COMBOTEROL

Package leaflet: Information for the patient

Comboterol, (25 µg + 125 µg)/inhalation dose, inhalation aerosol, suspension
Comboterol, (25 µg + 250 µg)/inhalation dose, inhalation aerosol, suspension
Salmeterolum + Fluticasoni propionas

Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Comboterol is and what it is used for
2. Important information before using Comboterol
3. How to use Comboterol
4. Possible side effects
5. How to store Comboterol
6. Contents of the pack and other information

1. What Comboterol is and what it is used for

Comboterol contains two active substances: salmeterol and fluticasone propionate.

• Salmeterol is a long-acting bronchodilator. Bronchodilators help keep the airways open. This makes it easier for air to flow into and out of the lungs. The effect lasts for at least 12 hours.
• Fluticasone propionate is a corticosteroid that reduces swelling and irritation in the lungs.

Your doctor has prescribed this medicine to prevent breathing problems associated with asthma.
To ensure proper asthma control, Comboterol must be used every day as directed by your doctor.
Comboterol helps prevent episodes of breathlessness and wheezing. However, it should not be used to treat sudden asthma attacks or sudden wheezing. If such an attack occurs, a fast-acting bronchodilator, such as salbutamol, should be used immediately. You should always have such a medicine available.

2. Important information before using Comboterol

When not to use Comboterol

• if the patient is allergic to salmeterol, fluticasone propionate, or to the excipient norflurane (HFA 134a).

Warnings and precautions
Before starting treatment with Comboterol, talk to your doctor, pharmacist, or
nurse if the patient has:

• heart disease, including irregular or rapid heartbeat,
• hyperthyroidism,
• high blood pressure,
• diabetes (Comboterol may increase blood glucose levels),
• low potassium levels in the blood,
• active or previously treated tuberculosis, or other lung infections.

Comboterol and other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken, including asthma medications and over-the-counter medicines. Comboterol should not be used with certain medicines.
Before starting Comboterol, inform your doctor if the patient is taking any of the following medicines:

• Beta-blockers (e.g. atenolol, propranolol, sotalol). Beta-blockers are commonly used to treat high blood pressure or other heart conditions.
• Medicines used to treat infections (e.g. ritonavir, ketoconazole, itraconazole, and erythromycin). Some of these medicines may increase the levels of fluticasone propionate or salmeterol in the body. This may increase the risk of side effects, including irregular heartbeat, or may worsen existing side effects.
• Corticosteroids (taken orally or by injection). If the patient has recently taken such medicines, this may increase the risk of adrenal dysfunction.
• Diuretics used to treat high blood pressure.
• Other bronchodilators (such as salbutamol).
• Medicines containing xanthine derivatives, commonly used in the treatment of asthma.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor before using this medicine. The doctor will assess whether the patient can take Comboterol during this period.

Driving and operating machinery
It is unlikely that Comboterol will affect the ability to drive or operate machinery.

3. How to use Comboterol

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your
doctor, nurse, or pharmacist.

• Comboterol should be used daily until your doctor advises otherwise. Do not take a higher dose than recommended. If in doubt, consult your doctor or pharmacist.
• Do not stop using Comboterol or reduce the dose without first consulting your doctor.
• Comboterol should be inhaled into the lungs through the mouth.

Adults and adolescents aged 12 years and older:

• Comboterol (25 micrograms + 125 micrograms)/dose – two inhalations twice daily.
• Comboterol (25 micrograms + 250 micrograms)/dose – two inhalations twice daily.

Comboterol is not recommended for use in children under 12 years of age.
Your doctor will determine the lowest dose that effectively controls your symptoms.
If asthma symptoms are well controlled while taking Comboterol twice daily,
your doctor may recommend reducing the frequency of Comboterol to once daily. The dose may be taken:

• once daily in the evening, if symptoms occur at night,
• once daily in the morning, if symptoms occur during the day.

