Patient leaflet - Combisal 25 micrograms / 250 micrograms per Metered dose pressurised inhalation suspension

1. What Combisal is and what it is used for

Combisal contains two active substances: salmeterol (as xinafoate) and fluticasone propionate.

Salmeterol is a long-acting bronchodilator. Bronchodilators help the airways in the lungs to stay open. This makes it easier for air to get in and out. The effects last for at least 12 hours.
Fluticasone propionate is a corticosteroid which reduces swelling and irritation in the lungs. The doctor has prescribed this medicine to help prevent breathing problems such as asthma.

You must use Combisal every day as directed by your doctor. This will make sure that it works properly in controlling your asthma.

Combisal helps to stop breathlessness and wheeziness coming on. However Combisal should not be used to relieve a sudden attack of breathlessness or wheezing. If this happens you need to use a fast-acting ‘reliever’ (‘rescue’) inhaler, such as salbutamol. You should always have your fast-acting ‘reliever’ inhaler with you.

2. What you need to know before you use Combisal

Do not use Combisal:

If you are allergic (hypersensitive) to salmeterol, fluticasone propionate or to the other ingredient norflurane (HFA 134a).

Warnings and precautions

Talk to your doctor or pharmacist before taking Combisal if you have:

Heart disease, including an irregular or fast heartbeat.
Overactive thyroid gland.
High blood pressure.
Diabetes mellitus (Combisal may increase your blood sugar).
Low potassium in your blood.
Tuberculosis (TB) now, or in the past, or other lung infections.

Contact your doctor if you experience blurred vision or other visual disturbances.

Other medicines and Combisal

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines. This includes medicines for asthma or any medicines obtained without a prescription. This is because Combisal may not be suitable to be taken with some other medicines.

Tell your doctor if you are taking the following medicines, before starting to use Combisal:

ß blockers (such as atenolol, propranolol and sotalol). ß blockers are mostly used for high blood pressure or other heart conditions.
Medicines to treat infections (such as ketoconazole, itraconazole and erythromycin) including some medicines for HIV treatment (such as ritonavir, cobicistat-containing products). Some of these medicines may increase the amount of fluticasone propionate or salmeterol in your body. This can increase your risk of experiencing side effects with Combisal, including irregular heartbeats, or may make side effects worse. Your doctor may wish to monitor you carefully if you are taking these medicines.
Corticosteroids (by mouth or by injection). If you have had these medicines recently, this might increase the risk of this medicine affecting your adrenal gland.
Diuretics, also known as ‘water tablets’ used to treat high blood pressure.
Other bronchodilators (such as salbutamol).
Xanthine medicines. These are often used to treat asthma.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Driving and using machines

Combisal is not likely to affect your ability to drive or use machines.

For those who carry out sports activities

The use of the drug without therapeutic necessity constitutes doping and may still determine positivity to anti-doping tests.

3. How to use Combisal

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Use your Combisal every day, until your doctor advises you to stop. Do not take more than the recommended dose. Check with your doctor or pharmacist if you are not sure.
Do not stop taking Combisal or reduce the dose of Combisal without talking to your doctor first.
Combisal should be inhaled through the mouth into the lungs.
Use your Combisal always taking the count of the actuations.

The inhaler has been designed to deliver 120 actuations. However it is not possible to tell when the inhaler is empty and when the 120 puffs have been released. There may still be a small amount of fluid left over in the container.

Please make sure that your inhaler is replaced after you have released 120 puffs so that you can be certain that you are getting the right amount of your medicine in each puff.

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Salmeterol (as xinafoate)/Fluticasone Propionate COMBISAL 25 microgram/50 microgram per metered dose pressurised inhalation, suspension COMBISAL 25 microgram/125 microgram per metered dose pressurised inhalation, suspension COMBISAL 25 microgram/250 microgram per metered dose pressurised inhalation, suspension

Package Leaflet: Information for the patient

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it onto others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
1010422-P6.1

As with all inhalers, caregivers should ensure that children prescribed Combisal use the correct inhalation technique, as described above.

