Aderolio

Aderolio, 0.25 mg, tablets
Aderolio, 0.5 mg, tablets
Aderolio, 0.75 mg, tablets
Aderolio, 1.0 mg, tablets
Everolimus
Please read the following package leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

1. What Aderolio is and what it is used for

The active substance in Aderolio is everolimus.
Everolimus belongs to a group of medicines known as immunosuppressants. It is used in adult patients
to prevent the body's immune system from rejecting a transplanted kidney, heart, or liver.
Aderolio is taken in combination with other medicines, such as cyclosporine (in patients receiving a kidney or heart transplant), tacrolimus (in patients receiving a liver transplant), and corticosteroids.

2. Important information before using Aderolio

When not to use Aderolio

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

If any of the above points apply to the patient, tell the doctor and do not take Aderolio.
Warnings and precautions
Before starting treatment with Aderolio, discuss this with the doctor.

• Medicines that suppress the immune system, such as Aderolio, reduce the body's ability to fight infections. If the patient has a fever or feels unwell, or develops symptoms such as cough or a burning sensation when passing urine, and these symptoms are severe or persist for several days, contact the doctor or the transplant centre.
  Seek immediate medical advice from the doctor or transplant centre if the patient develops confusion, speech disturbances, memory loss, headache, vision problems or seizures, as these may be symptoms of a rare but very serious condition called "progressive multifocal leukoencephalopathy" (PML).

• If the patient has recently undergone major surgery or still has an unhealed surgical wound, Aderolio may increase the risk of wound-healing complications.

• Medicines that suppress the immune system, such as Aderolio, increase the risk of developing cancer, particularly of the skin and lymphatic system. Therefore, exposure to sunlight and ultraviolet (UV) radiation should be minimized by wearing protective clothing and frequently applying sunscreen with a high sun protection factor.

• The doctor will monitor kidney function, blood lipid (fat) and blood sugar levels, and the amount of protein in the urine.

• If the patient has impaired liver function or has had a liver disease in the past, inform the doctor. The doctor may need to adjust the dose of Aderolio.

• If the patient develops respiratory symptoms (e.g. cough, difficulty breathing, wheezing), consult the doctor. The doctor will decide whether and how to continue treatment with Aderolio and/or whether other medicines are needed.

• Aderolio may reduce semen production in men, thereby reducing fertility. This effect is usually reversible. Men planning fatherhood should discuss treatment with their doctor.

Elderly patients (aged 65 years and older)
Experience with the use of Aderolio in elderly patients is limited.
Children and adolescents (under 18 years of age)
Aderolio must not be used in children and adolescents after kidney, heart or liver transplantation.
Aderolio and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. This includes medicines available without a prescription. Some medicines may affect how Aderolio works in the body. It is very important to inform the doctor if the patient is taking any of the following medicines:

• immunosuppressive medicines other than cyclosporine, tacrolimus or corticosteroids;
• antibiotics such as rifampicin, rifabutin, clarithromycin, erythromycin or telithromycin;
• antiviral medicines such as ritonavir, efavirenz, nevirapine, nelfinavir, indinavir or amprenavir, 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 rhythm disorders, such as verapamil, nicardipine or diltiazem;
• dronedarone, a medicine used to regulate heart rhythm;
• medicines used to lower blood cholesterol levels, such as atorvastatin, pravastatin or fibrates;
• medicines used to treat acute epileptic seizures or as sedatives before or during surgery or other medical procedures, such as midazolam;
• octreotide, a medicine used to treat acromegaly, a rare hormonal disorder usually occurring in middle-aged adults;
• imatinib, a medicine used to inhibit the growth of abnormal cells;
• St John's wort (Hypericum perforatum), a herbal remedy used to treat depression;
• Cannabidiol (used, among others, in the treatment of epileptic seizures).

If the patient needs to be vaccinated, consult the doctor first.
Aderolio with food and drink
Food may affect the absorption of Aderolio. To maintain a consistent drug level in the body, Aderolio should always be taken the same way—either always with food or always on an empty stomach.
Do not take Aderolio with grapefruit juice or grapefruit. These affect how Aderolio works in the body.
Pregnancy, breastfeeding and fertility
Women who are pregnant should not take Aderolio unless the doctor considers it absolutely necessary. Women of childbearing potential should use an effective method of contraception during treatment with Aderolio and for 8 weeks after stopping treatment.
If the patient suspects she may be pregnant, she should consult the doctor or pharmacist before taking Aderolio.
Breastfeeding is not recommended during treatment with Aderolio. It is not known whether the medicine passes into human milk.
Aderolio may affect male fertility.
Driving and operating machinery
No studies on the effect of the medicine on the ability to drive and operate machinery have been conducted.
Aderolio contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, consult the doctor before taking this medicine.