It is very important that your doctor instructs you on how many inhalations to take and how often.
If you are using Comboterol for asthma, your doctor will regularly monitor your symptoms.
If asthma symptoms worsen or asthma control deteriorates, you must
contact your doctor immediately. This may include worsening wheezing, more frequent chest tightness, or the need to use a higher dose of a fast-acting inhaled medicine to relieve breathing difficulties. In such a case, continue using Comboterol, but do not increase the number of inhalations. Your symptoms may worsen and your condition may deteriorate. Contact your doctor, as you may require additional treatment.

Instructions for using the inhaler:

• Your doctor, nurse, or pharmacist should instruct you on the correct use of the inhaler. They should periodically check that you are using the inhaler properly. Incorrect use of Comboterol or improper inhaler technique may result in the medicine not providing the expected improvement in asthma.
• The medicine is contained in a pressurized canister within a plastic casing with a mouthpiece.
• On the front of the inhaler is a dose counter indicating how many doses of medicine remain. As the inhaler is used, the number shown on the counter usually decreases after every 5 to 7 doses released. The counter shows an approximate number of remaining doses.
• Handle the inhaler carefully to avoid dropping it, as this may cause the counter to reset or display incorrectly.

Checking the inhaler

1. Before first use, check that the inhaler works. Remove the mouthpiece cap by gently pressing the sides of the cap with your thumb and index finger.
2. To ensure the inhaler works, shake it vigorously, point the mouthpiece away from you, and release 4 doses into the air. The counter should display 120, corresponding to the total number of doses in the inhaler. If the inhaler has not been used for one week or longer, remove the mouthpiece cap, shake the inhaler vigorously, and release two doses into the air.

Using the inhaler
It is important to begin breathing slowly and as steadily as possible even before using the inhaler.

1. Use the inhaler while standing or sitting.
2. Remove the mouthpiece cap from the inhaler. Check the mouthpiece inside and outside to ensure it is clean and free of foreign objects (Figure A).

3. Shake the inhaler 4 or 5 times to remove any foreign particles and ensure the contents are evenly mixed (Figure B).

4. Hold the inhaler upright with your fingers, placing your thumb under the base of the inhaler, below the mouthpiece. Breathe out deeply, as fully as possible (Figure C).

5. Place the mouthpiece in your mouth and seal your lips tightly around it. Do not bite the mouthpiece (Figure D).

6. Begin a slow and deep inhalation. Immediately after starting to inhale through your mouth, press down on the inhaler to release a dose of medicine, then continue inhaling slowly and deeply (Figure D).
7. Hold your breath, remove the inhaler from your mouth, and remove your finger from the top of the inhaler. Hold your breath for several seconds, or as long as comfortable, then breathe out slowly (Figure E).

8. If your doctor has prescribed two inhalations, wait approximately 30 seconds before repeating steps 3–7.
9. Rinsing your mouth with water and spitting it out and/or brushing your teeth after inhalation helps prevent hoarseness and oral thrush.
10. After inhalation, always replace the mouthpiece cap to prevent dust from entering. Securely attach the cap until you hear a click. If you do not hear a click when attaching the cap, remove it, turn it around, and try again. Do not use excessive force.

Do not rush steps 4, 5, 6, and 7. It is important to breathe as slowly as possible just before inhalation. To ensure correct technique, initially practice using the inhaler in front of a mirror. Visible "mist" escaping from the inhaler, mouth, or nose during inhalation indicates incorrect technique. Repeat the steps starting from step 3.
If you have difficulty coordinating your breath with inhalation, your doctor may recommend using the inhaler with a spacer device. Your doctor, nurse, or pharmacist should instruct you on the correct use of the inhaler with a spacer, how to maintain the spacer, and answer any related questions. If you use a spacer, do not stop using it or change the type of spacer without consulting your doctor or nurse. If you stop using a spacer or change its type, your doctor may need to adjust the dose of Comboterol required to control your asthma symptoms. Always consult your doctor before making any changes to your asthma treatment.
People with weak hands may find it easier to hold the inhaler with both hands. Grip the inhaler with both index fingers on top and both thumbs underneath, below the mouthpiece.
When the counter displays "40", remember that a replacement inhaler will soon be needed. Replace the inhaler when the counter reaches "0", as the remaining medicine may be insufficient for a full dose. Never attempt to reset the counter, as it cannot be adjusted.

