Adrenaclick

• Amedra Phramaceuticals LLC

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of epinephrine injection in children.

Geriatric

No information is available on the relationship of age to the effects of epinephrine injection in geriatric patients. However, elderly patients are more likely to have age-related heart disease which may require caution in patients receiving epinephrine injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Dihydroergotamine
• Isocarboxazid
• Linezolid
• Phenelzine
• Tranylcypromine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amitriptyline
• Amoxapine
• Bucindolol
• Carteolol
• Carvedilol
• Clomipramine
• Desipramine
• Digoxin
• Dilevalol
• Dothiepin
• Doxepin
• Entacapone
• Halothane
• Imipramine
• Iobenguane I 123
• Levalbuterol
• Levobunolol
• Lofepramine
• Metipranolol
• Nadolol
• Nortriptyline
• Opipramol
• Oxprenolol
• Penbutolol
• Pindolol
• Propranolol
• Protriptyline
• Rasagiline
• Sotalol
• Tertatolol
• Timolol
• Trimipramine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Labetalol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Angina pectoris (severe chest pain) or
• Asthma or
• Blood vessel problems or
• Depression, history of or
• Diabetes or
• Heart attack or
• Heart disease (eg, coronary artery disease, organic heart disease) or
• Heart rhythm problems (eg, arrhythmia) or
• Hypertension (high blood pressure) or
• Hyperthyroidism (overactive thyroid) or
• Parkinson's disease—Use with caution. May make these conditions worse.

Anaphylaxis is a life-threatening reaction and requires immediate medical attention. Check with your doctor right away, or go to an emergency room as soon as possible, even if you feel better after using this medicine.

Tell your doctor if you develop symptoms of an infection (such as redness that does not go away, swelling, warmth, or tenderness) at the injection site.

This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor.

Do not inject this medicine into your buttocks. Epinephrine may not work as well and may cause gas gangrene. Check with your doctor or go to the hospital emergency room right away to get additional treatment.

Do not inject this medicine into your hands or feet. There is already less blood flow to the hands and feet, and epinephrine could make that worse and cause damage to these tissues. If you accidentally inject epinephrine into your hands or feet, check with your doctor or go to the hospital emergency room right away.

This medicine may worsen the condition of patients with heart disease or heart rhythm problems. Check with your doctor right away if you have chest pain or tightness, decreased urine output, dilated neck veins, extreme fatigue, irregular heartbeat, swelling of the face, fingers, feet, or lower legs, troubled breathing, or weight gain. You might also feel dizzy or faint, or you might have a fast, pounding, or uneven heartbeat.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abnormal or decreased touch sensation
• anxiety
• arm, back, or jaw pain
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• blurred vision
• chest pain or discomfort
• chest tightness or heaviness
• cold, pale, or bluish color of the skin of the fingers or toes
• dizziness
• fainting
• fast, slow, irregular, pounding, or racing heartbeat or pulse
• fear or nervousness
• headache
• nausea or vomiting
• numbness, tingling, or pain in the fingers
• paleness of the skin
• pounding in the ears
• restlessness
• shakiness in the legs, arms, hands, or feet
• stroke
• sweating
• trembling or shaking of the hands or feet
• troubled breathing
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur:

• Agitation
• coldness of the skin
• coma
• confusion
• decreased awareness or responsiveness
• decreased urine output
• depression
• drowsiness
• hostility
• irritability
• lightheadedness, dizziness, fainting
• muscle twitching
• rapid weight gain
• rapid, deep breathing
• seizures
• severe sleepiness
• stomach cramps
• swelling of the face, ankles, or hands
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

None.

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)].

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)].

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 events 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 Adrenaclick 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)].

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)].

