InfoCons Consumer Protection informs you – Adempas – Package Leaflet

Before anything else

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 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.

ℹ️ 1. What Adempas is and what it is used for

Adempas contains the active substance riociguat, a guanylate cyclase (sGC) -stimulator.

Pulmonary arterial hypertension (PAH) .

Adempas is used to treat children from 6 years of age with pulmonary arterial hypertension. In these patients, the wall of the blood vessels of the lungs are thickened and therefore the vessels become narrowed. Adempas is taken together with certain other medicines (so-called endothelin receptor antagonists).

In patients with pulmonary hypertension, the blood vessels that carry blood from the heart to the lungs become narrowed, making it harder for the heart to pump blood to the lungs, and leading to high blood pressure in the vessels. Because the heart must wo rk harder than normal, people with pulmonary hypertension feel tired, dizzy and short of breath. Adempas widens the blood vessels that lead from the heart to the lungs, reducing symptoms of the disease and better allowing patients to carry out physical activity better.

⚠️ 2. What you need to know before you use Adempas

Do not use Adempas if you

• use PDE5 inhibitors such as sildenafil, tadalafil, vardenafil . These are medicines to treat high blood pressure in lung arteries or to treat erectile dysfunction.
• have severe ly reduced liver function .
• are allergic to riociguat or any of the other ingredients of this medicine (listed in section 6).
• are pregnant.
• use 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.
• use other medicines similar to Adempas called soluble guanylate cyclases stimulator s, such as 70 vericiguat . Ask your doctor if you are not sure.
• have low blood pressure before you start treatment with Adempas. To start with Adempas your systolic blood press ure value needs to be
• 90 mmHg or more if you are 6 to 11 years old,
• 95 mmHg or more if you are12 to 17 years old.
• 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 use Adempas.

Warnings and precautions

Talk to your doctor or pharmacist before using 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 medic ine.
• have recently had serious bleeding from the lung s 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,
• take medicines to lower blood pressure or to increase urination,
• have heart or circulation problems 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 -occlusi ve 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 .

Children and adolescents

You have been prescribed Adempas granules for oral suspension. For PAH pati ents of 6 years and older that weigh 50 kg and more, Adempas is also available as tablets. Patients may be switc hed between granules for oral suspension and tablets 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.

Other medicines and Adempas

Tell your doctor or pharmacist if you are using , have recently used or might use any other medicines, in particular :

• Do not take the following medicines with Adempas
• PDE5 inhibitors such as sildenafil, tadalafil , or vardenafil . These are medicines to treat high blood pressure in lung arteries or to treat erectile dysfunction.
• 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 .
• other soluble guanylate cyclase stimulators , such as vericiguat .
• Medicines that can change the level of Adempas in the blood , for example
• ketoconazole, posaconazole, itraconazole , to treat fungal infection s.
• abacavir, atazanavir, cobicistat, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, rilpivirine, ritonavir , to treat HIV infections .
• phenytoin, carbamazepine, phenobarbitone , to treat epilepsy .

71 – St. John’s Wort , to treat depression .

• ciclosporin , to prevent rejection of transplanted organs .
• erlotinib, gefitinib , to treat cancer .
• bosentan , to treat pulmonary arterial hypertension .
• antacids such as aluminium hydroxide / magnesium hydroxide , to treat indigestion or heartburn . Take antacids at least 2 hours before or 1 hour after using Adempas .

If you are taking these medicines, you may experience more side effects, or Adempas may not work as expected.

• Medicines whose effect may be influence d by Adempas , for example
• granisetron, to treat nausea or vomiting.
• erlotinib , to treat cancer.

If you are taking th ese medicines, ask your doctor whether their doses need to be changed.

Adempas with food

Adempas can generally be taken with or without food.

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

Pregnancy and breast -feeding

• 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.

Driving and using machines

Adempas moderate ly influence s 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).

Adempas contains sodium benzoate

This medicine contains 1.8 mg sodium benzoate (E 211) in each mL oral suspension.

Adempas contains sodium

This medicine contains 0.5 mg sodium in each mL oral suspension. This medicine contains less than 1 mmol sodium (23 mg) per mL oral suspension , that is to say essentially “sodium -free”.

💊 3. How to use Adempas

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

Adempas is available as a tablet or granules for oral suspension.

Tablets are available for use by adults and children weighing at least 50 kg. Granules for oral suspension are available for children weighing less than 50 kg.

How to start treatment 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.

72 – 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.

