Basic Dental Emergency Kit Epinephrine, Albuterol Sulfate, Nitroglycerin, Diphenhydramine Hydrochloride, Aspirin Kit — NDC 83220-002-08 (Billing 83220-0002-08)
This is a package of Basic Dental Emergency Kit Epinephrine, Albuterol Sulfate, Nitroglycerin, Diphenhydramine Hydrochloride, Aspirin Kit from Best Dental Kit LLC, marketed since Jan 2023 and currently FDA-listed. It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 83220-002-08 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 83220 labeler · 002 product · 08 package
- Package marketed since
- Jan 30, 2023
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2026
- Barcode (UPC-A, from the NDC)
- 3 8322000208 6
- FDA record last changed
- Jul 24, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
- RxCUI (RxNorm): 198039
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Nitrate Vasodilator class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
This is a prescription kit intended for use in dental settings during medical emergencies. It contains epinephrine (used to treat severe allergic reactions and anaphylaxis), albuterol sulfate (typically used to relieve acute breathing difficulty), nitroglycerin (commonly used for chest pain related to heart conditions), diphenhydramine hydrochloride (typically used to reduce allergic reactions), and aspirin (commonly used for pain and heart-related symptoms). This product is marketed without an approved FDA application.
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 5, 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 83220-0002-08 You're viewing this Main listing | 1 KIT in 1 KIT * 25 TABLET in 1 BOTTLE * 1 POUCH in 1 BLISTER PACK / 2 TABLET in 1 POUCH * 1 mL in 1 VIAL * 10 TABLET, CHEWABLE in 1 BOTTLE, PLASTIC * 1 CANISTER in 1 CARTON / 200 AEROSOL, METERED in 1 CANISTER * 1 SYRINGE, GLASS in | 2023-01-30 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Deluxe Dental Emergency Kit 83220-0001-11 | Best | 25 tablets | — | — | FDA listed | — |
| Basic Dental Emergency Kitthis 83220-0002-08 | Best | 25 tablets | — | — | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
This is label-wide narrative text, not a normalized exact-product ingredient list. A label can cover multiple strengths or packages.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 5, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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Manufacturer & labeler
More NDCs from Best Dental Kit LLC labeler code 83220
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Epinephrine injection is indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which includes bees, wasps, hornets, yellow jackets and fire ants), and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media), and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. Epinephrine injection is intended for immediate administration in patients who are determined to be at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions.
Anaphylactic reactions may occur within minutes after exposure and consist of flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with a fall in blood pressure, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, wheezing, dyspnea due to laryngeal spasm, pruritus, rashes, urticaria, or angioedema. Epinephrine injection is intended for immediate administration as emergency supportive therapy only and is not a replacement or substitute for immediate medical care.
Epinephrine injection is a non-selective alpha and beta-adrenergic receptor agonist, indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis.
INDICATIONS AND USAGE Albuterol Sulfate Inhalation Aerosol is indicated in adults and children 4 years of age and older for the treatment or prevention of bronchospasm with reversible obstructive airway disease and for the prevention of exercise-induced bronchospasm.
1 INDICATIONS AND USAGE Nitroglycerin sublingual tablets are indicated for the acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease. Nitroglycerin sublingual tablets are nitrate vasodilator indicated for relief of an attack or prophylaxis of angina pectoris due to coronary artery disease. (1)
INDICATIONS AND USAGE Diphenhydramine Hydrochloride Injection is effective in adults and pediatric patients, other than premature infants and neonates, for the following conditions when the oral form is impractical: Antihistaminic For amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled and for other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.
Motion Sickness For active treatment of motion sickness. Antiparkinsonism For use in parkinsonism, when oral therapy is impossible or contraindicated, as follows: parkinsonism in the elderly who are unable to tolerate more potent agents, mild cases of parkinsonism in other age groups and in other cases of parkinsonism in combination with centrally acting anticholinergic agents.
Uses temporarily relieves minor aches and pains due to: headache muscle pain toothache menstrual pain colds minor pain of arthritis temporarily reduces fever
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Patients greater than or equal to 30 kg (66 lbs): 0.3 mg ( 2 ) Patients 15 to 30 kg (33 lbs-66 lbs): 0.15 mg ( 2 ) Inject intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Each device is a single-dose injection.
2.1Recommended Dosage According to Patient Body Weight Patients greater than or equal to 30 kg (approximately 66 pounds or more): 0.3 mg Patients 15 kg to 30 kg (33 pounds to 66 pounds): 0.15 mg
2.2Administration Instructions Inject the single-dose epinephrine injection intramuscularly or subcutaneously into the anterolateral aspect of the thigh, through clothing if necessary. Do not inject intravenously, and do not inject into buttocks, into digits, hands or feet [see Warnings and Precautions (5.2)]. Instruct caregivers of young children who are prescribed an epinephrine injection and who may be uncooperative and kick or move during an injection to hold the leg firmly in place and limit movement prior to and during an injection [see Warnings and Precautions (5.2)].
Each epinephrine injection is a single-dose of epinephrine injection for single use. Since the doses of epinephrine delivered from epinephrine injection are fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary. With severe persistent anaphylaxis, repeat injections with an additional epinephrine injection may be necessary.
More than two sequential doses of epinephrine should only be administered under direct medical supervision [see Warnings and Precautions (5.1)]. The epinephrine solution in the viewing window of epinephrine injection should be inspected visually for particulate matter and discoloration.
DOSAGE AND ADMINISTRATION For treatment of acute episodes of bronchospasm or prevention of asthmatic symptoms, the usual dosage for adults and children 4 years of age and older is two inhalations repeated every 4 to 6 hours. More frequent administration or a larger number of inhalations is not recommended. In some patients, one inhalation every 4 hours may be sufficient.
Each actuation of Albuterol Sulfate Inhalation Aerosol delivers 108 mcg of albuterol sulfate (equivalent to 90 mcg of albuterol base) from the mouthpiece. It is recommended to prime the inhaler before using for the first time and in cases where the inhaler has not been used for more than 2 weeks by releasing four “test sprays” into the air, away from the face. Exercise Induced Bronchospasm Prevention: The usual dosage for adults and children 4 years of age and older is two inhalations 15 to 30 minutes before exercise.
To maintain proper use of this product, it is important that the mouthpiece be washed and dried thoroughly at least once a week. The inhaler may cease to deliver medication if not properly cleaned and dried thoroughly (see PRECAUTIONS, Information for Patients section). Keeping the plastic mouthpiece clean is very important to prevent medication buildup and blockage.
The inhaler may cease to deliver medication if not properly cleaned and air dried thoroughly. If the mouthpiece becomes blocked, washing the mouthpiece will remove the blockage. If a previously effective dose regimen fails to provide the usual response, this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.
2 DOSAGE AND ADMINISTRATION Administer one tablet under the tongue or in the buccal pouch at the first sign of an acute anginal attack. Allow tablet to dissolve without swallowing. One additional tablet may be administered every 5 minutes until relief is obtained.
