Package Insert: Information for the Patient

Lonsurf 15 mg/ 6,14 mg Film-Coated Tablets

Lonsurf 20 mg/ 8,19 mg Film-Coated Tablets

trifluridina/tipiracilo

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Lonsurf is a type of chemotherapy for cancer that belongs to the group of medications called “cytostatic antimetabolite medications”.

Lonsurf contains two different active principles: trifluridin and tipiracil.

• Trifluridin prevents the growth of cancerous cells.
• Tipiracil prevents trifluridin from degrading in the body, helping trifluridin to act for a longer time.

Lonsurf is used to treat adults with colon or rectal cancer (also known as colorectal cancer) and stomach cancer (including cancer of the junction between the esophagus and the stomach).

• It is used when cancer has spread to other parts of the body (metastasis).
• It is used when other treatments have not worked – or when other treatments are not suitable for you.
• •Lonsurf may be administered in combination with bevacizumab. It is essential that you also read the prospectus for bevacizumab. If you have any doubts about this medication, ask your doctor.

Do not take Lonsurf:

• if you are allergic to trifluridin or tipiracil or any of the other ingredients of this medication (listed in section 6).

Do not take Lonsurf if the above applies to you. If you are unsure, consult your doctor before taking Lonsurf.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Lonsurf if:

If you are unsure, consult your doctor before taking Lonsurf.

The treatment may cause the following side effects (see section 4):

Tests and controls

Your doctor will perform a blood test before each cycle of Lonsurf. Start a new cycle every 4 weeks. The tests are necessary because Lonsurf may occasionally affect your blood cells.

Children and adolescents

This medication is not indicated for use in children and adolescents under 18 years of age. This is because the medication may not work or may not be safe.

Other medications and Lonsurf

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. This includes over-the-counter medications and herbal medications. This is because Lonsurf may affect the way other medications work. Similarly, other medications may affect the way Lonsurf works.

In particular, inform your doctor or pharmacist if you are taking medications used to treat HIV, such as zidovudine. This is because zidovudine may not work as well if you are taking Lonsurf. Consult your doctor if you need to switch to another HIV medication.

Inform your doctor before taking Lonsurf if any of the above applies (or if you are unsure).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication. Lonsurf may harm the fetus.

If you become pregnant, you and your doctor must decide whether the benefits of Lonsurf outweigh the risk of harming the fetus.

Do not breastfeed while taking Lonsurf as it is unknown whether Lonsurf passes into breast milk.

Contraceptives

You must not become pregnant while taking this medication. This is because the medication may harm the fetus.

You and your partner must use effective contraceptive methods while taking this medication. You must continue to do this for 6 months after stopping the medication. If you or your partner become pregnant during this period, inform your doctor or pharmacist immediately.

Fertility

Lonsurf may affect your ability to have children. Consult your doctor before using it.

Driving and operating machinery

It is unknown whether Lonsurf affects your ability to drive or operate machinery. Do not drive or use tools or machinery if you experience symptoms that affect your ability to concentrate and react.

Lonsurf contains lactose

If your doctor has told you that you have a certain sugar intolerance, consult with him before taking this medication.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

How much to take

When to take Lonsurf

You will take Lonsurf for 10 days during the first 2 weeks, and then rest for 2 weeks. This 4-week period is called a "cycle". The specific dosing program is as follows:

•Week 1

- take the dose 2 times a day for 5 days

- then rest for 2 days – do not take the medication

•Week 2

- take the dose 2 times a day for 5 days

- then rest for 2 days – do not take the medication

•Week 3

- Do not take the medication

•Week 4

- Do not take the medication

Then start again with another cycle of 4 weeks following the previous schedule.

How to take it

If you take more Lonsurf than you should

If you take more Lonsurf than you should, talk to your doctor or go to the hospital immediately. Bring your medication box(s) with you.

