Symptoms:
Overdose or inadvertent intravascular or intra-osseus injection of adrenaline may cause cerebral haemorrhage resulting from a sharp rise in blood pressure. Fatalities may also result from pulmonary oedema because of peripheral vascular constriction together with cardiac stimulation.
Management:
Pressor effects of adrenaline may be counteracted by rapidly acting vasodilators or alpha-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug, such as levarterenol.
If an adrenaline overdose induces pulmonary oedema that interferes with respiration, treatment consists of a rapidly acting alpha-adrenergic blocking drug such as phentolamine and/or intermittent positive-pressure respiration.
Adrenaline overdose can also cause transient bradycardia followed by tachycardia, and these may be accompanied by potentially fatal cardiac arrhythmias. Treatment of arrhythmias may consist of administration of beta-adrenergic blocking drugs.
The expiration period for EpiPen® auto injector is 20 months from the date of manufacture. The expiry date is indicated on the label and EpiPen® auto injector should not be used after this date. Replace the auto injector by expiration date or earlier if the solution is discoloured or contains a precipitate. Check the solution periodically through the viewing window of the unit to make sure the solution is clear and colourless.
Shelf life after opening: the EpiPen® auto injector must be discarded immediately after use.
There are no known absolute contraindications to the use of EpiPen® auto injector during an allergic emergency.5
Adrenaline and its salts are rapidly destroyed in solution with oxidising agents. The solution darkens in colour upon exposure to air or light.
Sodium chloride,
Sodium metabisulfite (E223),
Hydrochloric acid (for pH adjustment),
Water for injections
Repeated dose toxicity studies were not performed in conjunction with this application. Side effects associated with adrenaline's alpha and beta receptor activity may include palpitations, tachycardia, and hypertension as well as undesirable effects on the central nervous system, sweating, nausea and vomiting, respiratory difficulty, pallor, dizziness, weakness, tremor, headache, apprehension, nervousness and anxiety. Cardiac arrhythmias may follow administration of adrenaline.
Evaluation of undesirable effects is based on the following frequency information:
-Very common (>1/10)
-Common (>1/100 to < 1/10)
-Uncommon (>1/1 000 to < 1/100)
-Rare (>1/10 000 to < 1/1 000)
-Very rare (< 1/10 000)
-Not known (Frequency cannot be estimated from the available data)
|
Organ System |
Frequency |
Adverse drug reaction |
|
Infections and infestations |
Frequency not known |
Injection site infection * |
|
Psychiatric disorders |
Frequency not known |
Anxiety |
|
Nervous system disorders |
Frequency not known |
Headache, dizziness, tremor |
|
Cardiac disorders |
Rare |
Stress cardiomyopathy |
|
Frequency not known |
Tachycardia, cardiac arrhythmia | |
|
Vascular disorders |
Frequency not known |
Hypertension, peripheral ischaemia following accidental injection of the pens in hands or feet |
|
Gastrointestinal disorders |
Frequency not known |
Nausea, vomiting |
|
Skin and subcutaneous tissue disorders |
Frequency not known |
Hyperhidrosis |
|
General disorders and administration site condition |
Frequency not known |
Asthenia |
* rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene) are known from post-marketing experience
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Adrenaline has been utilised in the treatment of allergic emergencies for many years. No preclinical studies have been performed in connection with this application.
Pharmacotherapeutic group: Cardiac stimulants excluding cardiac glycosides, adrenergic and dopaminergic agents
ATC-code: C01CA24
Adrenaline is one of the catecholamines which are a group of sympathomimetic amines containing a catechol moiety. Adrenaline activates an adrenergic receptive mechanism on effector cells and imitates all actions of the sympathetic nervous system except those on the arteries of the face and sweat glands. Adrenaline acts on both alpha and beta receptors and is the most potent alpha receptor activator.
The strong vasoconstrictor action of adrenaline through its effect on alpha adrenergic receptors acts quickly to counter vasodilation and increased vascular permeability which can lead to loss of intravascular fluid volume and hypotension during anaphylactic reactions. Adrenaline through its action on beta receptors on bronchial smooth muscles causes bronchial smooth muscle relaxation which alleviates wheezing and dyspnoea. Adrenaline also alleviates pruritus, urticaria and angioedema and may be effective in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis.
