Adempas 0.5 mg film-coated tablets

• 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 has been written as though the person taking the medicine is reading it. If you are giving this medicine to your child, please replace “you” with “the child” throughout.

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

• take PDE5 inhibitors such as sildenafil, tadalafil, vardenafil. These are medicines to treat high blood pressure in lung arteries or erectile dysfunction.
• have severely reduced liver function.
• are allergic to riociguat or any of the other ingredients of this medicine (listed in section 6).
• are pregnant.
• take nitrates or nitric oxide donors such as amyl nitrite. These are medicines often used to treat high blood pressure, chest pain or heart disease. This also includes recreational drugs called poppers.
• take other medicines similar to Adempas called soluble guanylate cyclase stimulators, such as vericiguat. Ask your doctor if you are not sure.
• have low blood pressure before you take Adempas the first time. To start with Adempas your systolic blood value should be
  • 90 mmHg or more if your age is between 6 and 12 years,
  • 95 mmHg or more if you are 12 years old or older.
• have increased blood pressure in your lungs associated with scarring of the lungs, of unknown cause called idiopathic pulmonary pneumonia.

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

Talk to your doctor or pharmacist before taking Adempas if you

• have pulmonary veno-occlusive disease, a disease which makes you feel short of breath because fluid builds-up in the lungs. He or she may decide to provide you with an alternative medicine.
• have recently had serious bleeding from the lungs and airways.
• have undergone treatment to stop coughing up blood (bronchial arterial embolisation).
• take medicines that prevent the blood from clotting since this may cause bleeding from the lungs. Your doctor will regularly test your blood and measure blood pressure.
• The doctor may decide to monitor the blood pressure, if you
  • have symptoms of low blood pressure like dizziness, lightheadedness or fainting, or
  • take medicines to lower blood pressure or to increase urination, or
  • have heart or circulation problems
  • are older than 65 years as low blood pressure is more likely in this age group.

Inform your doctor if

• you are on dialysis or if the kidneys do not work properly, as use of this medicine is not recommended.
• your liver does not work properly.

While using Adempas, talk to your doctor if you

• feel short of breath during treatment with this medicine. This can be caused by a build-up of fluid in the lungs. If this is due to pulmonary veno-occlusive disease your doctor may stop treatment with Adempas.
• start or stop smoking during treatment with this medicine, because this may influence the level of riociguat in your blood.

• Chronic thromboembolic pulmonary hypertension (CTEPH)
  • Adempas is not recommended for use in CTEPH patients less than 18 years of age.
• Pulmonary arterial hypertension (PAH)
  • You have been prescribed Adempas tablets. For PAH patients of 6 years and older that weigh less than 50 kg, Adempas is also available as granules for oral suspension.
    Patients may switch between tablets and oral suspension during therapy due to body weight changes.
    Efficacy and safety have not been shown in the following paediatric populations:
    • Children less than 6 years because of safety concerns.

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

• Do not take medicines used for
  • high blood pressure or heart disease such as nitrates and amyl nitrite, or another soluble guanylate cyclase stimulator such as vericiguat. Do not take these medicines together with Adempas.
  • high blood pressure in lung arteries, as you must not take certain medicines such as sildenafil, tadalafil together with Adempas. Other medicines for high blood pressure in the lung arteries, such as bosentan and iloprost, can be used with Adempas, but you should inform the doctor.
  • erectile dysfunction such as sildenafil, tadalafil, vardenafil. Do not take these medicines together with Adempas.

• The following medicines can increase the level of Adempas in the blood which increases the risk of side effects
  • fungal infections such as ketoconazole, posaconazole, itraconazole
  • HIV infection such as abacavir, atazanavir, cobicistat, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, rilpivirine, ritonavir.
  • epilepsy such as phenytoin, carbamazepine, phenobarbitone.
  • depression such as St. John’s Wort.
  • preventing rejection of transplanted organs such as ciclosporin.
  • cancer such as erlotinib, gefitinib.
  • nausea, vomiting such as granisetron.
  • to treat stomach disease or heartburn called antacids such as aluminium hydroxide / magnesium hydroxide. Take antacids at least 2 hours before or 1 hour after using Adempas.

Adempas can generally be taken with or without food.

However, if your blood pressure tends to be low, take Adempas either always with food or always without food.

• Birth control: Women and female adolescents of childbearing potential must use effective contraception during treatment with Adempas. Talk to your doctor about suitable methods of contraception you may use to prevent pregnancy. In addition you should take monthly pregnancy tests.
• Pregnancy: Do not use Adempas during pregnancy.
• Breast-feeding: Breast-feeding is not recommended while using this medicine because it might harm the baby. Inform your doctor if you are currently breast-feeding, or planning to breast-feed before using this medicine. Your doctor will decide with you to either stop breast-feeding or to stop using Adempas.

Adempas moderately influences the ability to cycle, drive and use machines. It may cause side effects such as dizziness. You should be aware of the side effects of this medicine before cycling, driving or using machines (see section 4).

If you have been told by a doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium free”.

Your doctor will tell you what dose of Adempas to take.

• Treatment usually starts with a low dose.
• Your doctor will slowly increase your dose depending on how you respond to the treatment.
• During the first weeks of treatment the doctor will need to measure your blood pressure at least every two weeks. This is required to decide on the correct dose of your medicine.