3. How to use Aderolio

Your doctor decides the dose and timing at which you should take Aderolio.
This medicine should always be used exactly as prescribed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
Dosage

• The usual starting dose for patients after kidney or heart transplantation is 1.5 mg per day, and for patients after liver transplantation it is 2.0 mg per day.
• The daily dose is usually divided into two doses – one taken in the morning and one in the evening.

How to take Aderolio
This medicine is intended for oral use only.
Do not crush the tablets.
Swallow the tablets whole with a glass of water.
The first dose should be taken as soon as possible after kidney or heart transplantation, and approximately
four weeks after liver transplantation.
Patients after kidney or heart transplantation should take Aderolio concomitantly with cyclosporine in the form of a microemulsion, and patients after liver transplantation should take it concomitantly
with tacrolimus.
Do not switch from Aderolio to everolimus tablets for oral suspension without first consulting your doctor.
Monitoring during treatment with Aderolio
Your doctor may adjust the dose based on the blood concentration of the drug and your response to treatment. Your doctor will order regular blood tests to monitor the blood levels of everolimus and cyclosporine. Kidney function, blood lipid and glucose levels, and the amount of protein in the urine will also be closely monitored.
Taking more than the recommended dose of Aderolio
If you have taken more than the recommended dose, contact your doctor immediately.
Missing a dose of Aderolio
If you forget to take a dose of Aderolio, take it as soon as you remember, and then take the next dose at the usual time. Consult your doctor. Do not take a double dose to make up for a missed tablet.
Stopping Aderolio
Do not stop taking this medicine without your doctor's advice. Continue taking the medicine for as long as immunosuppressive therapy is required to prevent rejection of the transplanted kidney, heart, or liver. Stopping treatment with Aderolio increases the risk of rejection of the transplanted organ.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Aderolio is taken together with other medicines, so it is not always certain whether adverse reactions are caused by this medicine or by other medicines.
The following adverse reactions require immediate medical attention:

• infections,
• pneumonia,
• allergic reactions,
• fever and development of bruising under the skin, which may appear as red spots, with unexplained fatigue, confusion, yellowing of the skin or eyes, reduced urine output (thrombotic microangiopathy, haemolytic uraemic syndrome) or without these symptoms.

If any of the following symptoms occur in a patient, treatment with Aderolio should be discontinued and immediate medical advice must be sought:

• persistent or worsening symptoms related to the lungs/breathing, such as cough, difficulty breathing or wheezing,
• fever, general malaise, chest pain or abdominal pain, chills, burning sensation during urination,
• swelling of the face, lips, tongue or throat,
• difficulty swallowing,
• spontaneous bruising or bleeding without obvious cause,
• rash,
• pain, unusual warmth, swelling or discharge from a surgical wound.

Other reported adverse reactions include:
Very common (may affect more than 1 in 10 people)

• infections (viral, bacterial and fungal),
• lower respiratory tract infections, such as lung infections, including pneumonia,
• upper respiratory tract infections, such as sore throat and common cold,
• urinary tract infections,
• anaemia (reduced number of red blood cells),
• low white blood cell count, leading to increased risk of infection, reduced platelet count, which may cause bleeding and/or bruising under the skin,
• high levels of fats (lipids [cholesterol and triglycerides]) in the blood,
• onset of diabetes (high blood sugar levels),
• low blood potassium levels,
• anxiety,
• difficulty sleeping (insomnia),
• headache,
• fluid accumulation around the heart, which (if significant) may reduce the heart's ability to pump blood,
• high blood pressure,
• venous thrombosis (blockage of a large vein by a blood clot),
• fluid accumulation in the lungs and the chest cavity, which (if significant) may cause shortness of breath,
• cough,
• shortness of breath,
• diarrhoea,
• nausea,
• vomiting,
• stomach (abdominal) pain,
• generalised pain,
• fever,
• fluid accumulation in tissues,
• impaired wound healing.

