SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Asmavent® CFC-free Inhaler 100 micrograms

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each metered dose (ex-valve) contains 100 micrograms salbutamol (as salbutamol sulphate).

Each delivered dose (ex-actuator) contains 80 micrograms salbutamol (as sulphate). Asmavent® contains (HFA 134A) and does not contain any chlorofluorocarbons For full list of excipients, see Section 6.1.

3    PHARMACEUTICAL FORM

Pressurised inhalation, suspension.

The inhaler comprises an aluminium canister fitted with a metering valve, which is inserted into a light blue standard plastic actuator fitted with a removable blue plastic mouthpiece cover, marked with “ASMAVENT”, “CFC-free”, “100”, “salbutamol” and “neolab”.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Asmavent® CFC-free Inhaler is indicated in the management of asthma, for the relief of asthma symptoms such as wheezing and shortness of breath, on an as required basis. Asmavent® CFC-free Inhaler should be used to relieve symptoms when they occur and to prevent symptoms in those circumstances recognised by the patient to precipitate an asthma attack, for example before exercise or unavoidable allergen exposure.

Asmavent® CFC-free Inhaler can be used for the relief of symptoms in mild, moderate or severe asthma providing that reliance on the inhaler does not delay the introduction and use of regular inhaled corticosteroid therapy.

Asmavent® CFC-free Inhaler may also be used in the treatment of the reversible component of airways obstruction.

4.2 Posology and method of administration

For inhalation use.

ADULTS (including the elderly): For the relief of acute asthma symptoms including bronchospasm and for the relief of wheezing, shortness of breath and attacks of acute dyspnoea, one inhalation (100 micrograms) may be administered as a single minimum starting dose. This may be increased to two inhalations if necessary.

To prevent exercise-induced or allergen-induced symptoms two inhalations should be taken 10-15 minutes prior to exercise or allergen exposure.

For chronic therapy, two inhalations up to four times a day.

CHILDREN: This product is not recommended for use in children 12 years of age and under.

For optimum results, Asmavent^® CFC-free Inhaler should be used as required.

For all patients, the maximum recommended dose, when Asmavent^® CFC-free Inhaler is used on demand as required for the relief of symptoms, should not exceed 8 inhalations in 24 hours. Each dose should not usually be repeated more often than every 4 hours. However reliance on such frequent supplementary use, or a sudden increase in dose, or if a dose appears to be less effective than usual, indicates poorly controlled or deteriorating asthma.

Asmavent CFC-free Inhaler cannot be used with any spacing device at this time. If a patient needs a spacing device an alternative product, which can be used with such a device, will need to be prescribed instead of Asmavent® CFC-free Inhaler.

Instructions for Use

1. The mouthpiece cover should be removed and the patient should check inside and outside to make sure that the mouthpiece is clean and that there is no dust, dirt or foreign objects. If it needs cleaning the instructions for cleaning outlined below should be followed. If the inhaler gets very cold, patients should be instructed to take the metal canister out of the plastic actuator and warm it in their hands for a few

minutes before use. Patients should never use anything else to warm it up. The inhaler should be shaken prior to use.

2.    The inhaler should be held upright with the thumb on the base, below the mouthpiece. Patients should breathe out as far as is comfortable and then....

3.    Immediately place the mouthpiece in the mouth between the teeth, and close their lips around it. Patients should be instructed to be careful not to bite the mouthpiece.

4.    Breathe in slowly. Just after starting to breathe in through the mouth, patients should press down on the top of the inhaler to release a spray, while still breathing in steadily and deeply.

5.    Patients should hold their breath, remove the inhaler from the mouth, and take their finger from the top of the inhaler. Patients should continue holding their breath for about 10 seconds, or as long as is comfortable, prior to breathing out slowly.

Patients should be instructed not to rush stages 3, 4 and 5.

It is important that patients breathe in as slowly as possible just before using the inhaler. Patients should be instructed to try practising in front of a mirror for the first few times. If patients see mist or spray coming from the inhaler or the sides of the mouth, they should start again from stage 2.