Adempas is for oral use. The tablets should be taken 3 times a day, every 6 to 8 hours.

Crushed tablets:

If you have difficulty swallowing the whole tablet, talk to your doctor about other ways to take Adempas. The tablet may be crushed and mixed with water or a soft food immediately before you take it.

The recommended starting dose is a 1-mg tablet taken 3 times a day for 2 weeks.

Your doctor will increase the dose every 2 weeks 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 you Adempas at the highest dose you are comfortable on. The best dose will be selected by your doctor. For some patients lower doses 3 times a day might be sufficient.

You may be at greater risk of low blood pressure. Your doctor may adjust the dose.

If you smoke, it is recommended that you stop before starting treatment, as smoking may reduce the effectiveness of these tablets. Please tell your doctor if you smoke or stop smoking during treatment. Your doctor may need to adjust your dose.

Please contact the doctor if you took more Adempas than you should and if you notice any side effects (see section 4). If your blood pressure drops (which can make you feel dizzy) then you may need immediate medical attention.

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

Do not stop taking this medicine without talking to your doctor first. If you stop taking this medicine, your disease may worsen. If you have not taken this medicine for 3 days or more, please tell your doctor before you start taking it again.

To avoid interactions, Adempas and PDE5 inhibitors (sildenafil, tadalafil) must not be taken at the same time.

• If you switch to Adempas
  • do not start Adempas for at least 24 hours after your last dose of sildenafil and at least 48 hours after your last dose of tadalafil.
• If you switch from Adempas
  • stop using Adempas at least 24 hours before you start using sildenafil or tadalafil.

Very common: may affect more than 1 in 10 people

• dizziness
• headache
• indigestion (dyspepsia)
• diarrhoea
• feeling sick (nausea)
• vomiting
• swelling of limbs (oedema peripheral)

Common: may affect up to 1 in 10 people

• inflammation in the digestive system (gastroenteritis)
• low levels of red blood cells (anaemia). Symptoms are pale skin, weakness or breathlessness
• irregular, hard or rapid heartbeat (palpitations)
• low blood pressure (hypotension)
• nose bleed (epistaxis)
• difficulty breathing through your nose (nasal congestion)
• inflammation of the stomach (gastritis)
• heartburn (gastro-oesophageal reflux disease)
• difficulty in swallowing (dysphagia)
• pain in the stomach, intestine or abdomen (gastrointestinal and abdominal pain)
• constipation
• bloating (abdominal distension)

In general, side effects observed in children aged 6 to less than 18 years treated with Adempas were similar to those observed in adults. The most frequent side effects in children were:

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

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, Website: https://yellowcard.mhra.gov.uk 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.

• The active substance is riociguat.
  Adempas 0.5 mg film-coated tablets
  Each film-coated tablet contains 0.5 mg riociguat.
  Adempas 1 mg film-coated tablets
  Each film-coated tablet contains 1 mg riociguat.
  Adempas 1.5 mg film-coated tablets
  Each film-coated tablet contains 1.5 mg riociguat.
  Adempas 2 mg film-coated tablets
  Each film-coated tablet contains 2 mg riociguat.
  Adempas 2.5 mg film-coated tablets
  Each film-coated tablet contains 2.5 mg riociguat.
• The other ingredients are:
  Tablet core: cellulose microcrystalline, crospovidone (type B), hypromellose 5 cP, lactose monohydrate, magnesium stearate and sodium laurilsulfate (see end of section 2 for further information on lactose and sodium).
  Tablet-coat: hydroxypropylcellulose, hypromellose 3 cP, propylene glycol (E 1520) and titanium dioxide (E 171).
  Adempas 1 mg and 1.5 mg tablets also contain iron oxide yellow (E 172).
  Adempas 2 mg and 2.5 mg tablets also contain iron oxide yellow (E 172) and iron oxide red (E 172).

Adempas is a film-coated tablet (tablet):

Adempas 0.5 mg film-coated tablets

• White, round, biconvex tablets of 6 mm, marked with the Bayer cross on one side and 0.5 and an “R” on the other side.

Adempas 1 mg film-coated tablets

• Pale yellow, round, biconvex tablets of 6 mm, marked with the Bayer cross on one side and 1 and an “R” on the other side.

Adempas 1.5 mg film-coated tablets

• Yellow-orange, round, biconvex tablets of 6 mm, marked with the Bayer cross on one side and 1.5 and an “R” on the other side.

Adempas 2 mg film-coated tablets

• Pale orange, round, biconvex tablets of 6 mm, marked with the Bayer cross on one side and 2 and an “R” on the other side.

Adempas 2.5 mg film-coated tablets

• Red-orange, round, biconvex tablets of 6 mm, marked with the Bayer cross on one side and 2.5 and an “R” on the other side.

They are available in cartons of:

• 42 tablets: 2 transparent calendar blisters of 21 tablets each.
• 84 tablets: 4 transparent calendar blisters of 21 tablets each.
• 90 tablets: 5 transparent blisters of 18 tablets each.
• 294 tablets: 14 transparent calendar blisters of 21 tablets each.

Not all pack sizes may be marketed.