ADEMPAS 1 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for theuser

Adempas 0.5 mg film-coated tablets

Adempas 1 mg film-coated tablets

Adempas 1.5 mg film-coated tablets

Adempas 2 mg film-coated tablets

Adempas 2.5 mg film-coated tablets

riociguat

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

• 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 on to 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.
• This leaflet was written as if the person taking the medicine is an adult. If you are giving this medicine to your child, please replace “you” with “your child” throughout this leaflet.

Contents of the pack

1. What is Adempas and what is it used for
2. What you need to know before you take Adempas
3. How to take Adempas
4. Possible side effects
5. Storage of Adempas
6. Contents of the pack and other information

1. What is Adempas and what is it used for

Adempas contains the active substance riociguat, a stimulator of soluble guanylate cyclase (sGC) that works by widening the blood vessels that carry blood from the heart to the lungs.

Adempas is used to treat certain forms of pulmonary hypertension in adults and children, a disease in which these blood vessels become narrowed, making it harder for the heart to pump blood through them, and causing an increase in blood pressure in these vessels. Because the heart has to work harder than normal, people with pulmonary hypertension feel tired, dizzy, and have difficulty breathing.

By widening the narrowed arteries, Adempas improves the ability to perform physical activity, i.e., to walk a greater distance.

Adempas is used in these two types of pulmonary hypertension:

• Chronic thromboembolic pulmonary hypertension (CTEPH)

Adempas tablets are used to treat CTEPH in adult patients. In CTEPH, the blood vessels in the lungs are blocked or narrowed by blood clots. Adempas can be used in patients with CTEPH who cannot undergo surgery or after surgery in those patients in whom pulmonary hypertension persists or recurs.

• Certain types of pulmonary arterial hypertension (PAH)

Adempas tablets are used to treat PAH in adults and children under 18 years of age with a body weight of at least 50 kg. In PAH, the walls of the blood vessels in the lungs are thickened and the vessels are narrowed. Adempas is only indicated in certain forms of PAH, such as idiopathic PAH (where the cause of PAH is unknown), heritable PAH, and PAH caused by connective tissue disorders. Your doctor will check these aspects. Adempas can be taken alone or with other medicines used to treat PAH.

2. What you need to know before you take Adempas

Do not take Adempas if:

• you are taking PDE5 inhibitors (e.g., sildenafil, tadalafil, vardenafil). These are medicines used to treat high blood pressure in the blood vessels of the lungs (PAH) or erectile dysfunction;
• you have severe liver problems(severe hepatic impairment);

• you are allergic to riociguat or any of the other ingredients of this medicine (listed in section 6);
• you are pregnant;
• you are taking nitrates or nitric oxide donors (such as amyl nitrite) in any form, medicines often used to treat high blood pressure, chest pain, or heart disease. This also includes recreational drugs known as “poppers”;
• you are taking other medicines similar to Adempas (soluble guanylate cyclase stimulator, such as vericiguat). Ask your doctor if you are not sure;
• you have low blood pressure(systolic blood pressure: in children from 6 to <12 years of age below 90 mmhg, in patients ≥12 <95 mmhg) before starting treatment with this medicine;< li>
• you have an increase in blood pressurein the lungs associated with lung scarring, of unknown cause (idiopathic pulmonary fibrosis).

If any of these conditions apply to you, talk to your doctor firstand do not take Adempas.

Warnings and precautions

Talk to your doctor or pharmacist before starting Adempas if:

• you have recently had a severe lung hemorrhage;
• you have received treatment to stop coughing up blood(bronchial artery embolization);
• you are taking medicines to thin your blood(anticoagulants) as this may cause bleeding in the lungs. Your doctor will perform blood tests and blood pressure measurements periodically;
• you feel short of breath, as this may be caused by fluid accumulation in the lungs. Talk to your doctor if this happens;

you have any symptoms of low blood pressure(hypotension) such as dizziness, lightheadedness, or fainting, or if you are taking medicines to lower blood pressure or medicines that cause increased urination, or if you have heart or circulation problems. Your doctor may decide to monitor your blood pressure. If you are over 65 years old, you have a higher risk of developing low blood pressure;

• you are on dialysisor your kidneys do not work properly(creatinine clearance <30 ml min), as the use of this medicine is not recommended;< li>
• you have moderate liver problems(hepatic impairment);
• you start or stop smokingduring treatment with this medicine, as it may affect the level of riociguat in your blood.

Children and adolescents

The use of Adempas tablets should be avoided in children under 6 years of age and adolescents weighing less than 50 kg. The safety and efficacy of Adempas have not been established in the following pediatric populations:

• Children under 6 years of age, for safety reasons.
• Children with PAH with too low blood pressure:

from 6 to <12 years of age <90 mmhg at the start treatment.< p>

from 12 to <18 years of age <95 mmhg at the start treatment.< p>

• Children and adolescents with other forms of this disease, i.e., CTEPH, if under 18 years of age.

