibility of tachyphylaxis and should be prepared with an alternative pressor to mitigate unaccept
Read more...able responsiveness. 5.3 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.
Dosage and Administration:
2 dosage and administration should be administered by trained healthcare providers. (2.1) ephedrine sulfate injection, 50 mg/ml, must be diluted before administration as an intravenous bolus dose. (2.1) bolus intravenous injection: 5 mg to 10 mg as needed, not to exceed 50 mg. (2.1) 2.1 general dosage and administration instructions ephedrine sulfate injection must be diluted before administration as an intravenous bolus to achieve the desired concentration. dilute with normal saline or 5% dextrose in water. inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. discard unused portion. 2.2 dosing for the treatment of clinically important hypotension in the setting of anesthesia ephedrine sulfate injection should be administered by trained healthcare providers. the recommended dosages for the treatment of clinically important hypotension in the setting of anesthesia is an initial dose of 5 mg to
Read more... 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 prepare 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 0.9% sodium chloride injection. withdraw an appropriate dose of the 5 mg/ml solution prior to bolus intravenous administration.
Dosage Forms and Strength:
3 dosage forms and strengths ephedrine sulfate injection, usp is a clear, colorless sterile solution and a single-dose 1 ml vial that contains 50 mg/ml ephedrine sulfate usp, equivalent to 38 mg ephedrine base. injection: 50 mg/ml ephedrine sulfate in single-dose vial (3)
Contraindications:
4 contraindications none none (4)
Adverse Reactions:
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 most common adverse reactions during treatment: nausea, vomiting, and tachycardia. (6) to report suspected adverse reactions, contact amneal pharmaceuticals at 1-877-835-5472 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.
Drug Interactions:
7 drug interactions 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 ant
Read more...agonists, 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.
Overdosage:
10 overdosage overdose of ephedrine 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.
Description:
11 description ephedrine is an alpha- and beta-adrenergic agonist and a norepinephrine-releasing agent. ephedrine sulfate injection, usp is a clear, colorless, sterile solution for intravenous injection. it must be diluted before intravenous administration. the chemical name of ephedrine sulfate is (1r,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 structural formula is depicted below: ephedrine sulfate, usp is a white to off-white powder; it is freely soluble in water and slightly soluble in alcohol. each ml contains ephedrine sulfate, usp 50 mg (equivalent to 38 mg ephedrine base) in water for injection. the ph is adjusted with sodium hydroxide and/or glacial acetic acid if necessary. the ph range is 4.5 to 7.0. l
Clinical Pharmacology:
12 clinical pharmacology 12.1 mechanism of action ephedrine sulfate is a sympathomimetic amine that directly acts as an agonist at α- and Ã-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. 12.2 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 Ã-adrenergic receptors in the lungs promotes bronchodilation. the overall cardiovascular effect from ephedrine is the result of a balance among α-1 adrenoceptor
Read more...-mediated vasoconstriction, Ã-2 adrenoceptor-mediated vasoconstriction, and Ã-2 adrenoceptor-mediated vasodilatation. stimulation of the Ã-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) ] . 12.3 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 intravenous 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) ] .
Mechanism of Action:
12.1 mechanism of action ephedrine sulfate is a sympathomimetic amine that directly acts as an agonist at α- and Ã-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:
12.2 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 Ã-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, Ã-2 adrenoceptor-mediated vasoconstriction, and Ã-2 adrenoceptor-mediated vasodilatation. stimulation of the Ã-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) ] .
Pharmacokinetics:
12.3 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 intravenous 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) ] .
Nonclinical Toxicology:
13 nonclinical toxicology 13.1 carcinogenesis, mutagenesis, impairment of fertility carcinogenesis: two-year feeding studies in rats and mice conducted under the national toxicology program (ntp) demonstrated no evidence of carcinogenic potential with ephedrine sulfate at doses up to 10 mg/kg/day and 27 mg/kg/day (approximately 2 times and 3 times the maximum human recommended dose on a mg/m 2 basis, respectively). mutagenesis: ephedrine sulfate tested negative in the in vitro bacterial reverse mutation assay, the in vitro mouse lymphoma assay, the in vitro sister chromatid exchange, the in vitro chromosomal aberration assay, and the in vivo rat bone marrow micronucleus assay. impairment of fertility: there was no impact on fertility or early embryonic development in a study in which male rats were administered intravenous bolus doses of 0, 2, 10, or 60 mg/kg ephedrine sulfate (up to 12 times the maximum recommended human dose of 50 mg based on body surface area) for 28 days prior to m
Read more...ating and through gestation and females were treated for 14 days prior to mating through gestation day 7.
Carcinogenesis and Mutagenesis and Impairment of Fertility:
13.1 carcinogenesis, mutagenesis, impairment of fertility carcinogenesis: two-year feeding studies in rats and mice conducted under the national toxicology program (ntp) demonstrated no evidence of carcinogenic potential with ephedrine sulfate at doses up to 10 mg/kg/day and 27 mg/kg/day (approximately 2 times and 3 times the maximum human recommended dose on a mg/m 2 basis, respectively). mutagenesis: ephedrine sulfate tested negative in the in vitro bacterial reverse mutation assay, the in vitro mouse lymphoma assay, the in vitro sister chromatid exchange, the in vitro chromosomal aberration assay, and the in vivo rat bone marrow micronucleus assay. impairment of fertility: there was no impact on fertility or early embryonic development in a study in which male rats were administered intravenous bolus doses of 0, 2, 10, or 60 mg/kg ephedrine sulfate (up to 12 times the maximum recommended human dose of 50 mg based on body surface area) for 28 days prior to mating and through gestatio
Read more...n and females were treated for 14 days prior to mating through gestation day 7.
Clinical Studies:
14 clinical studies 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.
How Supplied:
16 how supplied/storage and handling ephedrine sulfate injection usp, 50 mg/ml is a clear, colorless sterile solution and supplied in 1 ml single-dose glass vials. each ml contains 50 mg of ephedrine sulfate usp, equivalent to 38 mg ephedrine base. it is available as follows: 50 mg/ml (1 ml) 1 ml single-dose vial: ndc 70121-1637-1 10 vials in a carton: ndc 70121-1637-7 25 vials in a carton: ndc 70121-1637-5 vial stoppers are not manufactured with natural rubber latex. store ephedrine sulfate injection usp, 50 mg/ml, at 20° to 25°c (68° to 77°f); excursions permitted between 15° to 30°c (59° to 86°f) [see usp controlled room temperature]. store in carton until time of use. for single-dose only. discard unused portion. manufactured by: amneal pharmaceuticals pvt. ltd. parenteral unit ahmedabad 382213, india distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 10-2021-02
Package Label Principal Display Panel:
Principal display panel ndc 70121-1637-1 ephedrine sulfate injection usp, 50 mg/ml (1 ml) rx only amneal pharmaceuticals llc vial label ndc 70121-1637-7 ephedrine sulfate injection usp, 50 mg/ml (1 ml) rx only amneal pharmaceuticals llc carton label (10 vials in 1 carton) ndc 70121-1637-5 ephedrine sulfate injection usp, 50 mg/ml (1 ml) rx only amneal pharmaceuticals llc carton label (25 vials in 1 carton) 1 1 1