Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from insect stings or bites, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. 

Adrenalinis indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock.

Inspect visually for particulate matter and discoloration prior to administration; solution should be clear and colorless.  Do not use if the solution is colored or cloudy, or if it contains particulate matter. 

Inject Adrenalin intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary.  When administering to a child, to minimize the risk of injection related injury, hold the leg firmly in place and limit movement prior to and during an injection.  The injection may be repeated every 5 to 10 minutes as necessary.  For intramuscular administration, use a needle long enough (at least 1/2 inch) to ensure the injection is administered into the muscle.  Monitor the patient clinically for the severity of the allergic reaction and potential cardiac effects of the drug, and repeat as needed.  Do not administer repeated injections at the same site, as the resulting vasoconstriction may cause tissue necrosis. 

Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 to 0.5 mL) of undiluted Adrenalin administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.5 mg (0.5 mL) per injection, repeated every 5 to 10 minutes as necessary.  Monitor clinically for reaction severity and cardiac effects. 

Children less than 30 kg (66 lbs): 0.01 mg/kg (0.01 mL/kg) of undiluted Adrenalin administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.3 mg (0.3 mL) per injection, repeated every 5 to 10 minutes as necessary.  Monitor clinically for reaction severity and cardiac effects.  

Dilute 1 mL (1 mg) of epinephrine from its vial to 1,000 mL of a 5 percent dextrose or 5 percent dextrose and sodium chloride solution to produce a 1 mcg per mL dilution. Administration in saline solution alone is not recommended. If indicated, administer whole blood or plasma separately.

Whenever possible, give infusions of epinephrine into a large vein. Avoid using a catheter tie-in technique, because the obstruction to blood flow around the tubing may cause stasis and increased local concentration of the drug. Avoid the veins of the leg in elderly patients or in those suffering from occlusive vascular diseases.

To provide hemodynamic support in septic shock associated hypotension in adult patients, the suggested dosing infusion rate of intravenously administered epinephrine is 0.05 to 2 mcg/kg/min, and is titrated to achieve a desired mean arterial pressure (MAP). The dosage may be adjusted periodically, such as every 10 to 15 minutes, in increments of 0.05 to 0.2 mcg/kg/min, to achieve the desired blood pressure goal.

After hemodynamic stabilization, wean incrementally over time, such as by decreasing doses of epinephrine every 10 minutes to determine if the patient can tolerate gradual withdrawal.

Adrenalin diluted in 5 percent dextrose solutions or 5 percent dextrose and sodium chloride solutions are stable for 4 hours at room temperature or 24 hours under refrigerated conditions.

Adrenalin injection: clear, colorless solution supplied as 1 mg/1 mL in a single dose clear glass vial and as 30 mg/30 mL (1 mg/mL) in a multiple dose amber glass vial.

{ "type": "p", "children": [], "text": "Adrenalin injection: clear, colorless solution supplied as 1 mg/1 mL in a single dose clear glass vial and as 30 mg/30 mL (1 mg/mL) in a multiple dose amber glass vial." }

None.

{ "type": "p", "children": [], "text": "None." }

Injection into the anterolateral aspect of the thigh (vastus lateralis muscle) is the most appropriate location for administration because of its location, size, and available blood flow.  Injection into (or near) smaller muscles, such as in the deltoid, is not recommended.

Do not administer repeated injections of epinephrine at the same site, as the resulting vasoconstriction may cause tissue necrosis. 

Do not inject into buttock. Injection into the buttock may not provide effective treatment of anaphylaxis and has been associated with the development of Clostridial infections (gas gangrene). 

Do not inject into digits, hands, or feet. Epinephrine is a strong vasoconstrictor.  Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area and tissue necrosis.

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site.

Avoid extravasation of epinephrine into the tissues, to prevent local necrosis. When Adrenalin is administered intravenously, check the infusion site frequently for free flow.  Blanching along the course of the infused vein, sometimes without obvious extravasation, may be attributed to vasa vasorum constriction with increased permeability of the vein wall, permitting some leakage. This also may progress on rare occasions to superficial slough. Hence, if blanching occurs, consider changing the infusion site at intervals to allow the effects of local vasoconstriction to subside.

There is potential for gangrene in a lower extremity when infusions of catecholamine are given in an ankle vein.

Antidote for Extravasation Ischemia:To prevent sloughing and necrosis in areas in which extravasation has taken place, infiltrate the area with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of phentolamine, an adrenergic blocking agent. Use a syringe with a fine hypodermic needle, with the solution being infiltrated liberally throughout the area, which is easily identified by its cold, hard, and pallid appearance. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours.

Because individual response to epinephrine may vary significantly, monitor blood pressure frequently and titrate to avoid excessive increases in blood pressure.

Patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types may experience severe, prolonged hypertension when given epinephrine.

Epinephrine increases cardiac output and causes peripheral vasoconstriction, which may result in pulmonary edema.

Epinephrine constricts renal blood vessels, which may result in oliguria or renal impairment.

Epinephrine may induce cardiac arrhythmias and myocardial ischemia in patients, especially patients suffering from coronary artery disease, or cardiomyopathy.

Adrenalin contains sodium bisulfite which may cause mild to severe allergic reactions including anaphylaxis or asthmatic episodes in susceptible individuals.  However, the presence of bisulfite in this product should not preclude its use for the treatment of serious allergic or other emergency situations even if the patient is sulfite-sensitive, as the alternatives to using epinephrine in a life-threatening situation may not be satisfactory.

Common adverse reactions to systemically administered epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and respiratory difficulties.  These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with heart disease, hypertension, or hyperthyroidism [ see Warnings and Precautions (5.7)] .

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The true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine.  Adverse reactions reported in observational trials, case reports, and studies are listed below by body system:

{ "type": "p", "children": [], "text": "The true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine.  Adverse reactions reported in observational trials, case reports, and studies are listed below by body system:" }

Cardiovascular: angina, arrhythmias, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, ventricular ectopy and stress cardiomyopathy. 

{ "type": "p", "children": [], "text": "\nCardiovascular: angina, arrhythmias, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, ventricular ectopy and stress cardiomyopathy. \n\n " }

Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [ see Warnings and Precautions (5.7)] .

{ "type": "p", "children": [], "text": "Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease\n \n [\n \n see Warnings and Precautions (5.7)]\n \n .\n\n " }

Neurological: disorientation, impaired memory, panic, psychomotor agitation, sleepiness, tingling. 

{ "type": "p", "children": [], "text": "\nNeurological: disorientation, impaired memory, panic, psychomotor agitation, sleepiness, tingling. \n\n " }

Psychiatric: anxiety, apprehensiveness, restlessness.

{ "type": "p", "children": [], "text": "\nPsychiatric: anxiety, apprehensiveness, restlessness.\n\n " }

Other:

{ "type": "p", "children": [], "text": "\nOther:\n\n " }

Patients with Parkinson’s disease may experience psychomotor agitation or a temporary worsening of symptoms [ see Warnings and Precautions (5.7)] . 

{ "type": "p", "children": [], "text": "Patients with Parkinson’s disease may experience psychomotor agitation or a temporary worsening of symptoms\n \n [\n \n see Warnings and Precautions (5.7)]\n \n . \n\n " }

Diabetic patients may experience transient increases in blood sugar.

{ "type": "p", "children": [], "text": "Diabetic patients may experience transient increases in blood sugar." }

Injection into the buttock has resulted in cases of gas gangrene [ see Warnings and Precautions (5.1)] .

{ "type": "p", "children": [], "text": "Injection into the buttock has resulted in cases of gas gangrene\n \n [\n \n see Warnings and Precautions (5.1)]\n \n .\n\n " }

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported following epinephrine injection in the thigh [ see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported following epinephrine injection in the thigh\n \n [\n \n see Warnings and Precautions (5.2)].\n \n \n" }

Cardiac arrhythmias are more common among patients receiving any of the following drugs [ see Warnings and Precautions (5.7)and Adverse Reactions (6)] .

Risk Summary

Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, do not identify a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.  However, there are risks to the mother and fetus associated with epinephrine use during labor or delivery (see Clinical Considerations).  In animal reproduction studies, epinephrine administered by the subcutaneous route to pregnant rabbits, mice, and hamsters, during the period of organogenesis, resulted in adverse developmental effects (including gastroschisis, and embryonic lethality, and delayed skeletal ossification) at doses approximately 2 times the maximum recommended daily intramuscular, subcutaneous, or intravenous dose (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.  In the United States 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 embryo/fetal risk

During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. The prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries.

Management of anaphylaxis during pregnancy is similar to management in the general population. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in pregnant and non-pregnant patients. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care.

Hypotension associated with septic shock is a medical emergency in pregnancy which can be fatal if left untreated.  Delaying treatment in pregnant women with hypotension associated with septic shock may increase the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of epinephrine on the fetus.

Labor or Delivery

Epinephrine usually inhibits spontaneous or oxytocin induced contractions of the pregnant human uterus and may delay the second stage of labor. Avoid epinephrine during the second stage of labor. In dosage sufficient to reduce uterine contractions, the drug may cause a prolonged period of uterine atony with hemorrhage. Avoid epinephrine in obstetrics when maternal blood pressure exceeds 130/80 mmHg.

Although epinephrine may improve maternal hypotension associated with septic shock and anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia. 

Data

Animal Data

In an embryofetal development study with pregnant rabbits dosed during the period of organogenesis (on days 3 to 5, 6 to 7 or 7 to 9 of gestation), epinephrine caused teratogenic effects (including gastroschisis) at doses approximately 15 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). Animals treated on days 6 to 7 had decreased number of implantations.

In an embryofetal development study, pregnant mice were administered epinephrine (0.1 to 10 mg/kg/day) on Gestation Days 6 to 15. Teratogenic effects, embryonic lethality, and delays in skeletal ossification were observed at approximately 3 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 2 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days).

In an embryofetal development study with pregnant hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine produced reductions in litter size and delayed skeletal ossification at doses approximately 2 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2basis at a maternal subcutaneous dose of 0.5 mg/kg/day).

Risk Summary

There is no information regarding the presence of epinephrine in human milk or the effects of epinephrine on the breastfed infant or on milk production. However, due to its poor oral bioavailability and short half-life, epinephrine exposure is expected to be very low in the breastfed infant.

Epinephrine is the first-line medication of choice for treatment of anaphylaxis; it should be used in the same manner for anaphylaxis in breastfeeding and non-breastfeeding patients.

Clinical use data support weight-based dosing for treatment of anaphylaxis in pediatric patients, and other reported clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults. 

Safety and effectiveness of epinephrine in pediatric patients with septic shock have not been established.

Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects.  However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine.  Therefore, for the treatment of anaphylaxis, consider starting with a lower dose to take into account potential concomitant disease or other drug therapy.

Clinical studies of epinephrine for the treatment of hypotension associated with septic shock 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.

Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients.  Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation.  Epinephrine overdosage can also cause transient bradycardia followed by tachycardia and these may be accompanied by potentially fatal cardiac arrhythmias.  Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm).  Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block.  Myocardial ischemia and infarction, cardiomyopathy, extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and renal insufficiency have also been reported.

{ "type": "p", "children": [], "text": "Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients.  Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation.  Epinephrine overdosage can also cause transient bradycardia followed by tachycardia and these may be accompanied by potentially fatal cardiac arrhythmias.  Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm).  Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block.  Myocardial ischemia and infarction, cardiomyopathy, extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and renal insufficiency have also been reported." }

Epinephrine is rapidly inactivated in the body and treatment following overdose with epinephrine is primarily supportive.  Treatment of pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators or α-adrenergic blocking drugs.  If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug.

{ "type": "p", "children": [], "text": "Epinephrine is rapidly inactivated in the body and treatment following overdose with epinephrine is primarily supportive.  Treatment of pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators or α-adrenergic blocking drugs.  If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug." }

Adrenalin (epinephrine injection, USP) is a clear, colorless, sterile solution containing 1 mg/mL epinephrine, packaged as 1 mL of solution in a single dose clear glass vial or 30 mL of solution in a multiple dose amber glass vial.  In the 1 mL vial, each 1 mL of Adrenalin solution contains 1 mg epinephrine, 7.3 mg sodium chloride, 0.457 mg sodium metabisulfite, 1 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, 5.32 mg of 4% hydrochloric acid to adjust pH, and water for injection.  In the 30 mL vial, each 1 mL of Adrenalin solution contains 1 mg epinephrine, 6.15 mg sodium chloride, 0.457 mg sodium metabisulfite, 0.920 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, 5.18 mg of 4% hydrochloric acid to adjust pH, 5.25 mg chlorobutanol as a preservative and water for injection. The pH range is 2.2-5.0. 

{ "type": "p", "children": [], "text": "Adrenalin (epinephrine injection, USP) is a clear, colorless, sterile solution containing 1 mg/mL epinephrine, packaged as 1 mL of solution in a single dose clear glass vial or 30 mL of solution in a multiple dose amber glass vial.  In the 1 mL vial, each 1 mL of Adrenalin solution contains 1 mg epinephrine, 7.3 mg sodium chloride, 0.457 mg sodium metabisulfite, 1 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, 5.32 mg of 4% hydrochloric acid to adjust pH, and water for injection.  In the 30 mL vial, each 1 mL of Adrenalin solution contains 1 mg epinephrine, 6.15 mg sodium chloride, 0.457 mg sodium metabisulfite, 0.920 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, 5.18 mg of 4% hydrochloric acid to adjust pH, 5.25 mg chlorobutanol as a preservative and water for injection. The pH range is 2.2-5.0. " }

Epinephrine is a sympathomimetic catecholamine.  The chemical name of epinephrine is: 1,2-Benzenediol, 4-[(1R)-1-hydroxy-2-(methylamino)ethyl]-, or (-)-3,4-Dihydroxy-α-[2-(methylamino)ethyl]benzyl alcohol.

{ "type": "p", "children": [], "text": "Epinephrine is a sympathomimetic catecholamine.  The chemical name of epinephrine is: 1,2-Benzenediol, 4-[(1R)-1-hydroxy-2-(methylamino)ethyl]-, or (-)-3,4-Dihydroxy-α-[2-(methylamino)ethyl]benzyl alcohol." }

The chemical structure of epinephrine is:

{ "type": "p", "children": [], "text": "The chemical structure of epinephrine is:" }

The molecular weight of epinephrine is 183.2.

{ "type": "p", "children": [], "text": "The molecular weight of epinephrine is 183.2." }

Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin.

{ "type": "p", "children": [], "text": "Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin." }

Epinephrine acts on both alpha and beta-adrenergic receptors.  The mechanism of the rise in blood pressure is 3-fold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), and peripheral vasoconstriction.

Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid. 

Intramuscular and subcutaneous use for anaphylaxis

Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension.

Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis.

Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder.

Intravenous use for hypotension associated with septic shock

When administered parenterally, epinephrine has a rapid onset and short duration of action.

Following intravenous administration of epinephrine, increases in systolic blood pressure and heart rate are observed. Decreases in systemic vascular resistance and diastolic blood pressure are observed at low doses of epinephrine because of β2-mediated vasodilation, but are overtaken by α1-mediated peripheral vasoconstriction at higher doses leading to increase in diastolic blood pressure. The onset of blood pressure increase following an intravenous dose of epinephrine is < 5 minutes and the time to offset blood pressure response occurs within 15 minutes. Most vascular beds are constricted including renal, splanchnic, mucosal and skin.

Epinephrine causes mydriasis when administered parenterally. 

Following intravenous injection, epinephrine is rapidly cleared from the plasma with an effective half-life of < 5 minutes. A pharmacokinetic steady state following continuous intravenous infusion is achieved within 10‑15 minutes. In patients with septic shock, epinephrine displays dose-proportional pharmacokinetics in the infusion dose range of 0.03 to 1.7 mcg/kg/min.

Epinephrine is extensively metabolized with only a small amount excreted unchanged.

Epinephrine is rapidly degraded to vanillylmandelic acid, an inactive metabolite, by monoamine oxidase and catechol-O-methyltransferase that are abundantly expressed in the liver, kidneys and other extraneuronal tissues. The tissues with the highest contribution to removal of circulating exogenous epinephrine are the liver (32%), kidneys (25%), skeletal muscle (20%), and mesenteric organs (12%).

