Teriflunomide Zentiva: detailed information

Package leaflet: Information for the patient

Teriflunomide Zentiva 14 mg film-coated tablets

Equivalent medicine
Please read this entire leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet. 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. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

What Teriflunomide Zentiva is and what it is used for
What you need to know before taking Teriflunomide Zentiva
How to take Teriflunomide Zentiva
Possible side effects
How to store Teriflunomide Zentiva
Contents of the pack and other information

1. What is Teriflunomide Zentiva and what is it used for

What is Teriflunomide Zentiva
Teriflunomide Zentiva contains the active substance teriflunomide, which is an immunomodulatory agent and
modulates the immune system to limit its attacks on the nervous system.
What Teriflunomide Zentiva is used for
Teriflunomide Zentiva is used in adults, children and adolescents (aged 10 years and older) for the treatment of relapsing-remitting multiple sclerosis (MS).
What is multiple sclerosis
MS is a long-term disease affecting the central nervous system (CNS), a system composed of the brain and spinal cord. In multiple sclerosis, inflammation destroys the protective covering (called myelin) that surrounds the nerves of the CNS. This loss of myelin is called demyelination. It prevents nerves from functioning properly.
People with relapsing forms of multiple sclerosis experience repeated attacks (relapses) of physical symptoms caused by improper nerve function. These symptoms vary from patient to patient, but usually include:

difficulty walking
vision problems
balance problems.

Symptoms may disappear completely after a relapse, but over time some problems may persist between relapses. This can lead to physical disability that may interfere with daily activities.
How Teriflunomide Zentiva works
Teriflunomide Zentiva helps protect the central nervous system from immune system attacks by limiting the increase of certain white blood cells (lymphocytes). This reduces the inflammation that causes nerve damage characteristic of MS.

2. What you need to know before taking Teriflunomide Zentiva

Do not take Teriflunomide Zentiva if:

you are allergic to teriflunomide or to any of the other ingredients of this medicine (listed in section 6),
you have developed a severe skin rash or skin peeling, blistering and/or mouth sores after taking teriflunomide or leflunomide,
you have severe liver problems,
you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding,
you have any severe condition affecting the immune system (e.g. acquired immunodeficiency syndrome (AIDS)),
you have any severe bone marrow disorder or if you have low numbers of red blood cells or white blood cells in your blood or a reduced platelet count,
you have a severe infection,
you have severe kidney problems requiring dialysis,
you have very low levels of protein in your blood (hypoproteinemia).

If you have any doubts, consult your doctor or pharmacist before taking this medicine.
Warnings and precautions
Talk to your doctor or pharmacist before taking Teriflunomide Zentiva if:

you have liver problems and/or consume large amounts of alcohol. Your doctor will request blood tests before and during treatment to monitor liver function. If blood test results show a liver problem, your doctor may ask you to stop treatment with Teriflunomide Zentiva. See section 4.
you have high blood pressure (hypertension), whether controlled or not with medication. Teriflunomide Zentiva may cause an increase in blood pressure. Your doctor will check your blood pressure before starting treatment and regularly thereafter. See section 4.
you have an infection. Before taking Teriflunomide Zentiva, your doctor will check that your white blood cell and platelet counts are adequate. Since Teriflunomide Zentiva reduces the number of white blood cells in the blood, this may affect your ability to fight infections. If you suspect you have any infection, your doctor may perform blood tests to monitor white blood cells. Viral infections, including herpes viruses, such as oral herpes or herpes zoster (shingles), may occur during treatment with teriflunomide. In some cases, serious complications may arise. You must inform your doctor immediately if you suspect any symptoms of a herpes virus infection. See section 4.
you have severe skin reactions.
you have respiratory symptoms.
you experience weakness, numbness, and pain in your hands or feet.
you need to receive a vaccination.
you are taking leflunomide together with Teriflunomide Zentiva.
you are switching to or from treatment with Teriflunomide Zentiva. You will need a specific blood test (calcium level). Falsely low calcium levels may be observed.

Talk to your doctor or pharmacist:
if you develop skin ulcers or notice impaired wound healing during treatment with Teriflunomide Zentiva.
if you are scheduled for or have recently undergone major surgery or if you still have an unhealed wound after surgery, as Teriflunomide Zentiva may impair wound healing.
Respiratory reactions
Inform your doctor if you experience unexplained cough or shortness of breath (dyspnea). Your doctor may carry out further investigations.
Children and adolescents
Teriflunomide Zentiva is not indicated 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 those caring for them:

Pancreatic inflammation has been observed in patients taking teriflunomide. Your child’s doctor may perform blood tests if pancreatic inflammation is suspected.

