LONSURF 20 mg/8.19 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Lonsurf 15 mg/ 6.14 mg film-coated tablets

Lonsurf 20 mg/ 8.19 mg film-coated tablets

trifluridine/tipiracil

Read all of 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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Lonsurf and what is it used for

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

Lonsurf contains two different active substances: trifluridine and tipiracil.

• Trifluridine prevents the growth of cancer cells.
• Tipiracil prevents trifluridine from being broken down in the body, helping trifluridine to work for longer.

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

• It is used when the 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 given in combination with bevacizumab. It is important that you also read the package leaflet for bevacizumab. If you have any questions about this medicine, ask your doctor.

2. What you need to know before you take Lonsurf

Do not take Lonsurf:

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

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

Warnings and precautions

Talk to your doctor or pharmacist before starting Lonsurf if:

• you have kidney problems
• you have liver problems

If you are not sure, talk to your doctor before taking Lonsurf.

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

• A decrease in the number of a certain type of white blood cell (neutropenia) that are important for protecting the body against bacterial or fungal infections. As a result of neutropenia, fever (febrile neutropenia) and blood infection (septic shock) may occur.
• A decrease in the number of red blood cells (anemia).
• A decrease in the number of platelets in the blood (thrombocytopenia) that are important for stopping bleeding and that act by aggregating and coagulating blood vessel lesions.
• Gastrointestinal problems.

Tests and checks

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

Children and adolescents.

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

Other medicines and Lonsurf

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription and herbal medicines. This is because Lonsurf may affect the way other medicines work. Similarly, other medicines may affect the way Lonsurf works.

In particular, tell your doctor or pharmacist if you are taking medicines used to treat HIV, such as zidovudine. This is because zidovudine may not work as well if you are taking Lonsurf. Ask your doctor if you should switch to a different medicine for HIV.

Tell your doctor before taking Lonsurf if any of the above applies to you (or if you are not sure).

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Lonsurf may harm the fetus.

If you become pregnant, you and your doctor must decide if the benefits of Lonsurf are greater than the risk of harm to the fetus.

Do not breast-feed while taking Lonsurf as it is not known whether Lonsurf passes into breast milk.

Contraception

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

You and your partner must use effective contraception while you are taking this medicine. You must continue to use this contraception for 6 months after stopping the medicine. If you or your partner become pregnant during this time, you should tell your doctor or pharmacist immediately.

Fertility

Lonsurf may affect your ability to have children. Ask your doctor for advice before taking it.

Driving and using machines

It is not known if Lonsurf affects your ability to drive or use machines. Do not drive or use tools or machines if you have symptoms that affect your ability to concentrate and react.

Lonsurf contains lactose

If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

3. How to take Lonsurf

Follow exactly the instructions for administration of this medicine given by your doctor. If you are not sure, talk to your doctor or pharmacist.

How much to take

• Your doctor will decide the correct dose for you – the dose depends on your weight and height and whether you have kidney problems.
• Lonsurf comes in two doses. Your doctor may prescribe both doses to reach your prescribed dose.
• Your doctor will tell you how many tablets to take each time.
• You will take one dose twice a day.

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 schedule is as follows:

• Week 1
  • take the dose twice a day for 5 days
  • then rest for 2 days – do not take the medicine
• Week 2
  • take the dose twice a day for 5 days
  • then rest for 2 days – do not take the medicine
• Week 3
  • do not take the medicine
• Week 4
  • do not take the medicine

Then you will start again with another 4-week cycle following the above schedule.

How to take it

• Take this medicine by mouth.
• Swallow the tablets whole with a glass of water.
• Take the tablets within 1 hour after breakfast and dinner.
• Wash your hands after handling this medicine.

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. Take your medicine box(es) 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 forgotten doses.

If you have any further questions on the use of 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 when taken alone or in combination with bevacizumab:

Serious side effects

Tell your doctor immediatelyif you experience any of the following serious side effects (many of these side effects are detected in blood tests – for example those that affect your blood cells):

• Neutropenia (very common), febrile neutropenia (common) and septic shock (rare). The signs include chills, fever, sweating or other signs of bacterial or fungal infection (see section 2).
• • Anemia (very common). The signs include shortness of breath, tiredness or pale skin (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). The signs include severe stomach or abdominal pain that may be associated with vomiting, intestinal obstruction or partial obstruction, fever or abdominal inflammation.
  • Thrombocytopenia (very common). The signs include bruising or unusual bleeding (see section 2).
  • Pulmonary embolism (uncommon): blood clots in the lungs. The signs include difficulty breathing and chest pain or leg pain.
  • Interstitial lung disease has been reported in patients receiving this medicine. The signs include difficulty breathing, shortness of breath with cough or fever.

Some of these serious side effects may cause death.

Other side effects

Tell your doctor if you experience any of the following side effects. Many of the side effects are detected in blood tests – for example those that affect your blood cells. Your doctor will be looking out for these side effects in the results of your blood tests.

