Package Insert: Information for theuser

Adempas 0.5 mg film-coatedtablets

Adempas 1 mg film-coatedtablets

Adempas 1.5 mg film-coatedtablets

Adempas 2 mg film-coatedtablets

Adempas 2.5 mg film-coatedtablets

riociguat

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

• This package insert has been written as if you, the person taking the medicine, are reading it. If you are administering this medicine to your child, please replace “you” with “your child” throughout the package insert.

1. What is Adempas and for what it is used

2. What you need to know before starting to take Adempas

3. How to take Adempas

4. Possible side effects

5. Storage of Adempas

6. Contents of the package and additional information

Adempas contains the active ingredient riociguat, a guanylate cyclase (GCs) stimulator that acts by widening the blood vessels that go from the heart to the lungs.

Adempas is usedinthe treatment of certain forms of pulmonary hypertension in adults and children, a disease in which these blood vessels constrict, making it more difficult 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 constricted arteries, Adempas improves the ability to perform physical activity, that is, to walk a greater distance.

Adempas is used in these two types of pulmonary hypertension:

• Chronic thromboembolic pulmonary hypertension (CTEPH)

The Adempas tablets are used to treat CTEPH in adult patients. In CTEPH, the blood vessels of the lung are blocked or constricted by blood clots. Adempas can be used in patients with CTEPH in whom a surgical intervention cannot be performed or in those patients in whom pulmonary hypertension persists or recurs after surgery.

• Certain types of pulmonary arterial hypertension (PAH)

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

Do not take Adempas if:

−You takephosphodiesterase type 5 inhibitors(such as sildenafil, tadalafil, vardenafil). These are medications for treating high blood pressure in the pulmonary arteries (PAH) or erectile dysfunction;

• tieneserious liver problems(severe hepatic insufficiency);

− areallergicto riociguat or to any of the other components of this medication (listed in section 6);

− arepregnant;

−You takenitratesornitric oxide donors(such as amyl nitrite) in any form, medications frequently used to treat high blood pressure, chest pain, or heart disease. This also includes recreational drugs known as “poppers”;

• You take othermedications similar to Adempas (soluble guanylate cyclase stimulators, such as vericiguat). Consult your doctor if you are unsure;
• You havelow blood pressure(systolic blood pressure:in children aged6to <12years old below 90mmHg, in patients≥12yearsbelow<95>
• You have anincrease in blood pressurein the lungs associated with pulmonary fibrosis, of unknown cause (idiopathic pulmonary fibrosis).

If you have any of these conditions,talk to your doctorfirst and do not take Adempas.

Warnings and precautions

Consult your doctor or pharmacist before starting Adempas if:

• You have recently had asevere pulmonary hemorrhage;
• You have received treatment to stop amassive bleeding(bronchial arterial embolization);
• You are takingblood thinners(anticoagulants) as this may cause bleeding in the lungs. Your doctor will perform regular blood tests and blood pressure measurements;
• You experiencedifficulty breathing, as this may be caused by fluid accumulation in the lungs. Talk to your doctor if this occurs;

You have any symptoms oflow blood pressure(hypotension) such as dizziness, vertigo, or fainting, or if you are taking medications to lower blood pressure or medications that cause an increase in 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 taking medications fortreating fungal infections(e.g., ketoconazole, posaconazole, itraconazole) or medications fortreatment of HIV infection(e.g., abacavir, atazanavir, cobicistat, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, lamivudine, rilpivirina, ritonavir, and tenofovir). Your doctor will monitor your health and may consider a lower initial dose of Adempas;
• tienemoderate liver problems(hepatic insufficiency);
• You start or stopsmokingduring treatment with this medication, as this may affect the level of riociguat in the blood.

.

Children and adolescents

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

•Children <6

•Children with PAH with a blood pressure that is too low:

o6 to <12

o12 to <18

•Children and adolescents with other forms of this disease, i.e., HPTEC, if <18

Other medications and Adempas

Inform your doctor or pharmacist if you are taking, have taken recently, or may take any other medication, particularly medications used for the treatment of:

−High blood pressure or heart disease (such asnitrates and amyl nitrite) in any form or anothersoluble guanylate cyclase stimulator(such asvericiguat). Do not take these medications with Adempas.

−PAH in the pulmonary arteries (the pulmonary arteries) as you should not take certain medications (sildenafil or tadalafil) with Adempas. Other medications for PAH in the pulmonary arteries such asbosentanandiloprostmay be used with Adempas, but you should inform your doctor.

−Erectile dysfunction (such assildenafil, tadalafil, vardenafil) as you should not take these medications with Adempas.

−Fungal infections (such asketoconazole, posaconazole, itraconazole) or

−HIV infection (such asabacavir, atazanavir, cobicistat, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, rilpivirina, ritonavir). Alternative treatment options may be considered. If you are already taking one of these medications 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 transplant rejection (ciclosporin).

−Muscle or joint pain (acetylsalicylic acid).

−Cancer (such aserlotinib, gefitinib).

−Gastrointestinal disorders or heartburn (antacids, such asaluminum hydroxide/magnesium hydroxide). These medications should be taken at least 2 hours before or 1 hour after taking Adempas.

−Nausea, vomiting (such as granisetron).

Smoking

If yousmoke, it is recommended that you stop as smoking reduces the effectiveness of these tablets. Inform your doctor if you smoke or stop smoking during treatment. Your dose may need to be adjusted.

Control of pregnancy, pregnancy, and breastfeeding

Control of pregnancy

Women and adolescents of childbearing age should 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 intend to become pregnant, consult your doctor or pharmacist before taking this medication.