Other medicines and Teriflunomide Zentiva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

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

Pregnancy and breastfeeding
Do not take Teriflunomide Zentiva if you are pregnant or suspect you may be pregnant. If you become pregnant while taking Teriflunomide Zentiva, the risk of birth defects in the baby increases. Women of childbearing potential must not take this medicine without using reliable contraceptive methods.
If your daughter starts menstruating while taking Teriflunomide Zentiva, you must inform the doctor, who will provide specialist advice regarding contraception and potential risks in case of pregnancy.
Inform your doctor if you plan to become pregnant after stopping treatment with Teriflunomide Zentiva, because you must ensure that most of this medicine has been eliminated from your body before planning a pregnancy. Elimination of the active substance may take up to 2 years naturally. This period can be reduced to a few weeks by taking certain medicines that accelerate the elimination of Teriflunomide Zentiva from the body.
In any case, blood testing must confirm that the active substance has been sufficiently eliminated from your body, and you must wait for confirmation from your doctor that the level of Teriflunomide Zentiva in the blood is low enough to allow pregnancy.
For further information on laboratory tests, consult your doctor.
If you suspect pregnancy while taking Teriflunomide Zentiva or within two years after stopping treatment, you must stop taking Teriflunomide Zentiva and contact your doctor immediately to have a pregnancy test. If the test confirms pregnancy, your doctor may recommend treatment with certain medicines to rapidly and sufficiently eliminate Teriflunomide Zentiva from the body, as this may reduce the risk to the fetus.
Contraception
You must use an effective method of contraception during and after treatment with Teriflunomide Zentiva. Teriflunomide remains in the blood for a long time after stopping treatment. Continue using effective contraception after stopping treatment.

Continue until blood levels of Teriflunomide Zentiva are sufficiently low. Your doctor will monitor these levels.
Consult your doctor about the most suitable contraceptive method for you and if any change in contraception is needed. Do not take Teriflunomide Zentiva if you are breastfeeding, as teriflunomide passes into breast milk.

Driving and using machines
Teriflunomide Zentiva may cause dizziness, which could impair your ability to concentrate and react. Do not drive or operate machinery if you experience this symptom.
Teriflunomide Zentiva contains lactose
Teriflunomide Zentiva contains lactose (a type of sugar). If you have been told by your doctor that you have an intolerance to certain sugars, contact your doctor before taking this medicine.
Teriflunomide Zentiva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take Teriflunomide Zentiva

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.
Treatment with Teriflunomide Zentiva must be supervised by a physician experienced in the treatment of multiple sclerosis.
Adults
The recommended dose is one 14 mg tablet per day.
Children and adolescents (aged 10 years and older)
The dose depends on body weight:

Children with body weight above 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.

Teriflunomide Zentiva 14 mg film-coated tablets are not suitable for pediatric patients with body weight less than or equal to 40 kg.
Other teriflunomide-containing medicines with lower dosages are available (such as 7 mg film-coated tablets).
Children and adolescents who reach a stable body weight above 40 kg will be instructed by their doctor to switch to one 14 mg tablet per day.
Route/method of administration
Teriflunomide Zentiva is for oral use. Teriflunomide Zentiva should be taken every day as a single daily dose at any time of the day.
The tablet should be swallowed whole with some water.
Teriflunomide Zentiva may be taken with or without food.
If you take more Teriflunomide Zentiva than you should
If you have taken too much Teriflunomide Zentiva, contact your doctor immediately. You may experience adverse effects similar to those described in section 4 below.
If you forget to take Teriflunomide Zentiva
Do not take a double dose to make up for the missed tablet. Take the next dose at the scheduled time.
If you stop taking Teriflunomide Zentiva
Do not stop using Teriflunomide Zentiva or change the dose without first talking to your doctor.
If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The following side effects may occur with this medicine.

Serious side effects
Some side effects may be or may become serious. Contact your doctor immediately if you notice any of the following serious side effects.

