This information is intended for use by health professionals

1. Name of the medicinal product

Tilade CFC-Free Inhaler 2mg per actuation pressurised inhalation suspension

2. Qualitative and quantitative composition

One metered dose (ex-valve) contains 2 mg nedocromil sodium.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Pressurised inhalation suspension.

Tilade CFC-Free Inhaler/Syncroner/Fisonair contains a new propellant, HFA-227, and does not contain any chlorofluorocarbons (CFCs).

4. Clinical particulars
4.1 Therapeutic indications

Tilade CFC-Free is recommended for the treatment of bronchial asthma where regular preventative anti-inflammatory therapy is indicated and, in particular, in patients whose asthma is not adequately controlled by bronchodilators alone. Tilade CFC-Free may be given in addition to all existing therapies and in many cases will provide added therapeutic benefit.

4.2 Posology and method of administration

Posology

For inhalation use.

Adults, including the elderly and children over 6 years of age.

The initial dose is 4 mg (2 actuations) four times daily. Once control of symptoms has been achieved it may be possible to reduce the dose to a maintenance dose of 4mg (2 actuations) twice daily.

Tilade CFC-Free is intended for regular daily use and should not be used for the relief of symptoms in an acute attack.

Tilade CFC-Free is not recommended for use in children 6 years of age and younger.

Concomitant Bronchodilator Therapy

Where a concomitant inhaled bronchodilator is prescribed it is recommended that this be administered prior to Tilade CFC-Free.

Concomitant Steroid Therapy

In patients currently treated with steroids, the addition of Tilade 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If a reduction of a steroid dose has been possible, Tilade CFC-Free should not be withdrawn until steroid cover has been re-instituted.

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 mouthpiece of the inhaler should be placed in the mouth and the lips closed around it prior to the patient beginning to breathe in. The patient should then be instructed to breathe in slowly and deeply through the mouth 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 10 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. If the patient needs two actuations they should be instructed to wait for about one minute before repeating the inhalation procedure. The dustcap should be replaced following use. To prevent excessive accumulation of powder the plastic body and mouthpiece cover should be rinsed in hand hot water twice a week and then thoroughly dried. If the Fisonair holding chamber is used this also should be washed in hand hot water 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 through 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 co-ordinate actuation of the inhaler with simultaneous breathing. However medication must still be inhaled slowly and deeply from the holding chamber. The standard mouthpiece, but not the Syncroner spacer device, is suitable for use with large volume holding chambers such as Fisonair.

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

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Tilade CFC-Free must not be used for the relief of an acute attack of bronchospasm.

Since therapy is prophylactic, it is important that Tilade CFC-Free 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 be advised to have relief medication available (such as an inhaled short-acting bronchodilator) 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 be re-instated if symptoms of asthma worsen - particularly during periods of stress, such as infection, illness, trauma, severe antigen challenge. Alternative therapeutic management may also need to be considered.

Withdrawal of Tilade 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 reoccur.

4.5 Interaction with other medicinal products and other forms of interaction

Nedocromil sodium has been used in association with numerous other drugs in man, including oral and inhaled β-adrenergic agonists, inhaled and oral corticosteroids, theophylline and other methylxanthines and ipratropium bromide. No harmful interactions have been observed in humans or animals.

4.6 Fertility, pregnancy and lactation

Administration of drugs during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.

Studies in pregnant and lactating animals have failed to reveal a hazard with nedocromil sodium. However, as with all new medicines, caution should be exercised during pregnancy (especially during the first trimester) and while breast feeding.

Pregnancy

There is no information on the use of nedocromil sodium formulated with propellant HFA-227 or with propellant HFA-227 alone in human pregnancy. However studies of HFA-227 administered to pregnant and lactating animals have not revealed any special risk and cumulative clinical experience with nedocromil sodium formulated with CFC propellants would suggest that nedocromil sodium has no adverse effects on fetal development. Nedocromil sodium formulated with propellant HFA-227 (in Tilade CFC-Free) should only be used in pregnancy where there is a clear need.

Breast-feeding

On the basis of animal studies and its physicochemical properties it is considered that only negligible amounts of nedocromil sodium may pass into human breast milk. There is no evidence to suggest that the use of nedocromil sodium during breast-feeding has any undesirable effects on the baby. However there is no experience to date with nedocromil sodium formulated with propellant HFA-227 or with propellant HFA-227 alone during lactation in female patients with asthma. Nedocromil sodium formulated with propellant HFA-227 (as in Tilade CFC-Free) should only be used in lactation where there is a clear need and its use should be restricted to those situations where it is felt that the expected benefit to the mother is likely to outweigh any potential risk to the neonate.