Your doctor will calculate and tell you the amount of oral suspension in millilitres (mL) you need to take. Do not adjust the dose yourself. The amount in mL needs to be measured with one of the blue syringe s included in the Adempas carton. Your doctor or pharmacist will tell you which blue syringe to use (5 mL or 10 mL).

Before you use

• Make sure the correct dose is written on the carton. If not, ask your pharmacist or doctor to provide it. Keep the carton until the granules for oral suspension are used up.
• Follow th e “Instruction s for Use” included in the carton on how to prepare and use Adempas oral suspension carefully to avoid any handling problems e.g., clumps or sediment in the suspension .
• All materials to prepare and take the oral suspension are provided with the medicine . Only use non-sparkling water to avoid bubbles .

Use only the syringes provided to administer Adempas to ensure correct dosing. Do not use any other method to take the suspension, such as alternative syringe, spoon etc.

How to take the medicine Adempas is for oral use . Take your Adempas dose 3 times a day, every 6 to 8 hours .

How much you have to use During the starting phase your doctor decides the dose of oral suspension every 2 weeks. The doctor will adjust the dose based on body weight and blood pressure. The maximum dose depends on the body weight. Your doctor will decide whether and when to switch between tablets and oral suspension during therapy due to body weight changes.

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

If you take more Adempas than you should

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

If you forget to use Adempas

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

If you stop using Adempas

Do not stop using 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 .

If you are switching between Adempas and sildenafil or tadalafil To avoid interactions, Adempas and PDE5 inhibitors (sildenafil, tadalafil) must not be taken at the same time .

• If you s witch to Adempas
• do not start Adempas for at least 24 hours after your last dose of sildenafil and at least 72 hours after your last dose of tadalafil.
• If you s witch from Adempas
• stop using Adempas at least 24 hours before you start using sildenafil or tadalafil.

73 If you have any further questions on 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. Some of these may be serious. If this happens , contact your doctor immediately as you may need urgent medical treatment.

Side effects in children In general, side effects observed in children 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) Overall list of possible side effects (in adult patients)

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 (palpitation s)
• 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)

Reporting of side effects

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 national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.

🌡️ 5. How to store Adempas

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 bottle label after “EXP”. The expiry date refers to the last day of that month.

Do not store above 30 °C.

Do not freeze.

After reconstitution the shelf life of the suspension is 14 days at room temperature .

Store the prepared suspension upright.

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 Adempas contains

• The active substance is riociguat.

After preparation , the oral suspension contains 10.5 g granules plus 200 mL water, which results in 208 mL suspension with 0.15 mg riociguat per mL.

• The other ingredients are anhydrous citric acid (E 330), flavour strawberry , hypromellose , mannitol (E 421); microcrystalline cellulose and carmellose sodium ; sodium benzoate (E 211) (see end of section 2 for further information on sodium benzoate and sodium) , sucralose (E 955), xanthan gum (E 415).

What Adempas looks like and contents of the pack

Adempas are white to off -white granules.

Content of the pack:

• 1 bottle (brown glass) containing 10.5 g Adempas granules , closed with a child -resistant screw cap.
• 1 water syringe 100 mL (for single use only) used to measure and add 200 mL of water to the bottle.
• 1 adapter for bottle and blue syringes .
• 2 blue syringes 5 mL with blue plunger to extract and orally administer Adempas (1 is a spare syringe) . The scale of the 5 mL blue syringe starts with 1 mL. The graduation marks are in increments of 0.2 mL.
• 2 blue syringes 10 mL with blue plunger to extract and orally administer Adempas (1 is a spare syringe ). The scale of the 10 mL blue syringe starts with 2 mL. The graduation marks are in increments of 0.5 mL.

Marketing Authorisation Holder

Bayer AG 51368 Leverkusen Germany

Manufacturer

Bayer AG Kaiser -Wilhelm -Allee 51368 Leverkusen Germany For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder .

België / Belgique / Belgien MSD Belgium Tél/Tel: +32(0)27766211 [email protected] Lietuva UAB Merck Sharp & Dohme Tel. +370 5 2780 247 [email protected] 75 България Мерк Шарп и Доум България ЕООД Teл.: +359 2 819 37 37 info-msdbg@ msd.com Luxembourg / Luxemburg MSD Belgium Tél/Tel: +32(0)27766211 [email protected] Česká republika Merck Sharp & Dohme s.r.o.

Tel.: +420 277 050 000 dpoc_czechslovak @msd.com Magyarország MSD Pharma Hungary Kft.

Tel.: +36 1 888 5300 hungary_msd@ msd.com Danmark MSD Danmark ApS Tlf.: + 45 4482 4000 [email protected] Malta Merck Sharp & Dohme Cyprus Limited Tel: 8007 4433 (+356 99917558) dpoccyprus @msd.com Deutschland MSD Sharp & Dohme GmbH Tel.: +49 (0) 89 20 300 4500 [email protected] Nederland Merck Sharp & Dohme B.V.

Tel: 0800 9999 000 (+31 23 5153153) medicalinfo.nl@ msd.com Eesti Merck Sharp & Dohme OÜ Tel: +372 614 4200 [email protected] Norge MSD (Norge) AS Tlf: + 47 32 20 73 00 [email protected] Ελλάδα MSD Α.Φ.Ε.Ε.

Τηλ: +30 210 98 97 300 dpoc.greece@ msd.com Österreich Merck Sharp & Dohme Ges.m.b.H.

Tel: +43 (0) 1 26 044 [email protected] España Merck Sharp & Dohme de España, S.A.

Tel: +34 91 321 06 00 msd_info@m sd.com Polska MSD Polska Sp. z o.o.

Tel.: +48 22 549 51 00 msdpolska@ msd.com France MSD France Tél: +33 (0)1 80 46 40 40 Portugal Merck Sharp & Dohme , Lda Tel.: +351 21 4465700 [email protected] Hrvatska Merck Sharp & Dohme d.o.o.

Tel: +385 1 6611 333 dpoc.croatia@ msd.com România Merck Sharp & Dohme Romania S.R.L.

Tel.: +40 21 529 29 00 msdromania@ msd.com Ireland Merck Sharp & Dohme Ireland (Human Health) Limited Tel: +353 (0)1 2998700 [email protected] Slovenija Merck Sharp & Dohme, inovativna zdravila d.o.o.

Tel: +386 1 520 4201 msd.slovenia@ msd.com Ísland Vistor ehf.

Sími: + 354 535 7000 Slovenská republika Merck Sharp & Dohme, s. r. o.

Tel.: +421 2 58282010 dpoc_czechslovak@ msd.com 76 Italia MSD Italia S.r.l.

Tel: 800 23 99 89 (+39 06 361911) [email protected] Suomi/Finland MSD Finland Oy Puh/Tel: + 358 (0)9 804 650 [email protected] Κύπρος Merck Sharp & Dohme Cyprus Limited Τηλ.: 800 00 673 (+357 22866700) dpoc cyprus@ msd.com Sverige Merck Sharp & Dohme (Sweden) AB Tel: +46 77 5700488 [email protected] Latvija SIA Merck Sharp & Dohme Latvija Tel.: +371 67025300 [email protected]

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu 77 Instructions for Use (IFU) Adempas 0.15 mg/mL 250 mL bottle containing 10.5 g Adempas granules for preparation of oral suspension Active ingredient: riociguat Preparation and administration of the oral suspension (granules -water -mixture) Before you start • Adempas suspension is for oral use only. ▪ Your child’s doctor will tell you the right dose volume and the frequency of administration.

• Always use the volume prescribed by your child’s doctor and have the correct dosing and frequency of administration written on the designated field on the outside of the box. Keep the box for the duration of use. If it is not written on the field, ask your child’s doctor or pharmacist to provide the relevant information. o Do not change the dose yourself.
• Read all sections of the Instructions for Use carefully before using Adempas for the first time and before administering each dose.
• Be sure you understand the instructions before starting.

If not, call your doctor or pharmacist .

• Keep the instructions for use so that you can refer to them later during the use of Adempas.
• Further information regarding Adempas can be found in the package leaflet.

Cautionary information: Do not unpack the single components until the instructions tell you to do so.

Do not use Adempas if any of the parts have been opened or are

damaged.

Do not use Adempas after the expiry date which is stated on the

box.

The box contains small parts. These can block the airways and

lead to the risk of suffocation. Keep out of the reach of babies and young children.

Do not use the blue syringes for multiple patients as this can lead

to infections.

Follow th is “Instruction s for Use” on how to prepare and use Adempas oral suspension and for any question contact your doctor, your pharmacist, or the local representative listed at the end of the Adempas package leaflet.

Packaging contents

Every box contains the following components

1 bottle with child -resistant screw cap containing Adempas granules 1 packaged 100 mL water syringe (for single use only) 1 packaged bottle adapter 2 packaged 5 mL blue syringes (1 is a spare syringe) 2 packaged 10 mL blue syringes (1 is a spare syringe ) Using Adempas

• Adempas suspension is for oral use only.
• Your child’s doctor will tell you the right dose volume and the frequency of administration.
• Always use the volume prescribed by your child’s doctor and have the correct dosing and frequency of administration written on the designated field on the outside of the box. Keep the box for the duration of use.