Specific Populations

Elderly

In a pharmacokinetic study of 45-minute epinephrine infusions given to healthy men aged 20 to 25 years and healthy men aged 60 to 65 years, the mean plasma metabolic clearance rate of epinephrine at steady state was greater among the older men (144.8 versus 78 mL/kg/min for a 0.0143 mcg/kg/min infusion).

Body Weight

Body weight has been found to influence epinephrine pharmacokinetics. Higher body weight was associated with a higher plasma epinephrine clearance and a lower concentration plateau.

Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted.

Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro.  Epinephrine was positive in the Salmonellabacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivomicronucleus assay.  Epinephrine is an oxidative mutagen based on the E. coliWP2 Mutoxitest bacterial reverse mutation assay.  This should not prevent the use of epinephrine under the conditions noted under Indications and Usage (1).

The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (15-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

Adrenalin 1 mg/mL Single Dose Vials:

{ "type": "p", "children": [], "text": "Adrenalin 1 mg/mL Single Dose Vials:" }

Each carton contains 25 single dose vials containing 1 mg/mL Adrenalin (epinephrine injection, USP) solution in a 3 mL clear glass vial.

{ "type": "p", "children": [], "text": "Each carton contains 25 single dose vials containing 1 mg/mL Adrenalin (epinephrine injection, USP) solution in a 3 mL clear glass vial." }

NDC: 70518-1342-00

{ "type": "p", "children": [], "text": "NDC: 70518-1342-00" }

NDC: 70518-1342-01

{ "type": "p", "children": [], "text": "NDC: 70518-1342-01" }

PACKAGING: 25 in 1 CARTON

{ "type": "p", "children": [], "text": "PACKAGING: 25 in 1 CARTON" }

PACKAGING: 1 mL in 1 VIAL. TYPE 0

{ "type": "p", "children": [], "text": "PACKAGING: 1 mL in 1 VIAL. TYPE 0" }

Vial and contents must be discarded 30 days after initial use.

{ "type": "p", "children": [], "text": "Vial and contents must be discarded 30 days after initial use." }

Store between 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive.  Protect from light and freezing.

{ "type": "p", "children": [], "text": "Store between 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive.  Protect from light and freezing." }

Inspect visually for particulate matter and discoloration prior to administration.  Do not use the solution if it is colored or cloudy, or if it contains particulate matter.

{ "type": "p", "children": [], "text": "Inspect visually for particulate matter and discoloration prior to administration.  Do not use the solution if it is colored or cloudy, or if it contains particulate matter." }

Repackaged and Distributed By:

{ "type": "p", "children": [], "text": "Repackaged and Distributed By:" }

Remedy Repack, Inc.

{ "type": "p", "children": [], "text": "Remedy Repack, Inc." }

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

{ "type": "p", "children": [], "text": "625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762" }

Advise patients or their caregivers about common adverse reactions associated with the use of epinephrine including an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety.  These symptoms and signs usually subside rapidly, especially with rest, quiet and recumbent positioning.

{ "type": "p", "children": [], "text": "Advise patients or their caregivers about common adverse reactions associated with the use of epinephrine including an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety.  These symptoms and signs usually subside rapidly, especially with rest, quiet and recumbent positioning." }

Warn patients with a good response to initial treatment about the possibility of recurrence of symptoms and instruct patients to obtain proper medical attention if symptoms return.

{ "type": "p", "children": [], "text": "Warn patients with a good response to initial treatment about the possibility of recurrence of symptoms and instruct patients to obtain proper medical attention if symptoms return." }

Warn patients with diabetes that they may develop increased blood glucose levels following epinephrine administration.

{ "type": "p", "children": [], "text": "Warn patients with diabetes that they may develop increased blood glucose levels following epinephrine administration." }

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site [see Warnings and Precautions (5.2)] .

{ "type": "p", "children": [], "text": "Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site\n \n [see Warnings and Precautions (5.2)]\n \n .\n\n " }

Repackaged By / Distributed By: RemedyRepack Inc.

{ "type": "p", "children": [], "text": "Repackaged By / Distributed By: RemedyRepack Inc." }

625 Kolter Drive, Indiana, PA 15701

{ "type": "p", "children": [], "text": "625 Kolter Drive, Indiana, PA 15701" }

(724) 465-8762

{ "type": "p", "children": [], "text": "(724) 465-8762" }

DRUG: Adrenalin

{ "type": "p", "children": [], "text": "DRUG: Adrenalin" }

GENERIC: epinephrine

{ "type": "p", "children": [], "text": "GENERIC: epinephrine" }

DOSAGE: INJECTION

{ "type": "p", "children": [], "text": "DOSAGE: INJECTION" }

ADMINSTRATION: INTRAMUSCULAR

{ "type": "p", "children": [], "text": "ADMINSTRATION: INTRAMUSCULAR" }

NDC: 70518-1342-0

{ "type": "p", "children": [], "text": "NDC: 70518-1342-0" }

NDC: 70518-1342-1

{ "type": "p", "children": [], "text": "NDC: 70518-1342-1" }

PACKAGING: 1 mL in 1 VIAL

{ "type": "p", "children": [], "text": "PACKAGING: 1 mL in 1 VIAL" }

OUTER PACKAGING: 25 in 1 CARTON

{ "type": "p", "children": [], "text": "OUTER PACKAGING: 25 in 1 CARTON" }

ACTIVE INGREDIENT(S):

{ "type": "p", "children": [], "text": "ACTIVE INGREDIENT(S):" }

{ "type": "ul", "children": [ "EPINEPHRINE 1mg in 1mL" ], "text": "" }

INACTIVE INGREDIENT(S):

{ "type": "p", "children": [], "text": "INACTIVE INGREDIENT(S):" }

{ "type": "ul", "children": [ "SODIUM CHLORIDE", "SODIUM METABISULFITE", "SODIUM HYDROXIDE", "TARTARIC ACID", "EDETATE DISODIUM", "HYDROCHLORIC ACID", "WATER" ], "text": "" }

Adrenalin® is available as a single-use 1 mL vial for intramuscular and subcutaneous use.

{ "type": "p", "children": [], "text": "Adrenalin® is available as a single-use 1 mL vial for intramuscular and subcutaneous use." }

Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from allergic reactions to insect stings, biting insects, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. The signs and symptoms associated with anaphylaxis include flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with hypotension, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, airway swelling, laryngospasm, bronchospasm, pruritus, urticaria or angioedema, swelling of the eyelids, lips, and tongue.

{ "type": "p", "children": [], "text": "Emergency treatment of allergic reactions (Type I), including anaphylaxis, which may result from allergic reactions to insect stings, biting insects, foods, drugs, sera, diagnostic testing substances and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. The signs and symptoms associated with anaphylaxis include flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with hypotension, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, airway swelling, laryngospasm, bronchospasm, pruritus, urticaria or angioedema, swelling of the eyelids, lips, and tongue." }

Inject Adrenalin® intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. When administering to a child, to minimize the risk of injection related injury, hold the leg firmly in place and limit movement prior to and during an injection. The injection may be repeated every 5 to 10 minutes as necessary. For intramuscular administration, use a needle long enough (at least 1/2 inch to 5/8 inch) to ensure the injection is administered into the muscle. Monitor the patient clinically for the severity of the allergic reaction and potential cardiac effects of the drug, with repeat doses titrated to effect. Do not administer repeated injections at the same site, as the resulting vasoconstriction may cause tissue necrosis.

{ "type": "p", "children": [], "text": "Inject Adrenalin® intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. When administering to a child, to minimize the risk of injection related injury, hold the leg firmly in place and limit movement prior to and during an injection. The injection may be repeated every 5 to 10 minutes as necessary. For intramuscular administration, use a needle long enough (at least 1/2 inch to 5/8 inch) to ensure the injection is administered into the muscle. Monitor the patient clinically for the severity of the allergic reaction and potential cardiac effects of the drug, with repeat doses titrated to effect. Do not administer repeated injections at the same site, as the resulting vasoconstriction may cause tissue necrosis." }

Inspect visually for particulate matter and discoloration prior to administration. Do not use if the solution is colored or cloudy, or if it contains particulate matter.

{ "type": "p", "children": [], "text": "Inspect visually for particulate matter and discoloration prior to administration. Do not use if the solution is colored or cloudy, or if it contains particulate matter." }

Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 mL to 0.5 mL) of undiluted Adrenalin® administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.5 mg (0.5 mL) per injection, repeated every 5 to 10 minutes as necessary. Monitor clinically for reaction severity and cardiac effects.

{ "type": "p", "children": [], "text": "\nAdults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3 mL to 0.5 mL) of undiluted Adrenalin® administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.5 mg (0.5 mL) per injection, repeated every 5 to 10 minutes as necessary. Monitor clinically for reaction severity and cardiac effects.\n " }

Children less than 30 kg (66 lbs): 0.01 mg/kg (0.01 mL/kg) of undiluted Adrenalin® administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.3 mg (0.3 mL) per injection, repeated every 5 to 10 minutes as necessary. Monitor clinically for reaction severity and cardiac effects.

{ "type": "p", "children": [], "text": "\nChildren less than 30 kg (66 lbs): 0.01 mg/kg (0.01 mL/kg) of undiluted Adrenalin® administered intramuscularly or subcutaneously in the anterolateral aspect of the thigh, up to a maximum of 0.3 mg (0.3 mL) per injection, repeated every 5 to 10 minutes as necessary. Monitor clinically for reaction severity and cardiac effects.\n " }

Adrenalin® 1 mg/mL epinephrine injection, 1 mL solution in a single-use clear glass vial.

{ "type": "p", "children": [], "text": "\nAdrenalin® 1 mg/mL epinephrine injection, 1 mL solution in a single-use clear glass vial.\n" }

None.

{ "type": "p", "children": [], "text": "None." }

5.1 Incorrect Locations of Injection

{ "type": "p", "children": [], "text": "\n5.1 Incorrect Locations of Injection\n" }

Injection into the anterolateral aspect of the thigh (vastus lateralis muscle) is the most appropriate location for administration because of its location, size, and available blood flow. Injection into (or near) smaller muscles, such as in the deltoid, is not recommended due to possible differences in absorption associated with this use.

{ "type": "p", "children": [], "text": "Injection into the anterolateral aspect of the thigh (vastus lateralis muscle) is the most appropriate location for administration because of its location, size, and available blood flow. Injection into (or near) smaller muscles, such as in the deltoid, is not recommended due to possible differences in absorption associated with this use." }

Do not administer repeated injections of epinephrine at the same site, as the resulting vasoconstriction may cause tissue necrosis.

{ "type": "p", "children": [], "text": "Do not administer repeated injections of epinephrine at the same site, as the resulting vasoconstriction may cause tissue necrosis." }

Do not inject into buttock. Injection into the buttock may not provide effective treatment of anaphylaxis and has been associated with the development of Clostridial infections (gas gangrene). Cleansing with alcohol does not kill bacterial spores, and therefore, does not lower this risk.

{ "type": "p", "children": [], "text": "Do not inject into buttock. Injection into the buttock may not provide effective treatment of anaphylaxis and has been associated with the development of Clostridial infections (gas gangrene). Cleansing with alcohol does not kill bacterial spores, and therefore, does not lower this risk." }

Do not inject into digits, hands, or feet. Epinephrine is a strong vasoconstrictor. Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area and has been associated with tissue necrosis.

{ "type": "p", "children": [], "text": "Do not inject into digits, hands, or feet. Epinephrine is a strong vasoconstrictor. Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area and has been associated with tissue necrosis." }

5.2 Serious Infections at the Injection Site

{ "type": "p", "children": [], "text": "\n5.2 Serious Infections at the Injection Site\n" }

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Clostridium spores can be present on the skin and introduced into the deep tissue with subcutaneous or intramuscular injection. While cleansing with alcohol may reduce presence of bacteria on the skin, alcohol cleansing does not kill Clostridium spores. To decrease the risk of Clostridium infection, do not inject Adrenalin® into the buttock [see Warnings and Precautions (5.1)]. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site.

{ "type": "p", "children": [], "text": "Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Clostridium spores can be present on the skin and introduced into the deep tissue with subcutaneous or intramuscular injection. While cleansing with alcohol may reduce presence of bacteria on the skin, alcohol cleansing does not kill Clostridium spores. To decrease the risk of Clostridium infection, do not inject Adrenalin® into the buttock [see Warnings and Precautions (5.1)]. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at the epinephrine injection site." }

5.3 Disease Interactions

{ "type": "p", "children": [], "text": "\n5.3 Disease Interactions\n" }

Some patients may be at greater risk for developing adverse reactions after systemic epinephrine administration. Despite these concerns, the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation.

{ "type": "p", "children": [], "text": "Some patients may be at greater risk for developing adverse reactions after systemic epinephrine administration. Despite these concerns, the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation." }

Patients with Heart Disease

{ "type": "p", "children": [], "text": "\nPatients with Heart Disease\n" }

Epinephrine should be administered with caution in patients who have heart disease, including patients with cardiac arrhythmias, coronary artery or organic heart disease, cerebrovascular disease, or hypertension. In such patients, or in patients who are on drugs that may sensitize the heart to arrhythmias, epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias [see Drug Interactions (7) and Adverse Reactions (6)].

{ "type": "p", "children": [], "text": "Epinephrine should be administered with caution in patients who have heart disease, including patients with cardiac arrhythmias, coronary artery or organic heart disease, cerebrovascular disease, or hypertension. In such patients, or in patients who are on drugs that may sensitize the heart to arrhythmias, epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias [see Drug Interactions (7) and Adverse Reactions (6)]." }

Other Patients and Diseases

{ "type": "p", "children": [], "text": "\nOther Patients and Diseases\n" }

Epinephrine should be administered with caution to patients with hyperthyroidism, Parkinson’s disease, diabetes mellitus, pheochromocytoma, elderly individuals, and pregnant women. Patients with Parkinson’s disease may experience psychomotor agitation or notice a temporary worsening of symptoms. Diabetic patients may experience transient increases in blood sugar.

{ "type": "p", "children": [], "text": "Epinephrine should be administered with caution to patients with hyperthyroidism, Parkinson’s disease, diabetes mellitus, pheochromocytoma, elderly individuals, and pregnant women. Patients with Parkinson’s disease may experience psychomotor agitation or notice a temporary worsening of symptoms. Diabetic patients may experience transient increases in blood sugar." }

5.4 Allergic Reactions Associated with Sulfite

{ "type": "p", "children": [], "text": "\n5.4 Allergic Reactions Associated with Sulfite\n" }

Adrenalin® contains sodium bisulfite which may cause mild to severe allergic reactions including anaphylaxis or asthmatic episodes in susceptible individuals. However, the presence of bisulfite in this product should not preclude its use for the treatment of serious allergic or other emergency situations even if the patient is sulfite-sensitive, as the alternatives to using epinephrine in a life-threatening situation may not be satisfactory.

{ "type": "p", "children": [], "text": "Adrenalin® contains sodium bisulfite which may cause mild to severe allergic reactions including anaphylaxis or asthmatic episodes in susceptible individuals. However, the presence of bisulfite in this product should not preclude its use for the treatment of serious allergic or other emergency situations even if the patient is sulfite-sensitive, as the alternatives to using epinephrine in a life-threatening situation may not be satisfactory." }

Common adverse reactions to systemically administered epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with heart disease, hypertension, or hyperthyroidism [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Common adverse reactions to systemically administered epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and respiratory difficulties. These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with heart disease, hypertension, or hyperthyroidism [see Warnings and Precautions (5.3)]." }

Due to the lack of randomized, controlled clinical trials of epinephrine for the treatment of anaphylaxis, the true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine. Adverse reactions reported in observational trials, case reports, and studies are listed below by body system:

{ "type": "p", "children": [], "text": "Due to the lack of randomized, controlled clinical trials of epinephrine for the treatment of anaphylaxis, the true incidence of adverse reactions associated with the systemic use of epinephrine is difficult to determine. Adverse reactions reported in observational trials, case reports, and studies are listed below by body system:" }

Cardiovascular: angina, arrhythmias, hypertension, pallor, palpitations, tachyarrhythmia,

{ "type": "p", "children": [], "text": "\nCardiovascular: angina, arrhythmias, hypertension, pallor, palpitations, tachyarrhythmia,\n " }

tachycardia, vasoconstriction, ventricular ectopy and stress cardiomyopathy.

{ "type": "p", "children": [], "text": "tachycardia, vasoconstriction, ventricular ectopy and stress cardiomyopathy." }

Angina may occur in patients with coronary artery disease [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Angina may occur in patients with coronary artery disease [see Warnings and Precautions (5.3)]." }

Arrhythmias, including fatal ventricular fibrillation, have occurred, particularly in patients with underlying organic heart disease or patients receiving drugs that sensitize the heart to arrhythmias [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Arrhythmias, including fatal ventricular fibrillation, have occurred, particularly in patients with underlying organic heart disease or patients receiving drugs that sensitize the heart to arrhythmias [see Warnings and Precautions (5.3)]." }

Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Rapid rises in blood pressure associated with epinephrine use have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [see Warnings and Precautions (5.3)]." }

Respiratory: respiratory difficulties.

{ "type": "p", "children": [], "text": "\nRespiratory: respiratory difficulties.\n " }

Neurological: dizziness, disorientation, excitability, headache, impaired memory, lightheadedness, nervousness, panic, psychomotor agitation, sleepiness, tingling, tremor, and weakness.

{ "type": "p", "children": [], "text": "\nNeurological: dizziness, disorientation, excitability, headache, impaired memory, lightheadedness, nervousness, panic, psychomotor agitation, sleepiness, tingling, tremor, and weakness.\n " }

Psychiatric: anxiety, apprehensiveness, restlessness. Gastrointestinal: nausea, vomiting.

{ "type": "p", "children": [], "text": "\nPsychiatric: anxiety, apprehensiveness, restlessness.\n \nGastrointestinal: nausea, vomiting.\n " }

Other:

{ "type": "p", "children": [], "text": "\nOther:\n" }

Patients with Parkinson’s disease may experience psychomotor agitation or a temporary worsening of symptoms [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Patients with Parkinson’s disease may experience psychomotor agitation or a temporary worsening of symptoms [see Warnings and Precautions (5.3)]." }

Diabetic patients may experience transient increases in blood sugar [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Diabetic patients may experience transient increases in blood sugar [see Warnings and Precautions (5.3)]." }

Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [see Warnings and Precautions (5.1)]. Adverse events experienced as a result of an injection into these areas include increased heart rate, local reactions including injection site pallor, coldness, hypoesthesia, and tissue loss, or injury at the injection site resulting in bruising, bleeding, discoloration, erythema, and skeletal injury.

{ "type": "p", "children": [], "text": "Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [see Warnings and Precautions (5.1)]. Adverse events experienced as a result of an injection into these areas include increased heart rate, local reactions including injection site pallor, coldness, hypoesthesia, and tissue loss, or injury at the injection site resulting in bruising, bleeding, discoloration, erythema, and skeletal injury." }

Injection into the buttock has resulted in cases of gas gangrene [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Injection into the buttock has resulted in cases of gas gangrene [see Warnings and Precautions (5.1)]." }

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported following epinephrine injection in the thigh [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported following epinephrine injection in the thigh [see Warnings and Precautions (5.2)]." }

Skin: sweating.

{ "type": "p", "children": [], "text": "\nSkin: sweating.\n " }

To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at

{ "type": "p", "children": [], "text": "\nTo report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at\n" }

1-800-828-9393 or FDA at 1-800-332-1088 or www.fda.gov/medwatch.

{ "type": "p", "children": [], "text": "\n1-800-828-9393 or FDA at 1-800-332-1088 or \n www.fda.gov/medwatch.\n \n" }

Epinephrine should be administered cautiously to patients taking other sympathomimetic agents because of the possibility of additive effects.

{ "type": "p", "children": [], "text": "Epinephrine should be administered cautiously to patients taking other sympathomimetic agents because of the possibility of additive effects." }

Patients who are concomitantly receiving cardiac glycosides, digitalis, diuretics, quinidine, and other antiarrhythmics should be observed carefully for the development of cardiac arrhythmias [see Warnings and Precautions (5.3) and Adverse Reactions (6)].

{ "type": "p", "children": [], "text": "Patients who are concomitantly receiving cardiac glycosides, digitalis, diuretics, quinidine, and other antiarrhythmics should be observed carefully for the development of cardiac arrhythmias [see Warnings and Precautions (5.3) and Adverse Reactions (6)]." }

Administer epinephrine cautiously to patients receiving halogenated hydrocarbon general anesthetics, such as halothane, as coadministration may result in arrhythmias.

{ "type": "p", "children": [], "text": "Administer epinephrine cautiously to patients receiving halogenated hydrocarbon general anesthetics, such as halothane, as coadministration may result in arrhythmias." }

The effects of epinephrine may be potentiated by tricyclic antidepressants such as imipramine, monoamine oxidase inhibitors (MAOI), levothyroxine sodium, and certain antihistamines, notably diphenhydramine, tripelannamine, and dexchlorpheniramine.

{ "type": "p", "children": [], "text": "The effects of epinephrine may be potentiated by tricyclic antidepressants such as imipramine, monoamine oxidase inhibitors (MAOI), levothyroxine sodium, and certain antihistamines, notably diphenhydramine, tripelannamine, and dexchlorpheniramine." }

The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta-adrenergic blocking drugs, such as propranolol.

{ "type": "p", "children": [], "text": "The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta-adrenergic blocking drugs, such as propranolol." }

The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha-adrenergic blocking drugs, such as phentolamine.

{ "type": "p", "children": [], "text": "The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha-adrenergic blocking drugs, such as phentolamine." }

Ergot alkaloids may reverse the pressor effects of epinephrine.

{ "type": "p", "children": [], "text": "Ergot alkaloids may reverse the pressor effects of epinephrine." }

Epinephrine should not be used to counteract circulatory collapse or hypotension caused by phenothiazines, as a reversal of the pressor effects of epinephrine may result in further lowering of blood pressure.

{ "type": "p", "children": [], "text": "Epinephrine should not be used to counteract circulatory collapse or hypotension caused by phenothiazines, as a reversal of the pressor effects of epinephrine may result in further lowering of blood pressure." }

8.1 Pregnancy

{ "type": "p", "children": [], "text": "\n8.1 Pregnancy\n" }

Teratogenic Effects: Pregnancy Category C.

{ "type": "p", "children": [], "text": "Teratogenic Effects: Pregnancy Category C." }

There are no adequate and well-controlled studies in pregnant women. Epinephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (fetal anoxia, spontaneous abortion, or both). Epinephrine is teratogenic in rabbits, mice and hamsters dosed during organogenesis.

{ "type": "p", "children": [], "text": "There are no adequate and well-controlled studies in pregnant women. Epinephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (fetal anoxia, spontaneous abortion, or both). Epinephrine is teratogenic in rabbits, mice and hamsters dosed during organogenesis." }

Epinephrine has been shown to have teratogenic effects (including gastroschisis and embryonic lethality) when administered subcutaneous in rabbits at approximately 15 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days).

{ "type": "p", "children": [], "text": "Epinephrine has been shown to have teratogenic effects (including gastroschisis and embryonic lethality) when administered subcutaneous in rabbits at approximately 15 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days)." }

In mice, teratogenic effects (including embryonic lethality) were observed at approximately 3 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 2 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days).

{ "type": "p", "children": [], "text": "In mice, teratogenic effects (including embryonic lethality) were observed at approximately 3 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 2 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days)." }

In hamsters, teratogenic effects were observed at approximately 2 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day for 4 days).

{ "type": "p", "children": [], "text": "In hamsters, teratogenic effects were observed at approximately 2 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day for 4 days)." }

8.2 Labor and Delivery

{ "type": "p", "children": [], "text": "\n8.2 Labor and Delivery\n" }

Use with caution during labor and delivery. Although epinephrine improves maternal hypotension associated with anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia.

{ "type": "p", "children": [], "text": "Use with caution during labor and delivery. Although epinephrine improves maternal hypotension associated with anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia." }

8.3 Nursing Mothers

{ "type": "p", "children": [], "text": "\n8.3 Nursing Mothers\n" }

It is not known whether epinephrine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when epinephrine is administered to a nursing woman.

{ "type": "p", "children": [], "text": "It is not known whether epinephrine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when epinephrine is administered to a nursing woman." }

8.4 Pediatric Use

{ "type": "p", "children": [], "text": "\n8.4 Pediatric Use\n" }

Clinical use data support weight-based dosing for treatment of anaphylaxis in pediatric patients, and other reported clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults.

{ "type": "p", "children": [], "text": "Clinical use data support weight-based dosing for treatment of anaphylaxis in pediatric patients, and other reported clinical experience with the use of epinephrine suggests that the adverse reactions seen in children are similar in nature and extent to those both expected and reported in adults." }

8.5 Geriatric Use

{ "type": "p", "children": [], "text": "\n8.5 Geriatric Use\n" }

Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, for the treatment of anaphylaxis, consider starting with a lower dose to take into account potential concomitant disease or other drug therapy.

{ "type": "p", "children": [], "text": "Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Therefore, for the treatment of anaphylaxis, consider starting with a lower dose to take into account potential concomitant disease or other drug therapy." }

Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Treatment consists of a rapidly acting α-adrenergic blocking drug and respiratory support.

{ "type": "p", "children": [], "text": "Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Treatment consists of a rapidly acting α-adrenergic blocking drug and respiratory support." }

Epinephrine is rapidly inactivated in the body and treatment following overdose with epinephrine is primarily supportive. If necessary, pressor effects may be counteracted by rapidly acting vasodilators or α-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug.

{ "type": "p", "children": [], "text": "Epinephrine is rapidly inactivated in the body and treatment following overdose with epinephrine is primarily supportive. If necessary, pressor effects may be counteracted by rapidly acting vasodilators or α-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug." }

Epinephrine overdosage can also cause transient bradycardia followed by tachycardia and these may be accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug such as propranolol.

{ "type": "p", "children": [], "text": "Epinephrine overdosage can also cause transient bradycardia followed by tachycardia and these may be accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug such as propranolol." }

Overdosage sometimes results in extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and kidney failure. Suitable corrective measures must be taken in such situations.

{ "type": "p", "children": [], "text": "Overdosage sometimes results in extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and kidney failure. Suitable corrective measures must be taken in such situations." }

Myocardial ischemia, myocardial infarction and cardiomyopathy have been noted in the literature following overdose of epinephrine.

{ "type": "p", "children": [], "text": "Myocardial ischemia, myocardial infarction and cardiomyopathy have been noted in the literature following overdose of epinephrine." }

Adrenalin® (epinephrine injection, USP) is a clear, colorless, sterile solution containing 1 mg/mL epinephrine, packaged as 1 mL of solution in a single-use clear glass vial. In the 1 mL vial, each 1 mL of Adrenalin® solution contains 1 mg epinephrine, 7.3 mg sodium chloride, 0.457 mg sodium metabisulfite, 1 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, hydrochloric acid to adjust pH, and water for injection. Each 1 mL of Adrenalin® solution contains 1 mg epinephrine, 6.15 mg sodium chloride, 0.457 mg sodium metabisulfite, 0.920 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, hydrochloric acid to adjust pH, 5.25 mg chlorobutanol as a preservative and water for injection. The pH range is 2.2-5.0.

{ "type": "p", "children": [], "text": "Adrenalin® (epinephrine injection, USP) is a clear, colorless, sterile solution containing 1 mg/mL epinephrine, packaged as 1 mL of solution in a single-use clear glass vial. In the 1 mL vial, each 1 mL of Adrenalin® solution contains 1 mg epinephrine, 7.3 mg sodium chloride, 0.457 mg sodium metabisulfite, 1 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, hydrochloric acid to adjust pH, and water for injection. Each 1 mL of Adrenalin® solution contains 1 mg epinephrine, 6.15 mg sodium chloride, 0.457 mg sodium metabisulfite, 0.920 mg sodium hydroxide, 2.25 mg tartaric acid, 0.20 mg disodium edetate dihydrate, hydrochloric acid to adjust pH, 5.25 mg chlorobutanol as a preservative and water for injection. The pH range is 2.2-5.0." }

Epinephrine is a sympathomimetic catecholamine. The chemical name of epinephrine is: 1,2-Benzenediol, 4-[(1R)-1-hydroxy-2-(methylamino)ethyl]-, or (-)-3,4-Dihydroxy-α-[2-(methylamino)ethyl]benzyl alcohol.

{ "type": "p", "children": [], "text": "Epinephrine is a sympathomimetic catecholamine. The chemical name of epinephrine is: 1,2-Benzenediol, 4-[(1R)-1-hydroxy-2-(methylamino)ethyl]-, or (-)-3,4-Dihydroxy-α-[2-(methylamino)ethyl]benzyl alcohol." }

The chemical structure of epinephrine is:

{ "type": "p", "children": [], "text": "The chemical structure of epinephrine is:" }

The molecular weight of epinephrine is 183.2.

{ "type": "p", "children": [], "text": "The molecular weight of epinephrine is 183.2." }

Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin.

{ "type": "p", "children": [], "text": "Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin." }

12.1 Mechanism of Action

{ "type": "p", "children": [], "text": "\n12.1 Mechanism of Action\n" }

Epinephrine acts on both alpha and beta-adrenergic receptors.

{ "type": "p", "children": [], "text": "Epinephrine acts on both alpha and beta-adrenergic receptors." }

12.2 Pharmacodynamics

{ "type": "p", "children": [], "text": "\n12.2 Pharmacodynamics\n" }

Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension.

{ "type": "p", "children": [], "text": "Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension." }

Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis.

{ "type": "p", "children": [], "text": "Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis." }

Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder.

{ "type": "p", "children": [], "text": "Epinephrine also alleviates pruritus, urticaria, and angioedema and may relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus and urinary bladder." }

Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid [see Warnings and Precautions (5.3)]." }

Epinephrine causes mydriasis when administered parenterally. 12.3 Pharmacokinetics

{ "type": "p", "children": [], "text": "Epinephrine causes mydriasis when administered parenterally.\n \n12.3 Pharmacokinetics\n" }

When administered parenterally, epinephrine has a rapid onset and short duration of action.

{ "type": "p", "children": [], "text": "When administered parenterally, epinephrine has a rapid onset and short duration of action." }

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

{ "type": "p", "children": [], "text": "13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility" }

Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted.

{ "type": "p", "children": [], "text": "Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted." }

Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro. Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine under the conditions noted under Indications and Usage (1).

{ "type": "p", "children": [], "text": "Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro. Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine under the conditions noted under Indications and Usage (1)." }

The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (15-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

{ "type": "p", "children": [], "text": "The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (15-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9." }

Certa Dose Epinephrine Kit (NDC 71754-001-01)

{ "type": "p", "children": [], "text": "\nCerta Dose Epinephrine Kit (NDC 71754-001-01)\n" }

KIT CONTENTS

{ "type": "p", "children": [], "text": "KIT CONTENTS" }

Epinephrine 1 mg/mL Vial (1 mL)

{ "type": "p", "children": [], "text": "Epinephrine 1 mg/mL Vial (1 mL)" }

2 x CERTA DOSE* 0.3 mL Syringe, Permanent Needle, 29 G x ½”

{ "type": "p", "children": [], "text": "2 x CERTA DOSE* 0.3 mL Syringe, Permanent Needle, 29 G x ½”" }

Epinephrine Package Insert

{ "type": "p", "children": [], "text": "Epinephrine Package Insert" }

IFU CERTA DOSE* 0.3 mL Syringe

{ "type": "p", "children": [], "text": "IFU CERTA DOSE* 0.3 mL Syringe" }

Par Adrenalin (1 Vial, NDC 42023-159-25) included in Certa Dose Epinephrine Kit 1 mL Adrenalin® (epinephrine injection, USP) solution 1 mg/mL in a 3 mL clear glass vial.