Common (may affect up to 1 in 10 people)

Inflammation of the pancreas which may include symptoms of abdominal pain, nausea or vomiting (frequency is common in pediatric patients and uncommon in adult patients).

Uncommon (may affect up to 1 in 100 people)

Allergic reactions which may include symptoms such as rash, hives, swelling of the lips, tongue or face, or sudden breathing difficulties
Severe skin reactions which may include symptoms such as rash, blisters, fever, or mouth ulcers
Severe infections or sepsis (a type of infection that may be life-threatening) which may include symptoms such as high fever, shaking, chills, reduced urine output, or confusion
Inflammation of the lungs which may include symptoms such as shortness of breath or persistent cough

Not known (frequency cannot be estimated from the available data)

Severe liver disease which may include symptoms such as yellowing of the skin or whites of the eyes, darker than normal urine, unexplained nausea and vomiting, or abdominal pain

Other side effects may occur with the following frequencies:
Very common (may affect more than 1 in 10 people):

Headache
Diarrhea, feeling unwell
Increased ALT (increase in levels of certain liver enzymes in the blood) detected by blood tests
Hair thinning

Common (may affect up to 1 in 10 people):

Influenza, upper respiratory tract infection, urinary tract infection, bronchitis, sinusitis, sore throat and discomfort when swallowing, cystitis, viral gastroenteritis, oral herpes, dental infection, laryngitis, fungal foot infection
Herpes virus infections, including oral herpes and herpes zoster (shingles), with symptoms such as blisters, burning, itching, numbness or pain of the skin, usually on one side of the upper body or face, and other symptoms such as fever and weakness
Laboratory findings: decreased number of red blood cells (anemia), changes in test results related to the liver and white blood cells (see section 2), and also increases in a muscle enzyme (creatine phosphokinase)
Mild allergic reactions
Feeling anxious
Tingling, weakness, numbness, tingling or pain in the lower back or legs (sciatica); numbness, tingling or pain in the hands and fingers (carpal tunnel syndrome)
Awareness of heartbeat
Increased blood pressure
Vomiting, toothache, upper abdominal pain
Rash, acne
Tendon, joint, bone pain, muscle pain (musculoskeletal pain)
Need to urinate more often than usual
Heavy menstrual bleeding
Pain
Lack of energy or feeling of weakness (asthenia)
Weight loss

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

Decreased number of platelets (mild thrombocytopenia)
Increased sensitivity, particularly of the skin; stabbing or pulsating pain in one or more nerves, nerve problems in the arms or legs (peripheral neuropathy)
Nail disorders, severe skin reactions
Post-traumatic pain
Psoriasis
Inflammation of the mouth/lips
Abnormal levels of fats (lipids) in the blood
Inflammation of the colon (colitis)

Rare (may affect up to 1 in 1,000 people):

Inflammation or damage to the liver

Not known (frequency cannot be estimated from the available data):

Pulmonary hypertension

Children (aged 10 years and older) and adolescents
The side effects listed above also apply to children and adolescents. The following additional information is important for children, adolescents, and those caring for them:
Common (may affect up to 1 in 10 people)

Inflammation of the pancreas

Reporting of suspected adverse reactions
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Teriflunomide Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp". The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Teriflunomide Zentiva contains
The active substance is teriflunomide. Each tablet contains 14 mg of teriflunomide.
The other components are monohydrate lactose, microcrystalline cellulose, corn starch, sodium starch glycolate (type A), hydroxypropylcellulose, magnesium stearate, hypromellose, calcium carbonate, triacetin, indigo carmine - aluminium lake (E132).

Description of the appearance of Teriflunomide Zentiva and contents of the pack
Teriflunomide Zentiva 14 mg film-coated tablets (tablets) are round, blue, 7 mm in diameter, with the imprint “C14” on one side.
Pack sizes in PA-AL-PVC/Al blisters containing: 14, 28, 84 or 98 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milan, Italy

Manufacturer
Coripharma ehf.
Reykjavikurvegur 78
IS-220 Hafnarfjordur
Iceland

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria, Bulgaria, Croatia, Czech Republic, Denmark, Germany, Iceland, Norway, Sweden: Teriflunomid Zentiva
Portugal, Romania, Spain: Teriflunomide Zentiva
Estonia, France, Hungary, Italy, Lithuania, Latvia, Poland, Slovakia: Teriflunomide Zentiva

Other sources of information
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco).