Tergio

Patient Information Leaflet

Tergio 14 mg film-coated tablets

teriflunomide
Generic medicine
Please read all of this leaflet carefully before you start 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 pass it on to others, even if they have the same symptoms as you, because it may 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

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

1. What Tergio is and what it is used for

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

What Tergio is used for
Teriflunomide is used in adults, children and adolescents aged 10 years and older (body weight above 40 kg) 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), which consists of the brain and spinal cord. In multiple sclerosis, inflammation destroys the protective sheath (called myelin) that surrounds the nerves of the CNS. This loss of myelin is called demyelination and prevents nerves from functioning properly.

People affected by the relapsing form of multiple sclerosis experience repeated episodes (relapses) of physical symptoms caused by improper nerve function. These symptoms vary from patient to patient, but generally include:

• difficulty walking
• visual 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 Tergio works
Tergio helps protect the central nervous system from attacks by the immune system 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 Tergio

Do not take Tergio:

• if you are allergic to teriflunomide or to any of the other ingredients of this medicine (listed in section 6)
• if you have developed a severe skin rash, 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, 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 the blood, or a low platelet count
• if you have a severe infection
• if you have severe kidney problems requiring dialysis
• if you have very low levels of protein in the 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 Tergio 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 liver problems, your doctor may ask you to stop treatment with Tergio. See section 4;
• you have high blood pressure (hypertension), whether controlled or uncontrolled by medication. Tergio 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 Tergio, your doctor will check that your white blood cell and platelet counts are adequate. Since Tergio 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. Infections caused by herpes viruses, 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;
• you have severe skin reactions;
• you have respiratory symptoms;
• you experience weakness, numbness, or pain in your hands or feet;
• you are due to receive a vaccination;
• you are taking leflunomide together with Tergio;
• you are switching to or from treatment with Tergio;
• you need to undergo a specific blood test (calcium level). Falsely low calcium levels may be observed.

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

• 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 Tergio
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 diarrhoea
• 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
• cholestyramine 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 Tergio if you are pregnant or suspect you are pregnant. If you become pregnant while taking Tergio, 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/adolescent daughter starts menstruating while taking teriflunomide, 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 Tergio, because before planning a pregnancy, you must ensure that most of this medicine has been eliminated from your body. 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 Tergio from the body.
In any case, a blood test must confirm that the active substance has been sufficiently eliminated from your body, and you must wait for your doctor’s confirmation that Tergio blood levels are low enough to allow pregnancy.
For further information on laboratory tests, consult your doctor.
If you suspect pregnancy while taking Tergio or within two years after stopping treatment, you must stop Tergio and contact your doctor immediately to perform a pregnancy test. If the test confirms pregnancy, your doctor may recommend treatment with certain medicines to rapidly and sufficiently eliminate Tergio 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 Tergio.
Teriflunomide remains in the blood for a long time after stopping treatment. Continue using effective contraception after stopping treatment.

• Continue until Tergio blood levels are sufficiently low. Your doctor will monitor them.
• Consult your doctor about the most suitable contraceptive method for you and in case of any need to change contraception.

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

3. How to take Tergio

Treatment with Tergio must be supervised by a physician experienced in the treatment of multiple sclerosis.
Take this medicine exactly as directed 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 (10 years of age or 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.

Tergio is available only as 14 mg film-coated tablets. Therefore, Tergio cannot be administered to patients requiring less than a full 14 mg dose. If an alternative dose is required, other teriflunomide-containing products offering such an option should be used.

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.

Route/Method of administration
Tergio is for oral use. Tergio 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.
Tergio may be taken with or without food.

If you take more Tergio than you should
If you have taken too much Tergio, contact your doctor immediately. You may experience adverse effects similar to those described in section 4 below.

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

If you stop taking Tergio
Do not stop using Tergio or change the dose without first discussing it with your doctor.

If you have any questions about the use of this medicine, consult 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 become serious. If you experience any of these, 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 paediatric patients and uncommon in adult patients).

Uncommon (may affect up to 1 in 100 people)

• Allergic reactions which may include symptoms such as skin rash, hives, swelling of the lips, tongue or face, or sudden breathing difficulties
• Severe skin reactions which may include symptoms such as skin 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 diseases 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
• Diarrhoea, nausea
• Increased ALT (elevation 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 number of red blood cells (anaemia), changes in liver function tests and white blood cell counts (see section 2), and increases in a muscle enzyme (creatine phosphokinase)
• Mild allergic reactions
• Feeling of anxiety
• Tingling, weakness, numbness, tingling or pain in the lower back or legs (sciatica); numbness, burning, tingling or pain in the hands and fingers (carpal tunnel syndrome)
• Awareness of your heartbeat
• Increased blood pressure
• Vomiting, toothache, upper abdominal pain
• Skin 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 number of platelets (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)

• Increased blood pressure in the lungs

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 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. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Tergio

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging 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 Tergio contains

• The active substance is teriflunomide. Each tablet contains 14 mg of teriflunomide.
• The other components are: Tablet core: monohydrate lactose (see section 2 “Tergio contains lactose”), maize starch, microcrystalline cellulose, sodium starch glycolate (see section 2 “Tergio contains sodium”), hydroxypropylcellulose, magnesium stearate, anhydrous colloidal silica. Tablet coating: hypromellose, titanium dioxide (E171), talc, macrogol 6000, indigo carmine - aluminium lake (E132).

Description of the appearance of Tergio and the contents of the pack
Light blue to pastel blue, round, biconvex (curved outward on both sides) film-coated tablets, approximately 7.6 mm in diameter, with “T” engraved on one side and “1” on the other.
Tergio is available in blister packs containing 28 or 84 tablets, perforated unit-dose blisters containing 28x1, 84x1 or 98x1 tablets, and bottles containing 84 or 98 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Viatris Healthcare Limited, Damastown Industrial Park, Mulhuddart, Dublin 15, DUBLIN, Ireland

Manufacturer
Mylan Hungary Kft.
Mylan utca 1., Komárom, 2900, Hungary

This medicinal product is authorized in the European Economic Area countries under the following names:
Croatia Tergio 14 mg filmom obložene tablete
Cyprus Tergio 14 mg film-coated tablets
Greece Tergio 14 mg film-coated tablets
Hungary Tergio 14 mg film-coated tablets
Iceland Tergio 14 mg film-coated tablets
Italy Tergio
Malta Tergio 14 mg film-coated tablets