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

• decreased appetite
• feeling very tired (fatigue)
• nausea
• decrease in the number of blood cells called leukocytes – may increase your risk of infection.
• swelling of the mucous membranes of the mouth

Common: may affect up to 1 in 10 people:

• fever
• hair loss
• weight loss
• changes in taste
• constipation
• feeling unwell
• low levels of albumin in the blood
• increased levels of bilirubin in the blood – may cause yellowing of the skin or eyes
• decrease in the number of white blood cells called lymphocytes – may increase your risk of infection
• swelling of your hands or feet or legs
• mouth pain or problems
• swelling of the mucous membranes – this can be inside the nose, throat, eyes, vagina, lungs or intestine
• increased levels of liver enzymes
• protein in your urine
• rash, itching or dry skin
• difficulty breathing, chest infection or lung infection
• viral infections
• joint pain
• feeling dizzy, headache
• high blood pressure
• mouth ulcers
• muscle pain

Uncommon: may affect up to 1 in 100 people:

• low blood pressure
• blood test results indicating problems with blood clotting making you bleed more easily
• heart palpitations, chest pain
• abnormal increase or decrease in heart rate
• increase in white blood cells
• increase in the number of white blood cells called monocytes

• increase in lactate dehydrogenase levels in your blood
• low levels of phosphate, sodium, potassium or calcium in your blood
• low levels of white blood cells called monocytes - may increase your risk of infection
• high levels of sugar in the blood (hyperglycemia), increased levels of urea, creatinine and potassium in your blood
• blood test results indicating inflammation (increased C-reactive protein)
• feeling dizzy (vertigo)
• runny nose or nosebleeds, problems with your sinuses
• sore throat, hoarse voice, voice problems
• redness, itching of the eyes, eye infection, watery eyes
• dehydration
• abdominal swelling, gas, indigestion
• inflammation in the lower part of the digestive tract
• swelling or bleeding of the intestine
• inflammation or increased acid in your stomach or esophagus, reflux
• tongue pain, gagging
• tooth decay, tooth problems, gum infections
• redness of the skin
• pain or discomfort in your arms or legs
• pain, including pain associated with cancer
• bone pain, muscle weakness or spasms
• feeling cold
• herpes (pain and blistering rash on the skin over affected nerve fibers due to nerve inflammation caused by the herpes zoster virus)
• liver disease
• inflammation or infection of the bile ducts
• kidney failure
• cough, sinus infection, throat infection
• bladder infection
• blood in urine
• problems with urination (urinary retention), loss of bladder control (incontinence)
• changes in menstrual cycle
• anxiety
• mild neurological problems.

• severe rash with itching, hives, acne
• excessive sweating, nail problems

• sleep problems or difficulty falling asleep

• feeling numbness or tingling in your hands or feet
• redness, swelling, pain in the palms of your hands and soles of your feet (hand and foot syndrome)

Rare: may affect up to 1 in 1000 people

• inflammation and infection of your intestine
• athlete's foot – fungal infection of the feet, yeast infections
• low levels of white blood cells called granulocytes - may increase your risk of infection
• swelling or pain in the big toe
• swelling in your joints
• high levels of sodium in your blood
• burning sensation, unpleasant increase or decrease in touch
• fainting (syncope)
• vision problems such as blurred vision, double vision, loss of vision, cataracts
• dry eyes
• ear pain
• inflammation in the upper part of the digestive tract
• pain in the upper or lower part of the digestive tract
• fluid accumulation in the lungs
• bad breath, gum problems, bleeding gums
• polyps inside the mouth
• inflammation or infection of your intestine
• increase in the diameter of the bile ducts
• redness of the skin, blisters, skin peeling
• sensitivity to light
• inflammation of your bladder
• changes in urine tests
• blood clots, for example in the brain or legs
• changes in your electrocardiogram (ECG)
• low levels of total protein in the blood

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Lonsurf

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 carton or blister after “EXP”. The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Packaging Contents and Additional Information

Lonsurf Composition

Lonsurf 15 mg/6.14 mg film-coated tablets

• The active ingredients are trifluridine and tipiracil. Each film-coated tablet contains 15 mg of trifluridine and 6.14 mg of tipiracil.
• The other ingredients are:

• Tablet core: lactose monohydrate, pregelatinized starch (from corn) 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), aluminum indigo carmine lacquer (E132), carnauba wax and talc.

Lonsurf 20 mg/8.19 mg film-coated tablets

• The active ingredients are trifluridine and tipiracil. Each film-coated tablet contains 20 mg of trifluridine and 8.19 mg of tipiracil.
• The other ingredients are:

• Tablet core: lactose monohydrate, pregelatinized starch (from corn) 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), aluminum indigo carmine lacquer (E132), carnauba wax and talc.

Product Appearance and Packaging Contents

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

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

Each package 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 aluminum blister foil has a desiccant layer incorporated.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Les Laboratoires Servier

50 rue Carnot

92284 Suresnes Cedex

France

Manufacturer

Les Laboratoires Servier Industrie

905, route de Saran

45520 Gidy

France

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder.

Date of Last Revision of this Leaflet:

Other Sources of Information

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