Tifay

Package leaflet: Information for the patient

TIFAY, 14 mg, coated tablets
teriflunomide
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

• Keep this leaflet for possible future reference.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are identical.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Tifay is and what it is used for

What Tifay is
Tifay contains the active substance teriflunomide, which is an immunomodulatory medicine that regulates the immune system to reduce its attack on the nervous system.
What Tifay is used for
This medicine is used in the treatment of adults, children, and adolescents (aged 10 years and older) with relapsing-remitting multiple sclerosis (MS).
What is multiple sclerosis (MS)
MS is a chronic disease that affects the central nervous system (CNS). The CNS consists of the brain and spinal cord. In multiple sclerosis, inflammatory processes damage the protective covering (called myelin) surrounding the nerves in the CNS. This process is known as demyelination. It prevents nerves from functioning properly.
In people with relapsing forms of multiple sclerosis, there are repeated attacks (relapses) of physical symptoms caused by impaired nerve function. Symptoms vary between patients but usually include:

• difficulty walking,
• vision problems,
• balance disturbances.

These symptoms may completely disappear after a relapse ends, but over time some problems may persist between relapses. This may lead to physical disability, making it difficult to perform daily activities.
How Tifay works
This medicine helps protect the central nervous system from the immune system by limiting the increase in number of certain white blood cells (lymphocytes). This reduces the inflammation that, in patients with MS, leads to nerve damage.

2. Important information before taking Tifay

When not to take Tifay:

• if the patient is allergic to teriflunomide or any of the other ingredients of this medicine (listed in section 6);
• if the patient has ever developed severe skin rash, skin peeling, blisters and/or oral ulceration after taking teriflunomide or leflunomide;
• if the patient has severe liver disease;
• if the patient is pregnant, suspects she may be pregnant, or is breastfeeding;
• if the patient has any severe diseases affecting the immune system, such as acquired immunodeficiency syndrome (AIDS);
• if the patient has any severe bone marrow disorders or has low numbers of red or white blood cells or reduced platelet count;
• if the patient has a severe infection;
• if the patient has severe kidney disease requiring dialysis;
• if the patient has very low levels of protein in the blood (hypoproteinemia).
  If in doubt, consult a doctor or pharmacist before taking this medicine.

Warnings and precautions
Before starting Tifay, discuss with your doctor or pharmacist if:

• the patient has liver function disorders and/or drinks large amounts of alcohol; the doctor may perform blood tests to check whether liver function is normal before and during treatment. If test results indicate impaired liver function, the doctor may discontinue Tifay. See section 4.
• the patient has high blood pressure (hypertension), regardless of whether it is controlled with medication or not. This medicine may increase blood pressure. The doctor will monitor the patient’s blood pressure before starting treatment and regularly thereafter. See section 4.
• the patient has an infection. Before administering Tifay, the doctor will ensure the patient has adequate levels of white blood cells and platelets in the blood. Since this medicine reduces the number of white blood cells, it may impair the ability to fight infections. The doctor may perform blood tests to check white blood cell count if the patient suspects an infection. Herpes virus infections, including cold sores or shingles, may occur during treatment with teriflunomide. In some cases, serious complications have occurred. Inform the doctor immediately if any signs of herpes virus infection are suspected. See section 4.
• the patient has experienced severe skin reactions.
• the patient has respiratory symptoms.
• the patient experiences weakness, numbness, or pain in hands and feet.
• the patient plans to receive vaccination.
• the patient is taking leflunomide together with this medicine.
• the patient is switching from another medicine to Tifay or from Tifay to another medicine.
• the patient is scheduled for a specific blood test (calcium level measurement). Calcium test results may be falsely low.

Respiratory system reactions
Inform the doctor if the patient develops unexplained cough or shortness of breath (difficulty breathing). The doctor may perform additional tests.

Children and adolescents
Teriflunomide is not intended for use in children under 10 years of age, as it has not been studied in patients with MS in this age group.
The warnings and precautions listed above also apply to children. The following information is important for children and their caregivers:

• cases of pancreatitis have been observed in patients receiving teriflunomide. The child’s doctor may perform blood tests if pancreatitis is suspected.

Tifay and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take, including over-the-counter medicines.
In particular, inform the doctor or pharmacist if the patient is taking any of the following medicines:

