SEREFLO Pressurised inhalation, suspension Ref.[50469] Active ingredients: Fluticasone Salmeterol

Sereflo is indicated in adults 18 years of age and older only.

Sereflo is not indicated for use in children, 12 years of age or younger, or adolescents, 13 to 17 years of age.

Posology

Route of administration: Inhalation use.

Patients should be made aware that Sereflo must be used daily for optimum benefit, even when asymptomatic.

Patients should be regularly reassessed by a doctor, so that the strength of Sereflo they are receiving remains optimal and is only changed on medical advice. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained.

Note: Sereflo is only available in two strengths, it is not available in a lower strength product containing salmeterol 25 microgram and fluticasone propionate 50 microgram, a strength which is available for other similar fixed-dose combination products containing these two actives and currently available on the market. Therefore, when it is appropriate to titrate down to a dose of inhaled corticosteroid below 125 micrograms, a change to an alternative fixed-dose combination of salmeterol and fluticasone propionate containing a lower dose of the inhaled corticosteroid is required.

Sereflo should not be used for patients with mild asthma and may not be appropriate for patients with mild to moderate asthma, in whom a low dose of the inhaled corticosteroid, either alone or with a long-acting β~2~ agonist, may be required. Sereflo could be considered for use in patients with moderate persistent asthma but only where control of symptoms cannot be maintained with a lower strength product containing a lower dose of the corticosteroid.

Where the control of symptoms is maintained with the lowest strength of such an alternative fixed-dose combination given twice daily then the next step could include a test of inhaled corticosteroid alone. As an alternative, patients requiring a long-acting β~2~ agonist could be titrated to salmeterol and fluticasone propionate given once daily in the opinion of the prescriber, it would be adequate to maintain disease control. In the event of once daily dosing when the patient has a history of nocturnal symptoms the dose should be given at night and when the patient has a history of mainly daytime symptoms the dose should be given in the morning.

Patients should be given the strength of Sereflo containing the appropriate fluticasone propionate dosage for the severity of their disease. If an individual patient should require dosages outside the recommended regimen, appropriate doses of β~2~ agonist and/or corticosteroid should be prescribed.

Recommended Doses

Adults 18 years and older

• Two inhalations of 25 micrograms salmeterol and 125 micrograms fluticasone propionate twice daily.

or

• Two inhalations of 25 micrograms salmeterol and 250 micrograms fluticasone propionate twice daily.

A short-term trial of salmeterol and fluticasone propionate may be considered as initial maintenance therapy in adults with moderate persistent asthma (defined as patients with daily symptoms, daily rescue use and moderate to severe airflow limitation) for whom rapid control of asthma is essential. In these cases, the recommended initial dose is two inhalations of 25 micrograms salmeterol and 50 micrograms fluticasone propionate twice daily. However Sereflo is not available in the lowest strength of this combination as currently available on the market and therefore an alternative fixed-dose combination of salmeterol and fluticasone propionate containing a lower dose of the inhaled corticosteroid would need to be prescribed for the initial maintenance therapy in adults with moderate persistent asthma. Without the lowest strength (25/50 microgram) of this fixed-dose combination, initiation of therapy in the majority of patients with asthma may be difficult and the lowest strength of the innovator product may be required.

The dose of the inhaled corticosteroid may need to be increased to achieve control of asthma symptoms but once control is attained treatment should be reviewed and the dose of the inhaled corticosteroid titrated downwards to the lowest dose at which effective control of symptoms is maintained.

Consideration may be given as to whether patients should be stepped down to an inhaled corticosteroid alone from the lowest strength combination product.

Regular review of patients as treatment is stepped down is important.

A clear benefit has not been shown as compared with inhaled fluticasone propionate alone used as initial maintenance therapy when one or two of the criteria of severity are missing. In general inhaled corticosteroids remain the first line treatment for most patients. Sereflo is not intended for the initial management of mild asthma or mild to moderate asthma. It is recommended to establish the appropriate dosage of inhaled corticosteroid before any fixed-combination can be used in patients with severe asthma.