No more than three tablets are recommended within a 15-minute period. If the pain persists after a total of 3 tablets in a 15-minute period, or if the pain is different than is typically experienced, seek prompt medical attention. Nitroglyce… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 0.3 mg (0.3 mg/0.3 mL) of clear and colorless solution in single-dose pre-filled auto-injector Injection, 0.3 mg: 0.3 mg/0.3 mL epinephrine injection, USP, pre-filled auto-injector ( 3 )
3 DOSAGE FORMS AND STRENGTHS Nitroglycerin Sublingual Tablets, USP are supplied as white to off-white, round, flat-faced tablets in three strengths: 0.3 mg (Debossed with “1” on one side and “C” on the other) 0.4 mg (Debossed with “2” on one side and “C” on the other) 0.6 mg (Debossed with “3” on one side and “C” on the other) Sublingual tablets, 0.3 mg; 0.4 mg; 0.6 mg (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None.
CONTRAINDICATIONS Albuterol Sulfate Inhalation Aerosol is contraindicated in patients with a history of hypersensitivity to albuterol or any other Albuterol Sulfate Inhalation Aerosol components.
4 CONTRAINDICATIONS Use of phosphodiesterase type 5 (PDE-5) inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil, or soluble guanylate cyclase (sGC) stimulators. (4.1, 7.1) Severe anemia (4.2) Increased intracranial pressure (4.3) Hypersensitivity to nitroglycerin sublingual tablets or to other nitrates or nitrites or any excipient (4.4) Circulatory failure and shock (4.5)
4.1PDE-5-Inhibitors and sGC-Stimulators Do not use nitroglycerin sublingual tablets in patients who are taking PDE-5 Inhibitors, such as avanafil, sildenafil, tadalafil, vardenafil hydrochloride. Concomitant use can cause severe hypotension, syncope, or myocardial ischemia [see Drug Interactions (7.1)] . Do not use nitroglycerin sublingual tablets in patients who are taking the soluble guanylate cyclase stimulators, such as riociguat.
Concomitant use can cause hypotension.
4.2Severe Anemia Nitroglycerin sublingual tablets are contraindicated in patients with severe anemia (large doses of nitroglycerin may cause oxidation of hemoglobin to methemoglobin and could exacerbate anemia).
4.3Increased Intracranial Pressure Nitroglycerin sublingual tablets may precipitate or aggravate increased intracranial pressure and thus should not be used in patients with possible increased intracranial pressure (e.g., cerebral hemorrhage or traumatic brain injury).
4.4Hypersensitivity Nitroglycerin sublingual tablets are contraindicated in patients who are allergic to nitroglycerin, other nitrates or nitrites or any excipient.
4.5Circulatory Failure and Shock Nitroglycerin sublingual tablets are contraindicated in patients with acute circulatory failure or shock.
CONTRAINDICATIONS Use in Neonates or Premature Infants This drug should not be used in neonates or premature infants. Use in Nursing Mothers Because of the higher risk of antihistamines for infants generally, and for neonates and prematures in particular, antihistamine therapy is contraindicated in nursing mothers. Use as a Local Anesthetic Because of the risk of local necrosis, this drug should not be used as a local anesthetic.
Antihistamines are also Contraindicated in the Following Conditions Hypersensitivity to diphenhydramine hydrochloride and other antihistamines of similar chemical structure.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS In conjunction with use, seek immediate medical or hospital care. ( 5.1 ) Do not inject intravenously, into buttock, or into digits, hands, or feet. ( 5.2 ) To minimize the risk of injection related injury, hold the child’s leg firmly in place and limit movement prior to and during injection when administering to young children.
( 5.2 ) Rare cases of serious skin and soft tissue infections have been reported following epinephrine injection. Advise patients to seek medical care if they develop signs or symptoms of infection. ( 5.3 ) The presence of a sulfite in this product should not deter use.
( 5.4 ) Administer with caution in patients with heart disease; may aggravate angina pectoris or produce ventricular arrhythmias. ( 5.5 )
5.1Emergency Treatment Epinephrine injection is intended for immediate administration as emergency supportive therapy and is not intended as a substitute for immediate medical care. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. More than two sequential doses of epinephrine should only be administered under direct medical supervision [see Indications and Usage (1), Dosage and Administration (2) and Patient Counseling Information (17)].
5.2Injection-Related Complications Epinephrine injection should only be injected into the anterolateral aspect of the thigh [see Dosage and Administration (2) and Patient Counseling Information (17)] . Do not inject intravenously Large doses or accidental intravenous injection of epinephrine may result in cerebral hemorrhage due to a sharp rise in blood pressure. Rapidly acting vasodilators can counteract the marked pressor effects of epinephrine if there is such inadvertent administration.
Do not inject into buttock Injection into the buttock may not provide effective treatment of anaphylaxis. Advise the patient to go immediately to the nearest emergency room for further treatment of anaphylaxis. Additionally, injection into the buttock has been associated with the development of Clostridial infections (gas gangrene).
Cleansing with alcohol does not kill bacterial spores, and therefore, does not lower the risk. Do not inject into digits, hands or feet Since epinephrine is a strong vasoconstrictor, accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area. Advise the patient to go immediately to the nearest emergency room and to inform the healthcare provider in the emergency room of the location of the accidental injection.
Treatment of such inadvertent administration should consist of vasodilation, in addition to further appropriate treatment of anaphylaxis [see Adverse Reactions (6)]. Hold leg firmly during injection Lacerations, bent needles, and embedded needles have been reported when epinephrine has been injected into the thigh of young children who are uncooperative and kick or move during an injection. To minimize the risk of injection related injury when administering, hold the child’s leg firmly in place and limit movement prior to and during injection.
5.3Serious Infections at the Injection Site 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 epinephrine injection into the buttock [see Warnings and Precautions (5.2)] . 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.
5.4Allergic Reactions Associat… [Excerpted — this section continues on DailyMed.]
⚠️ Warnings ▾
WARNINGS Paradoxical Bronchospasm: Inhaled albuterol sulfate can produce paradoxical bronchospasm that may be life threatening. If paradoxical bronchospasm occurs, Albuterol Sulfate Inhalation Aerosol should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister.
Deterioration of Asthma: Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses of Albuterol Sulfate Inhalation Aerosol than usual, this may be a marker of destabilization of asthma and requires re-evaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids. Use of Anti-inflammatory Agents: The use of beta-adrenergic-agonist bronchodilators alone may not be adequate to control asthma in many patients.
Early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids, to the therapeutic regimen. Cardiovascular Effects: Albuterol Sulfate Inhalation Aerosol, like other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of Albuterol Sulfate Inhalation Aerosol at recommended doses, if they occur, the drug may need to be discontinued.
In addition, beta-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Albuterol Sulfate Inhalation Aerosol, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Do Not Exceed Recommended Dose: Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest following an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected. Immediate Hypersensitivity Reactions: Immediate hypersensitivity reactions may occur after administration of albuterol sulfate, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.
WARNINGS Antihistamines should be used with considerable caution in patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy or bladder-neck obstruction. Local necrosis has been associated with the use of subcutaneous or intradermal use of intravenous diphenhydramine. Use in Pediatric Patients In pediatric patients, especially, antihistamines in overdosage may cause hallucinations, convulsions or death.
