1 Ml Ephedrine Sulfate 50 Mg/ml Injection

Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The recommended dosages 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.

Available data from randomized studies, case series, and reports of ephedrine sulfate use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, there are clinical considerations due to underlying conditions (see Clinical Considerations). In animal reproduction studies, decreased fetal survival and fetal body weights were observed in the presence of maternal toxicity after normotensive pregnant rats were administered 60 mg/kg intravenous ephedrine sulfate (12 times the maximum recommended human dose (MRHD) of 50 mg/day).  No malformations or embryofetal adverse effects were observed when pregnant rats or rabbits were treated with intravenous bolus doses of ephedrine sulfate during organogenesis at doses 1.9 and 7.7 times the MRHD, respectively [See data].

The estimated background risk of major birth defects and miscarriage for the indicated 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 2-4% and 15-20%, 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 6-17.  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 6-20.  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).

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.

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).

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] .

Ephedrine crosses the placental barrier [see Use in Specific Populations 8.1] .

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 gestation and females were treated for 14 days prior to mating through Gestation Day 7.