If you forget to take Lonsurf

• If you forget a dose, talk to your doctor or pharmacist.
• Do not take a double dose to make up for the missed doses.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The following side effects may occur with this medicine when taken alone or in combination with bevacizumab:when taken alone or in combination with bevacizumab:

Severe side effects

Inform your doctor immediatelyif you experience any of the following severe side effects (many of these side effects are detected in laboratory tests - for example, those affecting your blood cells):

• Neutropenia (very common), febrile neutropenia (common), and septic shock (rare). Symptoms include chills, fever, sweating, or other signs of bacterial or fungal infection (see section 2).
• • Anemia (very common). Symptoms include difficulty breathing, fatigue, or paleness (see section 2).
  • Vomiting (very common) and diarrhea (very common), which can cause dehydration if severe or persistent.
  • Severe gastrointestinal problems: abdominal pain (common), ascites (rare), colitis (uncommon), acute pancreatitis (rare), ileus (uncommon), and subileus (rare). Symptoms include severe stomach or abdominal pain that may be associated with vomiting, intestinal obstruction, or partial obstruction, fever, or abdominal inflammation.
  • Thrombocytopenia (very common). Symptoms include petechiae or unusual bleeding (see section 2).
  • Pulmonary embolism (uncommon): blood clots in the lungs. Symptoms include difficulty breathing and chest or leg pain.
  • Lung interstitial disease has been reported in patients receiving the medicine. Symptoms include difficulty breathing, shortness of breath, or fever.

Some of these severe side effects may cause death.

Other side effects

Inform your doctor if you experience any of the following side effects. Many of these side effects are detected in laboratory tests - for example, those affecting your blood cells. Your doctor will be aware of these side effects in your laboratory test results.

Very common: may affect more than 1 in 10 people:

Common: may affect up to 1 in 10 people:

Uncommon: may affect up to 1 in 100 people:

Rare: may affect 1 in 1000 people:

• Intestinal inflammation and infection
• Athlete's foot - fungal infection of the feet, fungal infections
• Decreased granulocyte count - may increase your risk of infection
• Swelling or pain in the big toe
• Swelling in your joints
• Increased sodium levels in your blood
• Unpleasant burning sensation, increased or decreased sense of touch
• Fainting (syncope)
• Visual problems such as blurred vision, double vision, loss of vision, cataracts
• Dry eyes
• Ears pain
• Upper gastrointestinal tract inflammation
• Pain in the upper or lower gastrointestinal tract
• Pulmonary edema
• Bad breath, gum problems, bleeding gums
• Mouth polyps
• Intestinal inflammation or infection
• Increased bile duct diameter
• Red skin, blisters, skin peeling
• Light sensitivity
• Urinary tract inflammation
• Changes in urine analysis
• Blood clots, for example in the brain or legs
• Changes in your electrocardiogram (ECG)
• Low total protein levels in blood

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the national reporting system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box or on the blister after “EXP”. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Lonsurf

Lonsurf 15 mg/6.14 mg film-coated tablets

• Core tablet: lactose monohydrate, pregelatinized maize starch and stearic acid (see section 2 “Lonsurf contains lactose”).
• Film coating: hypromellose, macrogol (8000), titanium dioxide (E171) and magnesium stearate.
• Printing ink: lacquer, iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171), aluminium lake indigo carmine (E132), carnauba wax and talc.

Lonsurf 20 mg/8.19 mg film-coated tablets

• Core tablet: lactose monohydrate, pregelatinized maize starch and stearic acid (see section 2 “Lonsurf contains lactose”).
• Film coating: hypromellose, macrogol (8000), titanium dioxide (E171), iron oxide red (E172) and magnesium stearate.
• Printing ink: lacquer, iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171), aluminium lake indigo carmine (E132), carnauba wax and talc.

Appearance of the product and contents of the pack

• Lonsurf 15 mg/6.14 mg is a white, biconvex, round, film-coated tablet, engraved with “15” on one side and “102” and “15 mg” on the other side, in grey ink.

• Lonsurf 20 mg/8.19 mg is a pale red, biconvex, round, film-coated tablet, engraved with “20” on one side and “102” and “20 mg” on the other side, in grey ink.

Each pack contains 20 film-coated tablets (2 blisters of 10 tablets each) or 40 film-coated tablets (4 blisters of 10 tablets each) or 60 film-coated tablets (6 blisters of 10 tablets each). The aluminium blister contains a desiccant.

Only some pack sizes may be marketed.

Marketing authorisation holder

Les Laboratoires Servier

50 rue Carnot

92284 Suresnes Cedex

France

Responsible for manufacturing

Les Laboratoires Servier Industrie

905, route de Saran

45520 Gidy

France

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder.

Date of the last revision of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu