CERTICAN 0.1 mg DISPERSIBLE TABLETS

Introduction

Package Leaflet: Information for the User

Certican 0.1 mg dispersible tablets

Certican 0.25 mg dispersible tablets

everolimus

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.

Contents of the pack and other information:

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

1. What is Certican and what is it used for

The active substance of Certican is everolimus.

Everolimus belongs to a group of medicines known as immunosuppressants. It is used in adults to prevent the immune system from rejecting a transplanted kidney, heart, or liver.

Certican is used together with other medicines, such as cyclosporin for kidney and heart transplants, tacrolimus for liver transplants, and corticosteroids.

2. What you need to know before you take Certican

Do not take Certican

• if you are allergic (hypersensitive) to everolimus or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic (hypersensitive) to sirolimus.

If any of the above applies to you, tell your doctor and do not take Certican.

Warnings and precautions

Consult your doctor before starting Certican:

• Medicines that suppress the immune system, such as Certican, reduce the body's ability to fight infections. It is advisable to consult your doctor or transplant center if you have a fever or feel unwell in general, or have local symptoms such as cough or burning sensation when urinating that may be severe or persistent for several days. Consult your doctor or transplant center immediately if you feel confused, have difficulty speaking, memory loss, headache, vision changes, or seizures, as these may be symptoms of a rare but serious condition called progressive multifocal leukoencephalopathy (PML).
• If you have recently undergone major surgery or still have an unhealed wound after surgery, Certican may increase the risk of wound healing problems.
• Medicines that suppress the immune system, such as Certican, increase the risk of developing cancer, particularly skin and lymphoid cancer. Therefore, you should limit your exposure to sunlight and UV rays by wearing protective clothing and applying sunscreen with a high protection factor frequently.
• Your doctor will monitor your kidney function, the amount of fat (lipids) and sugar in your blood, as well as the amount of protein in your urine.
• If you have liver problems or have previously had a disease that may have affected your liver, inform your doctor. Your doctor may need to adjust the dose of Certican you are taking.
• If you experience respiratory symptoms (e.g., cough, difficulty breathing, and shortness of breath), inform your doctor. Your doctor will decide whether you need to continue and how to continue treatment with Certican and/or whether you need to receive other medications to treat this condition.
• Certican may reduce sperm production in men, consequently reducing fertility. The effect is generally reversible. Male patients who wish to become fathers should discuss their treatment with their doctor.

Elderly (65 years and over)

There is limited experience with the administration of Certican in elderly patients.

Children and adolescents

Certican should not be used in children and adolescents with a kidney, heart, or liver transplant.

Other medicines and Certican

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines, including those obtained without a prescription.

Some medicines may affect how Certican works in your body. It is very important that you inform your doctor if you are taking any of the following medicines:

• immunosuppressive medicines other than cyclosporin, tacrolimus, or corticosteroids.
• antibiotic medicines, such as rifampicin, rifabutin, clarithromycin, erythromycin, or telithromycin.
• antiviral medicines, such as ritonavir, efavirenz, nevirapine, nelfinavir, indinavir, or amprenavir, which are used to treat HIV infection.
• medicines used to treat fungal infections, such as voriconazole, fluconazole, ketoconazole, or itraconazole.
• medicines used to treat epilepsy, such as phenytoin, phenobarbital, or carbamazepine.
• medicines used to treat high blood pressure or heart problems, such as verapamil, nicardipine, or diltiazem.
• dronedarone, a medicine used to help regulate heartbeats.
• medicines used to lower blood cholesterol, such as atorvastatin, pravastatin, or fibrates.
• medicines used to treat seizures or used as sedatives before or during surgery or other medical procedures, such as midazolam.
• cannabidiol (its use includes, among others, the treatment of epileptic seizures).
• octreotide, a medicine used to treat acromegaly, a rare hormonal disorder that usually occurs in middle-aged adults.
• imatinib, a medicine used to inhibit the growth of abnormal cells.
• St. John's Wort (Hypericum perforatum), a medicinal plant used to treat depression.

Taking Certican with food and drinks

The presence of food can affect the amount of Certican absorbed. To maintain constant levels in your body, you should always take Certican in the same way. You should take it always with food or always on an empty stomach.