Adrenaline is a naturally occurring substance produced by the adrenal medulla and secreted in response to exertion or stress. It is rapidly inactivated in the body mostly by the enzymes COMT and MAO. The liver is rich in these enzymes and is an important, although not essential, tissue in the degradation process. Much of the dose of adrenaline is accounted for by excretion of metabolites in the urine.
According to Remington's Pharmaceutical Sciences, the plasma half-life of adrenaline is about 2.5 min. However, by subcutaneous or intramuscular routes, local vasoconstriction retards absorption, so that the effects occur insidiously and last much longer than the half-life would predict.
March 2018
Mylan Products Ltd
Station Close
Potters Bar
Hertfordshire
EN6 1TL
United Kingdom
Adrenaline is sensitive to light. Keep the auto-injector in the outer carton
Do not store above 25 °C.
Do not refrigerate or freeze.
The immediate container/closure system consists of a glass cartridge sealed by a rubber plunger at one end and by a rubber diaphragm, which has been inserted into an aluminium hub with an attached stainless steel needle, at the other end. The glass cartridge contains the product.
The auto injector administration device:
Glass cartridge container:
Type I, borosilicate glass - complies with USP and Ph. Eur.
Diaphragm - Stopper:
PH 701/50/Black (butyl rubber plunger) - complies with USP and Ph. Eur.
Needle - Hub - Sheath:
Materials compatible with adrenaline injection.
Needle: Siliconised Type 304 stainless steel. The exposed needle length after activation is approximately 16 mm.
Hub: Anodized 3003 aluminium alloy
Sheath: Synthetic polyisoprene
The EpiPen® auto injector contains 2 ml of adrenaline injection 1 mg/ml in a prefilled disposable automatic injection device which is designed to deliver a single dose (0.3 ml) of 0.3 mg adrenaline when activated. After activation of the auto injector, 1.7 ml remains in the auto injector.
Pack sizes: 1 auto injector and 2 auto injectors.
PL 46302/0171
Adrenaline has been used for years in the treatment of allergic emergencies and its use is well documented in the literature. No clinical trials were performed in conjunction with this application.
Pregnancy:
Adrenaline should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Fertility:
As adrenaline is a substance that naturally occurs in the body, it is unlikely that this drug would have any detrimental effects on fertility.
All patients who are prescribed EpiPen® should be thoroughly instructed to understand the indications for use and the correct method of administration. It is strongly advised also to educate the patient's immediate associates (e.g. parents, caregivers, teachers) for the correct usage of EpiPen® in case support is needed in the emergency situation.
Adrenaline is ordinarily administered with extreme caution to patients who have a heart disease. Adrenaline should only be prescribed to those patients, and elderly individuals if the potential benefit justifies the potential risk.
There is a risk of adverse reactions following adrenaline administration in patients with high intraocular pressure, severe renal impairment, prostatic adenoma leading to residual urine, hypercalcaemia and hypokalaemia. In patients with Parkinson's disease, adrenaline may be associated with a transient worsening of Parkinson's symptoms such as rigidity and tremor.
Use of adrenaline with drugs that may sensitise the heart to arrhythmias, e.g., digitalis, mercurial diuretics, or quinidine, ordinarily is not recommended. Anginal pain may be induced by adrenaline in patients with coronary insufficiency.
Hyperthyroid individuals (hyperfunction of the thyroid gland), individuals with cardiovascular disease, hypertension (raised blood pressure), or diabetes, elderly individuals, pregnant women, and children under 25 kg body weight using EpiPen® auto injector may theoretically be at greater risk of developing adverse reactions after adrenaline administration.
Accidental injection into the hands or feet may result in loss of blood flow to the affected area and should be avoided. If there is an accidental injection into these areas, advise the patient to go immediately to the nearest emergency room or hospital casualty department for treatment.
The patient should be instructed to check the contents of the glass cartridge in the auto injector periodically through the viewing window of the unit to make sure the solution is clear and colourless. The auto injector should be discarded if discoloured or contains a precipitate. For emergency treatment use of an EpiPen® auto injector with discoloured contents may be recommended rather than to postpone the treatment.