Cleaning the inhaler
To prevent blockage, clean the inhaler at least once a week.
To clean the inhaler:

• Remove the mouthpiece cap.
• Do not remove the metal canister from the plastic casing during cleaning or at any other time.
• Wipe the mouthpiece inside and out, and the outside of the plastic casing, with a dry cloth or tissue.
• Replace the mouthpiece cap. When properly attached, a click should be heard. If no click is heard, remove the cap, turn it around, and reattach. Do not use excessive force.

Do not immerse the metal canister in water.

Accidental overdose of Comboterol
It is important to use the inhaler exactly as instructed. If you accidentally take more than the recommended dose, inform your doctor or pharmacist.
Possible symptoms include: faster than normal heartbeat, tremors, dizziness, headache, muscle weakness, and joint pain.
If higher doses have been used for a prolonged period, contact your doctor or pharmacist for advice, as high doses of Comboterol may reduce the adrenal glands' production of steroid hormones.

Missed dose of Comboterol
If you forget to take a dose, take the next dose at the scheduled time. Do not take a double dose to make up for a missed dose.

Stopping Comboterol
It is very important to take Comboterol every day as prescribed by your doctor. You should continue
taking the medicine until your doctor advises you to stop. Do not suddenly stop
taking Comboterol or reduce the dose, as your symptoms may worsen.
Additionally, abruptly stopping or reducing the dose of Comboterol may (very rarely) lead to adrenal gland dysfunction (adrenal insufficiency), which may cause adverse effects.
These adverse effects may include any of the following:

• abdominal pain,
• fatigue and loss of appetite, nausea,
• vomiting and diarrhoea,
• weight loss,
• headache and drowsiness,
• low blood sugar,
• low blood pressure and seizures.

When the body is under stress due to fever, injury (such as a car accident), infection, or surgery, adrenal insufficiency may worsen and any of the adverse effects listed above may occur. If you experience any of these adverse effects, inform your doctor or pharmacist. To prevent these symptoms, your doctor may prescribe additional corticosteroid tablets (e.g. prednisolone).

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
To reduce the risk of adverse effects, your doctor will recommend the lowest dose of
Comboterol that provides asthma control.
Allergic reactions: The patient may experience sudden breathing difficulties immediately after
using Comboterol. Worsening wheezing, cough, or shortness of breath may occur, as well as itching, rash (urticaria), and swelling (usually of the face, lips, tongue, or throat). The patient may also experience a sensation of very rapid heartbeat, weakness, or dizziness (which may lead to falling or loss of consciousness). If any of these symptoms occur suddenly after using Comboterol, stop using the medicine
immediately and contact your doctor without delay. Allergic reactions to Comboterol occur
not commonly (may occur in up to 1 in 100 patients taking the medicine).

Other adverse reactions:

Very common adverse reactions (may affect more than 1 in 10 patients):

• Headache – this adverse effect usually decreases during continued treatment.
• Increased incidence of colds has been reported in patients with COPD.

Common adverse reactions (may affect up to 1 in 10 patients):

• Oral and pharyngeal candidiasis (painful creamy-white lesions) in the mouth and throat, as well as tongue pain, hoarseness, loss of voice, and throat irritation. Rinsing the mouth with water and spitting it out and/or brushing teeth immediately after each inhalation may help. Your doctor may prescribe an antifungal medicine to treat candidiasis.
• Joint pain, joint swelling, and muscle pain.
• Muscle cramps.

Pneumonia (lung infection) in patients with chronic obstructive pulmonary disease (COPD)
(common adverse reaction)
The following adverse reactions have been observed in patients with chronic obstructive pulmonary disease (COPD):

• Pneumonia (lung infection) in patients with chronic obstructive pulmonary disease (COPD) (common adverse reaction). Tell your doctor if any of the following symptoms occur during treatment with Comboterol – these may be signs of lung infection:
  • Fever or chills.
  • Increased mucus production, change in mucus color.
  • Worsening cough or increased difficulty breathing.
• Easy bruising and traumatic fractures.
• Sinusitis (feeling of pressure and fullness in the nose, cheeks, and behind the eyes, sometimes with pulsating pain).
• Decreased blood potassium levels (the patient may experience irregular heartbeat, muscle weakness, or cramps).

