Theditrax

PACKAGE LEAFLET

Package leaflet: information for the patient

Theditrax 14 mg film-coated tablets

Teriflunomide
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 others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Theditrax is and what it is used for

What Theditrax is
Theditrax contains the active substance teriflunomide, which is an immunomodulatory agent that modulates the immune system to reduce its attacks on the central nervous system.

What Theditrax is used for
Theditrax is used in adults, children, and adolescents (aged 10 years and older) for the treatment of relapsing-remitting multiple sclerosis (MS).

What multiple sclerosis is
MS is a long-term disease affecting the central nervous system (CNS). The CNS consists of the brain and spinal cord. In multiple sclerosis, inflammation destroys the protective covering (called myelin) surrounding the nerves of the CNS. This loss of myelin is known as demyelination. This process prevents nerves from functioning properly.

People with the relapsing form of multiple sclerosis experience repeated attacks (relapses) of physical symptoms caused by impaired nerve function. These symptoms vary from patient to patient but usually include:

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

Symptoms may completely disappear after each relapse, but over time some problems may persist between relapses. This can lead to physical disability that may interfere with daily activities.

How Theditrax works
Theditrax 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 in MS.

2. What you need to know before taking Theditrax

Do not take Theditrax:

• if you are allergic to teriflunomide or to any of the other ingredients of this medicine (listed in section 6),
• if you have ever developed a severe skin rash, skin peeling, blisters and/or mouth ulcers after taking teriflunomide or leflunomide,
• if you have severe liver problems,
• if you are pregnant, think you might be pregnant, or are breastfeeding,
• if you have a serious condition affecting the immune system, for example acquired immunodeficiency syndrome (AIDS),
• if you have a serious bone marrow disorder or if you have a low number of red or white blood cells or a reduced number of platelets in your blood,
• 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 you are unsure, consult your doctor or pharmacist before taking this medicine.

Warnings and precautions
Talk to your doctor or pharmacist before taking Theditrax:

• if you have liver problems and/or if you consume large amounts of alcohol. Your doctor will carry out blood tests before and during treatment to check that your liver is functioning properly. If test results show a liver problem, your doctor may ask you to stop treatment with Theditrax. See section 4.
• if you have high blood pressure (hypertension), whether controlled by medication or not, as Theditrax may cause an increase in blood pressure. Your doctor will check your blood pressure before starting treatment and regularly thereafter. See section 4.
• If you have an infection. Before starting Theditrax, your doctor will ensure that your white blood cell and platelet counts are adequate. Since Theditrax reduces the number of white blood cells in the blood, it may affect your ability to fight infections. If you suspect you have an infection, your doctor may perform blood tests to monitor your white blood cells. Viral infections caused by the herpes virus, including 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.
• if you have severe skin reactions.
• if you have respiratory symptoms.
• if you experience weakness, numbness, or pain in your hands and feet.
• if you are due to receive a vaccination.
• if you are taking leflunomide with Theditrax.
• if you are switching to or from treatment with Theditrax.
• if you are due to have a specific blood test (calcium level). False low calcium levels may be detected.

Respiratory reactions
Inform your doctor if you develop unexplained cough or shortness of breath (dyspnea). Your doctor may perform further investigations.
Children and adolescents
Theditrax 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 their caregivers:

• 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 Theditrax
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 (often 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 disease in diabetics
• alosetron for the management of severe diarrhoea
• theophylline for asthma
• tizanidine, a muscle relaxant
• warfarin, an anticoagulant used to thin the blood (i.e. make it more fluid) 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 hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
• cholestyramine for high cholesterol or to relieve itching in liver diseases
• activated charcoal to reduce absorption of medicines or other substances

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

• Continue until Theditrax blood levels are sufficiently low – your doctor will check this.
• Consult your doctor about the best method of contraception for you and if any change is needed.

Do not take Theditrax while breastfeeding, as teriflunomide passes into breast milk.
Driving and using machines
Theditrax may cause dizziness, which could impair your ability to concentrate and react. You must not drive or operate machinery if you experience this symptom.
Theditrax contains lactose
Theditrax contains lactose (a type of sugar). If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Theditrax contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially "sodium-free".