If it is not written on the field, ask your child’s doctor or pharmacist to provide the relevant information.

• Do not change the dose yourself.
• Follow the detailed Instructions for Use given in the chapters below.
• Keep the instructions for use so that you can refer to them later during the use of Adempas.
• Take care to comply with the instructions concerning administration.

Preparing the oral suspension Preparation – Get ready The preparation of the suspension is done once with every new box.

Before preparing the oral suspension: a. Before you start, you will need the following equipment: ▪ Get two containers (suchas a cup or bowl)

• one container filled with drinking water,
• The other container empty. b. Obtain the following additional items:

▪ Container with at least 300 mL of non-carbonated drinking water at room temperature

• Tissue for soaking up any excess water. c. Thoroughly wash your hands with soap and dry them afterwards. d. Check the expiry date on the box.

Do not use the medicine if the medicine has expired.

Adding 200 mL of water to the 250 mL bottle with granules Every time you start a new box, use only the materials provided in the new box.

• Gently tap the bottle on your hand until granules flow freely .
• Be careful since the bottle is made of glass. a. Unscrew the child -resistant cap of the bottle (push down and turn counter -clockwise). b. Unpack the water syringe. c. Dip the opening of the water syringe into the container with water. d. Extract a volume of more than 100 mL. e. To do this, pull up the plunger rod towards you, and make sure that the opening of the water syringe stays below the water surface all the time. This will avoid air bubbles in the syringe. f. Take the syringe out of the water. g. Turn the water syringe in a way that the opening is facing upwards.

→ Any air bubbles will move to the top when holding the syringe upwards.

Tap it with your fingers to further move any air bubble to the top. h. Push the plunger rod until the upper ring of the plunger reaches the 100 mL mark. → When pressing the plunger, water can come out of the tip of the water syringe. This wastewater can be soaked up with a tissue.

Cautionary information:

The upper ring of the black plunger must be precisely in line with the 100 mL mark to be able to achieve the correct concentration of the suspension. i. Continue to hold the water syringe with the opening facing upwards and check the water in the syringe carefully:

• for correct volume,
• for air bubbles.

Small air bubbles are not critical, but big air bubbles must be removed .

j. If the water syringe is not loaded correctly or contains too

much air: a. Empty the water syringe b. Repeat steps c. to i. k. Place the filled water syringe on the upper edge of the bottle opening. l. Hold the bottle firmly.

Press the plunger rod down slowly.

The full volume of water must be transferred to the bottle. m. Repeat reconstitution steps (“c” to “ l”) one more time.

Cautionary information:

The bottle with granules to be filled in total with 200 mL of water (2 x 100 mL).

Fitting the adapter and mixing the oral suspension a. Unpack the bottle adapter. b. Push the adapter completely into the neck of the bottle. c. Close the bottle tightly with the screw cap. d. Shake the bottle gently for at least 60 seconds . → This is intended to provide a well -mixed suspension. e. Check whether the suspension is thoroughly mixed:

• no clumps,
• no sediment .

Cautionary information: For a correct dose: the suspension must not contain any clumps or sediment . Do not use the medicine as long as the suspension has clumps or sediment. f.

If there are clumps or sediment → turn the bottle upside down → shake in different directions → if required, wait some time and shake again until no clumps or sediments are left .

Do not add more water to the bottle.

The suspension has a shelf life of 14 days at room temperature. g. Write the date of expiry of the just prepared suspension on the label of the bottle Expiry date ( reconstitution date + 14 days) The shown pictogram is only an example.

Setting the prescribed dose with every new blue syringe Cautionary information: Once the dose has been fixed on the blue syringe, it cannot be changed. ▪ Do not remove the peelable label until you are prompted in the Instructions for Use.

84 ▪ The blue syringe features a red button to adjust the volume.

This button is initially covered by a peelable label. ▪ By pressing the red button the volume of the syringe is set, which can only be done once. ▪ Do not press the red button until the Instructions for Use tell you to do so.

Selecting a suitable blue syringe Blue syringes with different volumes are included in this box: ▪ 5 mL blue syringes for doses from 1 mL to 5 mL. ▪ 10 mL blue syringes for doses above 5 mL.

In case the prescribed dose is 11 mL:

Use 2 x 5.5 mL with the 10 mL blue syringe. a. Select one suitable blue syringe based on the dose prescribed by your child’s doctor. b. Unpack the blue syringe.

Setting the required dose on new blue syringe The blue syringe features a scale (mL). ▪ The scale of the 5 mL blue syringe starts with 1 mL.

