Intal CFC-free Inhaler

1. Name Of The Medicinal Product

Intal CFC-free Inhaler 5mg Pressurised Inhalation, Suspension

2. Qualitative And Quantitative Composition

The active component of Intal CFC-free is sodium cromoglicate 3.521% w/w. Each canister provides at least 112 actuations each containing 5 mg of sodium cromoglicate.

For excipients, see section 6.1.

3. Pharmaceutical Form

Intal CFC-free is presented as a metered dose inhaler, containing sodium cromoglicate as a suspension in a new non-CFC propellant, apaflurane (HFA-227), for inhalation. The product contains no chlorofluorocarbons (CFCs).

4. Clinical Particulars

4.1 Therapeutic Indications

Intal CFC-free is indicated for the preventative treatment of bronchial asthma, in adults and children.

4.2 Posology And Method Of Administration

Intal CFC-free is for oral inhalation use only. It is essential to instruct the patient how to use the inhaler correctly.

Adults and Children

The initial dose is two inhalations of the aerosol four times daily. Once adequate control of symptoms has been achieved it may be possible to reduce to a maintenance dose of one inhalation four times daily. However, the dose may be increased to two inhalations six or eight times daily in more severe cases or during periods of severe antigen challenge. An additional dose before exercise may also be taken.

Elderly

No current evidence for alteration of the recommended adult dose

Concomitant Bronchodilator Therapy

Where a concomitant aerosol bronchodilator is prescribed it is recommended that this be administered prior to Intal CFC-free.

Concomitant Steroid Therapy

In patients currently treated with steroids, the addition of Intal CFC-free to the regimen may make it possible to reduce the maintenance dose of steroids, or discontinue steroid therapy completely. The patient must be carefully supervised while the steroid dose is reduced; a rate of 10% weekly is suggested.

If reduction of a steroid dosage has been possible, Intal CFC-free should not be withdrawn until steroid cover has been reinstituted.

Method of Administration

If the inhaler is new, release 4 actuations prior to inhalation. If the inhaler has not been used for more than 3 days, release 2 actuations prior to inhalation.

The inhaler should be well shaken and the dustcap removed. The patient should be instructed to breathe in slowly and deeply and as inhalation begins the aerosol should be actuated by pressing the can down firmly with the first finger whilst continuing to breathe in. The breath should then be held for several seconds before exhaling into the air. To avoid condensation of moisture in the inhaler and blocking of the spray, exhalation through the inhaler should be avoided. The dustcap should be replaced following use. To prevent excessive accumulation of powder the plastic body and mouthpiece cover should be washed twice a week and then thoroughly dried. If the Fisonair holding chamber is used this should also should be washed twice a week and thoroughly dried.

Children and patients with difficulty in coordinating actuation of the inhaler with inhalation of the aerosol cloud, may benefit from using a holding chamber to assist inhalation of the medication. When using a holding chamber the procedure for inhalation is different from that with the standard mouthpiece or the Syncroner spacer device (in which the aerosol cloud is inhaled directly from the mouthpiece). The medication is first released into the holding chamber from which it is subsequently inhaled (in one or more breaths) until the chamber is empty. Thus, there is no need to coordinate actuation of the inhaler with simultaneous breathing, but the medication must be inhaled slowly and deeply from the holding chamber. The standard mouthpiece, but not the Syncroner pacer device, is suitable for use with a large volume holding chamber such as Fisonair.

Detailed instructions for the inhalation of Intal CFC-free from each of the three devices are provided in the respective Patient Information Leaflet supplied with each pack.

4.3 Contraindications

Intal CFC-free is contraindicated in patients with known hypersensitivity to sodium cromoglicate or to any of the other constituents.

4.4 Special Warnings And Precautions For Use

Intal CFC-free must not be used for relief of an acute attack of bronchospasm.

Since therapy is prophylactic, it is important that Intal CFC-free should be used regularly every day, in those patients who benefit, even if they become asymptomatic. The patient should also be advised that because several doses may be needed to establish benefit, relief may not be apparent immediately, but may take some weeks to develop.

Patients should have relief medication, such as an inhaled short-acting bronchodilator, available to relieve symptoms of acute asthma, and must be instructed to seek medical attention if their relief medication becomes less effective, or if more inhalations than usual are required to control symptoms.

In those cases where corticosteroid therapy has been reduced or discontinued, such therapy may need to be increased or reinstated if symptoms of asthma worsen - particularly during periods of stress, such as infection, illness, trauma, or severe antigen challenge. Alternative therapeutic management may also need to be considered.

Intal CFC-Free should be discontinued if eosinophilic pneumonia appears.

Withdrawal of INTAL CFC-free therapy

If it is necessary to withdraw this treatment, it should be done progressively over a period of one week. Symptoms of asthma may recur.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Sodium cromoglicate has been used for the treatment of a variety of indications in man for many years and no interactions with other drugs have been reported, nor are expected for sodium cromoglicate, due to its pharmacokinetic properties (no metabolism, moderate plasma protein binding, low plasma concentrations) and its high safety profile.