6.    If patients are to take another spray, they should keep the inhaler upright, and wait about half a minute before repeating steps 2 to 5.

7.    Once patients have finished using the inhaler, they should be instructed to always replace the mouthpiece cover to keep out dust and fluff and should make sure to replace the cover firmly and snap it into position.

People with weak hands may find it easier to operate the inhaler with both hands, by putting both forefingers on the top of the inhaler, and both thumbs on the bottom below the mouthpiece.

For detailed instructions for use, the patient should be referred to the Patient Information Leaflet included in each pack, with specific reference to the pictograms which accompany the instructions for use.

The inhaler should be cleaned at least once a week as described below, as it can become blocked, which will affect the way in which the inhaler works and will affect the amount of salbutamol which is inhaled.

1.    First remove the metal can from the plastic actuator and take off the mouthpiece cover.

2.    Rinse the plastic actuator, mouthpiece and mouthpiece cover in tap water; DO NOT place the metal can into water or clean the can using water. Make sure the water runs through the actuator from both ends to ensure that the actuator orifice is clear and not blocked.

3. The plastic components (actuator and mouthpiece cover) should be placed in a warm place to dry thoroughly before re-assembling the inhaler. Avoid drying near direct or excessive heat.

The patient should follow the cleaning instructions described in the Patient Information Leaflet carefully in order to ensure that the inhaler continues to work properly.

At first use of a new inhaler, or after a period when the inhaler has not been used (7 days or more), the inhaler should be shaken well and two sprays should be discharged prior to use, to prime the inhaler.

4.3 Contraindications

Hypersensitivity to the salbutamol or to any excipients listed in section 6.1.

Unlike intravenous salbutamol and occasionally salbutamol tablets, inhaled salbutamol is not suitable for the treatment of uncomplicated premature labour and should not be used to treat threatened abortion.

4.4 Special warnings and precautions for use

Patients’ inhaler technique should be checked to make sure that aerosol actuation is synchronised with inspiration of breath for optimum delivery of drug to the lungs. Patients should be warned that they may experience a different taste or feel on inhalation compared with their previous inhaler.

Bronchodilators are rarely the only or main treatment in patients with asthma and should not be the only or main treatment in patients with moderate, severe or unstable asthma. Asthma requires regular medical assessment, including pulmonary function tests, as patients with asthma are at risk of severe attacks and even death. If symptoms persist following the introduction of a short-acting bronchodilator consideration must be given to the need for inhaled and/or oral corticosteroid therapy. Consideration may need to be given to using maximum recommended doses of inhaled corticosteroids and/or oral corticosteroids in patients with more severe disease.

The dose or frequency of administration of salbutamol should only be increased on medical advice. If a previously effective dose of inhaled salbutamol fails to give relief lasting for at least three hours, the patient should be advised to seek medical advice.

Increasing use of bronchodilators, in particular short-acting inhaled p₂ agonists, to relieve symptoms, indicates deterioration of asthma control. The patient should be instructed to seek medical advice if short-acting relief bronchodilator treatment becomes less effective, or more inhalations than usual are required. In this situation the patient should be assessed and consideration given to the need for inhaled corticosteroids or an increase in the dose of anti-inflammatory therapy (e.g. an increase in the dose of inhaled corticosteroids or a course of oral corticosteroids).

Severe exacerbations of asthma must be treated in the normal way

Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with salbutamol. Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving salbutamol should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin

Salbutamol should be administered cautiously to patients with thyrotoxicosis.

Potentially serious hypokalaemia may result from p₂ agonist therapy, although mainly from parenteral and nebulised administration. Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids, diuretics and long-term laxatives. Serum potassium levels should be monitored in such situations.

Unwanted stimulation of cardiac adrenergic receptors can occur in patients taking P₂ agonist therapy.

4.5 Interaction with other medicinal products and other forms of interaction

Salbutamol and beta-blockers should not usually be prescribed together.

Hypokalaemia occurring with p₂ agonist therapy may be exacerbated by treatment with xanthines, steroids, diuretics and long-term laxatives.

