EPHEDRON

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.

The chemical name of ephedrine sulfate is benzenemethanol, α-[1-(methylamino)ethyl]-, [ R -( R , S )]-, sulfate (2:1) (salt), and the molecular weight is 428.54 g/mol.

Its structural formula is depicted below

Ephedrine sulfate is freely soluble in water and sparingly soluble in alcohol.

Each mL of the 50 mg/mL strength contains ephedrine sulfate 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.

The 50 mg/mL vial must be diluted before intravenous administration. structural formula.

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.

Lactation Aneurysm Angor History of heart disease Arrhythmia Atherosclerosis Cardiopathies Diabetes Closed angle glaucoma Pregnancy Hypertension Hyperthyroidism Benign prostate hypertrophy Myocardial Ischemia Cardiovascular disease Sports Tachycardia.

Ephedrine sulfate is a sympathomimetic amine that directly acts as an agonist at α.

• and β-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 β-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, 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. 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

IV 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.

ephedrine: Mechanism of action Ephedrine is a sympathomimetic amine acting directly on α and β receptors and indirectly by increasing the release of noradrenaline by sympathetic nerve endings.

Like any sympathomimetic agent, ephedrine stimulates the central nervous system, cardiovascular system, respiratory system, and digestive and urinary sphincters.

Ephedrine is also a monoamine oxidase inhibitor (MAO).

• Glycaemia (fluctuation)
• Hypokalaemia Hypersudation (Common)
• Hyperhidrosis (Common)
• Fatigue (Common)
• Coagulation disorder Hypersensitivity Anorexia Acute glaucoma (crystosis)
• Oral dryness (Common)
• Sialorrhoea Depression (Common)
• Anxiety (Common)
• Insomnia (Common)
• Mental confusion (Common)
• Nervousness (Common)
• Agitation (Common)
• Hallucination Psychosis
• Irritability Hypertension (Common)
• Tachycardia (Common)
• Palpitation (Common)
• Arrhythmia (Rare)
• Cardiomyopathy caused by stress Angor Hypotension Cardiac arrest Bradycardia Nausea (Common)
• Vomiting (Common)
• Muscle weakness (Common)
• Headache (Common)
• Trembling Brain haemorrhage
• Dyspnoea (Common)
• Pulmonary edema Urinary retention (Rare).

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.

Should be administered by trained healthcare providers Ephedrine sulfate injection, 50 mg/mL, must be diluted before administration as an intravenous bolus dose.

Bolus intravenous injection: 5 mg to 10 mg as needed, not to exceed 50 mg. 2.1 General Dosage and Administration Instructions Ephedrine sulfate injection, 50 mg/mL 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. 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 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.

Ephedrine sulfate injection, USP, 50 mg/mL, is a clear, colorless, sterile solution for intravenous injection supplied as follows: NDC Strength How Supplied 70756-611-25 50 mg/mL of ephedrine sulfate equivalent to 38 mg/mL of ephedrine base 1 mL fill in 2 mL clear glass vial; for single-dose (supplied in packages of 25) Vial stoppers are not manufactured with natural rubber latex.

Store ephedrine sulfate injection, 50 mg/mL, at 20° to 25°C (68° to 77°F); .

Store in carton until time of use.

For single dose only.

Discard unused portion.

Manufactured for

Lifestar Pharma LLC 1200 MacArthur Blvd.

Mahwah, NJ 07430 USA Made in India Revised: December 2021, V-03.

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.

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.

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.

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.

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.

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).

The safety and effectiveness of ephedrine sulfate in pediatric patients have not been established.

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 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 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.