SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Pulvinal™ Salbutamol 200 micrograms/metered dose inhalation powder.

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each actuation provides salbutamol 200 micrograms (metered dose) or 188 micrograms as emitted dose.

For excipients, see 6.1.

3.    PHARMACEUTICAL FORM

Inhalation powder administered from a multidose powder inhaler.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Pulvinal Salbutamol is indicated in adults, adolescents and children aged 4 to 11 years.

Pulvinal Salbutamol is indicated for the relief of symptoms of asthma, bronchospasm and/or reversible airways obstruction and for the prevention of exercise and allergen induced asthma.

Pulvinal Salbutamol is particularly suitable for the relief of symptoms in mild, moderate and severe asthma.

The use of an inhaled p₂-agonist must not delay the introduction of regular inhaled corticosteroid therapy.

4.2    Posology and method of administration

Pulvinal Salbutamol is for inhalation use only.

Each inhalation of Pulvinal Salbutamol provides 200 micrograms of salbutamol.

For the relief of asthma symptoms, including acute bronchospasm, and for managing intermittent episodes of asthma, one inhalation should be administered.

Use of Pulvinal Salbutamol should not exceed four inhalations (i.e. 800 micrograms) in 24hours.

For prevention of exercise or allergen induced asthmatic symptoms, one inhalation should be taken 10-15 minutes before challenge.

There is no need to adjust the dosage in elderly patients.

Paediatric Population

Relief of acute bronchospasm

Children aged 4 to 11 years 200 micrograms as required.

Children aged 12 years and over: Dose as per adult population.

Prevention of allergen or exercise-induced bronchospasm

Children aged 4 to 11 years 200 micrograms before challenge or exertion Children aged 12 years and over: Dose as per adult population.

Chronic Therapy

Children aged 4 to 11 years 200 micrograms four times a day.

On-demand use of Pulvinal Salbutamol should not exceed four times daily. Reliance on such frequent supplementary use, or a sudden increase in dose, indicates poorly controlled or deteriorating asthma (see section 4.4).

Children aged 12 years and over: Dose as per adult population.

Instructions for use -

Do not remove the cap protecting the inhaler until the moment of use.

Unscrew the protective cap and before twisting the inhaler, hold it upright and tap it gently against a hard surface to level the powder in the chamber.

Holding the inhaler upright press the blue button on the mouth piece and rotate the inhaler body anti-clockwise until the red mark on the body shows through the hole in the mouthpiece (dose-loading position).

While still holding the inhaler upright, rotate the inhaler body clockwise until the green mark on the body shows through the hole in the mouthpiece (dose-delivery position).

Breathe out deeply. While still holding the inhaler upright put the mouthpiece between your lips and breathe in through your mouth. Hold your breath for a few seconds.

To obtain full therapeutic benefit, it is essential that the patient follows the instructions for use (see patient information leaflet) carefully.

4.3. Contra-indications

Pulvinal Salbutamol is contra-indicated in patients with a history of hypersensitivity to either salbutamol or lactose (see Section 4.4. below).

Inhaled salbutamol preparations are not appropriate in the management of premature labour and in threatened abortion.

4.4 Special warnings and precautions for use

The dosage and frequency of administration of inhaled salbutamol should only be increased on medical advice. If a previously effective dose of Pulvinal Salbutamol fails to provide relief lasting for a minimum of three hours, or in the event of increased use of the product, the patient should be advised to seek medical advice, as this may be indicative of deteriorating asthma. In situations where asthma control may appear to be deteriorating, patients should be reassessed and consideration given to increasing anti-inflammatory therapy. Patients with severe or unstable asthma are at risk of acute severe episodes and even death and should not be treated only or mainly with bronchodilators.

Such patients may require regular medical assessment, including lung function testing, and may require treatment with the maximum recommended dose of inhaled corticosteroids and/or with oral corticosteroids.

Severe exacerbations of asthma must be treated in the usual way.

Salbutamol should be administered cautiously in patients affected by thyrotoxicosis. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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.

As for other drugs administered by inhalation, paradoxical bronchospasm can arise. In this case, immediately stop the administration and institute a suitable therapy.

4.5 Interaction with other medicinal products and other forms of interaction

Salbutamol should not be administered together with non-selective P-blockers. Concomitant administration of xanthine derivatives, diuretics or steroids may lead to severe hypokalaemia; serum potassium levels should be monitored carefully in such cases.

Salbutamol should be cautiously used in subjects under therapy with monoamine oxidase inhibitors or tricyclic antidepressants due to the possible strengthened effects of salbutamol on the vascular system.

As with the majority of drugs, salbutamol should not be administered during the first three months of pregnancy. Further use of the product during pregnancy should be restricted to those situations where the expected therapeutic benefit to the mother outweighs any possible risk to the foetus.

In animal studies, administration of salbutamol at very high doses resulted in some harmful effects on the foetus.

Salbutamol is likely to be secreted in breast milk and its effect on breast-fed neonates is not known. Hence, the product should be used in lactation only where the expected benefit to the mother outweighs any potential risk to the neonate.