{ "type": "p", "children": [], "text": "\nPar Adrenalin (1 Vial, NDC 42023-159-25) included in Certa Dose Epinephrine Kit \n 1 mL Adrenalin® (epinephrine injection, USP) solution 1 mg/mL in a 3 mL clear glass vial.\n \n" }

NDC 42023-159-25 1 mL vial

{ "type": "p", "children": [], "text": "NDC 42023-159-25 1 mL vial" }

Certa Dose Epinephrine Kit (NDC 71754-001-05)

{ "type": "p", "children": [], "text": "\nCerta Dose Epinephrine Kit (NDC 71754-001-05)\n" }

KIT CONTENTS

{ "type": "p", "children": [], "text": "KIT CONTENTS" }

5 Vials - Epinephrine 1 mg/mL (1 mL)

{ "type": "p", "children": [], "text": "5 Vials - Epinephrine 1 mg/mL (1 mL)" }

5 x CERTA DOSE* 0.3 mL Syringe, Permanent Needle, 29 G x ½”

{ "type": "p", "children": [], "text": "5 x CERTA DOSE* 0.3 mL Syringe, Permanent Needle, 29 G x ½”" }

Epinephrine Package Insert

{ "type": "p", "children": [], "text": "Epinephrine Package Insert" }

IFU CERTA DOSE* 0.3 mL Syringe

{ "type": "p", "children": [], "text": "IFU CERTA DOSE* 0.3 mL Syringe" }

Par Adrenalin (1 Vial, NDC 42023-159-25) included in Certa Dose Epinephrine Kit 1 mL Adrenalin® (epinephrine injection, USP) solution 1 mg/mL in a 3 mL clear glass vial.

{ "type": "p", "children": [], "text": "\nPar Adrenalin (1 Vial, NDC 42023-159-25) included in Certa Dose Epinephrine Kit 1 mL Adrenalin® (epinephrine injection, USP) solution 1 mg/mL in a 3 mL clear glass vial.\n" }

NDC 42023-159-25 1 mL vial

{ "type": "p", "children": [], "text": "NDC 42023-159-25 1 mL vial" }

Vial and contents must be discarded 30 days after initial use.

{ "type": "p", "children": [], "text": "Vial and contents must be discarded 30 days after initial use." }

Store between 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light and freezing.

{ "type": "p", "children": [], "text": "Store between 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light and freezing." }

Inspect visually for particulate matter and discoloration prior to administration. Do not

{ "type": "p", "children": [], "text": "Inspect visually for particulate matter and discoloration prior to administration. Do not" }

use the solution if it is colored or cloudy, or if it contains particulate matter.

{ "type": "p", "children": [], "text": "use the solution if it is colored or cloudy, or if it contains particulate matter." }

Advise patients or their caregivers about common adverse reactions associated with the use of epinephrine including an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety. These symptoms and signs usually subside rapidly, especially with rest, quiet and recumbent positioning.

{ "type": "p", "children": [], "text": "Advise patients or their caregivers about common adverse reactions associated with the use of epinephrine including an increase in heart rate, the sensation of a more forceful heartbeat, palpitations, sweating, nausea and vomiting, difficulty breathing, pallor, dizziness, weakness or shakiness, headache, apprehension, nervousness, or anxiety. These symptoms and signs usually subside rapidly, especially with rest, quiet and recumbent positioning." }

Warn patients with a good response to initial treatment about the possibility of recurrence of symptoms and instruct patients to obtain proper medical attention if symptoms return.

{ "type": "p", "children": [], "text": "Warn patients with a good response to initial treatment about the possibility of recurrence of symptoms and instruct patients to obtain proper medical attention if symptoms return." }

Warn patients with diabetes that they may develop increased blood glucose levels following epinephrine administration.

{ "type": "p", "children": [], "text": "Warn patients with diabetes that they may develop increased blood glucose levels following epinephrine administration." }

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth,

{ "type": "p", "children": [], "text": "Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported at the injection site following epinephrine injection for anaphylaxis. Advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth," }

swelling, or tenderness, at the epinephrine injection site [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "swelling, or tenderness, at the epinephrine injection site [see Warnings and Precautions (5.2)]." }

Certa Dose Epinephrine Convenience Kit (NDC 71754-001-01) Distributed By:

{ "type": "p", "children": [], "text": "Certa Dose Epinephrine Convenience Kit (NDC 71754-001-01) Distributed By:" }

Certa Dose

{ "type": "p", "children": [], "text": "Certa Dose" }

7351 E. Lowry Blvd #400

{ "type": "p", "children": [], "text": "7351 E. Lowry Blvd #400" }

Denver, Colorado 80230

{ "type": "p", "children": [], "text": "Denver, Colorado 80230" }

Epinephrine (NDC 42023-159-25) Included in Kit Distributed By:

{ "type": "p", "children": [], "text": "Epinephrine (NDC 42023-159-25) Included in Kit Distributed By:" }

Par Pharmaceutical

{ "type": "p", "children": [], "text": "Par Pharmaceutical" }

Chestnut Ridge, NY 10977

{ "type": "p", "children": [], "text": "Chestnut Ridge, NY 10977" }

Adrenalin® is a registered trademark of Par Sterile Products, LLC (Chestnut Ridge, NY). Registered Trademark No. 53,934

{ "type": "p", "children": [], "text": "Adrenalin® is a registered trademark of Par Sterile Products, LLC (Chestnut Ridge, NY). Registered Trademark No. 53,934" }

KIT CONTENTS

{ "type": "p", "children": [], "text": "\nKIT CONTENTS\n" }

Epinephrine 1 mg/mL Vial (1 mL)

{ "type": "p", "children": [], "text": "Epinephrine 1 mg/mL Vial (1 mL)" }

2 x CERTA DOSE* 0.3 mL Syringe, Permanent Needle, 29 G x ½” (FDA-cleared for use with epinephrine 1 mg/mL: K160589)

{ "type": "p", "children": [], "text": "2 x CERTA DOSE* 0.3 mL Syringe, Permanent Needle, 29 G x ½” (FDA-cleared for use with epinephrine 1 mg/mL: K160589)" }

Epinephrine Package Insert

{ "type": "p", "children": [], "text": "Epinephrine Package Insert" }

IFU CERTA DOSE* 0.3 mL Syringe

{ "type": "p", "children": [], "text": "IFU CERTA DOSE* 0.3 mL Syringe" }

Epinephrine in 0.9% Sodium Chloride Injection is indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock.

Epinephrine in Sodium Chloride Injection is a ready to administer product that requires no further dilution prior to infusion. Inspect visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the solution is colored or cloudy, or if it contains particulate matter. Discard all unused drug.

Whenever possible, give infusions of Epinephrine in 0.9% Sodium Chloride Injection into a large vein. Avoid using a catheter tie-in technique, because the obstruction to blood flow around the tubing may cause stasis and increased local concentration of the drug. Avoid the veins of the leg in elderly patients or in those suffering from occlusive vascular diseases.

To provide hemodynamic support in septic shock associated hypotension in adult patients, the suggested dosing infusion rate of intravenously administered Epinephrine in 0.9% Sodium Chloride Injection is 0.05 mcg/kg/min to 2 mcg/kg/min and is titrated to achieve a desired mean arterial pressure (MAP). The dosage may be adjusted periodically, such as every 10 to 15 minutes, in increments of 0.05 mcg/kg/min to 0.2 mcg/kg/min, to achieve the desired blood pressure goal. The ideal body weight (IBW) should be used as the weight parameter for dosing epinephrine in adult patients with septic shock associated hypotension.

After hemodynamic stabilization, wean incrementally over time, such as by decreasing doses of Epinephrine in 0.9% Sodium Chloride Injection every 30 minutes over a 12 to 24 hour period.

Injection: 16 mg Epinephrine in 250 mL 0.9% Sodium Chloride Injection (64 mcg/mL), is a clear, colorless, premixed solution in a ready to use, single-dose VIAFLO container.

{ "type": "p", "children": [], "text": "Injection: 16 mg Epinephrine in 250 mL 0.9% Sodium Chloride Injection (64 mcg/mL), is a clear, colorless, premixed solution in a ready to use, single-dose VIAFLO container." }

None.

{ "type": "p", "children": [], "text": "None." }

Because individual response to epinephrine may vary significantly, monitor blood pressure frequently and titrate to avoid excessive increases in blood pressure.

Patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types may experience severe, prolonged hypertension when given epinephrine.

Epinephrine increases cardiac output and causes peripheral vasoconstriction, which may result in pulmonary edema.

Epinephrine may induce cardiac arrhythmias and myocardial ischemia in patients, especially patients with coronary artery disease, or cardiomyopathy [see Adverse Reactions and Drug Interactions (7.3)].

Avoid extravasation of epinephrine into the tissues, to prevent local necrosis. When Epinephrine in 0.9% Sodium Chloride Injection is administered intravenously, check the infusion site frequently for free flow. Blanching along the course of the infused vein, sometimes without obvious extravasation, may be attributed to vasa vasorum constriction with increased permeability of the vein wall, permitting some leakage. This also may progress on rare occasions to a superficial slough. Hence, if blanching occurs, consider changing the infusion site at intervals to allow the effects of local vasoconstriction to subside.

There is potential for gangrene in a lower extremity when infusions of catecholamine are given in an ankle vein.

Antidote for Extravasation Ischemia: To prevent sloughing and necrosis in areas in which extravasation has taken place, infiltrate the area with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of phentolamine, an adrenergic blocking agent. Use a syringe with a fine hypodermic needle, with the solution being infiltrated liberally throughout the area, which is easily identified by its cold, hard, and pallid appearance. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours.

Epinephrine constricts renal blood vessels, which may result in oliguria or renal impairment.

Epinephrine in 0.9% Sodium Chloride Injection contains sodium metabisulfite which may cause mild to severe allergic reactions including anaphylaxis or asthmatic episodes, particularly in patients with a history of allergies. The presence of sodium metabisulfite in this product should not preclude its use for the treatment of hypotension associated with septic shock even if the patient is sulfite-sensitive, as the alternatives to using epinephrine in a life-threatening situation may not be satisfactory. In susceptible patients, consider using a formulation of epinephrine or another vasoconstrictor that does not contain sodium metabisulfite.

The following adverse reactions are discussed elsewhere in labeling:

{ "type": "p", "children": [], "text": "The following adverse reactions are discussed elsewhere in labeling: " }

{ "type": "", "children": [], "text": "" }

The following adverse reactions have been associated with use of epinephrine. 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.

{ "type": "p", "children": [], "text": "The following adverse reactions have been associated with use of epinephrine. 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. " }

Cardiovascular disorders: tachycardia, supraventricular tachycardia, ventricular arrhythmias (including fatal ventricular fibrillation), stress cardiomyopathy, myocardial ischemia, myocardial infarction, limb ischemia, pulmonary edema, hypertension

{ "type": "p", "children": [], "text": "\nCardiovascular disorders: tachycardia, supraventricular tachycardia, ventricular arrhythmias (including fatal ventricular fibrillation), stress cardiomyopathy, myocardial ischemia, myocardial infarction, limb ischemia, pulmonary edema, hypertension " }

Gastrointestinal disorders: nausea, vomiting

{ "type": "p", "children": [], "text": "\nGastrointestinal disorders: nausea, vomiting " }

Metabolic: insulin resistance, hypokalemia, lactic acidosis

{ "type": "p", "children": [], "text": "\nMetabolic: insulin resistance, hypokalemia, lactic acidosis " }

Nervous system disorders: headache, paresthesia, tremor, stroke, central nervous system bleeding, weakness, dizziness, disorientation, impaired memory, panic, psychomotor agitation, somnolence

{ "type": "p", "children": [], "text": "\nNervous system disorders: headache, paresthesia, tremor, stroke, central nervous system bleeding, weakness, dizziness, disorientation, impaired memory, panic, psychomotor agitation, somnolence " }

Psychiatric disorders: anxiety

{ "type": "p", "children": [], "text": "\nPsychiatric disorders: anxiety" }

Skin and subcutaneous tissue disorders: diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation.

{ "type": "p", "children": [], "text": "\nSkin and subcutaneous tissue disorders: diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation." }

Patients who are concomitantly receiving any of the following drugs should be observed carefully for the development of cardiac arrhythmias [see Warnings and Precautions (5.5) and Adverse Reactions (6)].

Risk Summary

Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, do not identify a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with hypotension associated with shock, and treatment with epinephrine should not be delayed (see Clinical Considerations). In animal reproduction studies, epinephrine administered by the subcutaneous route to pregnant rabbits, mice, and hamsters, during the period of organogenesis, resulted in adverse developmental effects (including gastroschisis, and embryonic lethality, and delayed skeletal ossification) at doses approximately 2 times the maximum recommended daily intravenous dose (see Data).

All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.

Disease-associated maternal and/or embryo/fetal risk

Hypotension associated with septic shock is a medical emergency in pregnancy which can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic shock may increase the risk of maternal and fetal morbidity and mortality. Do not withhold life-sustaining therapy for a pregnant woman.

Labor or Delivery

Epinephrine usually inhibits spontaneous or oxytocin induced contractions of the pregnant human uterus and may delay the second stage of labor. Avoid epinephrine during the second stage of labor. In dosage sufficient to reduce uterine contractions, the drug may cause a prolonged period of uterine atony with hemorrhage. Avoid epinephrine in obstetrics when maternal blood pressure exceeds 130/80 mmHg.

Although epinephrine improves maternal hypotension associated with anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia.

Animal Data

In an embryofetal development study with pregnant rabbits dosed during the period of organogenesis (on days 3 to 5, 6 to 7 or 7 to 9 of gestation), epinephrine caused teratogenic effects (including gastroschisis) at doses approximately 15 times the maximum recommended intramuscular,subcutaneous, or intravenous dose (on a mg/m2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). Animals treated on days 6 to 7 had decreased number of implantations.

In an embryofetal development study, pregnant mice were administered epinephrine (0.1 to 10

mg/kg/day) on Gestation Days 6 to 15. Teratogenic effects, embryonic lethality, and delays in skeletal ossification were observed at approximately 3 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 2 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days).

In an embryofetal development study with pregnant hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine produced reductions in litter size and delayed skeletal ossification at doses approximately 2 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day).

Risk Summary

There are no data on the presence of epinephrine or its metabolite in human milk, the effects of epinephrine on the breastfed infant, or on human milk production. However, because of its poor oral bioavailability and short half-life, transfer of epinephrine into breastmilk is expected to be low.

Treatment for hypotension associated with septic shock in breastfeeding patients should not be delayed.

Safety and effectiveness in pediatric patients have not been established.

Clinical studies of epinephrine for the treatment of hypotension associated with septic shock 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. Avoid veins in the leg in geriatric patients.

Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Epinephrine overdosage may also cause transient bradycardia followed by tachycardia and these may be accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Myocardial ischemia and infarction, cardiomyopathy, extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and renal insufficiency and failure have also been reported.

{ "type": "p", "children": [], "text": "Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Epinephrine overdosage may also cause transient bradycardia followed by tachycardia and these may be accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Myocardial ischemia and infarction, cardiomyopathy, extreme pallor and coldness of the skin, metabolic acidosis due to elevated blood lactic acid levels, and renal insufficiency and failure have also been reported. " }

Epinephrine is rapidly inactivated in the body and treatment following overdose is primarily supportive. Treatment of pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators (such as nitrites) or alpha-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug.

{ "type": "p", "children": [], "text": "Epinephrine is rapidly inactivated in the body and treatment following overdose is primarily supportive. Treatment of pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators (such as nitrites) or alpha-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug." }

Epinephrine in 0.9% Sodium Chloride Injection is a clear, colorless sterile solution containing 16 mg (64 mcg epinephrine base per mL which is equivalent to 116.4 mcg epinephrine bitartrate) epinephrine, USP in 250 mL VIAFLO bag. In 250 ml VIAFLO bag, each 1 mL of Epinephrine in 0.9% Sodium Chloride Injection solution contains 0.032 mg edetate disodium, 9 mg sodium chloride, 0.05 mg sodium metabisulfite, water for injection. Hydrochloric acid and/or sodium hydroxide to adjust pH range of 3.4 to 4.5.

{ "type": "p", "children": [], "text": "Epinephrine in 0.9% Sodium Chloride Injection is a clear, colorless sterile solution containing 16 mg (64 mcg epinephrine base per mL which is equivalent to 116.4 mcg epinephrine bitartrate) epinephrine, USP in 250 mL VIAFLO bag. In 250 ml VIAFLO bag, each 1 mL of Epinephrine in 0.9% Sodium Chloride Injection solution contains 0.032 mg edetate disodium, 9 mg sodium chloride, 0.05 mg sodium metabisulfite, water for injection. Hydrochloric acid and/or sodium hydroxide to adjust pH range of 3.4 to 4.5." }

This sterile solution is to be administered by the intravenous route.

