Teriflunomide HCS: detailed information

Patient Information Leaflet

Teriflunomide HCS 14 mg Film-coated Tablets

teriflunomide
Generic medicine
Please read 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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful to them.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

What Teriflunomide HCS is
Teriflunomide HCS contains the active substance teriflunomide, which is an
immunomodulatory agent and modulates the immune system to reduce its attacks on the
nervous system.
What Teriflunomide HCS is used for
Teriflunomide HCS 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 known as demyelination. It prevents nerves from functioning properly.
People with the relapsing form of multiple sclerosis experience repeated attacks (relapses) of physical symptoms caused by improper nerve function. These symptoms vary from patient to patient, but generally include:

difficulty walking
vision problems
balance problems.
Symptoms may completely disappear 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 HCS works
Teriflunomide HCS 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 HCS

Do not take Teriflunomide HCS

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Teriflunomide HCS 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 indicate liver problems, your doctor may ask you to stop treatment with Teriflunomide HCS. See section 4.
you have high blood pressure (hypertension), whether controlled or not with medication. Teriflunomide HCS 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 starting Teriflunomide HCS, your doctor will check that your white blood cell and platelet counts are adequate. Since Teriflunomide HCS 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 with herpes virus, including oral herpes or herpes zoster (shingles), may occur during treatment with teriflunomide. In some cases, severe complications have occurred. You must inform your doctor immediately if you suspect any symptoms of herpes virus infection. See section 4.
you have severe skin reactions.
you have respiratory symptoms.
you have weakness, numbness, or pain in your hands or feet.
you are due to receive a vaccination.
you are taking leflunomide together with Teriflunomide HCS.
you are switching to or from treatment with Teriflunomide HCS.
you need to undergo a specific blood test (calcium level). False low calcium levels may be observed.

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 HCS is not indicated in children under 10 years of age, as it has not been studied in paediatric 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 for those caring for them:

pancreatitis (inflammation of the pancreas) has been observed in patients taking teriflunomide. Your child’s doctor may perform blood tests if pancreatitis is suspected.

Other medicines and Teriflunomide HCS
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
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 diarrhoea);
theophylline (for asthma);
tizanidine (a muscle relaxant);
warfarin (an anticoagulant used to thin the blood to prevent clot formation);
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 hypercholesterolaemia (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 HCS if you are pregnant or suspect you are pregnant.
If you become pregnant while taking Teriflunomide HCS, the risk of birth defects in the baby increases. Women of childbearing potential must not take this medicine without using reliable contraception.
If your daughter begins menstruation while taking Teriflunomide HCS, 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 HCS, 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 HCS 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 your doctor’s confirmation that teriflunomide blood levels are low enough to allow pregnancy to begin.
For further information on laboratory tests, consult your doctor.
If you suspect pregnancy while taking Teriflunomide HCS or within two years after stopping treatment, you must stop taking Teriflunomide HCS and contact your doctor immediately for a pregnancy test. If the test confirms pregnancy, your doctor may recommend treatment with certain medicines to rapidly and sufficiently eliminate teriflunomide from your body, as this may reduce the risk to the foetus.

Contraception
You must use an effective method of contraception during and after treatment with Teriflunomide HCS. Teriflunomide remains in the blood for a long time after stopping treatment. Continue using effective contraception after stopping treatment, until blood levels of Teriflunomide HCS are sufficiently low. Your doctor will monitor these levels.
Discuss with your doctor the most suitable contraceptive method for you and if any change in contraception is needed.

Do not take Teriflunomide HCS if you are breastfeeding, as teriflunomide passes into breast milk.

Driving and using machines
Teriflunomide HCS may cause dizziness, which could impair your ability to concentrate and react. Do not drive or operate machinery if you experience this symptom.

Teriflunomide HCS contains lactose and sodium
Teriflunomide HCS 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.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take Teriflunomide HCS

Treatment with Teriflunomide HCS must be supervised by a physician experienced in the
treatment of multiple sclerosis.
Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor.
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.

Children and adolescents who reach a stable body weight above 40 kg will be instructed by their physician to switch to one 14 mg tablet per day.
Teriflunomide HCS is not available in the 7 mg dosage. For this dosage, you must take other teriflunomide-containing medicines available on the market. Please consult your doctor or pharmacist.
Route/method of administration
Teriflunomide HCS is for oral use. Teriflunomide HCS is taken every day as a single daily dose at any time of day. The tablet should be swallowed whole with some water.
Teriflunomide HCS may be taken with or without food.
If you take more Teriflunomide HCS than you should
If you have taken too much Teriflunomide HCS, contact your doctor immediately. You may experience adverse effects similar to those described in section 4 below.
If you forget to take Teriflunomide HCS
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 HCS
Do not stop using Teriflunomide HCS 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 everybody 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 paediatric patients and uncommon in adult patients). Uncommon (may affect up to 1 in 100 people)
allergic reactions which may include symptoms of skin rash, hives, swelling of the lips, tongue or face, or sudden breathing difficulties
severe skin reactions which may include symptoms of rash, blisters, fever, or mouth ulcers
severe infections or sepsis (a type of potentially life-threatening infection) which may include symptoms of high fever, shaking, chills, reduced urine output, or confusion
inflammation of the lungs which may include symptoms of shortness of breath or persistent cough

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

severe liver disease which may include symptoms of yellowing of the skin or whites of the eyes, dark 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
Diarrhoea, feeling unwell
Increased ALT (elevated 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, 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 red blood cell count (anaemia), changes in liver and white blood cell test results (see section 2), and 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 weak (asthenia)
Weight loss
Uncommon (may affect up to 1 in 100 people):
Decreased platelet count (mild thrombocytopenia)
Increased sensitivity, particularly of the skin; stabbing or pulsating pain in one or more nerves; nerve problems in 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 above) 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 side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. 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 HCS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and outer carton after EXP. The expiry date refers to the last day of that month.
This medicine does not require any 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 HCS contains

The active substance is teriflunomide. Each tablet contains 14 mg of teriflunomide.
The other components (excipients) are monohydrate lactose, maize starch, hydroxypropylcellulose (E463), microcrystalline cellulose (E460), sodium starch glycolate, magnesium stearate (E470b) and anhydrous colloidal silica in the tablet core; hypromellose, titanium dioxide (E171), macrogol and indigo carmine aluminium lake (E132) in the film coating (see section 2 “Teriflunomide HCS contains lactose and sodium”).

Description of the appearance of Teriflunomide HCS and pack contents
The film-coated tablets (tablets) are blue, round, biconvex, film-coated tablets with "14" printed on one side. Tablet diameter: approximately 7 mm.
Teriflunomide HCS 14 mg film-coated tablets are available in boxes containing:

14, 28, 30, 84, 90 and 98 film-coated tablets in blisters.
14, 28, 84 and 98 film-coated tablets in calendar blister packs.
14 x 1 and 28 x 1 film-coated tablet in unit dose perforated blisters.
14 x 1 and 28 x 1 film-coated tablet in unit dose perforated blisters, calendar pack.

Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
HCS BV, H Kennisstraat 53, B 2650 Edegem, Belgium
Manufacturer
KRKA-FARMA d.o.o., V. Holjevca 20/E, 10450 Jastrebarsko, Croatia
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
Local representative for Italy
KRKA Farmaceutici Milano S.r.l. - Italy