Breastfeeding

If you are breastfeeding or intend to breastfeed, consult your doctor or pharmacist before taking this medication, as it may harm your baby. You should not breastfeed while taking this medication. Your doctor will decide whether to stop breastfeeding or stop treatment with Adempas.

Driving and operating machinery

Adempas moderately affects the ability to ride a bike, drive, and use machines. It may cause side effects such as dizziness. Before riding a bike, driving, or using machines, you should be aware of theside effectsof this medication (see section 4).

Adempas contains lactose

If a doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Adempas contains sodium

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

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

The treatment should only be initiated and controlled by a doctor experienced in the treatment of high blood pressure in the pulmonary arteries. During the first weeks of treatment, your doctor will need to monitor your blood pressure at regular intervals. Adempas is available in different doses, and by checking your blood pressure at the beginning of treatment, your doctor will ensure that you are taking the appropriate 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, taken 3 times a day for 2 weeks.

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

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

During the first weeks of treatment, your doctor will need to measure your blood pressure at least every 2 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 suits you.Your doctor will determine the best dose.For some patients, lower doses taken 3 times a day may be sufficient.

Special considerations for patients with renal or hepatic problems

Inform 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.

Patients aged 65 and over

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

Special considerations for patients who smoke

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

If you take more Adempas than you should

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

If you forget to take Adempas

Do not take a double dose to compensate for the missed doses. If you forget to take a dose, continue with the next dose as scheduled.

If you interrupt treatment with Adempas

Do not stop taking this medication without first discussing it with your doctor, as this medication prevents the progression of the disease. If you interrupt treatment with this medication for 3 days or more, inform your doctor before resuming treatment.

If you change treatment between sildenafilo or tadalafilo and Adempas

A pause should be made between the previous medications and the new ones to avoid interactions:

Switch to Adempas

• Take or administer Adempas no earlier than 24 hours after stopping treatment with sildenafilo.
• Take or administer Adempas no earlier than 48 hours after stopping treatment with tadalafilo for adults and 72 hours for children.

Switch from Adempas

• Stop taking or administering Adempas at least 24 hours before starting to use a PDE5 inhibitor (e.g., sildenafilo or tadalafilo).

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The mostserious side effects in adultsare:

•coughing up blood (hemoptysis) (frequent side effect, may affect up to 1 in 10 people),

•acute pulmonary hemorrhagethat may cause coughing up blood, fatal cases have been observed (infrequent 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 frequent:may affect more than 1 in 10 people

- headache

- dizziness

- indigestion (dispepsia)

- swelling of the extremities (peripheral edema)

- diarrhea

- feeling or being unwell (nausea or vomiting)

Frequent:may affect up to 1 in 10 people

- inflammation of the stomach (gastritis)

- inflammation in the digestive system (gastroenteritis)

-decrease in the number of red blood cells (anemia) that translates to pale skin, weakness or difficulty breathing

- sensation of irregular, strong or rapid heartbeat (palpitation)

- low blood pressure (hypotension)

- nasal bleeding (epistaxis)

- difficulty breathing through the nose (nasal congestion)

- abdominal pain, intestinal or stomach pain (gastrointestinal and abdominal pain)

- heartburn (gastroesophageal reflux disease)

- difficulty swallowing (dysphagia)

- constipation

- abdominal distension

Side effects in children

In general, the side effects observed in childrenaged 6 to 17 yearstreated with Adempas were similar to those observed in adults. The mostfrequent side effects in childrenwere:

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

This medication does not require special storage conditions.

Do not use this medication after the expiration date that appears on the blister pack and on the container after "CAD". The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. By doing so, you will help protect the environment.

Composition of Adempas

- The active ingredient is riociguat.

Adempas 0.5 mg film-coated tablets

Cada tablet contains 0.5 mg of riociguat.

Adempas 1 mg film-coated tablets

Cada tablet contains 1 mg of riociguat.

Adempas 1.5 mg film-coated tablets

Cada tablet contains 1.5 mg of riociguat.

Adempas 2 mg film-coated tablets

Cada tablet contains 2 mg of riociguat.

Adempas 2.5 mg film-coated tablets

Cada tablet contains 2.5 mg of riociguat.

- The other components are:

Core tablet:microcrystalline cellulose, crospovidone (type B), hypromellose 5 cP, lactose monohydrate, magnesium stearate and sodium lauryl sulfate (see section 2 for more information on lactose).

Coating:hydroxypropylcellulose, hypromellose 3 cP, propylene glycol (E1520) and titanium dioxide (E171).

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

The Adempas 2 mg and 2.5 mg tablets also contain yellow iron oxide (E172) and red iron oxide (E 172).

Appearance of the medicinal product and contents of the pack

Adempas is a film-coated tablet:

Adempas 0.5 mg film-coated tablets

• 0.5 mg tablet:round, biconvex, white 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:round, biconvex, pale yellow 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:round, biconvex, yellow-orange 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:round, biconvex, pale orange 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:round, biconvex, reddish-orange 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 blister packs with a calendar of 21 tablets each.
• 84 tablets: four transparent blister packs with a calendar of 21 tablets each.
• 90 tablets: five transparent blister packs with 18 tablets each.
• 294 tablets: fourteen transparent blister packs with a calendar of 21 tablets each.

Only some pack sizes may be marketed.

Marketing authorisation holder

Bayer AG

51368 Leverkusen

Germany

Manufacturer responsible

Bayer AG

Kaiser-Wilhelm-Allee

51368 Leverkusen

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder.

Last update of the summary of product characteristics:MM/AAAA.

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.