4.6 Pregnancy And Lactation

As with all medication, caution should be exercised especially during the first trimester of pregnancy. Although there is no information with the new HFA-227 formulation in human pregnancy cumulative clinical experience with sodium cromoglicate formulated with CFC propellants, suggests that the active ingredient sodium cromoglicate has no adverse effects on foetal development. In addition, both the new HFA-227 propellant and sodium cromoglicate have been separately shown to be free of adverse effects on the foetus in laboratory animals. It should only be used in pregnancy where there is a clear need.

It is not known whether sodium cromoglicate is excreted in human breast milk but on the basis of its physico-chemical properties this is considered unlikely. There is no evidence to suggest that the use of sodium cromoglicate has any undesirable effects on the baby, however, there is no experience to date with either the new HFA-227 propellant alone or formulated with sodium cromoglicate, during lactation in asthmatic patients. It should only be used in lactation where there is a clear need.

4.7 Effects On Ability To Drive And Use Machines

Intal CFC-free has no known effect on ability to drive or operate machinery.

4.8 Undesirable Effects

Mild throat irritation, coughing and transient bronchospasm may occur. Headache and rhinitis have also been reported in clinical trials of Intal CFC-free. Hypersensitivity reactions, including angioedema, bronchospasm, hypotension and collapse, have been reported extremely rarely, in patients using inhaled sodium cromoglicate.

As with other inhalation therapy, paradoxical bronchospasm may occur immediately after administration: in such cases immediate treatment with a fast-acting bronchodilator is required and immediate medical attention must be sought. Therapy with Intal CFC-free should be discontinued and alternative treatment instituted.

Very rare cases of eosinophilic pneumonia have been reported.

4.9 Overdose

Animal studies have shown that sodium cromoglicate has a very low local or systemic toxicity and extended human studies have not revealed any safety hazard with products containing sodium cromoglicate. Overdosage is therefore unlikely to cause problems, but, if suspected, treatment should be supportive and directed to the control of the relevant symptoms.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Sodium cromoglicate inhibits the activation of many of the cell types involved in the development and progression of asthma. Thus, sodium cromoglicate inhibits the release of inflammatory mediators including cytokines from mast cells and reduces the chemotactic activity of eosinophils and neutrophils. Activation of and mediator release from monocytes and macrophages in vitro is also reduced by sodium cromoglicate.

The diverse range of activities of the drug may be explained by the ability of sodium cromoglicate to block chloride channels in different cell types which are important in cell activation.

In acute bronchial provocation tests in humans, sodium cromoglicate has been shown to inhibit or diminish the asthmatic reaction to antigen, exercise and to a range of non-specific triggers including cold air, sulphur dioxide, hypertonic saline and bradykinin. Antigen-induced increased bronchial hyperactivity to histamine is prevented and a reduction in bronchial mucus eosinophils and antigen-specific IgE occurs after 4 weeks treatment of asthmatic subjects with sodium cromoglicate.

5.2 Pharmacokinetic Properties

ACT code: Antiallergic agents, excl. corticosteroids RO3BC01.

After inhalation in man via a metered dose inhaler approximately 10% of a dose of sodium cromoglicate is absorbed from the respiratory tract. The remainder is either exhaled or deposited in the oropharynx, or swallowed and eliminated via the alimentary tract, as only a small amount (1%) of the dose is absorbed from the gastrointestinal tract. The rate of absorption of sodium cromoglicate from the respiratory tract is slower than the elimination rate (t_½ of 1.5-2h). Hence, the drug remains effectively in the lungs to produce its local therapeutic effect and is then cleared rapidly from the systemic circulation. No substantial increase in plasma concentration occurs during repeated dose therapy.

Sodium cromoglicate is moderately and reversibly bound to plasma proteins (≈ 65%) and is not metabolised in humans. It is excreted unchanged in both urine and bile in approximately equal proportions.

5.3 Preclinical Safety Data

Pre-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Polyvidone K30

Polyethylene glycol (PEG) 600

Apaflurane (HFA 227 - a non ozone depleting propellant).

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

30 months.

6.4 Special Precautions For Storage

Do not refrigerate or freeze.

As the aerosol inhaler canister is pressurised it should be protected from heat or direct sunlight and should not be punctured or incinerated even when empty.

6.5 Nature And Contents Of Container

The aluminium can is fitted with a metering valve which delivers 112 actuations each containing 5 mg of sodium cromoglicate.

Intal CFC-free Inhaler: The cartoned pack consists of an aerosol canister and a plastic adaptor with a dustcap.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS, UK

8. Marketing Authorisation Number(S)

PL 04425/0179

9. Date Of First Authorisation/Renewal Of The Authorisation

23 May 2001

10. Date Of Revision Of The Text

27 September 2011

LEGAL CLASSIFICATION

POM