If you or your child find it difficult to use the inhaler, either your doctor or other healthcare provider may recommend using an AeroChamber Plus^®spacer device with your inhaler. Your doctor, nurse, pharmacist or other healthcare provider should show you how to use the spacer with your inhaler and how to care for your spacer and will answer any questions you may have. It is important that if you are using a spacer device with your inhaler that you do not stop using the spacer without talking to your doctor or nurse first. Other spacer devices are not recommended for use with Combisal and you should not switch from the AeroChamber Plus^®device to another. It is also important that you do not change or stop using the spacer without talking to your doctor, they will know how to modify the therapy. Always talk to your doctor before making any changes to your asthma treatment. Older children and people with weak hands may find it easier to hold the inhaler with both hands. Put the two forefingers on top of the inhaler and both thumbs on the bottom below the mouthpiece.

Cleaning your inhaler

To stop your inhaler blocking, it is important to clean it at least once a week. To clean your inhaler:

Remove the mouthpiece cover.
Do not remove the metal canister from the plastic casing at any time.
Wipe the inside and outside of the mouthpiece and the plastic casing with a dry cloth or tissue.
Replace the mouthpiece cover. It will ‘click’ into place when fitted correctly.
Do not use too much force.
Do not wash or put any parts of your inhaler in water. If you use more Combisal than you should

It is important to use the inhaler as instructed. If you accidentally take a larger dose than recommended, talk to your doctor or pharmacist. You may notice your heart beating faster than usual and that you feel shaky. You may also have dizziness, a headache, muscle weakness and aching joints. If you have used larger doses for a long period of time, you should talk to your doctor or pharmacist for advice. This is because larger doses of Combisal may reduce the amount of steroid hormones produced by the adrenal gland.

If you forget to use Combisal

Do not take a double dose to make up for a forgotten dose. Just take your next dose at the usual time. If you stop using Combisal

It is very important that you take your Combisal every day as directed. Keep taking it until your doctor tells you to stop. Do not stop or suddenly reduce your dose of Combisal. This could make your breathing worse. In addition, if you suddenly stop taking Combisal or reduce your dose of Combisal this may (very rarely) cause you to have problems with your adrenal gland (adrenal insufficiency) which sometimes causes side effects. These side effects may include any of the following:

Stomach pain.
Tiredness and loss of appetite, feeling sick.
Sickness and diarrhoea.
Weight loss.
Headache or drowsiness.
Low levels of sugar in your blood.
Low blood pressure and seizures (fits).

When your body is under stress such as from fever, trauma (such as a car accident), infection, or surgery, adrenal insufficiency can get worse and you may have any of the side effects listed above.

If you get any side effects, talk to your doctor or pharmacist. To prevent these symptoms occurring, your doctor may prescribe extra corticosteroids in tablet form (such as prednisolone).

If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. To reduce the chance of side effects, your doctor will prescribe the lowest dose of Combisal to control your asthma.

Allergic reactions: you may notice your breathing suddenly gets worse immediately after using Combisal. You may be very wheezy and cough or be short of breath.

You may also notice itching, a rash (hives) and swelling (usually of the face, lips, tongue or throat), or you may suddenly feel that your heart is beating very fast or you feel faint and light headed (which may lead to collapse or loss of consciousness). If you get any of these effects or if they happen suddenly after using Combisal, stop using Combisal and tell your doctor straight away.

Allergic reactions to Combisal are uncommon (they affect less than 1 person in 100).

Other side effects are listed below:

Very Common (may affect more than 1 in 10 people)

Headache - this usually gets better as
treatment continues.
Increased number of colds have been reported in patients with COPD.

Common (may affect up to 1 in 10 people)

Thrush (sore, creamy-yellow, raised patches) in the mouth and throat. Also sore tongue and hoarse voice and throat irritation. Rinsing your mouth out with water and spitting it out immediately and/or brushing your teeth after taking each dose of your medicine may help. Your doctor may prescribe an anti-fungal medication to treat the thrush.
Aching, swollen joints and muscle pain.
Muscle cramps.