• leflunomide, methotrexate, and other medicines affecting the immune system (often called immunosuppressants or immunomodulators);
• rifampicin (used to treat tuberculosis and other infections);
• carbamazepine, phenobarbital, phenytoin, used to treat epilepsy;
• St. John’s wort (herbal remedy for depression);
• repaglinide, pioglitazone, nateglinide, or rosiglitazone, used to treat diabetes;
• daunorubicin, doxorubicin, paclitaxel, or topotecan, used to treat cancer;
• duloxetine, used to treat depression, urinary incontinence, or kidney disease in diabetic patients;
• alosetron, used to treat severe diarrhea;
• theophylline, used to treat asthma;
• tizanidine (muscle relaxant);
• warfarin (anticoagulant) used to thin the blood (i.e. make it more fluid) to prevent clots;
• oral contraceptives (containing ethinylestradiol and levonorgestrel);
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin, used to treat infections;
• indometacin, ketoprofen, used to treat inflammation or pain;
• furosemide, used to treat heart conditions;
• cimetidine, used to reduce gastric acid secretion;
• zidovudine, used to treat HIV infection;
• rosuvastatin, simvastatin, atorvastatin, pravastatin, medicines used to treat hypercholesterolemia (high blood cholesterol);
• sulfasalazine, used for inflammatory bowel disease and rheumatoid arthritis;
• cholestyramine, used in cases of high blood cholesterol or itching in liver disease;
• activated charcoal, used to reduce absorption of medicines or other substances.

Pregnancy and breastfeeding
Do not take this medicine if the patient is pregnant or suspects she may be pregnant.
There is an increased risk of birth defects in the unborn child if the patient becomes pregnant while taking Tifay or if she was pregnant during treatment. Women of childbearing potential who do not use effective contraception must not take this medicine.
If a girl starts menstruating while taking this medicine, inform the doctor, who will provide specialist advice regarding contraception and potential risks in case of pregnancy.
If a woman plans to become pregnant after stopping Tifay, she should inform her doctor, as it is essential to ensure the medicine is no longer in the body before attempting pregnancy. Elimination of the active substance may take up to 2 years. This period can be shortened to several weeks by taking specific medicines that accelerate removal of the drug from the body.
In both cases, blood testing must confirm that the active substance has been sufficiently eliminated from the body. The treating doctor should confirm that blood levels of teriflunomide are low enough to allow pregnancy.
More information about laboratory tests is available from the doctor.
If a woman suspects she became pregnant while taking this medicine or within two years after stopping treatment, she must stop taking Tifay and immediately contact her doctor for a pregnancy test. If pregnancy is confirmed, the doctor may recommend appropriate treatment to rapidly and adequately eliminate the medicine from the body to reduce risk to the unborn child.

Contraception
During treatment with this medicine and after stopping it, women should use an effective method of contraception. Teriflunomide remains in the blood for a long time after stopping treatment. For this reason, effective contraception should continue after treatment ends.

• This method should be used until blood levels of Tifay are sufficiently low (as confirmed by the doctor).
• Discuss with the doctor the most suitable contraceptive method for the patient, and in case of any need to change the contraceptive method.

Do not take Tifay while breastfeeding, as teriflunomide passes into human milk.

Driving and operating machinery
This medicine may cause dizziness, which may impair concentration and reaction ability. Patients experiencing these symptoms should not drive or operate machinery.

Tifay contains lactose and sodium
This medicine contains lactose (a type of sugar). If the patient has been previously diagnosed with intolerance to certain sugars, consult a doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. the medicine is considered "sodium-free".

3. How to take Tifay

Treatment with Tifay will be supervised by a physician experienced in the treatment of multiple sclerosis.
This medicine should always be taken as directed by your doctor. If in doubt, consult your doctor.
Use in adults
The recommended dose is one 14 mg tablet per day.
Use in children and adolescents (aged 10 years and older)
The dose depends on body weight:

• Children with body weight greater than 40 kg: one 14 mg tablet per day.
• Children with body weight less than or equal to 40 kg: one 7 mg tablet per day.

Tifay is available only as a 14 mg tablet. If your doctor has prescribed teriflunomide at a dose of 7 mg per day, the Tifay tablet should be divided into two equal halves along the break line, and one half taken, corresponding to 7 mg. If in doubt, consult your doctor.
Children and adolescents who achieve a stable body weight above 40 kg will be informed by their doctor to change the dose to one 14 mg tablet per day.
Route and method of administration
This medicine is administered orally. It is taken daily at any time of day as a single daily dose.
The tablet may be divided into two equal doses.
Tablets should be swallowed with a small amount of water.
This medicine may be taken with food or independently of meals.
Taking more Tifay than prescribed
If more Tifay than prescribed has been taken, contact your doctor immediately. Adverse reactions may occur similar to those described in section 4 below.
Missing a dose of Tifay
Do not take a double dose to make up for a missed tablet. Take the next dose according to the prescribed dosing schedule.
Stopping Tifay treatment
Do not stop taking this medicine or change the dose without first consulting your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following adverse effects may occur after using this medicine.
Serious adverse effects
Some adverse effects may be or may become serious. If any of these symptoms occur, contact your doctor immediately.
Common (may occur in up to 1 in 10 people)

• inflammation of the pancreas (pancreatitis), which may cause symptoms such as abdominal pain, nausea or vomiting (frequency: common in children and adolescents, and uncommon in adult patients).

