Patient Information Leaflet

Revatio 10 mg/ml Oral Powder for Suspension

sildenafil

Read this leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must 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 leaflet. See section 4.

Revatio contains the active ingredient sildenafil which belongs to a group of medicines called phosphodiesterase type 5 (PDE5) inhibitors.

Revatio reduces blood pressure in the lungs by dilating the blood vessels in the lungs. Revatio is used to treat high blood pressure in the blood vessels of the lung (pulmonary arterial hypertension) in adults and children and adolescents between 1 to 17 years.

Do not take Revatio

• if you are allergic to sildenafil or any of the other ingredients in this medicine (see section 6).

• if you are taking medicines that contain nitrates or nitric oxide donors such as amyl nitrite (“poppers”). These medicines are often used to relieve chest pain (or angina). Revatio may increase the effects of these medicines. Inform your doctor if you are taking any of these medicines. If you are unsure, consult your doctor or pharmacist.

• if you are taking riociguat. This medicine is used to treat pulmonary hypertension (i.e., high blood pressure in the lungs) and chronic thromboembolic pulmonary hypertension (i.e., high blood pressure in the lungs caused by clots). Phosphodiesterase type 5 inhibitors, such as Revatio, have shown to increase the hypotensive effect of this medicine. If you are taking riociguat or are unsure, consult your doctor.

• if you have recently had a stroke, a heart attack, or if you have severe liver disease or very low blood pressure (<90 mmHg).

• if you are taking a medicine to treat fungal infections such as ketoconazole or itraconazole or medicines that contain ritonavir (for HIV/AIDS).

• if you have previously experienced vision loss due to a problem with blood flow to an eye nerve called non-arteritic anterior ischemic optic neuropathy (NAION).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Revatio if:

• you have a disease caused by a blockage or narrowing of a vein in the lungs instead of a blockage or narrowing of an artery.
• you have a serious heart problem.
• you have a problem with the heart's pumping chambers.
• you have high blood pressure in the blood vessels of the lungs.
• you have low blood pressure at rest.
• you lose a large amount of body fluids (dehydration) which can occur when you sweat a lot or do not drink enough liquids. This can happen if you are sick with fever, vomiting, or diarrhea.
• you have a rare inherited eye disease (retinitis pigmentosa).
• you have an abnormality of red blood cells (sickle cell anemia), blood cancer (leukemia), bone marrow cancer (multiple myeloma), or any disease or deformity of the penis.
• you have an active stomach ulcer or bleeding disorders (such as hemophilia) or nosebleeds.
• you are taking medicines for erectile dysfunction.

When phosphodiesterase type 5 inhibitors, including sildenafil, are used to treat erectile dysfunction (ED), the following visual adverse effects have been reported with an unknown frequency: sudden, temporary, or permanent partial or complete loss of vision in one or both eyes. If you experience a sudden loss of vision, stop taking Revatio and inform your doctor immediately (see also section 4).

Sudden, prolonged, and sometimes painful erections have been observed in men taking sildenafil. If you have an erection that lasts for more than 4 hours, stop taking Revatio and consult your doctor immediately (see also section 4).

Special precautions in patients with kidney or liver problems

Inform your doctor if you have kidney or liver problems, as a dose adjustment may be necessary.

Children

Revatio should not be administered to children under 1 year.

Taking Revatio with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medicine.

• Medicines that contain nitrates or nitric oxide donors such as amyl nitrite (“poppers”). These medicines are often used to relieve chest pain or angina (see section 2. Before taking Revatio).
• Inform your doctor or pharmacist if you are taking riociguat.
• Treatments for pulmonary hypertension (e.g., bosentan, iloprost).
• Medicines that contain St. John's Wort (herbal medicine), rifampicin (used to treat bacterial infections), carbamazepine, phenytoin, and phenobarbital (used, among others, to treat epilepsy).
• Medicines that inhibit blood coagulation (e.g., warfarin) although no adverse effects have been reported.
• Medicines that contain erythromycin, clarithromycin, telithromycin (antibiotics used to treat certain bacterial infections), saquinavir (for HIV/AIDS), or nefazodone (for depression), as a dose adjustment may be necessary.
• Alpha-blocker therapy (e.g., doxazosin) for the treatment of hypertension or prostate problems, as the combination of the two medicines may cause symptoms of reduced blood pressure (e.g., dizziness, fainting).
• Medicines that contain sacubitril/valsartan, used to treat heart failure.

Taking Revatio with food and drinks

Do not take grapefruit juice while being treated with Revatio.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medicine. Revatio should not be used during pregnancy unless absolutely necessary.

Revatio should not be administered to women of childbearing age unless adequate contraceptive methods are used.

Revatio passes into breast milk at very low levels and is not expected to harm your baby.

Driving and operating machinery

Revatio may cause dizziness and affect your vision. You should know how you react to this medicine before driving vehicles or operating machinery.

Revatio contains sorbitol

Revatio 10 mg/ml powder for oral suspension contains 250 mg of sorbitol per ml of reconstituted suspension.

Sorbitol is a source of fructose. If your doctor has told you that you (or your child) have a condition where you cannot digest certain sugars, or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which the patient cannot break down fructose, consult your doctor before taking this medicine.

Revatio contains sodium benzoate

Revatio 10 mg/ml powder for oral suspension contains 1 mg of sodium benzoate per ml of reconstituted suspension. Sodium benzoate may increase levels of a substance called bilirubin. High levels of bilirubin can cause jaundice (yellowing of the skin and eyes) and may also cause brain damage (encephalopathy) in newborns (up to 4 weeks old).

Revatio contains sodium

Revatio 10 mg/ml powder for oral suspension contains less than 1 mmol (23 mg) of sodium per ml of reconstituted suspension; 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.

For adults, the recommended dose is 20 mg three times a day (taken at intervals of 6 to 8 hours) taken with or without food.

Use in children and adolescents

For children and adolescents aged 1 to 17 years, the recommended dose is 10 mg (1 ml of oral suspension) three times a day for children and adolescents weighing 20 kg or less, or 20 mg (2 ml of oral suspension) three times a day in children and adolescents weighing more than 20 kg, administered with or without food. In children, higher doses than those recommended should not be used.

The oral suspension must be shaken well for at least 10 seconds before use.

Instructions for reconstituting the oral suspension

Your pharmacist should reconstitute (prepare) the oral suspension before administering it.

When reconstituting the oral suspension it is a liquid. If the powder has not been reconstituted, the oral suspension should be reconstituted by following the instructions below.

Note:Regardless of the dose you take, you must use a total volume of 90 ml (3 x 30 ml) of water to reconstitute the contents of the bottle.of water to reconstitute the contents of the bottle.

1. Gently shake the bottle to release the powder.
2. Remove the cap.
3. Measure 30 ml of water filling the measuring cup (included in the package) to the mark and add to the bottle. Measure another 30 ml of water using the measuring cup and add to the bottle. (figure 1)

1. Replace the cap and shake vigorously for at least 30 seconds. (figure 2)

1. Remove the cap.
2. Using the measuring cup, measure another 30 ml of water and add to the bottle. Always add a total of 90 ml (3 x 30 ml) of water, regardless of the dose you take. (figure 3)

1. Replace the cap and shake the bottle vigorously for at least 30 seconds. (figure 4)

1. Remove the cap.
2. Insert the adapter into the neck of the bottle (as indicated in figure 5 below). An adapter is provided so that you can fill the oral dosing syringe with the medication from the bottle. Replace the cap.

1. Write the expiration date of the reconstituted oral suspension on the label of the bottle (the expiration date of the reconstituted oral suspension is 30 days from the date of reconstitution). After this date, the unused oral suspension should be discarded or returned to your pharmacist.

Instructions for use

Your pharmacist will indicate how to measure the medication using the oral dosing syringe included in the package. Once the oral suspension has been reconstituted, it should only be administered using the oral dosing syringe included in each package. See the following instructions before using the oral suspension.

1. Shake the reconstituted oral suspension bottle closed for at least 10 seconds before using it. Remove the cap. (figure 6)

1. With the bottle upright, on a flat surface, insert the tip of the oral dosing syringe into the adapter. (figure 7)

1. Invert the bottle holding the oral dosing syringe in place. Pull the plunger of the oral dosing syringe slowly until the mark indicating your dose (taking 1 ml results in a dose of 10 mg, taking 2 ml results in a dose of 20 mg). To measure exactly the dose, the top edge of the plunger should be aligned with the appropriate mark on the oral dosing syringe. (figure 8)

1. If you see large bubbles, gently push the plunger back into the syringe. This will reintroduce the medication into the bottle. Repeat this step 3 times.
2. Replace the bottle with the oral dosing syringe still in place. Remove the oral dosing syringe from the bottle.
3. Insert the tip of the oral dosing syringe into the mouth. Point the tip of the oral dosing syringe towards the inside of the cheek. Push the plunger of the oral dosing syringe slowly. Do not release the medication quickly. If the medication is administered to a child, make sure they are seated or upright before administering the medication. (figure 9)

1. Replace the cap of the bottle, leaving the adapter on the bottle. Clean the oral dosing syringe as indicated below.

Cleaning and storage of the oral dosing syringe:

1. After each administration, clean the oral dosing syringe. Remove the plunger and clean both parts with water.
2. Dry the two parts. Push the plunger back into the syringe. Store it in a clean and safe place along with the medication.

If you take more Revatio than you should

You should not take more medication than your doctor recommends.

If you have taken more medication than advised, consult your doctor immediately.

Taking more Revatio than you should may increase the risk of known side effects.

If you forget to take Revatio

If you have forgotten to take Revatio, take the dose as soon as you remember and continue taking your medication at the usual times. Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Revatio

Stopping treatment with Revatio abruptly may lead to worsening of your symptoms. Do not stop taking Revatio unless your doctor tells you to. Your doctor will indicate how to reduce the dose over a few days before stopping it completely.