Applies to epinephrine: compounding powder, inhalation aerosol, inhalation solution, injectable kit, injectable solution, intravenous solution, subcutaneous suspension

General

Due to the lack of randomized, controlled clinical trials for the treatment of anaphylaxis, the true incidence of adverse reactions associated with the systemic use of this drug is difficult to determine. The most commonly reported adverse reactions include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and/or respiratory difficulties.[Ref]

Cardiovascular

Frequency not reported: Tachycardia, supraventricular tachycardia, ventricular arrhythmias, myocardial ischemia, myocardial infarction, limb/peripheral ischemia, palpitations, angina, arrhythmias, hypertension, vasoconstriction, ventricular ectopy, ventricular fibrillation, cold extremities, electrocardiogram changes, stress cardiomyopathy[Ref]

Nervous system

Frequency not reported: Headache, paresthesia, tremor, stroke, central nervous system bleeding, dizziness, cerebral hemorrhage, memory impaired, lightheadedness, psychomotor agitation, tingling, Parkinsonism aggravated, syncope, convulsions, subarachnoid hemorrhage, hemiplegia[Ref]

Psychiatric

Frequency not reported: Nervousness, excitability, anxiety, apprehension, restlessness, disorientation, panic, hallucinations, psychosis, fear, sleeplessness/insomnia, tenseness, confusion, irritability[Ref]

Local

Frequency not reported: Extravasation, injection site pallor, coldness at injection site, hypoesthesia at injection site, injury at injection site, local ischemic necrosis[Ref]

Dermatologic

Frequency not reported: Diaphoresis, pallor, piloerection, skin blanching, skin necrosis with extravasation, necrotizing fasciitis, flushing/redness of skin and face, hyperhidrosis[Ref]

Metabolic

Frequency not reported: Hypoglycemia, hyperglycemia, insulin resistance, hypokalemia, lactic acidosis, insulin secretion inhibited, metabolic acidosis, anorexia[Ref]

Respiratory

Frequency not reported: Pulmonary edema, rales, respiratory difficulty, dyspnea, bronchospasm, hypoxia of mucosa[Ref]

Renal

Frequency not reported: Renal insufficiency[Ref]

Hypersensitivity

Hypersensitivity side effects have been extremely unusual. Contact dermatitis has been associated with ocularly applied epinephrine (the active ingredient contained in Adrenaclick) These reactions have typically presented with lid edema and a thick yellow discharge.

Gastrointestinal

Frequency not reported: Nausea, vomiting, bowel necrosis, hypersalivation[Ref]

Genitourinary

Frequency not reported: Urinary retention, difficult micturition[Ref]

Hematologic

Frequency not reported: Thrombocytosis[Ref]

Musculoskeletal

Frequency not reported: Myonecrosis[Ref]

Other

Frequency not reported: Chest pain, weakness, gas gangrene, asthenia[Ref]

Ocular

Frequency not reported: Corneal endothelial damage[Ref]

Endocrine

Frequency not reported: Growth hormone secretion stimulated[Ref]

Some side effects of Adrenaclick may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Use only if the potential benefit justifies the potential risk to the fetus. AU TGA pregnancy category: A US FDA pregnancy category: C Comments: -Use with caution during labor and delivery; avoid use during second stage of labor. -Avoid use in obstetrics when maternal blood pressure exceeds 130/80 mmHg.

Animal studies have revealed evidence of teratogenicity at higher doses. Injection of this drug may also cause fetal tachycardia, cardiac irregularities, extrasystoles, and increased heart sounds. There are no controlled data in human pregnancy. Use with caution during labor and delivery; while this drug improves maternal hypotension associated with anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia. Use should be avoided during the second stage of labor as this drug may reduce uterine contractions and cause a prolonged period of uterine atony with hemorrhage. AU TGA pregnancy category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Substance Name

Epinephrine

CAS Registry Number

51-43-4

Drug Class

Adrenergic Agonists

Adrenergic alpha-Agonists

Adrenergic beta-Agonists

Antiglaucoma Agents

Bronchodilator Agents

Catecholamines

Mydriatics

Sympathomimetics

Vasoconstrictor Agents