Paediatric population

The safety and efficacy of Sereflo in children, 12 years and younger and adolescents, 13-17 years of age have not been established. No data are available. Sereflo is not recommended for use in children and adolescents under 18 years of age.

Note: Neither of the two available strengths of this fixed-dose combination of salmeterol xinafoate and fluticasone propionate can be used in the management of asthma in children as the maximum authorised dose of fluticasone propionate for use in children is 100 microgram twice daily. This dose of fluticasone propionate can only be attained by use of a lower strength of this fixed-dose combination than is currently available for Sereflo.

Use of a lower strength of this fixed-dose combination can only be obtained by downward dose titration to the lowest strength of this fixed dose combination (containing 50 micrograms of fluticasone propionate). This is not available as Sereflo. Therefore the healthcare provider should down-titrate patients to the lowest strength (25/50 microgram) by using the innovator product.

Spacer devices

Use of a spacer device with Sereflo is recommended in patients who have, or are likely to have difficulties in coordinating actuation of the inhaler with inspiration of breath. Limited data available from a single dose pharmacokinetic study PRC/CRD/13/11 (with spacers washed in detergent solution and drip dried prior to use) demonstrate an increase in systemic exposure when the Volumatic spacer device is used compared with the AeroChamber Plus spacer device (see section 4.4). Patients should be instructed in the proper use and care of their inhaler and spacer and their technique checked to ensure optimum delivery of the inhaled drug to the lungs.

Either the Volumatic spacer device or the AeroChamber Plus spacer device can be used (depending on National Guidance).

Use of a spacer device is recommended ONLY for Sereflo containing salmeterol 25 microgram and fluticasone propionate 250 microgram (the high strength inhaler). A spacer device is not recommended for use with Sereflo containing salmeterol 25 microgram and fluticasone propionate 125 microgram (the mid/lower strength inhaler). If a spacer device is required for use with this mid/lower strength, the patient will have to change to an alternative fixed-dose combination of salmeterol and fluticasone propionate containing salmeterol 25 microgram and fluticasone propionate 125 microgram which is authorised for use with a spacer device.

Patients should continue to use the same make of spacer device, either the Volumatic spacer device or the AeroChamber Plus spacer device, as switching between spacer devices can result in changes in the dose delivered to the lungs (see section 4.4).

Re-titration to the lowest effective dose should always follow the introduction or change of a spacer device.

If a patient has previously used an alternative product and spacing device and is then transferred to these new fixed-dose combination inhalers with or without a spacing device, re-titration of their dose to the lowest effective dose should always be carried out.

Special patient groups

There is no need to adjust the dose in elderly patients or in those with renal impairment. There are no data available for use of salmeterol and fluticasone propionate in patients with hepatic impairment.

Instructions for Use

Patients should be instructed in the proper use of their inhaler (see patient information leaflet)

During inhalation, the patient should preferably sit or stand. The inhaler has been designed for use in a vertical position.

Testing the inhaler

Before using for the first time patients should remove the mouthpiece cover by gently squeezing the sides of the cover, shake the inhaler well, hold the inhaler between the fingers and thumb with their thumb on the base, below the mouthpiece and release four puffs into the air to make sure that it works. The inhaler should be shaken immediately before releasing each puff. If the inhaler has not been used for a week or more remove the mouthpiece cover, the patients should shake the inhaler well and release two puffs into the air.