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

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

If you experience any of the following side effects, stop taking Revatio and inform your doctor immediately (see also section 2):

• if you experience a sudden reduction or loss of vision (unknown frequency)
• if you have an erection that lasts for more than 4 hours. Prolonged and sometimes painful erections have been reported after taking sildenafil in men (unknown frequency)

Adults

The side effects reported very frequently (may affect more than 1 in 10 patients) were, headache or facial flushing, indigestion, diarrhea, and pain in arms and legs.

The side effects reported frequently (may affect up to 1 in 10 patients) are: skin infection, flu-like symptoms, nasal congestion, reduction in red blood cell count (anemia), fluid retention, difficulty sleeping, anxiety, migraine, tremor, tingling sensation, burning sensation, reduced sense of touch, bleeding in the back of the eye, visual disturbances, blurred vision, and light sensitivity, color perception effects, eye irritation, red or bloodshot eyes, dizziness, bronchitis, nasal bleeding, runny nose, cough, stuffy nose, stomach inflammation, gastroenteritis, burning sensation, hemorrhoids, abdominal distension, dry mouth, hair loss, skin redness, night sweats, muscle pain, back pain, and increased body temperature.

The side effects reported infrequently (may affect up to 1 in 100 patients) included: reduced visual acuity, double vision, abnormal sensation in the eye, penile bleeding, presence of blood in semen and/or urine, and breast enlargement in men.

Also, skin eruptions, decreased or sudden loss of hearing, and reduced blood pressure have been reported with an unknown frequency (the frequency cannot be estimated with the available data).

Children and adolescents

The following severe side effects were reported frequently (may affect up to 1 in 10 patients): pneumonia, right heart failure, cardiac shock, high blood pressure in the lungs, chest pain, dizziness, respiratory infections, bronchitis, viral infections in the stomach and intestines, urinary tract infections, and tooth perforations.

The following severe side effects were considered related to treatment and reported infrequently (may affect up to 1 in 100 patients): allergic reaction (such as skin rash, facial inflammation, lips and tongue inflammation, sneezing, difficulty breathing or swallowing), convulsions, irregular heartbeat, hearing disturbances, shortness of breath, digestive tract inflammation, and sneezing due to airway flow alterations.

The side effects reported very frequently (may affect more than 1 in 10 patients) were headache, vomiting, throat infection, fever, diarrhea, flu, and nasal bleeding.

The side effects reported frequently (may affect up to 1 in 10 patients) were nausea, increased erections, pneumonia, and runny nose.

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 leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the bottle after CAD. The expiration date is the last day of the month indicated.

Powder

Do not store above 30°C.

Store in the original container to protect it from moisture.

Reconstituted oral suspension

Store below 30°C or in the refrigerator between 2°C and 8°C. Do not freeze. Discard any remaining oral suspension after 30 days of reconstitution.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of empty containers and unused medications. This will help protect the environment.

Composition of Revatio

• The active ingredient is sildenafil (as citrate).

After reconstitution, each ml of oral suspension contains 10 mg of sildenafil (as citrate). A reconstituted oral suspension bottle (112 ml) contains 1.12 g of sildenafil (as citrate).

• The other components are:Oral suspension powder:sorbitol (E240) (see section 2 “Revatio contains sorbitol”), anhydrous citric acid, sucralose, sodium citrate (E331) (see section 2 “Revatio contains sodium”), xanthan gum, titanium dioxide (E171), sodium benzoate (E211) (see section 2 “Revatio contains sodium benzoate” and “Revatio contains sodium”) and anhydrous colloidal silica;Granny Smith apple flavor:maltodextrin, concentrated apple juice, gum arabic, pineapple juice concentrate, anhydrous citric acid, natural flavors.

Appearance of Revatio and packaging contents

Revatio is presented as a white to off-white oral suspension powder that, when reconstituted with water, gives a white oral suspension with a grape flavor.

A 125 ml amber glass bottle (with a polypropylene screw cap) contains 32.27 g of oral suspension powder.

Once reconstituted, the bottle contains 112 ml of oral suspension, of which 90 ml will be used to administer the doses.

Format: 1 bottle.

Each package also contains a polypropylene measuring cup (graduated to mark 30 ml), an oral dosing syringe made of polypropylene (3 ml) with an HDPE plunger, and a LDPE bottle adapter.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

Upjohn EESV, Rivium Westlaan 142, 2909 LD Capelle aan den IJssel, Netherlands.

Manufacturer:

Fareva Amboise, Zone Industrielle, 29 route des Industries, 37530 Pocé-sur-Cisse, France

Mylan Hungary Kft., Mylan utca 1, Komárom, 2900, Hungary.

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Spain

Viatris Pharmaceuticals, S.L.U.

Tel: +34 900 102 712

Last review date of this leaflet:

Other sources of information

Detailed information about this medicine is available on the European Medicines Agency website:http://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan medicines.