As in adults, antihistamines may diminish mental alertness in pediatric patients. In the young pediatric patient, particularly, they may produce excitation. Use in the Elderly (approximately 60 years or older) Antihistamines are more likely to cause dizziness, sedation and hypotension in elderly patients.
Warnings Reye's syndrome: Children and teenagers who have or are recovering from chicken pox or flu-like symptoms should not use this product. When using this product, if changes in behavior with nausea and vomiting occur, consult a doctor because these symptoms could be an early sign of Reye's syndrome, a rare but serious illness. Allergy alert: Aspirin may cause a severe allergic reaction which may include: hives facial swelling asthma (wheezing) shock Stomach bleeding warning: This product contains an NSAID, which may cause severe stomach bleeding.
The chance is higher if you are age 60 or older have had stomach ulcers or bleeding problems take a blood thinning (anticoag… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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. Common adverse reactions to systemically administered epinephrine include anxiety; apprehensiveness; restlessness; tremor; weakness; dizziness; sweating; palpitations; pallor; nausea and vomiting; headache; and/or respiratory difficulties.
These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in patients with hypertension or hyperthyroidism [see Warnings and Precautions (5.5)] . Cardiovascular Reactions Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or those receiving certain drugs [see Warnings and Precautions (5.5) and Drug Interactions (7)] . Rapid rises in blood pressure have produced cerebral hemorrhage, particularly in elderly patients with cardiovascular disease [see Warnings and Precautions (5.5)] .
Angina may occur in patients with coronary artery disease [see Warnings and Precautions (5.5)] . Rare cases of stress cardiomyopathy have been reported in patients treated with epinephrine. Reactions from Accidental Injection and/or Improper Technique Accidental injection into the digits, hands or feet may result in loss of blood flow to the affected area [see Warnings and Precautions (5.2)] .
Adverse reactions experienced as a result of accidental injections may include increased heart rate, local reactions including injection site pallor, coldness and hypoesthesia or injury at the injection site resulting in bruising, bleeding, discoloration, erythema or skeletal injury. Lacerations, bent needles, and embedded needles have been reported when epinephrine injection has been injected into the thigh of young children who are uncooperative and kick or move during an injection [see Warnings and Precautions (5.2)] .
Injection into the buttock has resulted in cases of gas gangrene [see Warnings and Precautions (5.2)] . Skin and Soft Tissue Infections 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 (5.3)] . Adverse reactions to epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and/or respiratory difficulties.
To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
ADVERSE REACTIONS Adverse reaction information concerning Albuterol Sulfate Inhalation Aerosol is derived from a 12-week, double-blind, double-dummy study which compared Albuterol Sulfate Inhalation Aerosol, a CFC 11/12 propelled albuterol inhaler, and an HFA-134a placebo inhaler in 565 asthmatic patients. The following table lists the incidence of all adverse events (whether considered by the investigator drug related or unrelated to drug) from this study which occurred at a rate of 3% or greater in the Albuterol Sulfate Inhalation Aerosol treatment group and more frequently in the Albuterol Sulfate Inhalation Aerosol treatment group than in the placebo group.
Overall, the incidence and nature of the adverse reactions reported for Albuterol Sulfate Inhalation Aerosol and a CFC 11/12 propelled albuterol inhaler were comparable. Adverse Experience Incidences (% of patients) in a Large 12-week Clinical Trial* *This table includes all adverse events (whether considered by the investigator drug related or unrelated to drug) which occurred at an incidence rate of at least 3% in the Albuterol Sulfate Inhalation Aerosol group and more frequent… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Cardiac Glycosides, Diuretics, and Anti-arrhythmics 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 (5.5)] . Antidepressants, Monoamine Oxidase Inhibitors, Levothyroxine, and Antihistamines The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine.
Beta-Adrenergic Blockers The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta- adrenergic blocking drugs, such as propranolol. Alpha-Adrenergic Blockers The vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha-adrenergic blocking drugs, such as phentolamine. Ergot Alkaloids Ergot alkaloids may also reverse the pressor effects of epinephrine.
Cardiac glycosides or diuretics: observe for development of cardiac arrhythmias. ( 7 ) Tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines: potentiate effects of epinephrine. ( 7 ) Beta-adrenergic blocking drugs: antagonize cardiostimulating and bronchodilating effects of epinephrine.
( 7 ) Alpha-adrenergic blocking drugs: antagonize vasoconstricting and hypertensive effects of epinephrine. ( 7 ) Ergot alkaloids: may reverse the pressor effects of epinephrine. ( 7 )
Drug Interactions Beta-Blockers: Beta-adrenergic-receptor blocking agents not only block the pulmonary effect of beta-agonists, such as Albuterol Sulfate Inhalation Aerosol, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma.
In this setting, cardioselective beta-blockers should be considered, although they should be administered with caution. Diuretics: The ECG changes and/or hypokalemia which may result from the administration of nonpotassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with nonpotassium-sparing diuretics.
Albuterol-Digoxin: Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol and digoxin on a chronic basis is unclear; nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and albuterol.
Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: Albuterol Sulfate Inhalation Aerosol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of albuterol on the cardiovascular system may be potentiated.
7 DRUG INTERACTIONS Ergotamine: increased bioavailability of ergotamine. Avoid concomitant use. (7.2) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 10/2021
7.1PDE-5-Inhibitors and sGC-Stimulators Nitroglycerin sublingual tablets are contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE-5). PDE-5-Inhibitors such as avanafil, sildenafil, vardenafil, and tadalafil have be… [Excerpted — this section continues on DailyMed.]
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Elderly patients may be at greater risk of developing adverse reactions. ( 5.5 , 8.5 )
8.1Pregnancy Risk Summary There are no available human data on the use of epinephrine injection in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended daily subcutaneous or intramuscular dose on a mg/m 2 basis (see Data) . Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans.
Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and 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. Data Animal Data In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days).
These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day).
8.2Lactation Risk Summary There are no data on the presence of epinephrine in human milk, or the effects of epinephrine on the breastfed infant or on milk production. Epinephrine is the first line-medication of choice for treatment of anaphylaxis; it should be used in the same manner in breastfeeding and no-breastfeeding patients.
8.4Pediatric Use Epinephrine injection may be administered to pediatric patients at a dosage appropriate to body weight [see Dosage and Administration (2.1)] . 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. Since the dose of epinephrine delivered from epinephrine injection is fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary.
8.5Geriatric Use Clinical studies for the treatment of anaphylaxis have not been performed in subjects aged 65 and ov… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available human data on the use of epinephrine injection in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, epinephrine administered by the subcutaneous route to rabbits, mice, and hamsters during the period of organogenesis was teratogenic at doses 7 times and higher than the maximum recommended daily subcutaneous or intramuscular dose on a mg/m 2 basis (see Data) . Epinephrine is the first-line medication of choice for the treatment of anaphylaxis during pregnancy in humans.
Epinephrine should be used for treatment of anaphylaxis during pregnancy in the same manner as it is used in non-pregnant patients. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and 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. Data Animal Data In an embryofetal development study with rabbits dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including gastroschisis and embryonic lethality) at doses approximately 40 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for two to three days). In an embryofetal development study with mice dosed during the period of organogenesis, epinephrine was shown to be teratogenic (including embryonic lethality) at doses approximately 8 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days).