Uncommon adverse reactions (may affect up to 1 in 100 patients):

• Increased blood sugar (glucose) levels (hyperglycaemia). In patients with diabetes, more frequent monitoring of blood glucose levels and adjustment of previously used antidiabetic medication doses may be necessary.
• Cataract (clouding of the eye lens).
• Very rapid heartbeat (tachycardia).
• Tremor and rapid or irregular heartbeat (palpitations) – these symptoms are usually not serious and tend to decrease during continued treatment.
• Atrial fibrillation.
• Ischaemic heart disease, characterized by chest pain or tightness, and shortness of breath.
• Sleep disturbances.
• Anxiety.
• Allergic skin rash.

Rare adverse reactions (may affect up to 1 in 1000 patients):

• Worsening wheezing or breathing difficulties occurring immediately after taking Comboterol. If such symptoms occur, stop using Comboterol immediately, use a fast-acting inhaled medicine to relieve breathing, and contact your doctor immediately.
• Comboterol may interfere with the body's normal production of steroid hormones, especially when high doses are used for prolonged periods. These effects may include:
  • Slowed growth in children and adolescents,
  • Reduced bone mass,
  • Glaucoma,
  • Increased body weight,
  • Rounded (moon-shaped) face (Cushing's syndrome). Your doctor will regularly check for these adverse effects and ensure that you are using the lowest dose of Comboterol that controls asthma.
• Behavioural changes such as excessive excitability and irritability (these effects occur mainly in children).
• Irregular heartbeat or extra beats (arrhythmias). Inform your doctor, but do not stop using Comboterol unless instructed by your doctor.
• Fungal infection of the oesophagus, which may cause difficulty swallowing.

Adverse reaction of unknown frequency (frequency cannot be estimated from the available data):

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

Reporting of adverse reactions
If the patient experiences any adverse effects, including any adverse effects not listed in this leaflet, tell your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices
and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Comboterol

• Keep the medicine out of sight and reach of children.
• Do not use Comboterol after the expiry date stated on the pack following EXP. The expiry date refers to the last day of the stated month.
• After inhalation, place the cap on the mouthpiece, pressing it into position. Do not use excessive force.
• Do not store above 25°C.
• The metal container holds a pressurized suspension. Do not expose the container to temperatures above 50°C. Do not pierce or burn the container, even if it appears to be empty. Do not store in a cold place, as this may affect the proper functioning of the inhaler.
• As with most inhaled medicines in pressurized containers, the therapeutic effect of this medicine may be reduced if the container is cold.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Comboterol contains

• Each metered dose of Comboterol contains 25 micrograms (μg) of salmeterol (as salmeterol xinafoate) and either 125 or 250 micrograms (μg) of fluticasone propionate (delivered via valve). This corresponds to 21 micrograms of salmeterol and either 110 or 220 micrograms of fluticasone propionate delivered via inhaler (delivered dose).
• The other ingredient is the propellant gas norflurane (HFA 134a).

This medicine contains fluorinated greenhouse gases.
Each inhaler contains 12.5 g of HFA 134a (norflurane), equivalent to 0.0179 tonnes of CO₂-equivalent
(global warming potential GWP = 1430).

What Comboterol looks like and contents of the pack

• Comboterol is supplied in an inhaler containing the medicine as a pressurized suspension for oral inhalation into the lungs.
• The container holds a uniform white suspension.
• The pack consists of an aluminium container coated with plasma (FCP), closed with a metering valve, fitted with a plastic actuator with dose counter, and presented in a cardboard box.
• Pack sizes: 1 container containing 120 doses.

Marketing Authorisation Holder and Importer
Przedsiębiorstwo Farmaceutyczne LEK-AM Sp. z o.o.
ul. Ostrzykowizna 14A
05-170 Zakroczym
Poland
Tel.: +48 22 785 27 60
Fax: +48 22 785 27 60 ext. 106