Do not take Certican with grapefruit or grapefruit juice, as they may affect the effect of Certican in your body.

Pregnancy, breastfeeding, and fertility

If you are pregnant, do not take Certican unless your doctor thinks it is absolutely necessary. If you are a woman who can become pregnant, you should use an effective contraceptive method during treatment with Certican and for 8 weeks after stopping treatment.

If you think you may be pregnant, consult your doctor or pharmacist before taking Certican.

You should not breastfeed while taking Certican. It is not known whether Certican passes into breast milk.

Certican may affect male fertility.

Driving and using machines

Certican has no or negligible influence on the ability to drive and use machines.

Certican contains lactose

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

3. How to take Certican

Your doctor will decide what dose of Certican you should take and when you should take it.

Follow exactly the administration instructions of Certican given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Amount to be taken

• The normal starting dose is 1.5 mg/day for kidney and heart transplants and 2.0 mg/day for liver transplants.
• It is usually divided into two separate doses, one in the morning and one in the evening.

How to take Certican

Certican should be taken only by mouth.

You should take the first dose of this medicine as soon as possible after kidney and heart transplants and approximately four weeks after liver transplants.

You should take the tablets with cyclosporin for microemulsion in kidney and heart transplants and with tacrolimus in liver transplants.

Do not switch from Certican dispersible tablets to Certican tablets without consulting your doctor.

• Place the Certican dispersible tablets in approximately 25 ml of water in a plastic cup.
• The maximum amount of Certican that can be dispersed in 25 ml of water is 1.5 mg.
• Wait for 2 minutes to allow the tablets to dissolve and gently stir the cup before drinking the liquid.
• Then, immediately rinse the cup with another 25 ml of water and drink it completely.

Monitoring during your treatment with Certican

Your doctor may adjust your dose depending on the level of Certican in your blood and your response to treatment. Your doctor will perform regular blood tests to determine the levels of everolimus and cyclosporin in your blood. Your doctor will also carefully monitor your kidney function, blood lipids, blood sugar, and the amount of protein in your urine.

If you take more Certican than you should

If you take more tablets than you should, consult your doctor immediately.

If you forget to take Certican

If you forget to take your dose of Certican, take it as soon as you remember and then continue with your usual treatment schedule. Ask your doctor for advice. Do not take a double dose to make up for forgotten doses.

If you stop taking Certican

Do not stop taking the medicine unless your doctor tells you to. You will need to take this medicine for as long as you need to take immunosuppressants to prevent rejection of your transplanted kidney, heart, or liver. If you stop taking Certican, you may increase the risk of rejection of your transplanted organ.

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.

Because you are taking Certican with other medicines, it is not always clear whether the side effects are caused by Certican or by other medicines.

The following side effects need immediate medical attention:

• infections,
• inflammation of the lungs,
• allergic reactions,
• fever and skin hemorrhages that may appear as red spots, with or without unexplained fatigue, confusion, yellowing of the skin or eyes, decreased urine output (thrombotic microangiopathy, hemolytic uremic syndrome),

If you develop any of the following:

• persistent or worsening respiratory symptoms, such as cough, difficulty breathing, or wheezing,
• fever, feeling unwell, chest or abdominal pain, chills, burning sensation when urinating,
• swelling of the face, lips, tongue, or throat,
• difficulty swallowing,
• spontaneous bruising or bleeding without apparent reason,
• skin rash,
• pain, heat, swelling, or discharge at the surgery site

you should stop taking Certican and inform your doctor immediately.

Other side effects reported include:

Very common(may affect more than 1 in 10 patients)

• infections (viral, bacterial, and fungal infections),
• infections of the lower respiratory tract, such as pneumonia,
• infections of the upper respiratory tract, such as pharyngitis and common cold,
• urinary tract infections,
• anemia (reduced red blood cell count),
• low white blood cell count leading to a higher risk of infection, reduced platelet count in blood which can lead to bleeding and/or bruising under the skin,
• high levels of fats (lipids, cholesterol, and triglycerides) in the blood,
• onset of diabetes (high blood sugar),
• low potassium levels in the blood,
• anxiety,
• difficulty sleeping (insomnia),
• headache,
• fluid collection in the sac that surrounds the heart, which if severe, can decrease the heart's ability to pump blood,
• high blood pressure,
• venous thrombosis (blockage of a major vein by a blood clot),
• fluid collection in the lungs and thoracic cavity, which if severe, could make breathing difficult,
• cough,
• shortness of breath,
• diarrhea,
• nausea,
• vomiting,
• abdominal pain,
• general pain,
• fever,
• fluid accumulation in tissues,
• abnormal wound healing.

Common(may affect up to 1 in 10 patients)

• septicemia,
• wound infection,
• cancer and benign tumors,
• skin cancer,
• renal disorder with low platelet count in blood and low red blood cell count, with or without skin rash (thrombocytopenic purpura/hemolytic uremic syndrome),
• breakdown of red blood cells,
• low red blood cell and platelet count,
• rapid heartbeat,
• nosebleeds,
• reduced number of cells in the blood (symptoms may include weakness, bruising, and frequent infections),
• blood clotting in the blood vessels of the kidney, which can result in the loss of the graft, mostly during the first 30 days after kidney transplant,
• bleeding disorders,
• fluid-filled cyst,
• mouth or throat pain,
• pancreatitis,
• mouth ulcers,
• acne,
• hives and other allergic symptoms, such as swelling of the face or throat (angioedema),
• skin rash,
• joint pain,
• muscle pain,
• protein in the urine,
• kidney disorders,
• impotence,
• hernia at the surgery site,
• abnormal liver test results,
• menstrual disorders (including absent or heavy periods).

Uncommon(may affect up to 1 in 100 patients):

• lymphoma/post-transplant lymphoproliferative disorder,
• low testosterone levels,
• inflammation of the lungs,
• inflammation of the liver,
• jaundice,
• ovarian cysts.

Other side effects:

Other side effects have occurred in a small number of patients, but their exact frequency is unknown:

• abnormal protein accumulation in the lungs (symptoms may include persistent dry cough, fatigue, and difficulty breathing),
• inflammation of blood vessels,
• swelling, feeling of heaviness or tightness, pain, limited mobility of some parts of the body (this can occur in any part of the body and could indicate abnormal fluid accumulation in soft tissues due to a blockage of the lymphatic system, also known as lymphedema),
• severe skin rash with inflammation of the skin,
• low iron levels in the blood.

If you are unsure about any of these effects, tell your doctor.

In addition, side effects that you may not be aware of may occur, such as abnormal laboratory test results, including tests of kidney function. This means that your doctor will perform blood tests to monitor any changes in your kidneys during your treatment with Certican.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines (www.notificaRAM.es). By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Certican

• Keep Certican out of the sight and reach of children.
• Do not use Certican after the expiry date stated on the carton after EXP. The expiry date is the last day of the month indicated.
• This medicine does not require any special storage temperature.
• Keep the blister pack in the original packaging to protect it from light and moisture.
• Do not use this medicine if you notice that the packaging is damaged or shows signs of deterioration.
• Medicines should not be disposed of via wastewater or household waste. Return the packaging and any unused medicine to the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Content and Additional Information

Certican Composition

• The active ingredient is everolimus. Each dispersable tablet contains 0.1 mg or 0.25 mg of everolimus.
• The other components are:

• Certican 0.1 mg dispersable tablets: butylhydroxytoluene (E321), magnesium stearate, lactose monohydrate (1 mg), hypromellose, crospovidone, colloidal anhydrous silica, and anhydrous lactose (72 mg).
• Certican 0.25 mg dispersable tablets: butylhydroxytoluene (E321), magnesium stearate, lactose monohydrate (2 mg), hypromellose, crospovidone, colloidal anhydrous silica, and anhydrous lactose (179 mg).

Product Appearance and Container Content

• Certican 0.1 mg dispersable tablets are round, flat tablets, 7 mm in size, white to yellowish in color, scored, with the inscription “I” on one side and “NVR” on the other.
• Certican 0.25 mg dispersable tablets are round, flat tablets, 9 mm in size, white to yellowish in color, scored, with the inscription “JO” on one side and “NVR” on the other.

Certican dispersable tablets are available in containers containing 50, 60, 100, or 250 dispersable tablets. Not all pack sizes may be marketed. Certican is also available in tablet form.