The following side effects have also been reported in patients with Chronic Obstructive Pulmonary Disease (COPD):

Pneumonia and bronchitis (lung infection). Tell your doctor if you notice any of the following symptoms: increase in sputum production, change in sputum colour, fever, chills, increased cough, increased breathing problems.
Bruising and fractures.
Inflammation of sinuses (a feeling of tension or fullness in the nose, cheeks and behind the eyes, sometimes with a throbbing ache).
A reduction in the amount of potassium in the blood (you may get an uneven heartbeat, muscle weakness, cramp).
Uncommon (may affect up to 1 in 100 people)
- Increases in the amount of sugar (glucose) in your blood (hyperglycaemia). If you have diabetes, more frequent blood sugar monitoring and possibly adjustment of your usual diabetic treatment may be required.
- Cataract (cloudy lens in the eye).
- Very fast heartbeat (tachycardia).
- Feeling shaky (tremor) and fast or uneven heartbeat (palpitations) - these are usually harmless and get less as treatment continues.
- Chest pain.
- Feeling worried (this effect mainly occurs in children).
- Disturbed sleep.
- Allergic skin rash.

Rare (may affect up to 1 in 1000 people)

Breathing difficulties or wheezing that get worse straight after taking Combisal. If this happens stop using your Combisal inhaler. Use your fast-acting ‘reliever’ inhaler to help your breathing and tell your doctor straight away.
Combisal may affect the normal production of steroid hormones in the body, particularly if you have taken high doses for long periods of time. The effects include:
- Slowing of growth in children and adolescents.
- Thinning of the bones.
- Glaucoma.
- Weight gain.
- Rounded (moon shaped) face
  (Cushing’s Syndrome).

Your doctor will check you regularly for any of these side effects and make sure you are taking the lowest dose of Combisal to control your asthma.

Behavioural changes, such as being unusually active and irritable (these effects mainly occur in children).
Uneven heartbeat or the heart gives an extra beat (arrhythmias). Tell your doctor, but do not stop taking Combisal unless the doctor tells you to stop.
A fungal infection in the oesophagus (gullet), which might cause difficulties in swallowing.

Not known, (frequency cannot be estimated from the available data)

Depression or aggression. These effects are more likely to occur in children.
Blurred vision.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme (website: www.mhra.gov.uk/ yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store). By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Combisal

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and carton after EXP:. The expiry date refers to the last day of that month.
Do not store above 25°C.
Straight after use, replace the mouthpiece cover firmly and click it into position. Do not use excessive force.
The canister contains a pressurised liquid. Do not expose to temperatures higher than 50°C, and protect from direct sunlight. Do not pierce, break or burn the canister even when apparently empty.
As with most inhaled medicinal products in pressurised canisters, the therapeutic effect of this medicinal product may decrease when the canister is cold. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Combisal contains

Each metered dose (ex valve) contains 25 micrograms of salmeterol (as salmeterol xinafoate) and 50, 125 or 250 micrograms of fluticasone propionate. The other ingredient is propellant: norflurane (HFA 134a). This medicine contains fluorinated greenhouse gases. Each inhaler of 120 actuation contains 11.2 g of HFA-134a corresponding to 0.016 tonne CO2 equivalent (global warming potential GWP = 1, 430). What Combisal looks like and contents of the pack

Combisal is supplied to you in a metered dose inhaler which delivers your medicine in a pressurised suspension for you to inhale through your mouth into your lungs.
The pressurised canister contains a homogenous suspension for inhalation.
The canister is fitted into a plastic casing incorporating a mouthpiece and fitted with a purple dust cap.
Each pack contains 1 inhaler. Each inhaler contains 120 actuations.

Marketing Authorisation Holder and Manufacturer

Marketing authorisation holder

Genetic S.p.A.

Via G. Della Monica 26,

84083 Castel San Giorgio (SA)

Italy

Manufacturer