The graduation marks are in increments of 0.2 mL. ▪ The scale of the 10 mL blue syringe starts with 2 mL.

The graduation marks are in increments of 0.5 mL. a. Review the dose provided in the respective field on the outside of the box. b. If the information is not available:

Ask your doctor to provide it. c. Hold the blue syringe with the opening pointing upwards. d. Pull the plunger rod slowly until the upper margin reaches the mark of the volume to be administered.

When moving the plunger rod, you can hear a “Click” for each adjustable graduation mark .

Cautionary information: The upper edge of the plunger must be exactly in line with the correct mark of the volume to be administered .

Be careful, do not pull the plunger past the volume to be administered.

Be careful, do not press on the label when pulling the plunger. e. Remove the peelable label on the blue syringe completely .

You can now see the red button for setting the volume. f. Check the position of the plunger again. Ensure the upper edge of the plunger is exactly in line with the correct mark of the volume to be administered. g. If the position of the blue plunger does not match the required volume:

Adjust it accordingly. h. If the position of the blue plunger matches the required volume, p ush the red button once to fix the adjustment. → Pressing the red button will produce a clicking sound. → The required dose is now set.

Cautionary information: ▪ If you notice that the wrong dose has been selected (the red button has been pushed) use the appropriate spare blue syringe. ▪ Repeat steps “a” to “h” with a new blue syringe. i. Push the plunger upwards in the blue syringe as far as it goes.

The blue syringe can now be used.

Administering the oral suspension Shaking the oral suspension Follow the steps described below for each required administration.

Cautionary information: Allow the suspension to adjust to room temperature if it has been stored in the refrigerator. . a. Gently shake the bottle for at least 10 seconds before each dose. This is intended to provide a well -mixed suspension. b. Check whether the suspension is mixed thoroughly, i.e.:

• no clumps,
• no sediment . c. If there are clumps or sediment : Repeat former step “a”+“b”.

Note • Shaking can lead to formation of foam.

• Let the bottle stand until the foam dissolves.
• The larger opening visible on the adapter is used to connect the blue syringe.
• The surface of the bottle adapter should be free of liquid. d. Unscrew the bottle cap but keep the adapter on the top of the bottle. e. If there is any liquid on the adapter: Remove the liquid with a clean tissue.

87 Extracting the required dose a. Keep the bottle in the upright position. Insert the tip of the blue syringe fully into the large opening of the adapter. b. Turn the bottle upside down. c. Pull up the blue plunger rod slowly until it stops (i.e. until the set dose is reached). d. Carefully check for air in the blue syringe.

Smaller air bubbles are not critical. e. If there are large air bubbles:

• Return the suspension to the bottle by pushing back the plunger rod into the blue syringe as far as possible.
• Repeat steps “b” to “e” above . f. Return the bottle to the upright position. g. Remove the blue syringe carefully from the adapter. h. Hold the blue syringe upright and check whether:

→ the tip is filled, → the correct volume has been filled, → there are no large air bubbles. i. If there are large air bubbles or air in the tip:

• Insert the tip of the blue syringe again fully into the large opening of the adapter.
• Return the suspension to the bottle by pushing back the plunger rod into the blue syringe as far as it goes.
• Repeat steps “b” to “h” until no large air bubbles are visible. j. Close the bottle with the screw cap.

Administer the suspension immediately after filling the blue syringe.

88 Administration of prescribed dose a. Place the blue syringe into the mouth of the patient. b. Direct its tip into the cheek to allow for natural swallowing. c. Push the plunger rod down slowly until the plunger stops (blue syringe is completely empty). d. Ensure that the patient swallows the entire dose. e. Encourage the patient to drink liquid afterwards .

Cautionary information: ▪ The patient must swallow the full dose of medicine.

Cleaning and storage The blue syringe must be cleaned following every application Follow the steps listed below to clean the device. Altogether, three cycles of cleaning are necessary to ensure proper cleaning.

Cleaning Cautionary information: ▪ Do not clean the blue syringe in the dish washer. ▪ Never boil the blue syringe. a. Dip the tip of the blue syringe into the container of water. b. Withdraw water until plunger rod stops. c. Empty the blue syringe into the prepared empty container. d. Repeat steps “a” to “c” two more times . e. After cleaning, push the plunger rod back in until it stops. f. Dry the outer surface of the syringe with a clean tissue.

Storage Store the blue syringe in a clean and dry place until next use.

Keep away from sunlight.

Disposal Any unused medicine or waste material , syringes, and adapter should be disposed of in accordance with local requirements.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Adempas (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/13/907).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.