Package Insert: Information for the Patient

Utefos 400 mg Hard Capsules

Tegafur

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

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine 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 side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1.What Utefos is and for what it is used

2.What you need to know before starting to take Utefos

3.How to take Utefos

4.Possible side effects

5Storage of Utefos

6.Contents of the pack and additional information

Utefos is a medication for treating cancer. It belongs to a group of medications whose function is to prevent the multiplication of tumor cells.

Utefos is indicated only for adults for the treatment of patients with colorectal cancer and gastric cancer. It is also used for the treatment of patients with advanced gastrointestinal tumors (including those of the esophagus and pancreas) or when there are recurrences of the disease.

Treatment of patients with metastatic breast cancer.

Treatment of patients with advanced head and neck cancer or when it has spread to other parts of the body (stages III and IV).

Do not take Utefos

• if you are allergic to tegafur or 5-fluorouracil (5-FU) or any of the other ingredients of this medicine listed in section 6.

• if you are pregnant or breastfeeding.
• if you have bone marrow disorders (decreased white blood cells or platelets, which may be due to previous radiation or chemotherapy treatment).
• if you have severe liver disease.
• if you have a problem metabolizing medicines in the liver (known deficiency of the hepatic enzyme CYP2A6).
• if you know that you have no activity of the dihydropirimidina deshidrogenasa (DPD) enzyme (complete deficiency of DPD).
• if you are being treated or have been treated in the last 4 weeks with brivudina, as part of the treatment for herpes zoster (shingles or herpes).
• This medicine should not be used in adolescents, children or infants.

Warnings and precautions

During treatment, you will have periodic blood tests. If you have significant blood or gastrointestinal changes, your doctor will suspend the administration of the product. Once the symptoms have disappeared, the treatment can be restarted at low doses.

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

-You have liver or kidney problems.

-You are an elderly patient.

-You have or have had heart problems (alteration of heart rhythm, chest pain).

-You have or have had problems metabolizing similar medicines (5-fluorouracil).

-You have been treated with other anticancer medicines or have received radiation therapy. Your doctor may need to adjust your dose.

-You are taking anticoagulants or phenytoin.

-You know that you have a partial deficiency of the dihydropirimidina deshidrogenasa (DPD) enzyme activity.

-You are a relative of a person with partial or complete deficiency of the dihydropirimidina deshidrogenasa (DPD) enzyme.

DPD deficiency: DPD deficiency is a genetic condition that is not usually related to health problems, unless you are being treated with certain medicines. If you have a DPD deficiency and take Utefos, you will have a higher risk of severe adverse effects (listed in section 4, Possible adverse effects). It is recommended that you have a test to detect DPD deficiency before starting treatment. If you have no enzyme activity, you should not take Utefos. If you have reduced enzyme activity (partial deficiency), your doctor may prescribe a reduced dose. Although the test results for DPD deficiency are negative, you may still experience severe and potentially fatal adverse effects.

You must inform your doctor if you have any type of allergy or excessive reaction to Utefos, such as persistent diarrhea, as your doctor may need to modify the dose or suspend treatment.

You should not be vaccinated with a type of vaccine that contains live microorganisms while taking Utefos, as you may develop the disease against which you are being vaccinated.

Children and adolescents

This medicine is contraindicated in adolescents, children and infants.

Utefos with other medicines

Inform your doctor or pharmacist that you are taking, have taken recently or may need to take any other medicine.

It is especially important to inform your doctor if you are taking any of the following medicines:

• Medicines that decrease liver metabolism, such as some antifungal medicines (miconazole, ketoconazole, clotrimazole), melanin stimulants (methoxalen) or that increase liver metabolism (phenobarbital, rifampicin).
• Medicines to decrease blood coagulation (acenocoumarol, warfarin).
• Medicines for seizures or tremors (phenytoin).

You should not use any type of vaccine without consulting your doctor first. Some vaccines may cause severe infections while you are taking Utefos.

Utefos with food and drink

If you take this medicine with food, its absorption may be modified. Therefore, it is recommended to take it on an empty stomach, at least one hour before or after any meal.

You should not take Utefos with orange juice, as it may decrease the activity of this medicine.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medicine.

You should not take Utefos if you are pregnant or think you may be pregnant, as it may cause severe damage to your baby.

You should take reliable contraceptive measures, both if you are male and if you are a fertile woman, during treatment and for 3 months after finishing it. Consult your doctor.