Common (may affect less than 1 in 10 people)

• blood infection,
• wound infection,
• malignant and benign tumours,
• skin cancer,
• kidney damage with low platelet and red blood cell counts, with or without rash (thrombocytopenic purpura or haemolytic uraemic syndrome),
• breakdown of red blood cells,
• low red blood cell and platelet counts,
• rapid heartbeat,
• nosebleeds,
• low blood cell count (symptoms may include: weakness, bruising and frequent infections),
• formation of a blood clot in a blood vessel of the transplanted kidney, which may lead to graft loss, most commonly within the first 30 days after transplantation,
• bleeding disorders,
• cyst containing lymphatic fluid,
• mouth or throat pain,
• pancreatitis,
• mouth ulcers,
• acne,
• urticaria and other allergic reactions, such as facial or throat swelling (angioedema),
• rash,
• joint pain,
• muscle pain,
• presence of protein in urine,
• kidney function disorders,
• impotence,
• hernia at the surgical site,
• abnormal liver function test results,
• menstrual disorders (including absence of menstruation or heavy menstrual bleeding).

Uncommon (may affect less than 1 in 100 people)

• lymphatic tissue tumour (lymphoma/post-transplant lymphoproliferative disorder),
• low testosterone levels,
• pneumonia,
• hepatitis,
• jaundice,
• ovarian cyst.

Other adverse reactions:
Other adverse reactions occurred in a small number of people, but their exact frequency is unknown:

• abnormal accumulation of protein in the lungs (symptoms may include: persistent dry cough, feeling of fatigue and difficulty breathing),
• vasculitis,
• severe rash with skin swelling,
• swelling, feeling of heaviness or pressure, pain, limited mobility of a body part (may affect any area of the body and may be a sign of abnormal accumulation of fluid in soft tissues due to lymphatic vessel obstruction, also known as lymphoedema),
• low iron levels in the blood.

If any of the adverse reactions listed above cause concern to the patient, medical advice should be sought.
Other adverse reactions may also occur that the patient may not be aware of, such as abnormal laboratory test results, including kidney function tests. Therefore, during treatment with Aderolio, the doctor will perform blood tests to monitor changes in the kidneys.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
tel.: 22 49 21 301, fax: 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Aderolio

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and outer carton following EXP.
The expiry date refers to the last day of the specified month.
No special temperature requirements for storage of this medicine.
Store blisters in the original outer packaging to protect from light and moisture.
Do not use this medicine if the packaging is damaged or shows signs of having been opened.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This practice helps protect the environment.

6. Contents of the pack and other information

What Aderolio contains

• The active substance is everolimus.
  Aderolio 0.25 mg: Each tablet contains 0.25 mg of everolimus.
  Aderolio 0.5 mg: Each tablet contains 0.5 mg of everolimus.
  Aderolio 0.75 mg: Each tablet contains 0.75 mg of everolimus.
  Aderolio 1.0 mg: Each tablet contains 1 mg of everolimus.
• Other ingredients are: butylhydroxytoluene (E 321), magnesium stearate, lactose monohydrate, hypromellose (type 2910), crospovidone (type A), and lactose.

What Aderolio looks like and contents of the pack
Aderolio, 0.25 mg: White to yellowish, marbled, round, flat tablets with bevelled edges,
6 mm in diameter, embossed with the code "C" on one side and "NVR" on the other side.
Aderolio, 0.5 mg: White to yellowish, marbled, round, flat tablets with bevelled edges,
7 mm in diameter, embossed with the code "CH" on one side and "NVR" on the other side.
Aderolio, 0.75 mg: White to yellowish, marbled, round, flat tablets with bevelled edges,
8.5 mm in diameter, embossed with the code "CL" on one side and "NVR" on the other side.
Aderolio, 1.0 mg: White to yellowish, marbled, round, flat tablets with bevelled edges,
9 mm in diameter, embossed with the code "CU" on one side and "NVR" on the other side.
Pack sizes: 50, 60, 100 or 250 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

Manufacturer/Importer
Salutas Pharma GmbH
Otto-von-Guericke Allee 1
39179 Barleben, Germany
Novartis Pharma GmbH
Roonstrasse 25
90429 Nuremberg, Germany

For further information about the medicinal product and its names in other European Economic Area countries, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw, Poland
tel. 22 209 70 00