Other medicines and Adempas

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, in particular medicines used to treat:

• High blood pressure or heart disease (such as nitrates and amyl nitrite) in any form or other soluble guanylate cyclase stimulator (such as vericiguat). You should not take these medicines with Adempas.
• High blood pressure in the blood vessels of the lungs (pulmonary arteries) as you should not take certain medicines (sildenafil or tadalafil) with Adempas. Other medicines for high blood pressure in the blood vessels of the lungs, such as bosentan and iloprost, may be used with Adempas, but you should inform your doctor.
• Erectile dysfunction (such as sildenafil, tadalafil, vardenafil) as you should not take these medicines with Adempas.
• Fungal infections (e.g., ketoconazole, posaconazole, itraconazole) or
• HIV infection (e.g., abacavir, atazanavir, cobicistat, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, rilpivirine, ritonavir, and tenofovir). Alternative treatment options may be considered. If you are already taking one of these medicines and start treatment with Adempas, your doctor will monitor your health and may consider a lower initial dose of Adempas.
• Epilepsy (e.g., phenytoin, carbamazepine, phenobarbital).
• Depression (St. John's Wort).
• Prevention of organ rejection after transplantation (cyclosporine).
• Muscle or joint pain (niflamic acid).
• Cancer (such as erlotinib, gefitinib).
• Stomach upset or heartburn (antacids, such as aluminum hydroxide/magnesium hydroxide). These medicines should be taken at least 2 hours before or 1 hour after taking Adempas.
• Nausea, vomiting (such as granisetron).

Smoking

If you smoke, it is recommended that you stop smoking because smoking reduces the effectiveness of these tablets. Inform your doctor if you smoke or stop smoking during treatment. It may be necessary to adjust the dose.

Pregnancy, pregnancy testing, and breast-feeding

Pregnancy testing

Women and adolescent girls of childbearing age must use effective contraceptive methods during treatment with Adempas.

Pregnancy

Do not take Adempas during pregnancy. It is also recommended to perform monthly pregnancy tests. If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before taking this medicine.

Breast-feeding

If you are breast-feeding or plan to breast-feed, consult your doctor or pharmacist before taking this medicine, as it may harm your baby. You should not breast-feed while taking this medicine. Your doctor will decide whether to interrupt breast-feeding or interrupt treatment with Adempas.

Driving and using machines

Adempas may moderately affect your ability to ride a bicycle, drive, or use machines. It can cause side effects such as dizziness. Before riding a bicycle, driving, or using machines, you should be aware of the side effects of this medicine (see section 4).

Adempas contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

Adempas contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially “sodium-free”.

3. How to take Adempas

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, consult your doctor or pharmacist again.

Adempas tablets are available for patients 6 years of age or older and weighing at least 50 kg.

Treatment should only be started and controlled by a doctor with experience in the treatment of high blood pressure in the pulmonary arteries. During the first few weeks of treatment, your doctor will need to check your blood pressure at regular intervals. Adempas is available in different doses, and by checking your blood pressure at the start of treatment, your doctor will ensure that you are taking the right dose.

Crushed tablets:

If you have difficulty swallowing the whole tablet, consult your doctor about other ways to take Adempas. The tablet can be crushed and mixed with water or a soft food, such as apple sauce, immediately before taking it.

Dose

The recommended initial dose is 1 tablet of 1 mg, 3 times a day for 2 weeks.

Tablets should be taken 3 times a day, every 6 or 8 hours. They can be taken with or without food.

However, if you are prone to low blood pressure (hypotension), you should not alternate taking Adempas with or without food, as this may affect how you react to this medicine.

During the first few weeks of treatment, your doctor will need to measure your blood pressure at least every two weeks. Your doctor will increase the dose every 2 weeks up to a maximum of 2.5 mg 3 times a day (maximum daily dose of 7.5 mg), unless you experience very low blood pressure. In this case, your doctor will prescribe the highest dose of Adempas that you can tolerate. Your doctor will determine the best dose for you. For some patients, lower doses taken 3 times a day may be sufficient.

Special considerations for patients with kidney or liver problems

Tell your doctor if you have kidney or liver problems. Your doctor may adjust your dose.

If you have severe liver problems, do not take Adempas.

Patient over 65 years of age

If you are 65 years of age or older, your doctor will adjust your dose more carefully, as you have a higher risk of developing low blood pressure.

Special considerations for patients who smoke

Tell your doctor if you start or stop smoking during treatment with this medicine, as your doctor may adjust your dose.

If you take more Adempas than you should

Tell your doctor if you have taken more Adempas than you should and if you notice any side effects (see section 4). If you experience a sudden drop in blood pressure (which can make you feel dizzy), you may need immediate medical attention.

If you forget to take Adempas

Do not take a double dose to make up for forgotten doses. If you forget to take a dose, continue with the next dose as planned.

If you stop taking Adempas

Do not stop taking this medicine without talking to your doctor first, as this medicine prevents the progression of the disease. If you stop treatment with this medicine for 3 days or more, tell your doctor before restarting Adempas.