These effects were not seen in mice at approximately 4 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days). In an embryofetal development study with hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine was shown to be teratogenic at doses approximately 7 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day).
Pregnancy Teratogenic Effects Pregnancy Albuterol sulfate has been shown to be teratogenic in mice. A study in CD-1 mice given albuterol sulfate subcutaneously showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg (less than the maximum recommended daily inhalation dose for adults on a mg/m 2 basis) and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg (approximately 8 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis). The drug did not induce cleft palate formation at a dose of 0.025 mg/kg (less than the maximum recommended daily inhalation dose for adults on a mg/m 2 basis).
Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated subcutaneously with 2.5 mg/kg of isoproterenol (positive control). A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when albuterol sulfate was administered orally at 50 mg/kg dose (approximately 680 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis). In an inhalation reproduction study in SPRAGUE-DAWLEY rats, the a… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use Epinephrine injection may be administered to pediatric patients at a dosage appropriate to body weight [see Dosage and Administration (2.1)] . 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. Since the dose of epinephrine delivered from epinephrine injection is fixed, consider using other forms of injectable epinephrine if doses lower than 0.15 mg are deemed necessary.
Pediatrics The safety and effectiveness of Albuterol Sulfate Inhalation Aerosol in pediatric patients below the age of 4 years have not been established.
8.4Pediatric Use The safety and effectiveness of nitroglycerin in pediatric patients have not been established.
Pediatric Use Diphenhydramine should not be used in neonates and premature infants (see CONTRAINDICATIONS ). Diphenhydramine may diminish mental alertness, or in the young pediatric patient, cause excitation. Overdosage may cause hallucinations, convulsions or death (see WARNINGS and OVERDOSAGE ). See also DOSAGE AND ADMINISTRATION section.
🧓 Geriatric Use ▾
8.5Geriatric Use 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, epinephrine injection should be administered with caution in elderly individuals, who may be at greater risk for developing adverse reactions after epinephrine administration [see Warnings and Precautions (5.5) and Overdosage (10)] .
Geriatrics Albuterol Sulfate Inhalation Aerosol has not been studied in a geriatric population. As with other beta 2 -agonists, special caution should be observed when using Albuterol Sulfate Inhalation Aerosol in elderly patients who have concomitant cardiovascular disease that could be adversely affected by this class of drug.
8.5Geriatric Use Clinical studies of nitroglycerin sublingual tablets 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 ▾
10 OVERDOSAGE 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 vasodilators or alpha-adrenergic blocking drugs and/or respiratory support.
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, and kidney failure. Suitable corrective measures must be taken in such situations.
OVERDOSAGE The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed under ADVERSE REACTIONS , e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Albuterol Sulfate Inhalation Aerosol.
Treatment consists of discontinuation of Albuterol Sulfate Inhalation Aerosol together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Albuterol Sulfate Inhalation Aerosol.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg (approximately 6800 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis and approximately 3200 times the maximum recommended daily inhalation dose for children on a mg/m 2 basis). In mature rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/kg (approximately 3000 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis and approximately 1400 times the maximum recommended daily inhalation dose for children on a mg/m 2 basis).
In young rats, the subcutaneous median lethal dose is approximately 2000 mg/kg (approximately 14,000 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis and approximately 6400 times the maximum recommended daily inhalation dose for children on a mg/m 2 basis). The inhalation median lethal dose has not been determined in animals.
10 OVERDOSAGE
10.1Signs and Symptoms, Methemoglobinemia Nitrate overdosage may result in: severe hypotension, persistent throbbing headache, vertigo, palpitation, visual disturbance, flushing and perspiring skin (later becoming cold and cyanotic), nausea and vomiting (possibly with colic and even bloody diarrhea), syncope (especially in the upright posture), methemoglobinemia with cyanosis and anorexia, initial hyperpnea, dyspnea and slow breathing, slow pulse (dicrotic and intermittent), heart block, increased intracranial pressure with cerebral symptoms of confusion and moderate fever, paralysis and coma followed by clonic convulsions, and possibly death due to circulatory collapse.
Case reports of clinically significant methemoglobinemia are rare at conventional doses of organic nitrates. The formation of methemoglobin is dose-related and in the case of genetic abnormalities of hemoglobin that favor methemo… [Excerpted — this section continues on DailyMed.]
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Epinephrine acts on both alpha- and beta-adrenergic receptors.
12.2Pharmacodynamics 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.
When given intramuscularly or subcutaneously, epinephrine has a rapid onset and short duration of action.
CLINICAL PHARMACOLOGY Mechanism of Action In vitro studies and in vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta 2 -adrenergic receptors compared with isoproterenol. While it is recognized that beta 2 -adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there is a population of beta 2 -receptors in the human heart existing in a concentration between 10% and 50% of cardiac beta-adrenergic receptors. The precise function of these receptors has not been established.
(See WARNINGS, Cardiovascular Effects section.) Activation of beta 2 -adrenergic receptors on airway smooth muscle leads to the activation of adenylcyclase and to an increase in the intracellular concentration of cyclic-3',5'-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Albuterol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles.
Albuterol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway. Albuterol has been shown in most clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects.
Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes. Preclinical Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of the plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those in the whole brain.
Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta 2 -agonist and methylxanthines were administered concurrently. The clinical significance of these findings is unknown. Propellant HFA-134a is devoid of pharmacological activity except at very high doses in animals (380-1300 times the maximum human exposure based on comparisons of AUC values), primarily producing ataxia, tremors, dyspnea, or salivation.
These are similar to effects produced by the structurally related chlorofluorocarbons (CFCs), which have been used extensively in metered dose inhalers. In animals and humans, propellant HFA-134a was found to be rapidly… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Epinephrine acts on both alpha- and beta-adrenergic receptors.
Mechanism of Action In vitro studies and in vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta 2 -adrenergic receptors compared with isoproterenol. While it is recognized that beta 2 -adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there is a population of beta 2 -receptors in the human heart existing in a concentration between 10% and 50% of cardiac beta-adrenergic receptors. The precise function of these receptors has not been established.
(See WARNINGS, Cardiovascular Effects section.) Activation of beta 2 -adrenergic receptors on airway smooth muscle leads to the activation of adenylcyclase and to an increase in the intracellular concentration of cyclic-3',5'-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Albuterol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles.
Albuterol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway. Albuterol has been shown in most clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects.
Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes. Preclinical Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of the plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those in the whole brain.
Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta 2 -agonist and methylxanthines were administered concurrently. The clinical significance of these findings is unknown. Propellant HFA-134a is devoid of pharmacological activity except at very high doses in animals (380-1300 times the maximum human exposure based on comparisons of AUC values), primarily producing ataxia, tremors, dyspnea, or salivation.
These are similar to effects produced by the structurally related chlorofluorocarbons (CFCs), which have been used extensively in metered dose inhalers. In animals and humans, propellant HFA-134a was found to be rapidly absorbed and rapidly eliminated, with an elimination half-life of 3 to 27 minutes in animals and 5 to 7 minutes in humans. Time to maximum plasma concentration (Tmax) and mean residence time are both extremely short, leading to a transient appearance of HFA-134a in the blood with no evidence of accumulation.
