EPHEDRINE SULFATE injection

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

EPHEDRINE SULFATE (UNII: U6X61U5ZEG) (EPHEDRINE - UNII:GN83C131XS)

Available from:

Civica, Inc.

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Ephedrine sulfate injection is indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia. None Risk Summary 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% 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). 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. 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). 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. 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.

Product summary:

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 72572-151-01 10 Vials in a Carton: NDC 72572-151-10 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 for: Civica, Inc. Lehi, Utah 84043 Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Parenteral Unit Ahmedabad 382213, India Rev. 11-2021-01

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

EPHEDRINE SULFATE- EPHEDRINE SULFATE INJECTION
CIVICA, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
EPHEDRINE SULFATE
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
EPHEDRINE SULFATE
INJECTION. EPHEDRINE SULFATE INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2016
INDICATIONS AND USAGE
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)
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)
DOSAGE FORMS AND STRENGTHS
Injection: 50 mg/mL ephedrine sulfate in single-dose vial (3)
CONTRAINDICATIONS
None (4)
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)
ADVERSE REACTIONS
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
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