Because Asmavent® CFC-free Inhaler contains ethanol there is a theoretical potential for interaction in patients taking disulfiram or metronidazole. The amount of ethanol is small but it may be enough to precipitate a reaction in some sensitive patients.

4.6 Fertility, pregnancy and lactation

Asmavent® CFC-free Inhaler

There is no experience of this product in pregnancy and lactation in humans. An inhalation reproductive study with a salbutamol sulphate CFC-free formulation in rats did not exhibit any teratogenic effects. It should not be used in pregnancy and lactation unless the expected benefit to the mother is thought to outweigh any risk to the fetus or neonate.

Propellant HFA 134a

Studies of propellant HFA 134a administered to pregnant and lactating rats and rabbits have not revealed any special hazard.

Salbutamol

Pregnancy

The safe use of inhaled salbutamol during pregnancy has not been established. However, in animal studies there was evidence of reproductive toxicity (some harmful effects on the fetus at very high dose levels). No controlled clinical trials with salbutamol have been conducted in pregnant women. Rare reports of various congenital anomalies following intrauterine exposure to salbutamol (including cleft palate, limb defects and cardiac disorders) have been received. Some of the mothers were taking multiple medications during their pregnancies. Ventolin Evohaler should not be used during pregnancy unless clearly necessary. In mice and rabbits large doses of salbutamol have been shown to be teratogenic.

Lactation

As salbutamol probably secreted in breast milk, the use of Asmavent® CFC-free Inhaler in mothers who are breast-feeding requires careful consideration. It is not known whether salbutamol has any harmful effects on the neonate, and so its use should be restricted to situations where it is felt that the expected benefit to the mother will outweigh any potential risk to the neonate.

Fertility

There is no information on the effects of salbutamol on human fertility. There were no adverse effects on fertility in animals (see section 5.3).

4.7 Effects on ability to drive and use machines

No studies on effects on the ability to drive and use machines have been performed. On the basis of the pharmacodynamic profile of salbutamol, and the lack of reported relevant adverse drug reactions, salbutamol has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common ( ^ 1/10), common ( ^ 1/100 and <1/10), uncommon 1/1000 and <1/100), rare 1/10,000 and <1/1000) and very rare (<1/10,000) including isolated reports. Very common and common events were generally determined from clinical trial data. Rare and very rare events were generally determined from spontaneous data.

Immune system disorders

Very rare: Hypersensitivity reactions including angioedema, urticaria, bronchospasm, hypotension and collapse.

Metabolism and nutrition disorders

Rare: Hypokalaemia. Potentially serious hypokalaemia may result from p₂ agonist therapy.

Nervous system disorders

Common: Fine skeletal muscle tremor most obviously affecting the hands, headache.

Very rare: Hyperactivity (in children).

Cardiac disorders

Common: Tachycardia with or without peripheral vasodilatation.

Uncommon: Palpitations,

Very rare: Cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles)

Unknown: Myocardial Ischaemia* Vascular disorders

Rare: Peripheral vasodilatation.

Respiratory, thoracic and mediastinal disorders

Very rare: Paradoxical bronchospasm. As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing. This should be treated immediately with an alternative presentation or a different fast-acting inhaled bronchodilator. Asmavent^® CFC-free Inhaler should be discontinued immediately, the patient should be assessed, and alternative therapy instituted, if necessary.

Gastrointestinal disorders Uncommon: Mouth and throat irritation.

Musculoskeletal and connective tissue disorders Uncommon: Muscle cramps.

* reported spontaneously in post-marketing data therefore frequency regarded as unknown

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, website www.mhra.gov.uk/yellowcard

4.9 Overdose

Overdosage may result in skeletal muscle tremor, tachycardia, tenseness, headache and peripheral vasodilatation. The preferred antidote for overdosage with salbutamol is a cardioselective P-blocking agent, but P-blocking drugs should be used with caution in patients with a history of bronchospasm.

