Lonsurf 15 mg/6.14 mg film-coated tablets

Patient Information Leaflet

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 the entire 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 other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Lonsurf is and what it is used for

Lonsurf is a type of cancer chemotherapy belonging 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 the breakdown of trifluridine in the body, helping trifluridine to remain active for a longer period.

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 oesophagus and 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 bevacizumab package leaflet. If you have any questions about this medicine, ask your doctor.

2. What you need to know before starting Lonsurf

Do not take Lonsurf:

• if you are allergic to trifluridine or tipiracil, or to 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 unsure, consult 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 unsure, consult your doctor before taking Lonsurf.

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

• A decrease in the number of certain types of white blood cells (neutropenia), which 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), which are important for stopping bleeding and function by aggregating and clotting at sites of blood vessel injury.
• Gastrointestinal problems.

Tests and monitoring

Your doctor will perform a blood test before each cycle of Lonsurf. A new cycle begins every 4 weeks. These tests are necessary because Lonsurf can sometimes 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

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This includes medicines purchased without a prescription and herbal medicines. This is because Lonsurf may affect how other medicines work. Likewise, other medicines may affect how Lonsurf works.

In particular, inform 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. Consult your doctor about whether you should switch to a different medicine for HIV.

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

Pregnancy and breastfeeding

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

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

Do not breastfeed while taking Lonsurf, as it is unknown 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 contraceptive methods while taking this medicine. You must continue to do so for 6 months after stopping the medicine. If you or your partner becomes 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 using machines

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

Lonsurf contains lactose

If your doctor has informed you that you have an intolerance to certain sugars, consult him before taking this medicine.

3. How to take Lonsurf

Follow exactly the instructions given by your doctor for taking this medicine. If you are unsure, consult your doctor or pharmacist again.

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 is available in two strengths. Your doctor may prescribe both strengths to achieve your prescribed dose.
• Your doctor will tell you how many tablets to take each time.
• You will take one dose twice daily.

When to take Lonsurf

You will take Lonsurf for 10 days during the first 2 weeks, 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 daily for 5 days
  • then rest for 2 days – do not take the medicine
• Week 2
  • take the dose twice daily 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 schedule above.

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, speak to your doctor or go to hospital immediately. Take your medicine pack(s) with you.

If you forget to take Lonsurf

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

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

Serious adverse effects

Tell your doctor immediately if you experience any of the following serious adverse effects (many of these adverse effects are detected in blood tests—for example, those affecting your blood cells):

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

Some of these serious adverse effects may result in death.

Other adverse effects

Tell your doctor if you experience any of the following adverse effects. Many of these adverse effects are detected in laboratory tests—for example, those affecting your blood cells. Your doctor will monitor for these adverse effects in your test results.

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

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

Common: may affect up to 1 in 10 people:

• fever
• hair loss
• weight loss
• changes in taste
• constipation
• general feeling of discomfort
• low level of albumin in blood
• increased levels of bilirubin in blood—may cause yellowing of the skin or eyes
• decreased number of white blood cells called lymphocytes—may increase your risk of infections
• swelling of hands or legs or feet
• pain or problems in the mouth
• swelling of mucous membranes—this may occur in the nose, throat, eyes, vagina, lungs, or intestines
• increased liver enzyme levels
• protein in urine
• rash, itching, or dry skin
• shortness of breath, chest infection of the airways or lungs
• viral infections
• joint pain
• dizziness, 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

• more noticeable heartbeat, chest pain

• abnormally increased or decreased heart rate

• increase in white blood cells

• increase in the number of white blood cells called monocytes

• increased level of lactate dehydrogenase in your blood

• low levels of phosphate, sodium, potassium, or calcium in your blood

• reduced levels of white blood cells called monocytes—may increase your risk of infections

• high blood sugar (hyperglycemia), increased levels of urea, creatinine, and potassium in your blood

• blood test results indicating inflammation (increased C-reactive protein)

• spinning sensation (vertigo)

• runny or bleeding nose, sinus problems

• sore throat, hoarseness, voice problems

• red, itchy eyes, eye infection, watery eyes

• dehydration

• abdominal swelling, flatulence, 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, retching

• dental caries, dental problems, gum infections

• skin redness

• pain or discomfort in 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 nerves affected by inflammation due to 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

• non-serious neurological problems

• severe rash with itching, hives, acne

• excessive sweating, nail problems

• difficulty sleeping or falling asleep

• numbness or tingling in hands or feet

• redness, swelling, pain in the palms of hands and soles of feet (hand-foot syndrome)

Rare: may affect up to 1 in 1,000 people

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse 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 stated on the carton or blister pack after "EXP". The expiry date refers to the last day of the month indicated.

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 and packaging that you no longer need. This will help protect the environment.

6. Pack contents and other information

Composition of Lonsurf

Lonsurf 15 mg/6.14 mg film-coated tablets

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

• Other components are:

• Tablet core: monohydrate lactose, pregelatinized starch (from maize) and stearic acid (see section 2 “Lonsurf contains lactose”).

• Film coating: hypromellose, macrogol (8000), titanium dioxide (E171) and magnesium stearate.

• Printing ink: shellac, 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

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

• Other components are:

• Tablet core: monohydrate lactose, pregelatinized starch (from maize) 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: shellac, iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171), aluminium lake indigo carmine (E132), carnauba wax and talc.

Presentation of the product and pack contents

• Lonsurf 15 mg/6.14 mg is a white, biconvex, round film-coated tablet, marked 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, marked 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 incorporates a desiccant layer.

Only certain 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

Further information on this medicinal product is available upon request from the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet:

Other sources of information

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