You should not breastfeed your child while taking Utefos, as the baby may experience severe adverse effects.

If you would like to have a child during or after treatment, inform your doctor before starting treatment. You may be interested in seeking advice on sperm storage before starting treatment.

Driving and operating machines

When taking Utefos, you may feel dizzy, nauseous or disoriented, so until you observe the effects of the medicine, be especially careful when driving vehicles or operating machines.

Important information about some of the components of Utefos

This medicine contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medicine.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is:

Your doctor will calculate the dose of Utefos based on your body surface area and the type of cancer being treated. The usual daily dose ranges from 500 to 1,000 mg per square meter of body surface area, divided into 2 or 3 doses per day (every 8 or 12 hours), for3 to6 weeks, followed by a week of rest.

They will measure your height and weight to calculate your body surface area. Your doctor will calculate the dose you should take. This dose may be adjusted or changed over the course of treatment and temporarily suspended if your general condition changes.

Utefos can be used alone, but it can also be used in combination with other anticancer medications.

Your doctor may recommend administering Utefos along with folinic acid. Your doctor will indicate the dose of this medication and the days you should take it.

It is very important that you follow exactly the administration instructions for Utefos as indicated by your doctor. Your doctor will indicate what dose you need to take, when and how to take it, and for how long. Additionally, they will recommend regular check-ups and tests to monitor your general condition.

Recommended dose in special populations:

Use in patients over 65 years old:

It is advisable to perform more frequent follow-up on elderly patients being treated with tegafur who have kidney problems and/or heart problems, as well as those patients taking other medications that may interact with tegafur.

Patients with kidney problems:

Patients with kidney problems should be followed up frequently to detect the appearance of toxic effects or any eventual worsening of kidney function.

Patients with liver problems:

The effect has not been evaluated in patients with liver problems on the elimination of tegafur. Patients with severe liver disease should not take this medication.

Administration form:

This medication is taken orally.

It is recommended to take the capsules on an empty stomach, at least one hour before or after any meal.

Do not take the capsules with grapefruit juice (seeUtefos with food and drinks).

Use in children and adolescents

Children and adolescents should not take Utefos due to the lack of efficacy and safety data.

If you take more Utefos than you should

The symptoms or signs that may appear due to overdose are: loss of appetite (anorexia), nausea, vomiting, inflammation of the mucous membrane of the mouth, diarrhea, and, with greater severity, gastrointestinal ulceration and bleeding. Anemia may also appear, as well as possible toxicity in the skin or nervous system. Some of these adverse effects may have serious consequences.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20.

If you forgot to take Utefos

Do not take a double dose to compensate for the missed doses. Take the next dose at the scheduled time and consult your doctor.

If you interrupt treatment with Utefos

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

The end of treatment with Utefos does not produce adverse effects.

In case you are taking coumarin anticoagulants (for example, Sintrom) or phenytoin, the end of treatment with Utefos may require your doctor to adjust the doses.

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

Consult your doctor if you experience any of the following side effects:

• Persistent diarrhea: if you have 4 or more bowel movements per day or experience nighttime diarrhea.
• Vomiting: if you vomit more than once a day.
• Mucositis: if you experience pain, redness, swelling, or sores in your mouth.
• Dark stools or blood in your vomit.
• Hand and foot skin reaction: if you experience pain, swelling, and redness in your hands and/or feet.
• Fever or infection: if you have a temperature of 38°C or higher or other signs of infection.
• Easy bruising.

Possible side effects:

Very common side effects (may affect more than 1 in 10 people):

• Diarhea.
• Vomiting.
• Inflammation or ulceration of the mouth mucosa.
• Hair loss.
• Dizziness.
• Headache.
• Weakness.
• Coordination problems.
• Loss of appetite.

Common side effects (may affect up to 1 in 10 people):

• Blood abnormalities (decreased white blood cell, red blood cell, or platelet count).
• Allergic reactions.
• Skin rashes, including hand-foot syndrome (numbness, pain, swelling, or redness in the hands and feet).
• Gastritis.
• Ulcerative duodenitis, gastrointestinal bleeding.