4.7 Effects on ability to drive and use machines

Tilade CFC Free has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The following CIOMS frequency rating is used, when applicable:

Very common ≥ 10 %; Common ≥ 1 % and < 10 %;

Uncommon ≥ 0.1 % and < 1 %; Rare ≥ 0.01 % and < 0.1 %;

Very rare < 0.01%; Unknown (cannot be estimated from available data);

In clinical studies conducted in patients treated with nedocromil sodium metered dose inhaler, the following adverse events have been reported at the corresponding frequencies:

System organ class

Very common

(≥ 10 %)

Common

(≥ 1 % and < 10 % )

Frequency not known (cannot be estimated from available data)

Gastrointestinal disorders

Abdominal pain, vomiting, nausea

Dyspepsia

Respiratory, thoracic and mediastinal disorders

Cough, bronchospasm

Throat irritation, pharyngitis

Nervous system disorders

Headache

Dysgeusia

As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing, dyspnoea and/or tightness in the chest following administration. This requires immediate treatment with a fast-acting inhaled bronchodilator and immediate medical attention must be sought straightaway. Therapy with Tilade CFC-Free should be discontinued immediately and alternative treatment instituted.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Animal studies have not shown evidence of significant toxic effects with nedocromil sodium even at high doses, nor have extended human studies with nedocromil sodium revealed any safety hazard with the drug.

Overdosage is therefore unlikely to cause problems. However, if overdosage is suspected, treatment should be supportive and directed to the control of the relevant symptoms.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Tilade CFC-Free contains nedocromil sodium, a non-steroidal agent, which has anti-inflammatory properties when administered topically in the lung. In-vivo, ex-vivo and in-vitro studies have shown that nedocromil sodium has beneficial effects on cellular, humoral and neuronal mechanisms thought to be involved in the inflammation of bronchial asthma. In the treatment of bronchial asthma, nedocromil sodium reduces bronchospasm, cough and bronchial hyperreactivity and improves objective measurements of lung function.

5.2 Pharmacokinetic properties

Absorption

After inhalation of nedocromil sodium (in common with other drugs inhaled using an MDI) a small fraction (generally 10%) reaches the lungs, while a major portion of the dose is deposited in the mouth or oropharynx and swallowed. The oral absorption of nedocromil sodium from the gastrointestinal tract is low, being approximately 2% of an orally administered dose. Hence, nedocromil sodium measured in plasma following inhalation is considered to represent mainly the drug absorbed by the airways. After inhalation, plasma concentrations of nedocromil sodium reach a maximum within one hour post-dosing and decline with a half-life of 1-2 hours.

Distribution

Nedocromil sodium is moderately (80%) and reversibly bound to human plasma proteins, and is not metabolised in man or animals.

Elimination

In man nedocromil sodium is excreted unchanged in the urine (approximately 70%) and in faeces (approximately 30%). The plasma profiles of nedocromil sodium are similar following inhalation of Tilade, Tilade Mint, or Tilade CFC-Free, and are also similar in healthy volunteers and in asthmatic patients.

5.3 Preclinical safety data

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

6. Pharmaceutical particulars
6.1 List of excipients

1,1,1,2,3,3,3 - heptafluoropropane (HFA227)

povidone K30

macrogol 600

levomenthol

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store in a refrigerator or freezer. Protect from direct sunlight.

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

The aluminium can is fitted with a metering valve which delivers actuations each containing 2 mg of nedocromil sodium. Each canister contains 112 actuations.

Tilade CFC-Free Inhaler: The cartoned pack consists of;

an aerosol canister and a plastic adaptor with a dustcap

an aerosol canister and two plastic adaptors with dustcaps

Tilade CFC-Free Syncroner: The cartoned pack consists of either one or two aerosol canisters, each with a spacer device and a dustcap.

Tilade CFC-Free Fisonair: The cartoned pack consists of an aerosol canister and a plastic adaptor with a dustcap and a holding chamber.

6.6 Special precautions for disposal and other handling

Not applicable.

7. Marketing authorisation holder

Aventis Pharma Limited

410 Thames Valley Park Drive

Reading

Berkshire

RG6 1PT

UK

Trading as:

Sanofi

410 Thames Valley Park Drive

Reading

Berkshire

RG6 1PT

UK

8. Marketing authorisation number(s)

PL 04425/0342

9. Date of first authorisation/renewal of the authorisation

11 October 2005

10. Date of revision of the text

09 August 2019

LEGAL CLASSIFICATION

POM