4.7. Effects on Ability to Drive and Use Machines

None

4.8 Undesirable effects

Adverse events are listed below by system class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1,000 and <1/100), rare (>1/10,000 and < 1/1,000), very rare (<1/10,000), unknown (frequency cannot be estimated from the available data).

System Organ Class	Adverse Reaction	Frequency
Immune System Disorders	Hypersensitivity (including angioedema, urticaria, bronchospasm, hypotension, and collapse)	Very Rare
Metabolism & Nutrition Disorders	Hypokalaemia	Rare
Psychiatric Disorders	Hyperactivity (in children)	Rare
	Nervousness	Unknown
Nervous System Disorders	Headache Dizziness	Common Unknown
Cardiac Disorders	Tachycardia (with or without peripheral vasodilation)	Rare

	Cardiac arrhythmia (including atrial flutter, supraventricular tachycardia and	Very rare
	extrasystole)	Uncommon
	Palpitation
	Myocardial Ischaemia (see section 4.4)	Unknown
Vascular Disorders	Peripheral vasodilation	Rare
Respiratory, Thoracic, & Mediastinal Disorders	Paradoxical bronchospasm	Very rare
Musculoskeletal & Connective Tissue	Muscle tremor (mainly dose related)	Common
Disorders	Muscle cramps	Rare

Patients sensitive to the inhalation of a dry powder may occasionally develop throat irritation and cough; this can be minimised by rinsing the mouth after inhalation.

Potentially serious hypokalaemia may result from beta₂ agonist therapy. This effect may be potentiated by hypoxia and therefore be worse in acute severe asthma. Particular caution is advised in severe asthma.

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.

4.9. Overdose

Administration of inhaled salbutamol exceeding the recommended dosage does not generally produce harmful effects; should accidental overdose occur, a cardioselective ^-blocking agent should be used, though P-blockers are to be administered with caution in patients with a history of bronchospasm.

As salbutamol overdose may cause hypokalaemia, serum potassium should be monitored.

Salbutamol is a selective P2-stimulant providing marked bronchodilatation, which lasts 4-6 hours. This activity makes this drug particularly suitable for the management of asthma and related diseases characterised by a bronchospastic component.

5.2. Pharmacokinetic Properties

Only 10 % of inhaled salbutamol is deposited in the airways and the remainder is retained in the delivery system or is swallowed. The swallowed portion is absorbed through the gut wall, and passed via the liver to the systemic circulation. Salbutamol is readily absorbed from the gastro-intestinal tract and undergoes an extensive presystemic metabolism. The major metabolite is the sulphate conjugate, which is inactive. Up to 80 % of the dose administered is recovered in the 24-hour urine, either unchanged or in the form of inactive metabolites. Salbutamol does not appear to be metabolised in the lung where it exerts a local action. In general, inhaled doses are lower than oral doses and blood levels are correspondingly smaller and associated with less severe nonrespiratory side effects.

5.3. Preclinical Safety Data

Subacute and chronic toxicity: (inhalation, rat, 6 weeks) no evidence of toxicity or significant histological changes for doses up to 3.3 mg/kg over a time of 3 hours daily; (inhalation, rat) doses up to 0.6 mg/kg for 6 months did not produce toxic effects; (inhalation, dog, 12 weeks) no signs of toxicity or histological changes were observed following daily administration of 0.15 mg/kg; (oral, rat, 17-18 weeks and 18 months) dose-related (1-50 mg/kg) increase in the incidence of Harderian gland hypertrophy and in the amount of colloid material in the Rathke's pouch area of the pituitary gland. Both glands are involved in the production of melanophore-stimulating hormone (MSH) which has been associated with stimulation of the P-adrenergic receptors.

Reproduction toxicity: (rat) reproduction studies at 0.5 - 50 mg/kg oral doses revealed no teratogenic and/or significant adverse effects with the exception of a decreased pup survival at highest dose; (rabbit) oral daily doses up to 100 mg/kg in pregnant rabbits did not reveal dysmorphogenic effects; (mouse) subcutaneous injections of 0.025 mg/kg or oral doses up to 10 mg/kg did not induce any teratogenic effect, at very high doses cleft palate formation was observed.

Mutagenicity and carcinogenicity: no mutagenic potential was found in “in vitro” tests and no carcinogenic effects were seen in mice; in rats at very high doses an increase of benign mesovarian leiomyomas was found, as an expression of the excessive P-blocker pharmacological activity.

PHARMACEUTICAL PARTICULARS

6.1. List of Excipient(s)

Lactose monohydrate.

6.2. Incompatibilities

Not applicable.

6.3. Shelf Life

24 months.

6.4. Special Precautions for Storage

Do not store above 30 °C. Keep the container tightly closed.

6.5. Nature and Contents of Container

Multidose dry powder inhaler (Pulvinal®) consisting of a pale blue mouthpiece, a transparent body-reservoir, a deep blue base containing a desiccant and a blue protective cap.

Pulvinal Salbutamol provides 100 metered doses.

6.6. Instruction for Use/Handling and Disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Chiesi Limited 333 Styal Road Manchester M22 5LG

United Kingdom

8.    MARKETING AUTHORISATION NUMBER(S)

PL 08829/0152

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

1 March 2004

10 DATE OF REVISION OF THE TEXT

27/08/2015