The auto injectors should ONLY be injected into the anterolateral aspect of the thigh. Patients should be advised NOT to inject into the buttock. Large doses or accidental intravenous injection of adrenaline may result in cerebral haemorrhage due to sharp rise in blood pressure. Directions for proper use of the auto injectors must be followed in order to avoid intravenous injection. Rapidly acting vasodilators can counteract the marked pressor-effects of adrenaline.
In case of injection performed by a caregiver, immobilization of the patient's leg should be ensured during injection to minimize the risk of injection site laceration.
The needle should never be reinserted after use.
In patients with a thick subcutaneous fat layer, there is risk for adrenaline not reaching the muscle tissue resulting in a suboptimal effect.
The adrenaline solution contains sodium metabisulfite, a sulfite that may in other products cause allergic-type reactions including anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons. The alternatives to using adrenaline in a life-threatening situation may not be satisfactory. The presence of a sulfite in this product should not deter administration of the drug for treatment of serious allergic or other emergency situations.
Despite these concerns, adrenaline is essentially for the treatment of anaphylaxis. Therefore, patients with these conditions, and/or any other person who might be in a position to administer EpiPen® auto injector to a patient experiencing anaphylaxis should be carefully instructed in regard to the circumstances under which this life-saving medication should be used.
The patient/carer should be informed about the possibility of biphasic anaphylaxis which is characterised by initial resolution followed by recurrence of symptoms some hours later.
Patients with concomitant asthma may be at increased risk of severe anaphylactic reaction.
Patients should be warned regarding related allergens and should be investigated whenever possible so that their specific allergens can be characterised.
This medicinal product contains less than 1 mmol (23mg) per dose, i.e. essentially 'sodium-free'.
The patient's ability to drive and use machines may be affected by the anaphylactic reaction as well as by possible adverse reactions to adrenaline.
Do not remove blue safety cap until ready for use.
The EpiPen® auto injector should be used on the outer thigh. The injection is activated immediately once the orange end of the EpiPen® auto injector comes into contact with any skin or other surface.
The EpiPen® auto injector's are designed for easy use by the lay person and has to be considered as a first aid. The EpiPen® auto injector should simply be jabbed firmly against the outer portion of the thigh from a distance of approximately 10 cm. There is no need for more precise placement in the outer portion of the thigh. When EpiPen® auto injector is jabbed against the thigh, it releases a spring activated plunger, pushing a concealed needle into the thigh muscle and expelling a dose of adrenaline:
1. Grasp EpiPen® auto injector in dominant hand, with thumb closest to blue safety cap.
2. With the other hand pull off blue safety cap.
3. Hold the EpiPen® auto injector at a distance of approximately 10 cm away from the outer thigh. The orange tip should point towards the outer thigh.
4. Jab firmly into the outer thigh, so that the EpiPen® auto injector is at a right-angle (at a 90 degree angle) to the outer thigh.
5. Hold firmly in place for 3 seconds. The injection is now complete and the window of the auto injector is obscured. The EpiPen® auto injector should be removed (the orange needle cover will extend to cover needle) and safely discarded.
A small bubble may occur in the EpiPen® auto injector. It has no influence on either the use or the efficacy of the product.
28 March 1996
Caution is indicated in patients receiving drugs that may sensitise the heart to arrhythmias, including digitalis, mercurial diuretics or quinidine. The effects of adrenaline may be potentiated by tricyclic antidepressants and mono amine oxidase inhibitors (MAO-inhibitors) and catechol-O-methyl transferase inhibitors (COMT-inhibitors), thyroid hormones, theophylline, oxytocin, parasympatholytics, certain antihistamines (diphenhydramine, chlorpheniramine), levodopa and alcohol.
Pressor effects of adrenaline may be counteracted by rapidly acting vasodilators or alpha-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug, such as levarterenol.
Adrenaline inhibits the secretion of insulin, thus increasing the blood glucose level. It may be necessary for diabetic patients receiving adrenaline to increase their dosage of insulin or oral hypoglycaemic drugs.
The β-stimulating effect can be inhibited by simultaneous treatment with β-blocking drugs