Uncommon (may occur in up to 1 in 100 people)

• allergic reactions, which may cause symptoms including rash, hives, swelling of the lips, tongue or face, or sudden breathing difficulties;
• severe skin reactions, which may cause symptoms including skin rash, blisters on the skin, fever or mouth ulcers;
• severe infections or sepsis (a type of infection potentially life-threatening), which may cause symptoms including high fever, seizures, chills, reduced urine output or confusion;
• lung inflammation (pneumonitis), which may cause symptoms including shortness of breath or persistent cough.

Frequency not known (frequency cannot be estimated from available data):

• severe liver disease, which may cause symptoms including yellowing of the skin or whites of the eyes (jaundice), darker than usual urine, unexplained nausea and vomiting, or abdominal pain.

Other adverse effects may occur with the following frequencies:

Very common (may occur in more than 1 in 10 people)

• headache;
• diarrhoea, nausea;
• increased AlAT activity (elevation of certain liver enzyme levels in blood tests);
• hair thinning.

Common (may occur in up to 1 in 10 people)

• influenza, upper respiratory tract infection, urinary tract infection, bronchitis,
  sinusitis, sore throat and discomfort during swallowing, cystitis,
  viral gastroenteritis, dental infection, laryngitis, fungal foot infection;

• herpes virus infections, including cold sores and shingles, with symptoms such as blisters, burning, itching, tingling or pain in the skin, usually on one side of the upper body or face, and other symptoms such as fever and fatigue;

• laboratory findings: reduced number of red blood cells (anaemia), changes in liver function and white blood cell counts (see section 2), increased activity of muscle enzymes (creatine kinase) has also been observed;

• mild allergic reactions;

• feeling of anxiety;

• tingling sensation, feeling of weakness, numbness, tingling or pain in the lower back or leg (sciatica), tingling, burning, numbness or pain in the hands and fingers (carpal tunnel syndrome);

• sensation of "heart pounding";

• increased blood pressure;

• vomiting, toothache, epigastric pain;

• rash, acne;

• tendon, joint, bone pain (musculoskeletal pain), muscle pain;

• increased need to urinate;

• heavy menstrual bleeding;

• pain;

• lack of energy or feeling of weakness (asthenia);

• weight loss.

Uncommon (may occur in up to 1 in 100 people)

• reduced number of platelets (mild thrombocytopenia);
• increased sensitivity (especially of the skin), stabbing or pulsating pain along one or more nerves, nerve disorders affecting arms or legs (peripheral neuropathy);
• changes in nails, severe skin reactions;
• traumatic pain;
• psoriasis;
• inflammation of the mucous membrane of the mouth/lips;
• abnormal blood lipid levels;
• inflammation of the large intestine (colitis).

Rare (may occur in up to 1 in 1000 people)

• liver inflammation or damage.

Frequency not known (frequency cannot be estimated from available data)

• pulmonary hypertension.

Children (aged 10 years and older) and adolescents
The adverse effects listed above also apply to children and adolescents. The following additional information is important for children, adolescents and their caregivers:
Common (may occur in up to 1 in 10 people)

• pancreatitis.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder. Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store the medicine Tifay

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard packaging after:
"EXP". The expiry date refers to the last day of the stated month.
No special storage instructions apply.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What Tifay contains

• The active substance in Tifay is teriflunomide. Each Tifay tablet contains 14 mg of teriflunomide.
• Other ingredients are:
  • Tablet core: monohydrate lactose (see section 2 "Tifay contains lactose and sodium"), maize starch, microcrystalline cellulose type 101, hydroxypropylcellulose, sodium carboxymethyl starch (type A), talc, calcium stearate.
  • Tablet coating: hypromellose 2910 (6 mP), titanium dioxide (E 171), macrogol 8000, indigo carmine, aluminium lake (E 132).

What Tifay looks like and contents of the pack

Tifay 14 mg film-coated tablets are round, light blue, with a score line, approximately 7 mm in diameter.
The tablet can be divided into equal doses.
The carton contains blisters made of Aluminium/PVC/Aluminium/OPA, each containing 14 tablets.
Pack sizes contain either 28 or 84 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
STADA Arzneimittel AG
Stadastrasse 2 - 18
61118 Bad Vilbel
Germany

Importer
STADA Arzneimittel AG
Stadastrasse 2 - 18
61118 Bad Vilbel
Germany
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park,
Paola PLA 3000, Malta
Adalvo Limited
Malta Life Sciences Park, Building 1, Level 4,
Sir Temi Zammit Buildings,
San Gwann SGN 3000, Malta
KeVaRo GROUP Ltd
9 Tzaritza Elenora Str., office 23
Sofia 1618 Bulgaria

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Stada Pharm Sp. z o.o.
ul. Krakowiaków 44
02-255 Warszawa
Tel. +48 22 737 79 20

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Czech Republic TIFAY
Estonia TIFAY
Iceland TIFAY 14 mg filmuhúðaðar töflur
Lithuania TIFAY 14 mg plėvele dengtos tabletės
Latvia TIFAY 14 mg apvalkotās tabletes
Poland TIFAY
Hungary TIFAY 14 mg obložene tablete