If you switch between sildenafil or tadalafil and Adempas

A break is required between taking the previous medicines and the new ones to avoid interactions:

Switch to Adempas

• Take Adempas no earlier than 24 hours after stopping treatment with sildenafil.
• Take Adempas no earlier than 48 hours after stopping treatment with tadalafil for adults and 72 hours for children.

Switch from Adempas

• Stop taking Adempas at least 24 hoursbefore starting to use a PDE5 inhibitor (e.g., sildenafil or tadalafil).

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The most serious side effects in adultsare:

• coughing up blood (hemoptysis) (common side effect, may affect up to 1 in 10 people),
• acute pulmonary bleeding (pulmonary hemorrhage) that can cause coughing up blood, with some cases being fatal (uncommon side effect, may affect up to 1 in 100 people).

If this happens, contact your doctor immediately, as you may need urgent medical treatment.

General list of possible side effects:

Very common:may affect more than 1 in 10 people

• headache
• dizziness
• indigestion (dyspepsia)
• swelling of the limbs (peripheral edema)
• diarrhea
• feeling or being sick (nausea or vomiting)

Common:may affect up to 1 in 10 people

• stomach inflammation (gastritis)
• inflammation of the digestive system (gastroenteritis)
• decrease in the number of red blood cells (anemia) which can cause pale skin, weakness, or difficulty breathing
• feeling of irregular, strong, or fast heartbeat (palpitations)
• low blood pressure (hypotension)
• nosebleeds (epistaxis)
• difficulty breathing through the nose (nasal congestion)
• stomach, intestine, or abdominal pain (gastrointestinal and abdominal pain)
• heartburn (gastroesophageal reflux disease)
• difficulty swallowing (dysphagia)
• constipation
• abdominal swelling (abdominal distension)

Side effects in children

In general, the side effects seen in children from 6 to 17 years of agetreated with Adempas were similar to those seen in adults. The most common side effects in childrenwere:

• low blood pressure(hypotension) (may affect more than 1 in 10 people)
• headache(may affect up to 1 in 10 people)

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Adempas

Keep this medicine out of the sight and reach of children.

This medicine does not require any special storage conditions.

Do not use this medicine after the expiry date which is stated on the blister and on the carton after "EXP". The expiry date is the last day of the month shown.

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

6. Contents of the pack and other information

Composition of Adempas

• The active substance is riociguat.

Adempas 0.5 mg film-coated tablets

Each tablet contains 0.5 mg of riociguat.

Adempas 1 mg film-coated tablets

Each tablet contains 1 mg of riociguat.

Adempas 1.5 mg film-coated tablets

Each tablet contains 1.5 mg of riociguat.

Adempas 2 mg film-coated tablets

Each tablet contains 2 mg of riociguat.

Adempas 2.5 mg film-coated tablets

Each tablet contains 2.5 mg of riociguat.

• The other ingredients are:

Tablet core:microcrystalline cellulose, crospovidone (type B), hypromellose 5 cP, lactose monohydrate, magnesium stearate and sodium lauryl sulfate (see the end of section 2 for further information on lactose).

Film coating:hypromellose 3 cP, propylene glycol (E1520) and titanium dioxide (E171).

The 1 mg and 1.5 mg Adempas tablets also contain yellow iron oxide (E172)

The 2 mg and 2.5 mg Adempas tablets also contain yellow iron oxide (E172) and red iron oxide (E172).

Appearance and packaging

Adempas is a film-coated tablet:

Adempas 0.5 mg film-coated tablets

• 0.5 mg tablet:white, round, biconvex tablets, 6 mm in diameter, marked with the Bayer cross on one side and 0.5 and an "R" on the other.

Adempas 1 mg film-coated tablets

• 1 mg tablet:pale yellow, round, biconvex tablets, 6 mm in diameter, marked with the Bayer cross on one side and 1 and an "R" on the other.

Adempas 1.5 mg film-coated tablets

• 1.5 mg tablet:orange-yellow, round, biconvex tablets, 6 mm in diameter, marked with the Bayer cross on one side and 1.5 and an "R" on the other.

Adempas 2 mg film-coated tablets

• 2 mg tablet:pale orange, round, biconvex tablets, 6 mm in diameter, marked with the Bayer cross on one side and 2 and an "R" on the other.

Adempas 2.5 mg film-coated tablets

• 2.5 mg tablet:orange-red, round, biconvex tablets, 6 mm in diameter, marked with the Bayer cross on one side and 2.5 and an "R" on the other.

They are available in packs of:

• 42 tablets: two transparent calendar blisters, each containing 21 tablets.
• 84 tablets: four transparent calendar blisters, each containing 21 tablets.
• 90 tablets: five transparent blisters, each containing 18 tablets.
• 294 tablets: fourteen transparent calendar blisters, each containing 21 tablets.

Not all pack sizes may be marketed.

Marketing authorisation holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

You can request more information about this medicine from the local representative of the marketing authorisation holder.

Date of last revision of this leaflet:MM/AAAA.

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu.