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.

ceptable 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.

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). 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.

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.

d population are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryofetal risk untreated hypotension associated with spinal anesthesia for cesarean section is associated with an increase in maternal nausea and vomiting. a decrease in 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 [see clinical pharmacology 12.3 ] . monitoring of the newborn for signs and symptoms of metabolic acidosis may be required. monitoring of infant’s acid-base status is warranted to ensure that an episode of acidosis is acute and reversible. data animal data decreased fetal body weights were observed when pregnant rats were administered intravenous bolus doses of 60 mg/kg ephedrine sulfate (12 times the maximum recommended human dose (mrhd) of 50 mg based on body surface area) from gestation day 6 to 17. this dose was associated with evidence of maternal toxicity (decreased body weight of dams and abnormal head movements). no malformations or fetal deaths were noted at this dose. no effects on fetal body weight were noted at 10 mg/kg (1.9 times the mrhd of 50 mg). no evidence of malformations or embryo-fetal toxicity were noted in pregnant rabbits administered intravenous bolus doses up to 20 mg/kg ephedrine sulfate (7.7 times the maximum recommended human dose (mrhd) of 50 mg based on body surface area) from gestation day 6 to 20. this dose was associated with expected pharmacological maternal effects (increased respiration rate, dilated pupils, piloerection). decreased fetal survival and body weights in the presence of maternal toxicity (increased mortality) were noted when pregnant dams were administered intravenous bolus doses of 60 mg/kg epinephrine sulfate (approximately 12 times the mrhd based on body surface area) from gd 6 through lactation day 20. no adverse effects were noted at 10 mg/kg (1.9 times the mrhd). 8.2 lactation risk summary a single published case report indicates that ephedrine is present in human milk. however, no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ephedrine sulfate injection and any potential adverse effects on the breastfed child from ephedrine sulfate injection or from the underlying maternal condition. 8.4 pediatric use the safety and effectiveness of ephedrine sulfate in pediatric patients have not been established. animal toxicity data in a study in which juvenile rats were administered intravenous bolus doses of 2, 10, or 60 mg/kg ephedrine sulfate daily from postnatal day 35 to 56, an increased incidence of mortality was noted at the high dose of 60 mg/kg. the no-adverse-effect level was 10 mg/kg (approximately 1.9 times a maximum daily dose of 50 mg in a 60 kg person based on body surface area). 8.5 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. 8.6 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.

pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryofetal risk untreated hypotension associated with spinal anesthesia for cesarean section is associated with an increase in maternal nausea and vomiting. a decrease in 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 [see clinical pharmacology 12.3 ] . monitoring of the newborn for signs and symptoms of metabolic acidosis may be required. monitoring of infant’s acid-base status is warranted to ensure that an episode of acidosis is acute and reversible. data animal data decreased fetal body weights were observed when pregnant rats were administered intravenous bolus doses of 60 mg/kg ephedrine sulfate (12 times the maximum recommended human dose (mrhd) of 50 mg based on body surface area) from gestation day 6 to 17. this dose was associated with evidence of maternal toxicity (decreased body weight of dams and abnormal head movements). no malformations or fetal deaths were noted at this dose. no effects on fetal body weight were noted at 10 mg/kg (1.9 times the mrhd of 50 mg). no evidence of malformations or embryo-fetal toxicity were noted in pregnant rabbits administered intravenous bolus doses up to 20 mg/kg ephedrine sulfate (7.7 times the maximum recommended human dose (mrhd) of 50 mg based on body surface area) from gestation day 6 to 20. this dose was associated with expected pharmacological maternal effects (increased respiration rate, dilated pupils, piloerection). decreased fetal survival and body weights in the presence of maternal toxicity (increased mortality) were noted when pregnant dams were administered intravenous bolus doses of 60 mg/kg epinephrine sulfate (approximately 12 times the mrhd based on body surface area) from gd 6 through lactation day 20. no adverse effects were noted at 10 mg/kg (1.9 times the mrhd).

-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 (5.2) ] . 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) ] .

r to mating and through gestation and females were treated for 14 days prior to mating through gestation day 7.

station and females were treated for 14 days prior to mating through gestation day 7.