Use of the inhaler

1. Patients should remove the mouthpiece cover by gently squeezing the sides of the cover.
2. Patients should check inside and outside of the inhaler including the mouthpiece for the presence of loose objects
3. Patients should shake the inhaler well to ensure that any loose objects are removed and that the contents of the inhaler are evenly mixed.
4. Patients should hold the inhaler upright between fingers and thumb with their thumb on the base, below the mouthpiece.
5. Patients should breathe out as far as is comfortable and then place the mouthpiece in their mouth between their teeth and close their lips around it. Patients should be instructed not to bite the mouth piece.
6. Just after starting to breathe in through their mouth, patients should press firmly down on the top of the inhaler to release the medicine while still breathing in steadily and deeply.
7. While holding their breath, patients should take the inhaler from their mouth and take their finger from the top of the inhaler. Patients should continue holding their breath for as long as is comfortable.
8. To take a second inhalation, patients should keep the inhaler upright and wait about half a minute before repeating steps 3 to 7.
9. Patients should immediately replace the mouthpiece cover in the correct orientation by firmly pushing and snapping the cover into position. This does not require excessive force, the cover should click into position.

IMPORTANT

Patients should not rush stages 5, 6 and 7. It is important that patients start to breathe in as slowly as possible just before operating their inhaler. Patients should practise in front of a mirror for the first few times. If they see “mist” coming from the top of their inhaler or the sides of their mouth they should start again from stage 3.

Patients should get a replacement when the indicator shows the number ‘40’ and the colour on the dose indicator will change from green to red. Stop using the inhaler when the indicator shows ‘0’ as any puffs left in the device may not be enough to give a full dose. Never try to alter the numbers on the indicator or detach the indicator from the actuator. The indicator cannot be reset and is permanently attached to the actuator.

Patients should rinse their mouth out with water and spit out and/or brush their teeth after each dose of medicine, in order to minimize the risk of oropharyngeal candidiasis and hoarseness.

Cleaning (also detailed in patient information leaflet): The inhaler should be cleaned at least once a week.

1. Remove the mouth piece cover.
2. Do not remove the canister from the plastic casing.
3. Wipe the inside and outside of the mouthpiece and the plastic casing with a dry cloth or tissue.
4. Replace the mouthpiece cover in the correct orientation. This does not require excessive force, the cover should click into position.

DO NOT PUT THE METAL CANISTER IN WATER

There are no data available from clinical trials on overdose with salmeterol and fluticasone propionate as a fixed dose combination, however data on overdose with both medicinal products are given below:

The signs and symptoms of salmeterol overdose are dizziness, increases in systolic blood pressure, tremor, headache and tachycardia. If salmeterol and fluticasone propionate as a fixed dose combination therapy has to be withdrawn due to overdose of the β agonist component of the drug, provision of appropriate replacement steroid therapy should be considered. Additionally, hypokalaemia can occur and therefore serum potassium levels should be monitored. Potassium replacement should be considered.

Acute: Acute inhalation of fluticasone propionate doses in excess of those recommended may lead to temporary suppression of adrenal function. This does not need emergency action as adrenal function is recovered in a few days, as verified by plasma cortisol measurements.

Chronic overdose of inhaled fluticasone propionate: Adrenal reserve should be monitored and treatment with a systemic corticosteroid may be necessary. When stabilised, treatment should be continued with an inhaled corticosteroid at the recommended dose. Refer to section 4.4: risk of adrenal suppression.

In cases of both acute and chronic fluticasone propionate overdose, Sereflo therapy should be continued at a suitable dosage for symptom control.

2 Years.

Do not store above 25°C.

The canister contains a pressurised liquid. Do not expose to temperatures higher than 50°C, protect from direct sunlight. Do not pierce or burn the canister even when empty.

As with most inhaled medicinal products in pressurised canisters, the therapeutic effect of this medicinal product may decrease when the canister is cold.

Aluminium canister with a suitable metering valve and a polypropylene white actuator with pink or rubine red dust-caps having dose indicator in a sealed pouch containing desiccant. The actuator has a counter attached which shows how many actuations of medicine are left in the canister.

Each container is filled to deliver 120 doses.

Pack sizes:

1, 2 (bundled package 2x1) or 3 (bundled package 3x1) canisters containing 120 doses.

10 (bundled package 10x1) canisters containing 120 doses -hospital/pharmacy use only

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.