{ "type": "p", "children": [], "text": "This sterile solution is to be administered by the intravenous route." }

Epinephrine Bitartrate, USP is a sympathomimetic catecholamine (adrenergic agent) designated chemically as 1,2-Benzenediol, 4-[1-hydroxy-2-(methylamino)ethyl]-, (R)-,[R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1) (salt), a white or greyish-white or light brownish-grey, odourless, crystalline powder. Slowly darkens on exposure to air and light. It has the following structural formula:

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The molecular weight of epinephrine bitartrate is 333.3 and molecular formula is C9H13NO3 • C4H6O6.

{ "type": "p", "children": [], "text": "The molecular weight of epinephrine bitartrate is 333.3 and molecular formula is C9H13NO3 • C4H6O6. " }

Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin.

{ "type": "p", "children": [], "text": "Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin." }

VIAFLO container is a flexible plastic container fabricated from a multilayer sheeting composed of Polypropylene (PP), Polyamide (PA) and Polyethylene (PE). The amount of water that can permeate from the container into the overpouch is insufficient to affect the solution significantly. Solutions in contact with the flexible container can leach out certain of the container’s chemical components in very small amounts within the expiration period. The suitability of the container material has been confirmed by tests in animals according to USP biological tests for plastic containers.

{ "type": "p", "children": [], "text": "VIAFLO container is a flexible plastic container fabricated from a multilayer sheeting composed of Polypropylene (PP), Polyamide (PA) and Polyethylene (PE). The amount of water that can permeate from the container into the overpouch is insufficient to affect the solution significantly. Solutions in contact with the flexible container can leach out certain of the container’s chemical components in very small amounts within the expiration period. The suitability of the container material has been confirmed by tests in animals according to USP biological tests for plastic containers." }

Epinephrine acts on both alpha (α)- and beta (β)-adrenergic receptors. The mechanism of the rise in blood pressure is 3-fold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), and peripheral vasoconstriction.

When administered parenterally epinephrine has a rapid onset and short duration of action.

Following intravenous administration of epinephrine, increases in systolic blood pressure and heart rate are observed. Decreases in systemic vascular resistance and diastolic blood pressure are observed at low doses of epinephrine because of β2-mediated vasodilation, but are overtaken by α1-mediated peripheral vasoconstriction at higher doses leading to increase in diastolic blood pressure. The onset of blood pressure increase following an intravenous dose of epinephrine is < 5 minutes and the time to offset blood pressure response occurs within 20 min. Most vascular beds are constricted including renal, splanchnic, mucosal and skin.

Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid.

Following intravenous injection, epinephrine is rapidly cleared from the plasma with an effective half-life of < 5 min. A pharmacokinetic steady state following continuous intravenous infusion is achieved within 10 to 15 min. In patients with septic shock, epinephrine displays dose-proportional pharmacokinetics in the infusion dose range of 0.03 to 1.7 mcg/kg/min.

Epinephrine is extensively metabolized with only a small amount excreted unchanged. Epinephrine is rapidly degraded to vanillylmandelic acid, an inactive metabolite, by monoamine oxidase and catechol-O-methyltransferase that are abundantly expressed in the liver, kidneys and other extraneuronal tissues. The tissues with the highest contribution to removal of circulating exogenous epinephrine are the liver (32%), kidneys (25%), skeletal muscle (20%), and mesenteric organs (12%).

Specific Populations

Age

In a pharmacokinetic study of 45-minute epinephrine infusions given to healthy men aged 20 to 25 years and healthy men aged 60 to 65 years, the mean plasma metabolic clearance rate of epinephrine at steady state was greater among the older men (144.8 versus 78 mL/kg/min for a 14.3 ng/kg/min infusion).

Body Weight

Body weight has been found to influence epinephrine pharmacokinetics. Higher body weight was associated with a higher plasma epinephrine clearance and a lower concentration plateau.

Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted.

Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro. Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is a mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay.

The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (15-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

Epinephrine was associated with metabolic effects, decreased mesentery, coronary and renal conductance in a sheep model of septic shock. Data from hemolysis study have shown that epinephrine at 1:1000 dilution is non-hemolytic. Epinephrine infusion significantly increased the MAP (69 vs. 86 mmHg) and cardiac output (6.4 vs. 7.1 L/min) and decreased renal blood flow (330 vs. 247 mL/min).

Fourteen clinical studies from the literature documented that epinephrine increases the mean arterial pressure (MAP) in patients with hypotension associated with septic shock.

Epinephrine in 0.9% Sodium Chloride Injection is a clear and colorless solution filled in a single dose 250 mL VIAFLO container. Epinephrine in 0.9% Sodium Chloride Injection is supplied as a carton of 20 bags in a 16 mg/250 mL (64 mcg/mL) strength, NDC 0338-0024-20.

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Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light until ready to use. Store in overpouch until time of use.

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light until ready to use. Store in overpouch until time of use." }

Protect from alkalis and oxidizing agents.

{ "type": "p", "children": [], "text": "Protect from alkalis and oxidizing agents." }

VIAFLO container is not made with natural rubber latex, DEHP, or PVC.

{ "type": "p", "children": [], "text": "VIAFLO container is not made with natural rubber latex, DEHP, or PVC." }

Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA

{ "type": "p", "children": [], "text": "Manufactured for:\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USA" }

Made in Ireland

{ "type": "p", "children": [], "text": "Made in Ireland" }

Baxter and Viaflo are trademarks of Baxter International Inc. or its subsidiaries.

{ "type": "p", "children": [], "text": "Baxter and Viaflo are trademarks of Baxter International Inc. or its subsidiaries." }

CB-30-03-116

{ "type": "p", "children": [], "text": "CB-30-03-116" }

NDC 0338-0024-20

{ "type": "p", "children": [], "text": "NDC 0338-0024-20 " }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

Epinephrinein 0.9% Sodium Chloride Injection

{ "type": "p", "children": [], "text": "\nEpinephrinein 0.9% Sodium Chloride Injection \n" }

16 mg/250 mL (64 mcg/mL)

{ "type": "p", "children": [], "text": "\n16 mg/250 mL\n(64 mcg/mL)" }

250 mL

{ "type": "p", "children": [], "text": "\n250 mL\n" }

Warning: check concentration and infusion rate

{ "type": "p", "children": [], "text": "\nWarning: check concentration and infusion rate\n" }

For Intravenous Infusion Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Infusion Only\n" }

Ready to Use.

{ "type": "p", "children": [], "text": "\nReady to Use.\n" }

Single-Dose Only - Discard unused portion.

{ "type": "p", "children": [], "text": "\nSingle-Dose Only - Discard unused portion.\n" }

Not for Ophthalmic Use.

{ "type": "p", "children": [], "text": "\nNot for Ophthalmic Use.\n" }

Each mL contains Epinephrine Bitartrate 116.4 mcg which is equivalent to Epinephrine base 64 mcg, Edetate Disodium 0.032 mg, Sodium Chloride 9 mg, Sodium Metabisulfite 0.05 mg, Water for Injection. Hydrochloric Acid and/or Sodium Hydroxide to adjust pH range of 3.4 to 4.5.

{ "type": "p", "children": [], "text": "\nEach mL contains Epinephrine Bitartrate 116.4 mcg which is equivalent to Epinephrine base 64 mcg, Edetate Disodium 0.032 mg, Sodium Chloride 9 mg, Sodium Metabisulfite 0.05 mg, Water for Injection. Hydrochloric Acid and/or Sodium Hydroxide to adjust pH range of 3.4 to 4.5." }

Dosage: See Prescribing Information.

{ "type": "p", "children": [], "text": "\nDosage: See Prescribing Information." }

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light until ready to use. Store in overpouch until time of use.

{ "type": "p", "children": [], "text": "\nStore at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light until ready to use. Store in overpouch until time of use.\n" }

Store in overpouch until time of use.

{ "type": "p", "children": [], "text": "\nStore in overpouch until time of use.\n" }

After removing the overpouch, check for minute leaks by squeezing container firmly. If leaks are found, discard solution as sterility may be impaired.

{ "type": "p", "children": [], "text": "After removing the overpouch, check for minute leaks by squeezing container firmly. If leaks are found, discard solution as sterility may be impaired." }

VIAFLO container is not made with natural rubber latex, DEHP, or PVC.

{ "type": "p", "children": [], "text": "VIAFLO container is not made with natural rubber latex, DEHP, or PVC.\n" }

Baxter Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA

{ "type": "p", "children": [], "text": "\nBaxter\nManufactured for:\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USA" }

Made in Ireland

{ "type": "p", "children": [], "text": "Made in Ireland" }

EZPE8835 CB-35-05-612

{ "type": "p", "children": [], "text": "\nEZPE8835\nCB-35-05-612" }

DO NOT USETHIS PORT

{ "type": "p", "children": [], "text": "\nDO NOT USETHIS PORT\n" }

LOT

{ "type": "p", "children": [], "text": "\nLOT\n" }

EXP

{ "type": "p", "children": [], "text": "\nEXP\n" }

TO OPEN: TEAR AT NOTCH

{ "type": "p", "children": [], "text": "\nTO OPEN: TEAR AT NOTCH\n" }

NDC 0338-0024-20

{ "type": "p", "children": [], "text": "NDC 0338-0024-20 " }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

Epinephrinein 0.9% Sodium Chloride Injection

{ "type": "p", "children": [], "text": "\nEpinephrinein 0.9% Sodium Chloride Injection \n" }

16 mg/250 mL (64 mcg/mL)

{ "type": "p", "children": [], "text": "\n16 mg/250 mL\n(64 mcg/mL)" }

250 mL

{ "type": "p", "children": [], "text": "\n250 mL\n" }

Warning: check concentration and infusion rate

{ "type": "p", "children": [], "text": "\nWarning: check concentration and infusion rate\n" }

For Intravenous Infusion Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Infusion Only\n" }

Ready to Use.

{ "type": "p", "children": [], "text": "\nReady to Use.\n" }

Single-Dose Only - Discard unused portion.

{ "type": "p", "children": [], "text": "\nSingle-Dose Only - Discard unused portion.\n" }

Not for Ophthalmic Use.

{ "type": "p", "children": [], "text": "\nNot for Ophthalmic Use.\n" }

Each mL contains Epinephrine Bitartrate 116.4 mcg which is equivalent to Epinephrine base 64 mcg, Edetate Disodium 0.032 mg, Sodium Chloride 9 mg, Sodium Metabisulfite 0.05 mg, Water for Injection. Hydrochloric Acid and/or Sodium Hydroxide to adjust pH range of 3.4 to 4.5.

{ "type": "p", "children": [], "text": "\nEach mL contains Epinephrine Bitartrate 116.4 mcg which is equivalent to Epinephrine base 64 mcg, Edetate Disodium 0.032 mg, Sodium Chloride 9 mg, Sodium Metabisulfite 0.05 mg, Water for Injection. Hydrochloric Acid and/or Sodium Hydroxide to adjust pH range of 3.4 to 4.5." }

Dosage: See Prescribing Information.

{ "type": "p", "children": [], "text": "\nDosage: See Prescribing Information." }

TO OPEN: TEAR AT NOTCH. Do not use if overpouch has been previously opened or damaged. Use unit promptly once overpouch is removed.

{ "type": "p", "children": [], "text": "\nTO OPEN: TEAR AT NOTCH. Do not use if overpouch has been previously opened or damaged. Use unit promptly once overpouch is removed." }

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light until ready to use. Store in overpouch until time of use.

{ "type": "p", "children": [], "text": "\nStore at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Epinephrine is light sensitive. Protect from light until ready to use. Store in overpouch until time of use.\n" }

The container closure is not made with natural rubber latex.

{ "type": "p", "children": [], "text": "The container closure is not made with natural rubber latex." }

Baxter Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA

{ "type": "p", "children": [], "text": "\nBaxter\nManufactured for:\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USA" }

Made in Ireland

{ "type": "p", "children": [], "text": "Made in Ireland" }

EZPE8835 CB-10-01-260

{ "type": "p", "children": [], "text": "\nEZPE8835\nCB-10-01-260" }

(See Solution Container for Lot and Exp)

{ "type": "p", "children": [], "text": "(See Solution Container for Lot and Exp)" }

Neffy is indicated for emergency treatment of type I allergic reactions, including anaphylaxis, in adult and pediatric patients aged 4 years and older who weigh 15 kg or greater.

{ "type": "p", "children": [], "text": "\nNeffy is indicated for emergency treatment of type I allergic reactions, including anaphylaxis, in adult and pediatric patients aged 4 years and older who weigh 15 kg or greater.\n" }

The recommended dosage for patients aged 4 years and older who weigh 15 kg or greater is based on weight and the dosage is provided in Table 1. For nasal administration [see Dosage and Administration (2.2)].

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Recommended Dosage of Neffy Based on Patient's Weight</span> </caption> <col align="center" valign="middle" width="50%"/> <col align="center" valign="middle" width="50%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule"><span class="XmChange">Patients Weight</span></th><th align="center" class="Rrule">Dosage</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">30 kg or Greater</td><td align="center" class="Rrule">One spray of neffy 2 mg</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">15 kg to less than 30 kg</td><td align="center" class="Rrule">One spray of neffy 1 mg</td> </tr> </tbody> </table></div>

In the absence of clinical improvement or if symptoms worsen after the initial treatment, a second dose of neffy may be administered in the same nostril with a second nasal spray starting 5 minutes after the first dose.

Figure 1: Administration of Neffy

If neffy is frozen and is needed in an emergency, do not wait to thaw, seek emergency medical care immediately [see How Supplied/Storage and Handling (16)].

Nasal spray:

None.

{ "type": "p", "children": [], "text": "None." }

Clinical pharmacology studies with neffy included subjects with history of allergic rhinitis, but did not include subjects with underlying structural and anatomical nasal conditions (e.g., polyps, history of nasal fractures or injuries, or history of nasal surgery). Absorption of neffy may be affected by underlying structural and anatomical nasal conditions. Consider use of other epinephrine products given by other routes of administration for patients with underlying structural or anatomical nasal conditions.

Some patients may be at greater risk for developing adverse reactions after epinephrine administration. Despite these concerns, it should be recognized that the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation. Therefore, patients with these conditions, and/or any other person who might be in a position to administer neffy to a patient experiencing anaphylaxis should be carefully instructed in regard to the circumstances under which epinephrine should be used.

Epinephrine should be administered with caution to patients who have heart disease, including patients with cardiac arrhythmias, coronary artery disease, or hypertension. In such patients, or in patients who are on drugs that may sensitize the heart to arrhythmias, epinephrine may precipitate or aggravate angina pectoris, as well as produce ventricular arrhythmias [see Drug Interactions (7) and Adverse Reactions (6)].

Epinephrine can temporarily exacerbate the underlying condition or increase symptoms in patients with the following: hyperthyroidism, Parkinson's disease, diabetes, renal impairment. Epinephrine should be administered with caution in patients with these conditions, including elderly patients and pregnant women.

Epinephrine is the preferred treatment for serious allergic or other emergency situations even though neffy contains sodium metabisulfite, a sulfite that may in other products cause allergic-type reactions including anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons. The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulfite(s) in neffy should not deter administration of the drug for treatment of serious allergic or other emergency situations.