12.1Mechanism of Action Nitroglycerin forms free radical nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and result in vasodilatation.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Storage and Handling Protect from light. Epinephrine is light sensitive and should be stored in the carrying-case provided to protect it from light. Store at room temperature (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].
Do not refrigerate. Before using, check to make sure the solution in the auto-injector is clear and colorless. Replace the auto-injector if the solution is discolored (pinkish or brown color), cloudy, or contains particles.
Properly dispose of all used, unwanted, or expired epinephrine injection, USP.
HOW SUPPLIED Albuterol Sulfate Inhalation Aerosol is supplied as a pressurized aluminum canister, with an attached dose indicator, a yellow plastic actuator and orange dust cap each in boxes of one. Each actuation delivers 120 mcg of albuterol sulfate from the valve and 108 mcg of albuterol sulfate from the mouthpiece (equivalent to 90 mcg of albuterol base). Canisters with a labeled net weight of 6.7 g contain 200 inhalations (NDC 0781-7296-85).
Rx only. Store between 15° to 25°C (59° to 77°F). Store the inhaler with the mouthpiece down.
For best results, canister should be at room temperature before use. SHAKE WELL BEFORE USING. The yellow actuator supplied with Albuterol Sulfate Inhalation Aerosol should not be used with any other product canisters, and actuator from other products should not be used with a Albuterol Sulfate Inhalation Aerosol canister.
The correct amount of medication in each canister cannot be assured after 200 actuations and when the dose indicator display window shows zero, even though the canister is not completely empty. The canister should be discarded when the labeled number of actuations have been used. WARNING: Avoid spraying in eyes.
Contents under pressure. Do not puncture or incinerate. Exposure to temperatures above 120°F may cause bursting.
Keep out of reach of children. Albuterol Sulfate Inhalation Aerosol does not contain chlorofluorocarbons (CFCs) as the propellant. Distributed by: Sandoz Inc.
Princeton, NJ 08540 Copyright © 1996, 2011, 2012, 2017, 2018, 2020 All rights reserved. The trademarks depicted in this piece are owned by their respective companies. Revised: 12/2020
16 HOW SUPPLIED/STORAGE AND HANDLING Nitroglycerin Sublingual Tablets, USP are supplied as white to off white, round, flat-faced tablets in 3 strengths (0.3 mg, 0.4 mg, and 0.6 mg) in bottles. Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Nitroglycerin should be kept in the original glass container and must be tightly capped after each use to prevent loss of tablet potency.
HOW SUPPLIED Diphenhydramine Hydrochloride Injection, USP 50 mg/mL Storage Protect from light. Keep covered in carton until time of use. Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Product Inquiry call 1-877-845-0689. Manufactured by: Hikma Pharmaceuticals USA Inc.
Berkeley Heights, NJ 07922 Revised December 2019
📦 Storage and Handling ▾
Storage Protect from light. Keep covered in carton until time of use. Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Product Inquiry call 1-877-845-0689. Manufactured by: Hikma Pharmaceuticals USA Inc.
Berkeley Heights, NJ 07922 Revised December 2019
Other information save carton for full directions and warnings store at room temperature
🧪 Active Ingredient ▾
Active ingredient (in each tablet) Aspirin 325 mg (NSAID) 1 1 nonsteroidal anti-inflammatory drug
🧪 Inactive Ingredients ▾
Inactive ingredients corn starch, hypromellose, powdered cellulose, triacetin
🎯 Purpose ▾
Purposes Pain reliever/fever reducer
📋 Description ▾
11 DESCRIPTION Epinephrine injection, USP 0.3 mg is an auto-injector and a combination product containing drug and device components. Each epinephrine injection, USP 0.3 mg delivers a single dose of 0.3 mg epinephrine from epinephrine injection, USP (0.3 mL) in a sterile solution. Epinephrine injection, USP 0.3 mg contain 1.1 mL of epinephrine solution.
0.3mL epinephrine solution is dispensed for epinephrine injection, USP 0.3 mg when activated. The solution remaining after activation is not available for future use and should be discarded. Each 0.3 mL in epinephrine injection, USP 0.3 mg contains 0.3 mg epinephrine, 2.6 mg sodium chloride, not more than 1.5 mg chlorobutanol, 0.45 mg sodium bisulfite, hydrochloric acid and sodium hydroxide to adjust pH, and water for injection.
The pH range is 2.2-5.0. Epinephrine is a sympathomimetic catecholamine. Chemically, epinephrine is (-)-3,4-Dihydroxy-α-[(methylamino)methyl]benzyl alcohol with the following structure: Epinephrine solution deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown from the formation of melanin.
Replace epinephrine injection, USP if the epinephrine solution appears discolored (pinkish or brown color), cloudy, or contains particles. Thoroughly review the patient instructions and operation of epinephrine injection, USP with patients and caregivers prior to use [see Patient Counseling Information ( 17 )] . epistr
DESCRIPTION The active component of Albuterol Sulfate Inhalation Aerosol is albuterol sulfate, USP racemic α 1 [( tert- Butylamino)methyl]-4-hydroxy- m -xylene-α,α'-diol sulfate (2:1)(salt), a relatively selective beta 2 -adrenergic bronchodilator having the following chemical structure: Albuterol sulfate is the official generic name in the United States. The World Health Organization recommended name for the drug is salbutamol sulfate. The molecular weight of albuterol sulfate is 576.7, and the empirical formula is (C 13 H 21 NO 3 ) 2 •H 2 SO 4 .
Albuterol sulfate is a white to off-white crystalline solid. It is soluble in water and slightly soluble in ethanol. Albuterol Sulfate Inhalation Aerosol is a pressurized metered-dose aerosol unit for oral inhalation.
It contains a microcrystalline suspension of albuterol sulfate in propellant HFA-134a (1,1,1,2-tetrafluoroethane), ethanol, and oleic acid. Each actuation delivers 120 mcg albuterol sulfate, USP from the valve and 108 mcg albuterol sulfate, USP from the mouthpiece (equivalent to 90 mcg of albuterol base from the mouthpiece). Each canister provides 200 inhalations.
It is recommended to prime the inhaler before using for the first time and in cases where the inhaler has not been used for more than 2 weeks by releasing four “test sprays” into the air, away from the face. This product does not contain chlorofluorocarbons (CFCs) as the propellant. Albutstr
11 DESCRIPTION Nitroglycerin Sublingual Tablets, USP are stabilized sublingual compressed nitroglycerin tablet that contains 0.3 mg, 0.4 mg, or 0.6 mg nitroglycerin; as well as calcium stearate, croscarmellose sodium, silica dimethyl silylate and lactose monohydrate. Nitroglycerin, an organic nitrate, is a vasodilating agent. The chemical name for nitroglycerin is 1, 2, 3 propanetriol trinitrate and the chemical structure is: Molecular weight: 227.09 g/mol Nitroglycrn1
DESCRIPTION Diphenhydramine Hydrochloride Injection is a sterile, nonpyrogenic solution for intravenous or deep intramuscular use as an antihistaminic agent. Each mL contains diphenhydramine hydrochloride 50 mg and benzethonium chloride 100 mcg in Water for Injection. pH 4.0-6.5; sodium hydroxide and/or hydrochloric acid added, if needed, for pH adjustment. The chemical name of diphenhydramine hydrochloride is 2-(Diphenylmethoxy)-N,N-dimethylethylamine hydrochloride.