Marketing Authorization Holder and Manufacturer

Novartis Farmacéutica, S.A.

Gran Via de les Corts Catalanes, 764

08013 Barcelona,

Spain

Manufacturer

NOVARTIS FARMA, S.P.A.

Via Provinciale Schito, 131 (Torre Annunziata) (Naples) - Unknown - Italy

0815354111

NOVARTIS FARMACEUTICA, S.A.

Gran Via de les Corts Catalanes, 764 - 08013 Barcelona - Spain

NOVARTIS PHARMA GMBH

Roonstrasse 25

90429 Nürnberg–

Germany

NOVARTIS PHARMA, S.A.S.

8-10 rue Henri Sainte-Claire Deville

92500 Rueil-Malmaison

France

NOVARTIS SVERIGE AB

Torshamnsgatan 48, 16440 Kista – Sweden

NOVARTIS FINLAND OY

Metsanneidonkujaq (Espoo) - FIN-02130 – Finland

N.V. NOVARTIS PHARMA, S.A.

Medialaan 40, bus 1 (Vilvoorde) - 1800 - Belgium

2 246 1611

NOVARTIS HELLAS S.A.C.I.

National Road 1 12th Km (Metamorphosi, Athens) - GR-14451 - Greece

302102811712

NOVARTIS PHARMA GMBH

Jakov-Lind-Straße 5, Top 3.05 – 1020 Wien – Austria

NOVARTIS PHARMA BV

Haaksbergweg 16 - 1101 BX Amsterdam - Netherlands

NOVARTIS HEALTHCARE A/S

Edvard Thomsens Vej 14,3. (Copenhagen) - DK-2300 – Denmark

NOVARTIS FARMA-PRODUCTOS FARMACEUTICOS, S.A.

Avenida Professor Doutor Cavaco Silva, nº 10E (Taguspark, Porto Salvo) -

2740-255 – Portugal

NOVARTIS HUNGARY LTD.

Bartok Bela üt 43-47 (Budapest) - 1114 – Hungary

NOVARTIS POLAND SP.Z.O.O.

Ul. Marynarska, 15 (Warszawa) - 02-674 – Poland

NOVARTIS FARMA, S.P.A.

Viale Luigi Sturzo 43, 20154 - Milano (MI) – Italy

SANDOZ S.R.L.

Livezeni Street Nr. 7A, Targu Mures, 540472 – Romania

NOVARTIS PHARMA GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

This medicinal product is authorized in the Member States of the European Economic Areaand in the United Kingdom (Northern Ireland)under the following names:

Date of the last revision of this leaflet:09/2023

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

THIS INFORMATION IS INTENDED ONLY FOR MEDICAL PROFESSIONALS OR

HEALTHCARE PROFESSIONALS

Instructions for use and handling of dispersable tablets

Administration in a 10 ml syringe orally. Place Certican dispersable tablets in a syringe. The maximum amount of Certican that can be dispersed in a 10 ml syringe is 1.25 mg. Add water up to the 5 ml mark. Wait 90 seconds while gently shaking. After dispersion, apply directly to the mouth. Rinse the syringe with 5 ml of water and reapply to the mouth. Then drink between 10 and 100 ml of water or diluted syrup.

Administration with a plastic cup.Place Certican dispersable tablets in a plastic cup with approximately 25 ml of water. The maximum amount of Certican that can be dispersed in 25 ml of water is 1.5 mg. Wait for approximately 2 minutes to allow the tablets to disintegrate and gently shake before drinking. Immediately rinse the cup with an additional 25 ml of water and drink the entire contents.

Administration via nasogastric tube.Place Certican dispersable tablets in a small plastic measuring cup containing 10 ml of water and wait 90 seconds while gently shaking. Place the dispersion in a syringe and slowly inject (over 40 seconds) into a nasogastric tube. Rinse the measuring cup (and syringe) three times with 5 ml of water and inject into the tube. Finally, flush the tube with 10 ml of water. The nasogastric tube should be clamped for at least 30 minutes after administration of Certican.

If cyclosporine microemulsion is also administered via nasogastric tube, it should be administered before Certican. The two drugs should not be mixed.