Adverse Reactions with Neffy in Adult Subjects

The safety of neffy 2 mg is based on four clinical pharmacology studies in 175 healthy adults and adults with type I allergy without anaphylaxis, who did not have structural or anatomical nasal conditions [see Clinical Pharmacology (12.2, 12.3)]. The four clinical pharmacology studies were designed to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of one dose of neffy 2 mg sprayed into one nostril or two doses of neffy 2 mg sprayed into either the same or opposite nostril, administered 10 minutes apart, with PK and PD profiles of one or two dose(s) of epinephrine injection administered intramuscularly. The common adverse reactions that occurred with neffy 2 mg after one and two dose(s) are listed in Table 2.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 2: Adverse Reactions with One or Two Dose(s) of Neffy with Incidence Greater than or Equal to 2% in Adults [Studies 1, 2, 3, and 4]</span> </caption> <col align="left" valign="bottom" width="70%"/> <col align="right" valign="bottom" width="4%"/> <col align="left" valign="bottom" width="8%"/> <col align="right" valign="bottom" width="6%"/> <col align="left" valign="bottom" width="12%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" rowspan="3">Adverse Reaction<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th><th align="center" class="Rrule" colspan="2">Neffy 2 mg<br/> One Dose</th><th align="center" class="Rrule" colspan="2">Neffy 2 mg<br/> Two Doses<a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a></th> </tr> <tr class="Botrule"> <th align="center" class="Rrule" colspan="2">N = 134<a class="Sup" href="#footnote-3" name="footnote-reference-3">‡</a></th><th align="center" class="Rrule" colspan="2">N = 85<a class="Sup" href="#footnote-3">‡</a></th> </tr> <tr class="Last"> <th align="right" class="Rrule"> </th><th align="right" class="Rrule"> </th><th align="left" class="Rrule"> </th><th align="right" class="Rrule"> </th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Data include subjects with nasal allergen challenge induced rhinitis</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>Two nasal doses of neffy 2 mg were administered 10 minutes apart</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">‡</a> </dt> <dd>The trials used a crossover design and therefore the total number of subjects do not match the number of unique subjects (n = 175)</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">  Nasal discomfort</td><td align="right" class="Rrule">13</td><td align="left" class="Rrule">(10%)</td><td align="right" class="Rrule">11</td><td align="left" class="Rrule">(13%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Headache</td><td align="right" class="Rrule">8</td><td align="left" class="Rrule">(6%)</td><td align="right" class="Rrule">15</td><td align="left" class="Rrule">(18%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Rhinorrhea</td><td align="right" class="Rrule">4</td><td align="left" class="Rrule">(3%)</td><td align="right" class="Rrule">6</td><td align="left" class="Rrule">(7%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Dizziness</td><td align="right" class="Rrule">4</td><td align="left" class="Rrule">(3%)</td><td align="right" class="Rrule">2</td><td align="left" class="Rrule">(2%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Nausea</td><td align="right" class="Rrule">4</td><td align="left" class="Rrule">(3%)</td><td align="right" class="Rrule">2</td><td align="left" class="Rrule">(2%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Vomiting</td><td align="right" class="Rrule">3</td><td align="left" class="Rrule">(2%)</td><td align="right" class="Rrule">2</td><td align="left" class="Rrule">(2%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Throat irritation</td><td align="right" class="Rrule">2</td><td align="left" class="Rrule">(2%)</td><td align="right" class="Rrule">16</td><td align="left" class="Rrule">(19%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Feeling jittery</td><td align="right" class="Rrule">1</td><td align="left" class="Rrule">(1%)</td><td align="right" class="Rrule">9</td><td align="left" class="Rrule">(11%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Abdominal pain</td><td align="right" class="Rrule">1</td><td align="left" class="Rrule">(1%)</td><td align="right" class="Rrule">3</td><td align="left" class="Rrule">(4%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Tremor</td><td align="right" class="Rrule">0</td><td align="left" class="Rrule">(0%)</td><td align="right" class="Rrule">7</td><td align="left" class="Rrule">(8%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Nasal pruritus</td><td align="right" class="Rrule">0</td><td align="left" class="Rrule">(0%)</td><td align="right" class="Rrule">3</td><td align="left" class="Rrule">(4%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Sneezing</td><td align="right" class="Rrule">0</td><td align="left" class="Rrule">(0%)</td><td align="right" class="Rrule">3</td><td align="left" class="Rrule">(4%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Gingival pain</td><td align="right" class="Rrule">0</td><td align="left" class="Rrule">(0%)</td><td align="right" class="Rrule">3</td><td align="left" class="Rrule">(4%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Hypoesthesia oral</td><td align="right" class="Rrule">0</td><td align="left" class="Rrule">(0%)</td><td align="right" class="Rrule">3</td><td align="left" class="Rrule">(4%)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Nasal Congestion</td><td align="right" class="Rrule">0</td><td align="left" class="Rrule">(0%)</td><td align="right" class="Rrule">2</td><td align="left" class="Rrule">(2%)</td> </tr> </tbody> </table></div>

Adverse Reactions with Neffy in Pediatric Subjects 4 Years of Age and Older Weighing 15 kg or Greater

A single-arm clinical pharmacology study (Study 5) in pediatric subjects 4 to 17 years of age who weigh 15 kg or greater with type I allergy without anaphylaxis was conducted to assess the pharmacokinetic/pharmacodynamic (PK/PD) of neffy 1 mg and 2 mg [see Clinical Pharmacology (12.2, 12.3)]. Pediatric subjects (n=21) who weigh 30 kg or greater received one nasal dose of neffy 2 mg and common adverse reactions reported in these subjects include nasal discomfort (19%), intranasal paresthesia (19%), rhinorrhea (19%), sneezing (14%), epistaxis (10%), rhinalgia (10%), paresthesia (10%), fatigue (10%), and feeling jittery (10%). Pediatric subjects (n=21) who weigh 15 to less than 30 kg received one nasal dose of neffy 1 mg and common adverse reactions reported in these subjects include nasal congestion (19%), upper respiratory tract congestion (14%), dry throat (10%), nasal dryness (10%), and paresthesia (10%).

Adverse Reactions from Postapproval Use of Epinephrine Products

The following adverse reactions have been identified during postapproval use of epinephrine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular: angina, arrhythmias (including fatal ventricular fibrillation), cerebral hemorrhage, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, ventricular ectopy, and stress cardiomyopathy

Metabolism and Nutrition Disorders: transient hyperglycemia, sweating

Neurological: disorientation, impaired memory, panic, psychomotor agitation, sleepiness, tingling, weakness

Psychiatric: anxiety, apprehensiveness, restlessness

Respiratory: respiratory difficulties

Neffy may alter nasal mucosa for up to 2 weeks after administration, and thus may increase systemic absorption of nasal products, including neffy, potentially increasing the risk of adverse reactions associated with these products.

Patients who receive epinephrine while concomitantly taking cardiac glycosides, diuretics, or anti-arrhythmics should be observed carefully for the development of cardiac arrhythmias [see Warnings and Precautions (5.2) and Adverse Reactions (6)].

The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine, and catechol-O-methyl transferase (COMT) inhibitors such as entacapone.

The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta- adrenergic blocking drugs, such as propranolol.

The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha- adrenergic blocking drugs, such as phentolamine.

Ergot alkaloids may also reverse the pressor effects of epinephrine.

Risk Summary

Prolonged experience with epinephrine use in pregnant women over several decades, based on published literature, have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with anaphylaxis, and treatment with epinephrine should not be delayed (see Clinical Considerations). In animal reproduction studies, epinephrine administered by the subcutaneous route to pregnant rabbits, mice, and hamsters, during the period of organogenesis, resulted in adverse developmental effects (including gastroschisis, and embryonic lethality, and delayed skeletal ossification) at doses approximately 2 times the maximum recommended daily intramuscular, subcutaneous, or intravenous dose (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States 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 Embryo/Fetal Risk

During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate. Treatment of anaphylaxis during pregnancy should not be delayed.

Data

Animal Data

In an embryofetal development study with pregnant rabbits dosed during the period of organogenesis (on days 3 to 5, 6 to 7 or 7 to 9 of gestation), epinephrine caused teratogenic effects (including gastroschisis) at doses approximately 15 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). Animals treated on days 6 to 7 had decreased number of implantations.

In an embryofetal development study, pregnant mice were administered epinephrine (0.1 to 10 mg/kg/day) on Gestation Days 6 to 15. Teratogenic effects, embryonic lethality, and delays in skeletal ossification were observed at approximately 3 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 2 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days).

In an embryofetal development study with pregnant hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine produced reductions in litter size and delayed skeletal ossification at doses approximately 2 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day).

Risk Summary

There are no data on the presence of epinephrine or its metabolite in human milk, the effects on the breastfed infant, or the effects on human milk production. However, due to its poor oral bioavailability and short half-life, transfer of epinephrine into breastmilk is expected to be low. Treatment for anaphylaxis in breastfeeding patients should not be delayed.

The safety and effectiveness of neffy for emergency treatment of type I allergic reactions, including anaphylaxis, have been established in pediatric patients aged 4 years and older who weigh 15 kg or greater. Use of neffy for this indication is supported by extrapolation from the clinical pharmacology studies in adults that compared the PK/PD profile of neffy to epinephrine injection products with established safety and effectiveness for this indication and clinical pharmacology data (Study 5) in pediatric patients aged 4 years and older who weigh 15 kg or greater [see Adverse Reactions (6) and Clinical Pharmacology (12.2, 12.3)].

The safety and effectiveness of neffy have not been established in pediatric patients less than 4 years of age and who weigh less than 15 kg.

Clinical pharmacology studies of neffy for the emergency treatment of type I allergic reactions, including anaphylaxis, did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger adult subjects. However, other reported clinical experience with use of epinephrine for the treatment of anaphylaxis has identified that geriatric patients may be particularly sensitive to the effects of epinephrine. Neffy should be administered with caution in elderly patients who are at greater risk for developing adverse reactions after epinephrine administration.

Overdosage of epinephrine has been reported to produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Epinephrine overdosage can also cause transient bradycardia followed by tachycardia which may be accompanied by fatal cardiac arrhythmias; premature ventricular contractions followed by multifocal ventricular tachycardia; atrial tachycardia and occasionally by atrioventricular block; extreme pallor and coldness of the skin; metabolic acidosis; kidney failure.

{ "type": "p", "children": [], "text": "Overdosage of epinephrine has been reported to produce extremely elevated arterial pressure, which may result in cerebrovascular hemorrhage, particularly in elderly patients. Overdosage may also result in pulmonary edema because of peripheral vascular constriction together with cardiac stimulation. Epinephrine overdosage can also cause transient bradycardia followed by tachycardia which may be accompanied by fatal cardiac arrhythmias; premature ventricular contractions followed by multifocal ventricular tachycardia; atrial tachycardia and occasionally by atrioventricular block; extreme pallor and coldness of the skin; metabolic acidosis; kidney failure." }

Epinephrine is rapidly inactivated in the body and treatment following overdosage with epinephrine is primarily supportive. Treatment of epinephrine associated pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of epinephrine associated arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators or α-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug.

{ "type": "p", "children": [], "text": "Epinephrine is rapidly inactivated in the body and treatment following overdosage with epinephrine is primarily supportive. Treatment of epinephrine associated pulmonary edema consists of a rapidly acting alpha-adrenergic blocking drug (such as phentolamine mesylate) and respiratory support. Treatment of epinephrine associated arrhythmias consists of administration of a beta-adrenergic blocking drug (such as propranolol). If necessary, pressor effects may be counteracted by rapidly acting vasodilators or α-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug." }

Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

{ "type": "p", "children": [], "text": "Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations." }

Neffy contains epinephrine, a sympathomimetic catecholamine. Chemically, epinephrine is (-)-3,4-dihydroxy-α-[(methylamino)methyl] benzyl alcohol with molecular weight of 183.21 g/mol and the following structure:

{ "type": "p", "children": [], "text": "Neffy contains epinephrine, a sympathomimetic catecholamine. Chemically, epinephrine is (-)-3,4-dihydroxy-α-[(methylamino)methyl] benzyl alcohol with molecular weight of 183.21 g/mol and the following structure:" }

Neffy (epinephrine nasal spray) is supplied as single-dose nasal sprays containing 1 mg or 2 mg of epinephrine in 0.1 mL solution for nasal administration.

{ "type": "p", "children": [], "text": "Neffy (epinephrine nasal spray) is supplied as single-dose nasal sprays containing 1 mg or 2 mg of epinephrine in 0.1 mL solution for nasal administration." }

Inactive ingredients include benzalkonium chloride, disodium edetate, n-dodecyl beta-D-maltoside, sodium chloride, sodium metabisulfite, and hydrochloric acid or sodium hydroxide to adjust pH, in water for injection. The pH range is approximately 3 to 5.5.

{ "type": "p", "children": [], "text": "Inactive ingredients include benzalkonium chloride, disodium edetate, n-dodecyl beta-D-maltoside, sodium chloride, sodium metabisulfite, and hydrochloric acid or sodium hydroxide to adjust pH, in water for injection. The pH range is approximately 3 to 5.5." }

Epinephrine acts on both alpha and beta-adrenergic receptors.

Through its action on alpha-adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeability that occurs during anaphylaxis, which can lead to loss of intravascular fluid volume and hypotension.

Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis.

Epinephrine alleviates pruritus, urticaria, and angioedema. It may also relieve gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxer effects on the smooth muscle of the stomach, intestine, uterus, and urinary bladder.

Four clinical pharmacology studies of neffy in adults and one clinical pharmacology study in pediatric subjects who weigh 30 kg or greater are described below. All doses were administered by study staff unless otherwise stated.

Systolic Blood Pressure and Pulse Rate in Healthy Adult Subjects (Study 1)

Study 1 was conducted in healthy adult subjects (N=42) that compared the pharmacokinetics (PK) [see Clinical Pharmacology (12.3)] and pharmacodynamics (PD) (i.e., pulse rate (PR) and systolic blood pressure (SBP)) of epinephrine following:

In Study 1, SBP and PR responses were assessed as change from baseline over 60 minutes.

Results following one dose of all epinephrine products demonstrated an increase from baseline SBP and PR as shown in Figure 2. The median/mean increase in SBP and PR for neffy were within the range of both epinephrine injection treatments during the first 10 minutes post-dose. Thereafter, the median/mean SBP and PR responses for neffy were higher than both epinephrine injection treatments through 60 minutes post-dose.

Figure 2: Median Pulse Rate (PR) and Systolic Blood Pressure (SBP) Change from Baseline Following One Dose of Epinephrine in Healthy Subjects [Study 1]

Results following two nasal doses of neffy (in the same naris or opposite nares) in comparison to two intramuscular doses of epinephrine injection (using an auto-injector) showed a similar trend in median/mean SBP and PR responses.

The clinical meaning of SBP and PR responses observed in healthy subjects is unclear in the context of treating anaphylaxis.

Systolic Blood Pressure and Pulse Rate in Adult Patients with Type I Allergy without Anaphylaxis (Study 2)

Study 2 was conducted in adult patients with type I allergy without anaphylaxis (N=42) that compared the PK and PD of epinephrine following self-administered one nasal dose of neffy 2 mg to staff-administered one intramuscular dose of epinephrine injection 0.3 mg (using a needle-syringe product).

In Study 2, SBP and PR responses were assessed as a change from baseline over 60 minutes. The SBP and PR responses results in Study 2 were similar to Study 1.

Systolic Blood Pressure and Pulse Rate in Adult Patients with Nasal Allergen Challenge Induced Rhinitis (Study 3 and 4)

Study 3 and Study 4 were conducted in adult subjects with seasonal allergic rhinitis outside of allergy season (neffy is not approved for the treatment of allergic rhinitis). Subjects were required to have seasonal allergic rhinitis which was confirmed with a nasal allergen challenge (NAC) during screening and did not have any allergy symptoms prior to treatment. Allergic rhinitis symptoms were induced by spraying the known allergen into the subject's nostrils in which a minimum Total Nasal Symptom Score (TNSS) of ≥ 5 out of 12, with a congestion component of ≥ 2 out of 3 had to be reached.

Study 3 enrolled 36 subjects. In this cross-over study, subjects received epinephrine as each of the following:

In Study 3, SBP and PR responses were assessed as a change from baseline over 60 minutes. Results showed the following:

Study 4 enrolled 43 subjects. In this cross-over study, subjects received the following:

In Study 4, SBP and PR responses were assessed as a change from baseline over 60 minutes. Results showed the following:

Figure 3: Median Change from Baseline for Pulse Rate (PR) and Systolic Blood Pressure (SBP) Following Two Doses of Epinephrine Administered 10 Minutes Apart in Subjects with and without Nasal Allergen Challenge (NAC) Induced Rhinitis [Study 4]

<div class="scrollingtable"><table class="Noautorules" width="75%"> <col align="left" valign="top" width="100%"/> <tfoot> <tr> <td align="left">R/L: First dose administered in right naris followed by second dose administered in left naris 10 minutes apart.<br/> R/R: First dose administered in right naris followed by second dose administered in right naris 10 minutes apart.<br/> Epinephrine 0.3 mg was administered using needle-syringe product</td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left"> <p class="First"> <img alt="Figure 3" src="/dailymed/image.cfm?name=neffy-05.jpg&amp;setid=a1758142-a905-401d-8961-05829f51023a"/></p> </td> </tr> </tbody> </table></div>

Systolic Blood Pressure and Pulse Rate in Pediatric Patients Aged 4 Years and Older Weighing 15 kg or Greater with Type I Allergy without Anaphylaxis (Study 5)

Study 5 was a single-arm study conducted in pediatric patients who weighed 15 kg or greater (age range: 4 to 17 years) with type I allergy without anaphylaxis (N=42) that assessed the PK and PD of epinephrine following one nasal dose of neffy 1 mg (for subjects who weigh 15 kg to < 30 kg) and 2 mg (for subjects who weigh 30 kg or greater). The median change in SBP from baseline over the 60 minutes post-dose were numerically lower than in adults who received neffy 2 mg in Study 1 and 2, while the median change in PR from baseline over 60 minutes post-dose was within the range of adults who received neffy 2 mg in Study 1 and 2.