3. How to take Theditrax

Treatment with Theditrax will be supervised by a physician experienced in the treatment of multiple sclerosis.
Always 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: other medicinal products containing teriflunomide at different dosage strengths from this medicine are suitable for children and adolescents aged 10 years and older with body weight equal to or less than 40 kg; please ask your doctor or pharmacist about the availability of Theditrax tablets with a different dosage strength.

Children and adolescents who reach a stable body weight above 40 kg will be instructed by the doctor to switch to one 14 mg tablet per day.
Theditrax 14 mg film-coated tablets are not suitable for pediatric patients with body weight ≤ 40 kg.

Method of administration
Theditrax is for oral use. Theditrax should be taken once daily at any time of the day.
Swallow the tablet whole with some water.
Theditrax may be taken with or without food.

If you take more Theditrax than you should
If you have taken an excessive amount of Theditrax, contact your doctor immediately. Adverse effects similar to those described in section 4 may occur.

If you forget to take Theditrax
Do not take a double dose to make up for the forgotten tablet. Take the next dose at the scheduled time.

If you stop taking Theditrax
Do not stop taking Theditrax or change the dose without first talking to your doctor.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Serious side effects
Some side effects may be or may become serious; if any of the following occur, contact your doctor immediately.

Common (may affect up to 1 in 10 people)

• inflammation of the pancreas, which may include symptoms such as 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,
• serious infections or sepsis (a potentially life-threatening type of infection), 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 available data):

• a serious liver disease that may include symptoms such as yellowing of the skin or whites of the eyes, dark-colored 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 blood levels of certain liver enzymes) detected by laboratory 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 difficulty 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: a decrease in red blood cell count (anaemia), changes in liver function tests and white blood cell counts (see section 2), as well as increases in a muscle enzyme (creatine phosphokinase),
• mild allergic reactions,
• feeling anxious,
• tingling, weakness, numbness, tingling or pain in the lower back or leg (sciatica); numbness, burning, tingling or pain in the hands and fingers (carpal tunnel syndrome),
• awareness of heartbeat,
• increased blood pressure,
• malaise (vomiting), toothache, upper abdominal pain,
• rash, acne,
• tendon, joint, bone pain, muscle pain (musculoskeletal pain),
• need to urinate more often than usual,
• heavy menstrual periods,
• pain,
• lack of energy or feeling weak (asthenia),
• weight loss.

Uncommon (may affect up to 1 in 100 people)

• decreased number of platelets in the blood (mild thrombocytopenia),
• increased sensitivity, especially of the skin; stabbing or pulsating pain along 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 and 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 available data)

• Pulmonary hypertension.

Children (from 10 years of age) 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, consult your doctor or pharmacist. You may 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 Theditrax

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after the wording "Exp". The expiry date refers to the last day of that month.
Do not store above 30°C.
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. Contents of the pack and other information

What Theditrax contains
The active substance is teriflunomide.

• Each tablet contains 14 mg of teriflunomide.
• The other components are monohydrate lactose, maize starch, microcrystalline cellulose 102, sodium starch glycolate (type A), hydroxypropylcellulose, magnesium stearate, anhydrous colloidal silica, OparDry 03F220186 yellow film coating [Composed of: HPMC 2910/hydroxypropylmethylcellulose (E464), titanium dioxide (E171), talc (E553b), macrogol/PEG (E1521), yellow iron oxide (E172)] (see section 2 "Theditrax contains lactose").

Description of the appearance of Theditrax and contents of the pack
Film-coated pentagonal tablets, pale yellow to pastel yellow in colour, with dimensions of 7.3 ± 0.2 mm in diameter and 3.8 ± 0.5 mm in thickness, imprinted with (‘14’) on one side.
The medicine is packaged in a cardboard box containing blisters made of OPA/ALU/PVC-ALU.
Pack sizes: 28, 84 film-coated tablets
Not all pack sizes may be marketed.

Marketing Authorization Holder
Pharmathen SA,
6 Dervenakion str., 15351 Pallini Attiki, Greece

Manufacturer
Pharmathen International S.A.,
Industrial Park Sapes, Rodopi Prefecture, Block No 5, Rodopi 69300, Greece
Pharmathen SA,
6 Dervenakion str., 15351 Pallini Attiki, Greece

This medicinal product is authorised in the European Economic Area Member States under the following names: