Adrenalina Labesfal

EpiPen® auto injectors are automatic injection devices containing Adrenalina Labesfal for allergic emergencies. The auto injectors should be used only by a person with a history or an acknowledged risk of an anaphylactic reaction. The auto injectors are indicated in the emergency treatment of allergic reactions (anaphylaxis) to insect stings or bites, foods, drugs and other allergens as well as idiopathic or exercise induced anaphylaxis. Such 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, diarrhoea and abdominal cramps, involuntary voiding, wheezing, dyspnoea due to laryngeal spasm, pruritus, rashes, urticaria or angioedema.

For these reasons auto injectors should always be carried by such persons in situations of potential risks.

Adrenalina Labesfal is considered the first line drug of choice for allergic emergencies. Adrenalina Labesfal effectively reverses the symptoms of rhinitis, urticaria, bronchospasm and hypotension because it is a pharmacological antagonist to the effects of the chemical mediators on smooth muscles, blood vessels and other tissues. Adrenalina Labesfal is recommended as the initial and primary therapeutic agent in the treatment of anaphylaxis by every recognised authority in allergy, and its appropriate use in these circumstances is widely documented in medical literature.

Posology:

The EpiPen® auto injector is for adult intramuscular administration.

It is designed for easy use by the lay person and has to be considered as first aid. EpiPen® auto injector delivers a single dose 0.3 ml injection equal to 0.3 mg Adrenalina Labesfal when activated. Usual Adrenalina Labesfal adult dose for allergic emergencies is 0.3 mg. For paediatric use, the appropriate dosage may be 0.15 mg or 0.30 mg depending upon the body weight of the patient (0.01 mg/kg body weight). However, the prescribing physician has the option of prescribing more or less than these amounts based on careful assessment of each individual patient and recognising the life-threatening nature of reactions for which this is being prescribed.

The physician should consider using other forms of injectable Adrenalina Labesfal if lower doses are felt to be necessary for small children.

An initial dose should be administered as soon as symptoms of anaphylaxis are recognised. In the absence of clinical improvement or if deterioration occurs after the initial treatment, a second injection with an additional EpiPen® auto injector may be administered 5 - 15 minutes after the first injection. It is recommended that patients are prescribed two EpiPen® auto injectors which they should carry at all times.

As EpiPen® auto injector is designed as emergency treatment only, the patient should be advised to always seek medical help immediately.

A physician who prescribes EpiPen® auto injector should take appropriate steps to ensure that the patient understands the indications and use of this device thoroughly. The physician should review with the patient, or any other person who might be in a position to administer EpiPen® auto injector to a patient experiencing anaphylaxis, in detail, the patient instructions and operation of the EpiPen® auto injector.

Method of administration:

Inject the delivered dose of the EpiPen® auto injector (0.3 ml equal to 0.3 mg) into the anterolateral aspect of the thigh, through clothing if necessary. See detailed instructions for use, point 6.6

The patient/carer should be informed that following each use of EpiPen® auto injector:

- They should call for immediate medical assistance, ask for an ambulance and state 'anaphylaxis' even if symptoms appear to be improving

- Conscious patients should preferably lie flat with feet elevated but sit up if they have breathing difficulties. Unconscious patients should be placed on their side in the recovery position.

- The patient should if possible remain with another person until medical assistance arrives.

There are no known absolute contraindications to the use of EpiPen® auto injector during an allergic emergency.5

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.

Adrenalina Labesfal is ordinarily administered with extreme caution to patients who have a heart disease. Adrenalina Labesfal 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 Adrenalina Labesfal 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, Adrenalina Labesfal may be associated with a transient worsening of Parkinson's symptoms such as rigidity and tremor.

Use of Adrenalina Labesfal 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 Adrenalina Labesfal 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 Adrenalina Labesfal 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 Adrenalina Labesfal 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 Adrenalina Labesfal.

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 Adrenalina Labesfal not reaching the muscle tissue resulting in a suboptimal effect.

The Adrenalina Labesfal 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 Adrenalina Labesfal 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, Adrenalina Labesfal 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 Adrenalina Labesfal.

Repeated dose toxicity studies were not performed in conjunction with this application. Side effects associated with Adrenalina Labesfal'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 Adrenalina Labesfal.

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)

* 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

Symptoms:

Overdose or inadvertent intravascular or intra-osseus injection of Adrenalina Labesfal 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 Adrenalina Labesfal 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 Adrenalina Labesfal 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.

Adrenalina Labesfal 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.

Pharmacotherapeutic group: Cardiac stimulants excluding cardiac glycosides, adrenergic and dopaminergic agents

ATC-code: C01CA24

Adrenalina Labesfal is one of the catecholamines which are a group of sympathomimetic amines containing a catechol moiety. Adrenalina Labesfal 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. Adrenalina Labesfal acts on both alpha and beta receptors and is the most potent alpha receptor activator.

The strong vasoconstrictor action of Adrenalina Labesfal 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. Adrenalina Labesfal through its action on beta receptors on bronchial smooth muscles causes bronchial smooth muscle relaxation which alleviates wheezing and dyspnoea. Adrenalina Labesfal also alleviates pruritus, urticaria and angioedema and may be effective in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis.

Adrenalina Labesfal 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 Adrenalina Labesfal is accounted for by excretion of metabolites in the urine.

According to Remington's Pharmaceutical Sciences, the plasma half-life of Adrenalina Labesfal 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.

Adrenalina Labesfal and its salts are rapidly destroyed in solution with oxidising agents. The solution darkens in colour upon exposure to air or light.

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 Adrenalina Labesfal:

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.