Rare side effects (may affect up to 1 in 100 people):

• Disorientation.
• Drowsiness.
• Euphoria.
• Changes in liver function tests (bilirubin, alkaline phosphatase).
• Chest pain.
• Thrombosis in arteries or veins.
• Infection due to decreased immunity.
• Diplopia.
• Involuntary and uncontrolled eye movements.
• Light intolerance.
• Changes in coagulation tests.

In addition to the previous adverse reactions, the following adverse reactions have been reported for tegafur in combination with uracil:

Very common side effects (may affect more than 1 in 10 people):

• Reduction in the number of red or white blood cells or platelets (anemia, thrombocytopenia, leucopenia, neutropenia), bone marrow depression causing a reduction in blood cells. These side effects may cause weakness, make infections more likely, increase the risk of bleeding, or cause bruising. If you experience symptoms such as these, talk to your doctor. They will advise you whether to stop treatment for a while or change the dose.
• Nausea, mouth sores, anorexia, and abdominal pain.
• Feeling weak.
• Increased levels of certain liver enzymes (ALT, AST).

Common side effects (may affect up to 1 in 10 people):

• Fungal infection.
• Difficulty breathing, increased coughing, and throat inflammation.
• Dehydration and malnutrition.
• Insomnia, depression, and confusion.
• Alteration or loss of taste, numbness, or sensation of loss of sensation in the hands or feet.
• Excessive tearing, eye inflammation (conjunctivitis).
• Constipation, flatulence, indigestion, dry mouth, belching, intestinal obstruction.
• Peeling, skin discoloration, itching, sweating, dry skin, and nail changes.
• Muscle pain, back pain, joint pain.
• Fever, swelling, discomfort, chills, and pain.
• Weight loss.

Rare side effects (may affect up to 1 in 100 people):

• Infection, sepsis.
• Blood clotting problems.
• Irregular heartbeat, heart failure, myocardial infarction, and cardiac arrest.
• Circulatory collapse.
• Pulmonary embolism (blood clotting in the veins of the lungs).
• Intestinal inflammation, intestinal perforation.
• Liver inflammation, jaundice, and liver failure.
• Abnormal kidney function, urinary retention, and blood in the urine.
• Impotence.
• Chest pain.

Rare side effects (may affect up to 1 in 1000 people):

• Changes in the "white matter of the brain" (leucoencephalopathy).
• Alteration or loss of sense of smell (anosmia, parosmia).
• Interstitial pneumonia.
• Fatigue.

Very rare side effects (may affect fewer than 1 in 10,000 people):

• Pneumonia.
• Various blood cell abnormalities (hemolytic anemia, agranulocytosis, myelodysplastic syndrome, acute myeloid leukemia, acute leukemia), and disseminated intravascular coagulation.
• Memory loss, speech changes, abnormally decreased sensitivity to touch (hypoesthesia).
• Pancreatitis, stomach or intestinal ulcers, intestinal paralysis (ileus), ascites, ischemic colitis.
• Liver cirrhosis, rapid progression of liver inflammation (fulminant hepatitis).
• Skin changes similar to lupus erythematosus, other skin changes including blisters, urticaria with nodules, severe skin reaction with blisters (Stevens-Johnson syndrome).
• Acute renal failure, nephrotic syndrome (kidney disease), urinary incontinence, and multi-organ failure.

Some of these side effects may be serious; therefore, always contact your doctor immediately when you start experiencing a side effect. Your doctor may advise you to reduce the dose and/or stop taking Utefos temporarily. Your doctor may advise you to resume treatment with a lower dose. This will help reduce the likelihood of the side effect continuing or becoming severe.

Reporting side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Store below 30°C.

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

Do not use this medication after the expiration date that appears on the packaging, after CAD or EXP. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Utefos

The active ingredient is tegafur. Each hard capsule contains 400 mg of tegafur.

The other components (excipients) are: magnesium stearate, cornstarch, anhydrous lactose, and colloidal silica.

The components of the capsule coating are: titanium dioxide (E-171), indigotin (E-132), and gelatin

Appearance of the product and content of the container

Utefos is presented in the form of white and blue hard capsules.

Containers containing 20 or 60 hard capsules.

Holder of the marketing authorization

Mylan Pharmaceuticals, S.L.

C/Plom 2-4, 5th floor

08038 – Barcelona

Spain

Responsible for manufacturing

Prasfarma, S.L.

C/ Sant Joan, 11-15

08560 - Manlleu (Barcelona)

Spain

Date of the last review of this leaflet:September 2020

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/