Hypokalaemia may occur following overdose with salbutamol. Serum potassium levels should be monitored. Lactic acidosis has been reported in association with high therapeutic doses as well as overdoses of short-acting beta-agonist therapy, therefore monitoring for elevated serum lactate and consequent metabolic acidosis (particularly if there is persistence or worsening of tachypnea despite resolution of other signs of bronchospasm such as wheezing) may be indicated in the setting of overdose.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Selective p₂ adrenoceptor agonists.

ATC Code R03A C02.

At therapeutic doses it acts on the p₂-adrenoceptors of bronchial muscle providing short-acting (4-6 hour) bronchodilatation with a fast onset (within 5 minutes) in reversible airways obstruction.

5.2 Pharmacokinetic properties

Salbutamol administered intravenously has a half life of 4 to 6 hours and is cleared mainly via the renal route partly as unchanged drug and partly by metabolism to the inactive 4'-O-sulphate (phenolic sulphate) which is also excreted primarily in the urine. The faeces are a minor route of excretion.

After administration by the inhaled route between 10 and 20% of the dose reaches the lower airways. The remainder is retained in the delivery system or is deposited in the oropharynx from where it is swallowed. The fraction deposited in the airways is absorbed into the pulmonary tissues and circulation, but is not metabolised by the lung.

On reaching the systemic circulation it becomes accessible to hepatic metabolism and is excreted, primarily in the urine, as unchanged drug and as the phenolic sulphate.

The swallowed portion of an inhaled dose is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulphate. Both unchanged drug and conjugate are excreted primarily in the urine. Most of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours. Salbutamol is bound to plasma proteins to the extent of 10%.

5.3 Preclinical safety data Salbutamol

In common with other potent selective B₂ agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of fetuses were found to have cleft palate at 2.5mg/kg dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50mg/kg/day orally throughout pregnancy resulted in no significant fetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as the result of lack of maternal care. Reproductive studies in the rabbit at doses of 50mg/kg/day orally (i.e. much higher than the normal human dose) have shown fetuses with treatment related changes;

these included open eyelids (ablepharia), secondary palate clefts (palatoschisis), changes in ossification of the frontal bones of the cranium (cranioschisis) and limb flexure.

Propellant HFA 134a

In animal studies propellant HFA 134a has been shown to have no significant pharmacological effects other than at very high exposure concentrations, when narcosis and a relatively weak cardiac sensitising effect were found. The potency of the cardiac sensitisation was less than that of CFC-11 (trichlorofluoromethane).

In studies to detect toxicity, repeated high dose levels of propellant HFA 134a indicated that safety margins based on systemic exposure would be of the order 2200, 1314 and 381 for mouse, rat and dog with respect to humans.

There are no reasons to consider propellant HFA 134a as a potential mutagen, clastogen or carcinogen judged from in vitro and in vivo studies including long-term administration by inhalation in rodents.

Salbutamol sulphate - a CFC-free formulation

Safety studies with a salbutamol sulphate CFC-free formulation in rat and dog showed few adverse effects. These occurred at high doses and were consistent with the known effects of salbutamol inhalation.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Norflurane (HFA 134a) - this is a hydrofluoroalkane, non-chlorofluorocarbon (non-CFC) propellant; this product does not contain CFCs.

Ethanol Oleic Acid

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years.

6.4 Special precautions for storage

Do not store above 30°C.

The canister contains a pressurised liquid. Do not expose to temperatures higher than 50°C. Do not pierce the canister.

6.5 Nature and contents of container

An inhaler comprising an aluminium canister sealed with a metering valve, inserted into a polypropylene actuator with a polypropylene mouthpiece cover. Each canister contains 200 metered actuations.

6.6 Special precautions for disposal

As the canister is pressurised, it should not be punctured or disposed of by burning.

7 MARKETING AUTHORISATION HOLDER

Fannin (UK) Limited 42-46 Booth Drive Park Farm South Wellingborough Northamptonshire NN8 6GT UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 20417/0006

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

DATE OF REVISION OF THE TEXT

28/04/2014