The structural formula is as follows: C 17 H 21 NO • HCl MW 291.82 Diphenhydramine hydrochloride occurs as a white crystalline powder and is freely soluble in water a… [Excerpted — this section continues on DailyMed.]
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (Patient Information and Instructions for Use) A healthcare provider should review the patient instructions and operation of epinephrine injection, in detail, with the patient or caregiver. Epinephrine is essential for the treatment of anaphylaxis. Carefully instruct patients who are at risk of or with a history of severe allergic reactions (anaphylaxis) to insect stings or bites, foods, drugs, and other allergens, as well as idiopathic and exercise-induced anaphylaxis, about the circumstances under which epinephrine should be used.
Administration Instruct patients and/or caregivers in the appropriate use of epinephrine injection. Epinephrine injection should be injected into the middle of the outer thigh (through clothing if necessary). Instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during injection.
Lacerations, bent needles, and embedded needles have been reported when epinephrine injection has been injected into the thigh of young children who are uncooperative and kick during an injection [see Warnings and Precautions (5.2)] . Advise patients to seek immediate medical care in conjunction with administration of epinephrine injection. Complete patient information, including dosage, directions for proper administration and precautions can be found inside each epinephrine injection carton.
A printed label on the surface of epinephrine injection shows instructions for use and a diagram depicting the injection process. Training Instruct patients and/or caregivers to use the Trainer to familiarize themselves with the use of epinephrine injection in an allergic emergency. The Trainer may be used multiple times.
Adverse Reactions Epinephrine may produce symptoms and signs that include 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 signs and symptoms usually subside rapidly, especially with rest, quiet, and recumbency. Patients with hypertension or hyperthyroidism may develop more severe or persistent effects, and patients with coronary artery disease could experience angina.
Patients with diabetes may develop increased blood glucose levels following epinephrine administration. Patients with Parkinson’s disease may notice a temporary worsening of symptoms [see Warnings and Precautions (5.5)] . Accidental Injection Advise patients to seek immediate medical care in the case of accidental injection.
Since epinephrine is a strong vasoconstrictor when injected into the digits, hands or feet, treatment should be directed at vasodilation if there is such an accidental injection to these areas [see Warnings and Precautions (5.2)] . Serious Infections at the Injection Site Rare cases of 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 (5.3)] .
Pregnancy and Breastfeeding Inform patients that epinephrine injection has not been studied in pregnant women or breastfeeding mothers so the effects of epinephrine injection on pregnant women or breastfed infants are not known. Instruct patients to tell their healthcare provider if they are pregnant, become pregnant, or are thinking about becoming pregnant. Instruct patients to tell their healthcare provider if they plan to breastfeed their infant [see Use in Specific Populations (8.1, 8.2)] .
Storage and Handling Instruct patients to inspect the epinephrine solution visually through the viewing window periodically. Replace epinephri… [Excerpted — this section continues on DailyMed.]
📄 Keep Out of Reach of Children ▾
Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.
📄 Questions or Comments ▾
Questions? 1-800-331-4536 (Mon-Fri 9AM-5PM EST)
⚠️ Precautions ▾
PRECAUTIONS General Albuterol sulfate, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after use of any beta-adrenergic bronchodilator.
Large doses of intravenous albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-agonists, albuterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation.
Information for Patients See illustrated Patient's Instructions for Use . SHAKE WELL BEFORE USING. Patients should be given the following information: It is recommended to prime the inhaler before using for the first time and in cases where the inhaler has not been used for more than 2 weeks by releasing four “test sprays” into the air, away from the face.
KEEPING THE PLASTIC MOUTHPIECE CLEAN IS VERY IMPORTANT TO PREVENT MEDICATION BUILDUP AND BLOCKAGE. THE MOUTHPIECE SHOULD BE WASHED, SHAKEN TO REMOVE EXCESS WATER, AND AIR DRIED THOROUGHLY AT LEAST ONCE A WEEK. INHALER MAY CEASE TO DELIVER MEDICATION IF NOT PROPERLY CLEANED.
The mouthpiece should be cleaned (with the canister removed) by running warm water through the top and bottom for 30 seconds at least once a week. The mouthpiece must be shaken to remove excess water, then air dried thoroughly (such as overnight). Blockage from medication buildup or improper medication delivery may result from failure to thoroughly air dry the mouthpiece.
If the mouthpiece should become blocked (little or no medication coming out of the mouthpiece), the blockage may be removed by washing as described above. If it is necessary to use the inhaler before it is completely dry, shake off excess water, replace canister, test spray twice away from face, and take the prescribed dose. After such use, the mouthpiece should be rewashed and allowed to air dry thoroughly.
The action of Albuterol Sulfate Inhalation Aerosol should last up to 4 to 6 hours. Albuterol Sulfate Inhalation Aerosol should not be used more frequently than recommended. Do not increase the dose or frequency of doses of Albuterol Sulfate Inhalation Aerosol without consulting your physician.
If you find that treatment with Albuterol Sulfate Inhalation Aerosol becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, medical attention should be sought immediately. While you are taking Albuterol Sulfate Inhalation Aerosol, other inhaled drugs and asthma medications should be taken only as directed by your physician. Common adverse effects of treatment with inhaled albuterol include palpitations, chest pain, rapid heart rate, tremor, or nervousness.
If you are pregnant or nursing, contact your physician about use of Albuterol Sulfate Inhalation Aerosol. Effective and safe use of Albuterol Sulfate Inhalation Aerosol includes an understanding of the way that it should be administered. Use Albuterol Sulfate Inhalation Aerosol only with the actuator supplied with the product.
Discard the canister after 200 sprays have been used. In general, the technique for administering Albuterol Sulfate Inhalation Aerosol to children is similar to that for adults. Children should use Albuterol Sulfate Inhalation Aerosol under adult supervision, as instructed by the patient's physician.
( See Patient's Instructions for Use .) Drug Interactions Beta-Blockers: Beta-adrenergic-receptor blocking agents not only block the pulmonary effec… [Excerpted — this section continues on DailyMed.]
🍼 Nursing Mothers ▾
Nursing Mothers Plasma levels of albuterol sulfate and HFA-134a after inhaled therapeutic doses are very low in humans, but it is not known whether the components of Albuterol Sulfate Inhalation Aerosol are excreted in human milk. Because of the potential for tumorigenicity shown for albuterol in animal studies and lack of experience with the use of Albuterol Sulfate Inhalation Aerosol by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Caution should be exercised when albuterol sulfate is administered to a nursing woman.
🧬 Pharmacokinetics ▾
Pharmacokinetics In a single-dose bioavailability study which enrolled six healthy, male volunteers, transient low albuterol levels (close to the lower limit of quantitation) were observed after administration of two puffs from both Albuterol Sulfate Inhalation Aerosol and a CFC 11/12 propelled albuterol inhaler. No formal pharmacokinetic analyses were possible for either treatment, but systemic albuterol levels appeared similar. Clinical Trials In a 12-week, randomized, double-blind, double-dummy, active- and placebo-controlled trial, 565 patients with asthma were evaluated for the bronchodilator efficacy of Albuterol Sulfate Inhalation Aerosol (193 patients) in comparison to a CFC 11/12 propelled albuterol inhaler (186 patients) and an HFA-134a placebo inhaler (186 patients).
Serial FEV 1 measurements (shown below as percent change from test-day baseline) demonstrated that two inhalations of Albuterol Sulfate Inhalation Aerosol produced significantly greater improvement in pulmonary function than placebo and produced outcomes which were clinically comparable to a CFC 11/12 propelled albuterol inhaler. The mean time to onset of a 15% increase in FEV 1 was 6 minutes and the mean time to peak effect was 50 to 55 minutes. The mean duration of effect as measured by a 15% increase in FEV 1 was 3 hours.
In some patients, duration of effect was as long as 6 hours. In another clinical study in adults, two inhalations of Albuterol Sulfate Inhalation Aerosol taken 30 minutes before exercise prevented exercise-induced bronchospasm as demonstrated by the maintenance of FEV 1 within 80% of baseline values in the majority of patients. In a 4-week, randomized, open-label trial, 63 children, 4 to 11 years of age, with asthma were evaluated for the bronchodilator efficacy of Albuterol Sulfate Inhalation Aerosol (33 pediatric patients) in comparison to a CFC 11/12 propelled albuterol inhaler (30 pediatric patients).
Serial FEV 1 measurements as percent change from test-day baseline demonstrated that two inhalations of Albuterol Sulfate Inhalation Aerosol produced outcomes which were clinically comparable to a CFC 11/12 propelled albuterol inhaler. The mean time to onset of a 12% increase in FEV 1 for Albuterol Sulfate Inhalation Aerosol was 7 minutes and the mean time to peak effect was approximately 50 minutes. The mean duration of effect as measured by a 12% increase in FEV 1 was 2.3 hours.
In some pediatric patients, duration of effect was as long as 6 hours. In another clinical study in pediatric patients, two inhalations of Albuterol Sulfate Inhalation Aerosol taken 30 minutes before exercise provided comparable protection against exercise-induced bronchospasm as a CFC 11/12 propelled albuterol inhaler. Albut2
12.3Pharmacokinetics Absorption Nitroglycerin is rapidly absorbed following sublingual administration of nitroglycerin sublingual tablets. Mean peak nitroglycerin plasma concentrations occur at a mean time of approximately 6 to 7 minutes postdose (Table 1). Maximum plasma nitroglycerin concentrations (C max ) and area under the plasma concentration-time curves (AUC) increase dose-proportionally following 0.3 to 0.6 mg nitroglycerin.
The absolute bioavailability of nitroglycerin from nitroglycerin sublingual tablets is approximately 40% but tends to be variable due to factors influencing drug absorption, such as sublingual hydration and mucosal metabolism. Table 1 Mean Nitroglycerin (SD) Values 2 x 0.3 mg 1 x 0.6 mg Parameter Nitroglycerin Sublingual Tablets Nitroglycerin Sublingual Tablets C max , ng/mL 2.3 (1.7) 2.1 (1.5) T max , min 6.4 (2.5) 7.2 (3.2) AUC (0-∞) , min 14.9 (8.2) 14.9 (11.4) t ½ , min 2.8 (1.1) 2.6 (0.6) Distribution The volume of distribution (V Area ) of nitroglycerin following intravenous administration is
3.3L/kg. At plasma concentrations between 50 and 500 ng/mL, the binding of nitroglycerin to plasma proteins is approximately 60%, while that of 1,2- and 1,3-dinitroglycerin is 60% and 30%, respectively. Met… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics 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.
When given intramuscularly or subcutaneously, epinephrine has a rapid onset and short duration of action.
12.2Pharmacodynamics The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload).
Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear. Therapeutic doses of nitroglycerin may reduce systolic, diastolic, and mean arterial blood pressure. Effective coronary perfusion pressure is usually maintained, but can be compromised if blood pressure falls excessively, or increased heart rate decreases diastolic filling time.
Elevated central venous and pulmonary capillary wedge pressures, and pulmonary and systemic vascular resistance are also reduced by nitroglycerin therapy. Heart rate is usually slightly increased, presumably due to a compensatory response to the fall in blood pressure. Cardiac index may be increased, decreased, or unchanged.
Myocardial oxygen consumption or demand (as measured by the pressure-rate product, tension-time index, and stroke-work index) is decreased and a more favorable supply-demand ratio can be achieved. Patients with elevated left ventricular filling pressures and increased systemic vascular resistance in association with a depressed cardiac index are likely to experience an improvement in cardiac index. In contrast, when filling pressures and cardiac index are normal, cardiac index may be slightly reduced following nitroglycerin administration.
Consistent with the symptomatic relief of angina, digital plethysmography indicates that onset of the vasodilatory effect occurs approximately 1 to 3 minutes after sublingual nitroglycerin administration and reaches a maximum by 5 minutes postdose. Effects persist for at least 25 minutes following nitroglycerin administration.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility 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 under the conditions noted under [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 (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Animal carcinogenesis studies with sublingually administered nitroglycerin have not been performed. Carcinogenicity potential of nitroglycerin was evaluated in rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years. Rats developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes.
At high dose, the incidences of hepatocellular carcinomas in males was 48% and in females was 33%, compared to 0% in untreated controls. Incidences of testicular tumors were 52% vs. 8% in controls.
Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in mice. Nitroglycerin was mutagenic in Ames tests performed in 2 different laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with doses up to about 363 mg/kg/day, PO, or in ex vivo cytogenetic tests in rat and dog cells.
In a 3-generation reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for 6 months prior to mating of the F0 generation, with treatment continuing through successive F1 and F2 generations. The high dose was associated with decreased feed intake and body weight gain in both sexes at all matings. No specific effect on the fertility of the F0 generation was seen.
Infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the high-dose males. In this 3-generation study, there was no clear evidence of teratogenicity.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility 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 under the conditions noted under [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 (40-fold the highest human intramuscular or subcutaneous daily dose) during gestation days 3 to 9.
Carcinogenesis, Mutagenesis, and Impairment of Fertility In a 2-year study in SPRAGUE-DAWLEY ® rats, albuterol sulfate caused a dose-related increase in the incidence of benign leiomyomas of the mesovarium at the above dietary doses of 2 mg/kg (approximately 15 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis and approximately 6 times the maximum recommended daily inhalation dose for children on a mg/m 2 basis). In another study this effect was blocked by the coadministration of propranolol, a nonselective beta-adrenergic antagonist.
In an 18-month study in CD-1 mice, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 500 mg/kg (approximately 1700 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis and approximately 800 times the maximum recommended daily inhalation dose for children on a mg/m 2 basis). In a 22-month study in Golden Hamsters, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/kg (approximately 225 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis and approximately 110 times the maximum recommended daily inhalation dose for children on a mg/m 2 basis).