Pharmacokinetics assessments were performed in the clinical pharmacology studies described in the Pharmacodynamics subsection [see Clinical Pharmacology (12.2)].

Pharmacokinetics in Healthy Adult Subjects (Study 1)

See Pharmacodynamics (12.2) for a description for Study 1.

Following one nasal dose of neffy 2 mg in Study 1, the geometric mean plasma epinephrine concentration-time profile was overall within the range of that following one intramuscular dose of epinephrine injection 0.3 mg (using a needle-syringe product and an auto-injector product) 60 minutes post-dose. The epinephrine plasma concentration versus time profiles are shown in Figure 4. The pharmacokinetic parameters of epinephrine are summarized in Table 3.

Figure 4: Epinephrine Geometric Mean (90% Confidence Interval) Plasma Concentration-Time Profiles Following One Dose of Epinephrine in Healthy Subjects [Study 1]

<div class="scrollingtable"><table width="95%"> <caption> <span>Table 3: Geometric Mean (CV%) Plasma PK Parameters Following One Dose of Epinephrine in Healthy Subjects [Study 1]</span> </caption> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="10%"/> <col align="center" valign="middle" width="9%"/> <col align="center" valign="middle" width="16%"/> <col align="center" valign="middle" width="14%"/> <col align="center" valign="middle" width="14%"/> <col align="center" valign="middle" width="17%"/> <thead> <tr class="Botrule First"> <th align="center" class="Lrule Rrule" rowspan="2">Product</th><th align="center" class="Rrule" colspan="6">Pharmacokinetic Parameters [%CV]</th> </tr> <tr class="Last"> <th align="center" class="Rrule">GeoMean <br/>Cmax (pg/mL)</th><th align="center" class="Rrule">Median <br/>Tmax <br/>(min)</th><th align="center" class="Rrule">GeoMean<br/> AUC<span class="Sub">0-10min</span> (min*pg/mL)<a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a></th><th align="center" class="Rrule">GeoMean<br/> AUC<span class="Sub">0-20min</span> (min*pg/mL)</th><th align="center" class="Rrule">GeoMean<br/> AUC<span class="Sub">0-45min</span> (min*pg/mL)</th><th align="center" class="Rrule">GeoMean AUC<span class="Sub">0-60min</span> <br/> (min*pg/mL)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>Note: Based on within-study comparison results from Studies 1, 2, and 3, the epinephrine exposures in the first 10 minutes following neffy administration were generally within the range observed following epinephrine injection 0.3 mg (needle-syringe) </dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">Epinephrine 0.3 mg<br/> (Needle-Syringe)<br/> (N=42)</td><td align="center" class="Rrule">283 [62]</td><td align="center" class="Rrule">45</td><td align="center" class="Rrule">879 [120]</td><td align="center" class="Rrule">2032 [89]</td><td align="center" class="Rrule">6172 [67]</td><td align="center" class="Rrule">9217 [59]</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Neffy 2 mg<br/> (N=42)</td><td align="center" class="Rrule">341 [114]</td><td align="center" class="Rrule">30</td><td align="center" class="Rrule">704 [92]</td><td align="center" class="Rrule">2548 [102]</td><td align="center" class="Rrule">8156 [115]</td><td align="center" class="Rrule">10916 [116]</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">Epinephrine 0.3 mg <br/>(Auto-Injector)<br/> (N=42)</td><td align="center" class="Rrule">604 [79]</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">2771 [115]</td><td align="center" class="Rrule">5818 [83]</td><td align="center" class="Rrule">12227 [60]</td><td align="center" class="Rrule">14762 [57]</td> </tr> </tbody> </table></div>

Following two nasal doses of neffy 2 mg, administered 10 minutes apart, either into the same naris or opposite nares under normal nasal conditions, the Cmax and AUC0-60 min increased approximately dose proportionally compared to one nasal dose of neffy 2 mg in healthy adults. The systemic exposures of two doses of neffy 2 mg administered into the same naris or the opposite nares under normal nasal conditions were generally similar and comparable to that of two intramuscular injections of epinephrine 0.3 mg (using an auto-injector product), administered 10 minutes apart, after 20 to 30 minutes post-dose.

Pharmacokinetics in Adult Patients with Type I Allergy without Anaphylaxis (Study 2)

See the Pharmacodynamics (12.2) for a description for Study 2.

The geometric mean plasma epinephrine concentration time profile following one self-administered nasal dose of neffy 2 mg was numerically higher than that of one staff-administered intramuscular dose of epinephrine injection 0.3 mg (using a needle-syringe product) during the first 60 minutes post-dose (Study 2). The systemic exposure of epinephrine following one self-administered dose of neffy 2 mg in adult patients with type I allergy without anaphylaxis was similar to that following one staff-administered dose of neffy 2 mg in healthy adult subjects from Study 1.

Pharmacokinetics in Adult Patients with Nasal Allergen Challenge Induced Rhinitis (Studies 3 and 4)

See the Pharmacodynamics (12.2) for a description of Studies 3 and 4.

Figure 5: Epinephrine Geometric Mean Plasma Concentration-Time Profiles Following One or Two Dose(s) of Epinephrine in Adult Subjects with and without Nasal Allergen Challenge Induced Rhinitis [Study 3 and Study 4]

<div class="scrollingtable"><table class="Noautorules" width="75%"> <col align="left" valign="top" width="100%"/> <tfoot> <tr> <td align="left">a: Epinephrine geometric mean plasma concentration-time profiles following one dose of epinephrine in Study 3<br/> b: Epinephrine geometric mean plasma concentration-time profiles following two doses of epinephrine in Study 4<br/> R/L: First dose administered in right naris followed by second dose administered in left naris 10 minutes apart.<br/> R/R: First dose administered in right naris followed by second dose administered in right naris 10 minutes apart.<br/> Epinephrine 0.3 mg was administered using needle-syringe product</td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left"> <p class="First"> <img alt="Figure 5" src="/dailymed/image.cfm?name=neffy-07.jpg&amp;setid=a1758142-a905-401d-8961-05829f51023a"/></p> </td> </tr> </tbody> </table></div>

Pharmacokinetics in Pediatric Patients Aged 4 Years and Older Weighing 15 kg or Greater with Type I Allergy without Anaphylaxis (Study 5)

See the Pharmacodynamics (12.2) for a description for Study 5.

In pediatric patients with type I allergy without anaphylaxis who weigh 15 kg or greater (age range: 4 to 17 years), following one nasal dose of neffy 1 mg (for subjects who weigh 15 kg to < 30 kg) or 2 mg (for subjects who weigh 30 kg or greater) (Study 5), the geometric mean plasma epinephrine concentration time profiles for both weight groups were numerically higher than that of adults who received neffy 2 mg (Study 1 and 2).

Elimination:

Metabolism: Epinephrine is extensively metabolized with only a small amount excreted unchanged.

Epinephrine is rapidly degraded to vanillylmandelic acid, an inactive metabolite, by monoamine oxidase and catechol-O-methyltransferase that are abundantly expressed in the liver, kidneys and other extraneuronal tissues. The tissues with the highest contribution to removal of circulating exogenous epinephrine are the liver (32%), kidneys (25%), skeletal muscle (20%), and mesenteric organs (12%).

Specific Populations:

Age: In a PK study of 45-minute epinephrine intravenous infusions given to healthy male subjects aged 20 to 25 years and healthy male subjects aged 60 to 65 years, the mean plasma metabolic clearance rate of epinephrine at steady state was greater among the older male subjects compared to younger male subjects (144.8 versus 78 mL/kg/minute, respectively, for a 0.0143 mcg/kg/minute infusion).

Body Weight: Body weight has been found to influence epinephrine PK. Higher body weight was associated with a higher plasma epinephrine clearance and a lower concentration plateau.

Long-term studies to evaluate the carcinogenic potential of epinephrine have not been conducted. Epinephrine and other catecholamines have been shown to have mutagenic potential in vitro. Epinephrine was positive in the Salmonella bacterial reverse mutation assay, positive in the mouse lymphoma assay, and negative in the in vivo micronucleus assay. Epinephrine is an oxidative mutagen based on the E. coli WP2 Mutoxitest bacterial reverse mutation assay. This should not prevent the use of epinephrine where indicated [see Indications and Usage (1)]. The potential for epinephrine to impair reproductive performance has not been evaluated, but epinephrine has been shown to decrease implantation in female rabbits dosed subcutaneously with 1.2 mg/kg/day (15-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.

In a single-dose nasal toxicity study, treatment of neffy in rats induced epinephrine-related histopathological changes in the nose, such as minimal ulceration of the exposed mucosa (at ≥2.3-fold the recommended clinical dose of neffy 2 mg based on local surface area), and nasal passages, such as minimal to mild necrosis in the nasal turbinate and parietal wall in the rostral-most level (at ≥1.2-fold the recommended clinical dose of neffy 2 mg based on local surface area) on day 2. These findings were often associated with minimal to mild neutrophilic inflammation and were reversible after 14 days post-dose.

How Supplied

Neffy (epinephrine nasal spray) is available in 1 mg and 2 mg strengths as described in Table 4.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 4: Neffy Strengths and Package Configurations</span> </caption> <col align="center" valign="bottom" width="24%"/> <col align="left" valign="bottom" width="50%"/> <col align="center" valign="bottom" width="26%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Strength</th><th align="center" class="Rrule">Package Configuration</th><th align="center" class="Rrule">NDC</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">1 mg/0.1 mL</td><td align="left" class="Rrule">Carton containing two (2) blister packages each with a single-dose nasal spray for 1 time use</td><td align="center" class="Rrule">NDC 82580-010-02</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">2 mg/0.1 mL</td><td align="left" class="Rrule">Carton containing two (2) blister packages each with a single-dose nasal spray for 1 time use</td><td align="center" class="Rrule">NDC 82580-020-02</td> </tr> </tbody> </table></div>

Storage and Handling

Store at 68°F to 77°F (20°C to 25°C). Excursions permitted up to 122°F (50°C).

Do not freeze. Neffy freezes below 5°F (-15°C). If neffy freezes, it will not deliver epinephrine.

Administration

Risks Associated with Certain Coexisting Conditions

Advise patients with coexisting conditions (cardiac arrhythmia, coronary artery disease, hypertension, pulmonary edema, hyperthyroidism, renal impairment, Parkinson's disease, diabetes), for increased risks that may be associated with use of epinephrine [see Warnings and Precautions (5.2)].

Manufactured for ARS Pharmaceuticals Operations, Inc., 11682 El Camino Real, San Diego, CA 92130. Neffy is a registered trademark of ARS Pharmaceuticals Operations, Inc. Copyright © 2025 ARS Pharmaceuticals Operations, Inc. All rights reserved. This product's labeling may have been updated. For the most recent Prescribing Information, please visit www.neffy.com.

{ "type": "p", "children": [], "text": "Manufactured for ARS Pharmaceuticals Operations, Inc., 11682 El Camino Real, San Diego, CA 92130. Neffy is a registered trademark of ARS Pharmaceuticals Operations, Inc. Copyright © 2025 ARS Pharmaceuticals Operations, Inc. All rights reserved. This product's labeling may have been updated. For the most recent Prescribing Information, please visit www.neffy.com.\n" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="5%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <thead> <tr class="Botrule First Last"> <th align="center" class="Lrule Rrule" colspan="5">PATIENT INFORMATION<br/>NEFFY<span class="Sup">®</span> (ne'fee) <br/>(epinephrine nasal spray)<br/>For allergic emergencies (anaphylaxis)</th> </tr> </thead> <tfoot> <tr class="First"> <td align="left" colspan="4">This Patient Information has been approved by the U.S. Food and Drug Administration</td><td align="right" colspan="1">Revised: March 2025          </td> </tr> <tr class="Last"> <td align="left"></td><td align="left"></td><td align="left"></td><td align="left"></td><td align="left"></td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="5">Read this Patient Information leaflet carefully before you start using neffy and each time you get a refill. There may be new information. You, your caregiver, or others who may be in a position to administer neffy should know how to use it before you have an allergic emergency. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <dl class="Arabic"> <dt>1.</dt> <dd> <span class="Bold">What is the most important information I should know about neffy?</span> <br/>Neffy contains epinephrine, a medicine used to treat allergic emergencies (anaphylaxis). Anaphylaxis can be life-threatening, can happen in minutes, and can be caused by stinging and biting insects, allergy injections, foods, medicines, exercise, or other unknown causes. <br/>Symptoms of anaphylaxis may include:</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>trouble breathing </li> <li>wheezing</li> <li>hoarseness (changes in the way your voice sounds)</li> <li>hives (raised reddened rash that may itch)</li> <li>severe itching</li> <li>swelling of your face, lips, mouth, or tongue</li> <li>skin rash, redness, or swelling</li> <li>fast heartbeat</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>weak pulse</li> <li>feeling very anxious</li> <li>confusion</li> <li>stomach pain</li> <li>losing control of urine or bowel movements (incontinence)</li> <li>diarrhea or stomach cramps</li> <li>dizziness, fainting, or "passing out" (unconsciousness)</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"> <dl class="Arabic"> <dt>2.</dt> <dd> <span class="Bold">Always carry neffy with you because you may not know when anaphylaxis may happen</span>. It is recommended that you carry 2 neffy devices because you may need a second dose of neffy if symptoms continue or come back. Talk to your healthcare provider if you need additional devices to keep at work, school, or other locations. Tell your family members, caregivers, and others where you keep your neffy device and how to use it before you need it. You may be unable to speak in an allergic emergency.</dd> <dt>3.</dt> <dd> <span class="Bold">When you have an allergic emergency (anaphylaxis)</span> <ul class="Disc"> <li> <span class="Bold">Use neffy right away</span>.</li> <li> <span class="Bold">Get emergency medical help for further treatment of the allergic emergency (anaphylaxis), if needed after using neffy</span>. Before you receive neffy, your healthcare provider should talk to you about when to get emergency help. </li> </ul> </dd> </dl> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What is neffy?</span> <ul class="Disc"> <li>Neffy is a nasal spray used to treat life-threatening, allergic emergencies including anaphylaxis in adults and children aged 4 years and older who weigh 33 pounds or more (15 kilograms or more), who are at risk for or have a history of serious allergic emergencies. Each neffy contains a single dose of epinephrine.</li> <li>Neffy is for immediate self (or caregiver) administration in an allergic emergency.</li> <li>Neffy is for people who have been prescribed this medicine by their healthcare provider.</li> <li>It is not known if neffy is safe and effective in children who weigh less than 33 pounds (15 kilograms).</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Before using neffy, tell your healthcare provider about all your medical conditions, especially if you</span>:<ul class="Disc"> <li>have nasal problems including nasal polyps, history of injury such as a broken nose, or any past nasal surgery.</li> <li>have heart problems.</li> <li>have kidney problems.</li> <li>have low potassium levels in your blood.</li> <li>have Parkinson's disease.</li> <li>have thyroid problems.</li> <li>have high blood pressure.</li> <li>have diabetes.</li> <li>are pregnant or plan to become pregnant. It is not known if epinephrine will harm your unborn baby.</li> <li>are breastfeeding or plan to breastfeed. It is not known if epinephrine passes into your breastmilk.</li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins and herbal supplements. Tell your healthcare provider of all known allergies.<br/> <span class="Bold">Especially tell your healthcare provider if you take or use</span>: <ul class="Disc"> <li>other nasal sprays</li> <li>water pills (diuretics)</li> <li>medicines to treat depression such as tricyclic antidepressants or monoamine oxidase inhibitors (MAO inhibitors)</li> <li>medicines to treat abnormal heart beats (arrhythmias) such as cardiac glycosides </li> <li>medicines to treat Parkinson's disease such as catechol-O-methyl-transferase inhibitors (COMT inhibitors) and ergot alkaloids </li> <li>medicines for heart disease including alpha blockers (such as phentolamine) and beta blockers (such as propranolol) </li> <li>medicines for thyroid disease such as levothyroxine sodium</li> <li>medicines used in labor </li> <li>medicines to treat allergies such as diphenhydramine, tripelennamine or chlorpheniramine (antihistamines)</li> </ul>Neffy and other medicines may affect each other, causing side effects. Neffy may affect the way other medicines work, and other medicines may affect how neffy works.<br/> Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.<br/>Use neffy for the treatment of anaphylaxis as prescribed by your healthcare provider, regardless of your medical conditions or medicine you take. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">How should I use neffy?</span> <ul class="Disc"> <li>Read the Instructions for Use that come with neffy for detailed information about the right way to use the device. </li> <li>Use neffy exactly as your healthcare provider tells you to use it. Talk to your healthcare provider or pharmacist if you have questions about the use of neffy. </li> <li> <span class="Bold">Neffy is for use in the nose only</span>. Do not spray in the eyes or mouth.</li> <li>Each neffy has 1 dose of medicine and cannot be reused. Do not test or prime (pre-spray) the device. </li> <li>Your neffy comes in a carton with 2 devices. You may need to use a second neffy if symptoms continue or get worse. </li> <li>You should always carry 2 neffy devices with you.</li> <li>Neffy is given as a single dose in either nostril. If a second dose of neffy is needed, it should be given in the <span class="Bold">same nostril</span>, starting 5 minutes after the first dose.</li> <li> <span class="Bold">Do not</span> sniff during or after receiving a dose of neffy.</li> <li>If any liquid drips out of the nose, you may not receive the full dose of medicine. If your symptoms continue or get worse, give a second dose of neffy in the same nostril, starting 5 minutes after the first dose.</li> <li>Important: If symptoms continue or get worse after the first dose of neffy, a second dose is needed, <span class="Bold">even if you did not see liquid drip out of the nose</span>. Give the second dose in the same nostril, starting 5 minutes after the first dose.</li> <li>Get emergency help for further treatment of the anaphylactic episode, if needed, after using neffy. Before you receive neffy, your healthcare provider should talk to you about when to get emergency help.</li> <li>If you use too much neffy, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.</li> <li>For more information and video instructions on the use of neffy, go to www.neffy.com or call 1-877-MY-NEFFY (1-877-696-3339).</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What are the possible side effects of neffy</span>?<br/> <span class="Bold">Neffy may cause serious side effects.</span> <br/> <span class="Bold">If you have certain medical conditions, or take certain medicines, your condition may get worse or you may have more or longer lasting side effects when you use neffy.</span> Talk to your healthcare provider about all your medical conditions.<br/>Common side effects of neffy include:</td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>nasal discomfort</li> <li>throat irritation</li> <li>headache</li> <li>chest and nasal congestion</li> <li>feeling overly excited, nervous, or anxious</li> <li>nose bleed</li> <li>nose pain</li> <li>sneezing </li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>runny nose</li> <li>dry nose or throat</li> <li>tingling sensation, including in the nose</li> <li>feeling tired</li> <li>dizziness</li> <li>nausea</li> <li>vomiting</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</span> <br/>These are not all the possible side effects of neffy<span class="Bold">.</span> For more information, ask your healthcare provider or pharmacist.<br/> <span class="Bold">Call your doctor for medical advice about side effects</span>. <span class="Bold">You may report side effects to FDA at 1-800-FDA-1088</span>.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">How should I store neffy?</span> <ul class="Disc"> <li>Store neffy at room temperature between 68°F to 77°F (20°C to 25°C). </li> <li> <span class="Bold">Do not freeze. If neffy freezes, the device will not spray</span>.</li> <li> <span class="Bold">Storage of neffy at high temperatures up to 122°F (50°C) is allowed for a few days.</span> </li> <li>Your neffy has an expiration date. Replace neffy before the expiration date.</li> </ul> <span class="Bold">Keep neffy and all medicines out of the reach of children</span>. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">General information about the safe and effective use of neffy.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use neffy for a condition for which it was not prescribed. Do not give neffy to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about neffy that is written for health professionals. </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What are the ingredients in neffy?</span> <br/> <span class="Bold">Active Ingredient</span>: epinephrine<br/> <span class="Bold">Inactive Ingredients</span>: benzalkonium chloride, disodium edetate, n-dodecyl beta-D-maltoside, sodium chloride, sodium metabisulfite, and hydrochloric acid or sodium hydroxide to adjust pH, in water for injection. </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"5%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<thead>\n<tr class=\"Botrule First Last\">\n<th align=\"center\" class=\"Lrule Rrule\" colspan=\"5\">PATIENT INFORMATION<br/>NEFFY<span class=\"Sup\">®</span> (ne'fee) <br/>(epinephrine nasal spray)<br/>For allergic emergencies (anaphylaxis)</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First\">\n<td align=\"left\" colspan=\"4\">This Patient Information has been approved by the U.S. Food and Drug Administration</td><td align=\"right\" colspan=\"1\">Revised: March 2025          </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\"></td><td align=\"left\"></td><td align=\"left\"></td><td align=\"left\"></td><td align=\"left\"></td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">Read this Patient Information leaflet carefully before you start using neffy and each time you get a refill. There may be new information. You, your caregiver, or others who may be in a position to administer neffy should know how to use it before you have an allergic emergency. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<dl class=\"Arabic\">\n<dt>1.</dt>\n<dd>\n<span class=\"Bold\">What is the most important information I should know about neffy?</span>\n<br/>Neffy contains epinephrine, a medicine used to treat allergic emergencies (anaphylaxis). Anaphylaxis can be life-threatening, can happen in minutes, and can be caused by stinging and biting insects, allergy injections, foods, medicines, exercise, or other unknown causes. <br/>Symptoms of anaphylaxis may include:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>trouble breathing </li>\n<li>wheezing</li>\n<li>hoarseness (changes in the way your voice sounds)</li>\n<li>hives (raised reddened rash that may itch)</li>\n<li>severe itching</li>\n<li>swelling of your face, lips, mouth, or tongue</li>\n<li>skin rash, redness, or swelling</li>\n<li>fast heartbeat</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>weak pulse</li>\n<li>feeling very anxious</li>\n<li>confusion</li>\n<li>stomach pain</li>\n<li>losing control of urine or bowel movements (incontinence)</li>\n<li>diarrhea or stomach cramps</li>\n<li>dizziness, fainting, or \"passing out\" (unconsciousness)</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<dl class=\"Arabic\">\n<dt>2.</dt>\n<dd>\n<span class=\"Bold\">Always carry neffy with you because you may not know when anaphylaxis may happen</span>. It is recommended that you carry 2 neffy devices because you may need a second dose of neffy if symptoms continue or come back. Talk to your healthcare provider if you need additional devices to keep at work, school, or other locations. Tell your family members, caregivers, and others where you keep your neffy device and how to use it before you need it. You may be unable to speak in an allergic emergency.</dd>\n<dt>3.</dt>\n<dd>\n<span class=\"Bold\">When you have an allergic emergency (anaphylaxis)</span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Use neffy right away</span>.</li>\n<li>\n<span class=\"Bold\">Get emergency medical help for further treatment of the allergic emergency (anaphylaxis), if needed after using neffy</span>. Before you receive neffy, your healthcare provider should talk to you about when to get emergency help. </li>\n</ul>\n</dd>\n</dl>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What is neffy?</span>\n<ul class=\"Disc\">\n<li>Neffy is a nasal spray used to treat life-threatening, allergic emergencies including anaphylaxis in adults and children aged 4 years and older who weigh 33 pounds or more (15 kilograms or more), who are at risk for or have a history of serious allergic emergencies. Each neffy contains a single dose of epinephrine.</li>\n<li>Neffy is for immediate self (or caregiver) administration in an allergic emergency.</li>\n<li>Neffy is for people who have been prescribed this medicine by their healthcare provider.</li>\n<li>It is not known if neffy is safe and effective in children who weigh less than 33 pounds (15 kilograms).</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Before using neffy, tell your healthcare provider about all your medical conditions, especially if you</span>:<ul class=\"Disc\">\n<li>have nasal problems including nasal polyps, history of injury such as a broken nose, or any past nasal surgery.</li>\n<li>have heart problems.</li>\n<li>have kidney problems.</li>\n<li>have low potassium levels in your blood.</li>\n<li>have Parkinson's disease.</li>\n<li>have thyroid problems.</li>\n<li>have high blood pressure.</li>\n<li>have diabetes.</li>\n<li>are pregnant or plan to become pregnant. It is not known if epinephrine will harm your unborn baby.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if epinephrine passes into your breastmilk.</li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins and herbal supplements. Tell your healthcare provider of all known allergies.<br/>\n<span class=\"Bold\">Especially tell your healthcare provider if you take or use</span>: \t\t\t\t\t\t\t\t\t\t<ul class=\"Disc\">\n<li>other nasal sprays</li>\n<li>water pills (diuretics)</li>\n<li>medicines to treat depression such as tricyclic antidepressants or monoamine oxidase inhibitors (MAO inhibitors)</li>\n<li>medicines to treat abnormal heart beats (arrhythmias) such as cardiac glycosides </li>\n<li>medicines to treat Parkinson's disease such as catechol-O-methyl-transferase inhibitors (COMT inhibitors) and ergot alkaloids </li>\n<li>medicines for heart disease including alpha blockers (such as phentolamine) and beta blockers (such as propranolol) </li>\n<li>medicines for thyroid disease such as levothyroxine sodium</li>\n<li>medicines used in labor </li>\n<li>medicines to treat allergies such as diphenhydramine, tripelennamine or chlorpheniramine (antihistamines)</li>\n</ul>Neffy and other medicines may affect each other, causing side effects. Neffy may affect the way other medicines work, and other medicines may affect how neffy works.<br/> Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.<br/>Use neffy for the treatment of anaphylaxis as prescribed by your healthcare provider, regardless of your medical conditions or medicine you take. \t\t\t\t\t\t\t\t\t</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">How should I use neffy?</span>\n<ul class=\"Disc\">\n<li>Read the Instructions for Use that come with neffy for detailed information about the right way to use the device. </li>\n<li>Use neffy exactly as your healthcare provider tells you to use it. Talk to your healthcare provider or pharmacist if you have questions about the use of neffy. </li>\n<li>\n<span class=\"Bold\">Neffy is for use in the nose only</span>. Do not spray in the eyes or mouth.</li>\n<li>Each neffy has 1 dose of medicine and cannot be reused. Do not test or prime (pre-spray) the device. </li>\n<li>Your neffy comes in a carton with 2 devices. You may need to use a second neffy if symptoms continue or get worse. </li>\n<li>You should always carry 2 neffy devices with you.</li>\n<li>Neffy is given as a single dose in either nostril. If a second dose of neffy is needed, it should be given in the <span class=\"Bold\">same nostril</span>, starting 5 minutes after the first dose.</li>\n<li>\n<span class=\"Bold\">Do not</span> sniff during or after receiving a dose of neffy.</li>\n<li>If any liquid drips out of the nose, you may not receive the full dose of medicine. If your symptoms continue or get worse, give a second dose of neffy in the same nostril, starting 5 minutes after the first dose.</li>\n<li>Important: If symptoms continue or get worse after the first dose of neffy, a second dose is needed, <span class=\"Bold\">even if you did not see liquid drip out of the nose</span>. Give the second dose in the same nostril, starting 5 minutes after the first dose.</li>\n<li>Get emergency help for further treatment of the anaphylactic episode, if needed, after using neffy. Before you receive neffy, your healthcare provider should talk to you about when to get emergency help.</li>\n<li>If you use too much neffy, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.</li>\n<li>For more information and video instructions on the use of neffy, go to www.neffy.com or call 1-877-MY-NEFFY (1-877-696-3339).</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What are the possible side effects of neffy</span>?<br/>\n<span class=\"Bold\">Neffy may cause serious side effects.</span>\n<br/>\n<span class=\"Bold\">If you have certain medical conditions, or take certain medicines, your condition may get worse or you may have more or longer lasting side effects when you use neffy.</span> Talk to your healthcare provider about all your medical conditions.<br/>Common side effects of neffy include:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>nasal discomfort</li>\n<li>throat irritation</li>\n<li>headache</li>\n<li>chest and nasal congestion</li>\n<li>feeling overly excited, nervous, or anxious</li>\n<li>nose bleed</li>\n<li>nose pain</li>\n<li>sneezing </li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>runny nose</li>\n<li>dry nose or throat</li>\n<li>tingling sensation, including in the nose</li>\n<li>feeling tired</li>\n<li>dizziness</li>\n<li>nausea</li>\n<li>vomiting</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</span>\n<br/>These are not all the possible side effects of neffy<span class=\"Bold\">.</span> For more information, ask your healthcare provider or pharmacist.<br/>\n<span class=\"Bold\">Call your doctor for medical advice about side effects</span>. <span class=\"Bold\">You may report side effects to FDA at 1-800-FDA-1088</span>.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">How should I store neffy?</span>\n<ul class=\"Disc\">\n<li>Store neffy at room temperature between 68°F to 77°F (20°C to 25°C). </li>\n<li>\n<span class=\"Bold\">Do not freeze. If neffy freezes, the device will not spray</span>.</li>\n<li>\n<span class=\"Bold\">Storage of neffy at high temperatures up to 122°F (50°C) is allowed for a few days.</span>\n</li>\n<li>Your neffy has an expiration date. Replace neffy before the expiration date.</li>\n</ul>\n<span class=\"Bold\">Keep neffy and all medicines out of the reach of children</span>. \t\t\t\t\t\t\t\t\t</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">General information about the safe and effective use of neffy.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use neffy for a condition for which it was not prescribed. Do not give neffy to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about neffy that is written for health professionals. \t\t\t\t\t\t\t\t\t</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What are the ingredients in neffy?</span>\n<br/>\n<span class=\"Bold\">Active Ingredient</span>: epinephrine<br/>\n<span class=\"Bold\">Inactive Ingredients</span>: benzalkonium chloride, disodium edetate, n-dodecyl beta-D-maltoside, sodium chloride, sodium metabisulfite, and hydrochloric acid or sodium hydroxide to adjust pH, in water for injection. \t\t\t\t\t\t\t\t\t</td>\n</tr>\n</tbody>\n</table></div>" }

Dispense in this sealed carton

{ "type": "p", "children": [], "text": "Dispense in this sealed carton" }

NDC 82580-020-02Rx Only

{ "type": "p", "children": [], "text": "NDC 82580-020-02Rx Only" }

neffy® (epinephrine nasal spray)2 mg

{ "type": "p", "children": [], "text": "neffy®\n (epinephrine nasal spray)2 mg" }

For Use in the Nose Only (Single-dose)Read the Instructions for Use for completeinformation on how to use neffy.

{ "type": "p", "children": [], "text": "For Use in the Nose Only (Single-dose)Read the Instructions for Use for completeinformation on how to use neffy." }

Two (2) single-dose nasal spray devices

{ "type": "p", "children": [], "text": "Two (2) single-dose nasal spray devices" }

Dispense in this sealed carton

{ "type": "p", "children": [], "text": "Dispense in this sealed carton" }

NDC 82580-010-02 Rx Only

{ "type": "p", "children": [], "text": "NDC 82580-010-02 Rx Only" }

neffy® (epinephrine nasal spray) 1 mg

{ "type": "p", "children": [], "text": "neffy®\n(epinephrine nasal spray) 1 mg" }

For Use in the Nose Only (Single-dose) Read the Instructions for Use for complete information on how to use neffy.

{ "type": "p", "children": [], "text": "For Use in the Nose Only (Single-dose) Read the Instructions for Use for complete information on how to use neffy." }

Two (2) single-dose nasal spray devices

{ "type": "p", "children": [], "text": "Two (2) single-dose nasal spray devices" }