Albuterol sulfate was not mutagenic in the Ames test or a mutation test in yeast. Albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay. Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses up to 50 mg/kg (approximately 340 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis).
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Animal carcinogenesis studies with sublingually administered nitroglycerin have not been performed. Carcinogenicity potential of nitroglycerin was evaluated in rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years. Rats developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes.
At high dose, the incidences of hepatocellular carcinomas in males was 48% and in females was 33%, compared to 0% in untreated controls. Incidences of testicular tumors were 52% vs. 8% in controls.
Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in mice. Nitroglycerin was mutagenic in Ames tests performed in 2 different laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with doses up to about 363 mg/kg/day, PO, or in ex vivo cytogenetic tests in rat and dog cells.
In a 3-generation reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for 6 months prior to mating of the F0 generation, with treatment continuing through successive F1 and F2 generations. The high dose was associated with decreased feed intake and body weight gain in both sexes at all matings. No specific effect on the fertility of the F0 gene… [Excerpted — this section continues on DailyMed.]
📄 Patient Package Insert ▾
Patient Information EPINEPHRINE injection (ep-in-eph-rine), for intramuscular or subcutaneous use For allergic emergencies (anaphylaxis) Read this Patient Information leaflet carefully before you use epinephrine injection, and each time you get a refill. There may be new information. You, your parent, caregiver, or others who may be in a position to administer epinephrine injection 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. What is the most important information I should know about epinephrine injection? 1.
Epinephrine injection contains epinephrine, a medicine used to treat allergic emergencies (anaphylaxis). Anaphylaxis can be life-threatening, can happen within minutes, and can be caused by stinging and biting insects, allergy injections, foods, medicines, exercise, or other unknown causes. Symptoms of an anaphylaxis may include: trouble breathing wheezing hoarseness (changes in the way your voice sounds) hives (raised reddened rash that may itch) severe itching swelling of your face, lips, mouth, or tongue skin rash, redness, or swelling fast heartbeat weak pulse feeling very anxious confusion stomach pain losing control of urine or bowel movements (incontinence) diarrhea or stomach cramps dizziness, fainting, or “passing out” (unconsciousness) 2.
Always carry your epinephrine injection with you because you may not know when anaphylaxis may happen . Talk to your healthcare provider if you need additional units to keep at work, school, or other locations. Tell your family members, caregivers, and others where you keep your epinephrine injection and how to use it before you need it.
You may be unable to speak in an allergic emergency. 3. When you have an allergic emergency (anaphylaxis) Use epinephrine injection right away.
Get emergency medical help right away. You may need further medical attention. You may need to use a second epinephrine injection if symptoms continue or recur.
Only a healthcare provider should give additional doses of epinephrine if you need more than 2 injections for a single anaphylaxis episode. What is epinephrine injection? Epinephrine injection is a disposable, prefilled automatic injection device (auto-injector) used to treat life-threatening, allergic emergencies including anaphylaxis in people who are at risk for or have a history of serious allergic emergencies.
Each device contains a single dose of epinephrine. Epinephrine injection is for immediate self (or caregiver) administration and does not take the place of emergency medical care. You should get emergency medical help right away after using epinephrine injection.
Epinephrine injection is for people who have been prescribed this medicine by their healthcare provider. The epinephrine injection 0.3 mg auto-injector is for patients who weigh 66 pounds or more (30 kilograms or more). It is not known if epinephrine injection is safe and effective in children who weigh less than 33 pounds (15 kilograms).
Before using epinephrine injection, tell your healthcare provider about all your medical conditions, especially if you: have heart problems or high blood pressure have diabetes have thyroid problems have asthma have a history of depression have Parkinson's disease have any other medical conditions are pregnant or plan to become pregnant. It is not known if epinephrine will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if epinephrine passes into your breast milk.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Tell your healthcare provider of all known allergies. Especially tell your healthcare provider if you take certain asthma medicines.
Epinephrine injection and other medicines may affect each other, causing side effects. Epinephrine injection may affect t… [Excerpted — this section continues on DailyMed.]
📖 Instructions for Use ▾
Instructions for Use EPINEPHRINE injection (ep-in-eph-rine) for intramuscular or subcutaneous use For allergic emergencies (anaphylaxis) Read this Instructions for Use carefully before you use epinephrine injection and each time you get a refill. There may be new information. Before you need to use your epinephrine injection, make sure your healthcare provider shows you the right way to use it.
Parents, caregivers, and others who may be in a position to administer epinephrine injection should also understand how to use it well. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. If you have any questions, ask your healthcare provider.
Your epinephrine injection Step 1. Prepare epinephrine injection for injection Remove epinephrine injection from its protective carrying case. Pull off blue end caps.
You will now see a red tip. Grasp the epinephrine injection in your fist with the red tip pointing downward. See Figure A.
Note: The needle comes out of the red tip. To avoid an accidental injection, never put your thumb, fingers, or hand over the red tip. If an accidental injection happens, get medical help right away.
Step 2. Administer epinephrine injection If you are administering epinephrine injection to a young child, hold the leg firmly in place and limit movement prior to and while administering an injection. Put the red tip against the middle of the outer thigh (upper leg) at a 90° angle (perpendicular) to the thigh.
Press down hard and hold firmly against the thigh for approximately 10 seconds to deliver the medicine. See Figure B. Only inject into the middle of the outer thigh.
Do not inject into any other part of the body. Remove epinephrine injection from the thigh. Massage the area for 10 seconds.
Check the red tip. The injection is complete and you have received the correct dose of the medicine if you see the needle sticking out of the red tip. If you do not see the needle repeat Step 2.
Step 3. Get emergency medical help right away. You may need further medical attention.
You may need to use a second epinephrine injection if symptoms continue or recur. Step 4. After use Disposal Carefully cover the needle with the carrying case.
Lay the labeled half of the carrying case cover down on a flat surface. Use one hand to carefully slide the end of the epinephrine injection needle first, into the labeled carrying case cover. See Figure C.
After the needle is inside the labeled cover, push the unlabeled half of the carrying case cover firmly over the non-needle end of the epinephrine injection . See Figure D. Take your used epinephrine injection with you when you go to see a healthcare provider.
Tell the healthcare provider that you have received an injection of epinephrine. Show the healthcare provider where you received the injection. Give your used epinephrine injection to the healthcare provider for inspection and proper disposal.
Ask for a refill, if needed. Note: Epinephrine injection is a single-use injectable device that delivers a fixed dose of epinephrine. Epinephrine injection cannot be reused.
Do not attempt to reuse epinephrine injection after the device has been activated. It is normal for most of the medicine to remain in the auto-injector after the dose is injected. The correct dose has been administered if you see the needle sticking out of the red tip.
A separate epinephrine injection Trainer is available. The epinephrine injection Trainer has a beige color. The beige epinephrine injection Trainer contains no medicine and no needle.
Practice with your epinephrine injection Trainer, but always carry your real epinephrine injection in case of an allergic emergency. If you will be administering epinephrine injection to a young child, ask your healthcare provider to show you how to properly hold the leg in place while administering a dose. Do not try to take epinephrine injection.
For more information and video instructions on the use o… [Excerpted — this section continues on DailyMed.]
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