UTEFOS 400 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the Patient

Utefos 400 mg Hard Capsules

Tegafur

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 and other information:

1. What is Utefos and what is it used for
2. What you need to know before you take Utefos
3. How to take Utefos
4. Possible side effects

5 Storage of Utefos

1. Contents of the pack and further information

1. What is Utefos and what is it used for

Utefos is a medicine used to treat cancer. It belongs to a group of medicines whose function is to prevent the multiplication of tumor cells.

Utefos is indicated only in 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 esophagus and pancreas) or when there are relapses 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).

2. What you need to know before you take Utefos

Do not take Utefos

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

• If you are pregnant or breastfeeding.
• If you have bone marrow disorders (decrease in white blood cells or platelets, which may be due to previous treatment with radiation therapy or anticancer chemotherapy).
• 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 you have no activity of the dihydropyrimidine dehydrogenase (DPD) enzyme (complete DPD deficiency).
• If you are being treated or have been treated in the last 4 weeks with brivudine, as part of the treatment for herpes zoster (chickenpox or herpes).
• This medicine must not be used in adolescents, children, or infants.

Warnings and precautions

During treatment, you will have periodic blood tests. In case of significant blood or gastrointestinal alterations, your doctor will suspend the administration of the product. Once the symptoms have disappeared, treatment can be restarted at a low dose.

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 (arrhythmia, 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 the dose.
• You take anticoagulants or phenytoin.
• If you know you have a partial deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme.
• If you are a relative of a person with a partial or complete deficiency of the dihydropyrimidine dehydrogenase (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 suffering from serious side effects (indicated in section 4, Possible side effects). It is recommended that you undergo 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 results of the test for DPD deficiency are negative, serious and potentially fatal side effects may still occur.

You must inform your doctor if you suffer from any type of allergy or exaggerated 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 you are being treated with 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.

Taking Utefos with other medicines

Tell your doctor or pharmacist that you are taking, have recently taken, or might take any other medicines.

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

• Medicines that decrease liver metabolism, such as some medicines for fungal infections (miconazole, ketoconazole, clotrimazole), pigmentation stimulants (methoxsalen), or those that increase liver metabolism (phenobarbital, rifampicin).
• Medicines to decrease blood coagulation (acenocoumarol, warfarin).
• Medicines for seizures or tremors (phenytoin).

Do not use any type of vaccine without consulting your doctor first. Some vaccines may cause you to have serious infections while you are taking Utefos.

Taking Utefos with food and drink

If you take this medicine with food, its absorption may be altered. 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 grapefruit juice because it may decrease the activity of this medicine.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

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

You must use reliable contraceptive methods, both if you are a male or a female of childbearing age, during treatment and for 3 months after finishing it. Consult your doctor.

You should not breastfeed your child if you are taking Utefos, as the baby may have serious side effects.

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

Driving and using machines

When taking Utefos, you may feel dizzy, nauseous, or disoriented, so be careful when driving vehicles or using machines until you see how the medicine affects you.

Important information about some of the ingredients of Utefos

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

3. How to take Utefos

Follow exactly the administration instructions of this medicine 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 used 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), for 3 to 6 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 throughout 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 medicines.

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

It is very important that you follow exactly the administration instructions of Utefos that your doctor indicates. Your doctor will indicate what dose you need to take, when and how you should take it, and for how long. Additionally, your doctor will recommend periodic checks and tests to monitor your general condition.

Recommended dose in special populations:

Use in patients over 65 years of age:

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

Patient with kidney problems:

Patients with kidney problems should be monitored frequently to detect the onset of toxic effects or any worsening of kidney function.

Patient with liver problems:

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

Method of administration:

This medicine is taken orally.

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

You should not take the capsules with grapefruit juice (see Taking Utefos with food and drink).

Use in children and adolescents

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

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 mouth mucosa, diarrhea, and, with greater severity, gastrointestinal ulceration and bleeding. Anemia may also appear, as well as possible toxicity to the skin or nervous system. Some of these side effects may have serious consequences.

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

If you forget to take Utefos

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

If you stop taking Utefos

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

Stopping treatment with Utefos does not produce side effects.

In case you are taking coumarin anticoagulants (e.g., Sintrom) or phenytoin, stopping treatment with Utefos may require your doctor to adjust the doses.

4. Possible side effects

Like all medicines, Utefos can cause side effects, although not everybody gets them.

Get in touch with your doctor if some of the following side effects appear:

• Persistent diarrhea: if you have 4 or more bowel movements per day or have nocturnal diarrhea.
• Vomiting: if you vomit more than once a day.
• Mucositis: if you have pain, redness, swelling, or ulcers in the mouth.
• If you have very dark stools or blood in your vomit.
• Skin reaction on the hands and feet: if you have pain, swelling, and redness of 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):

• Diarrhea.
• Vomiting.
• Inflammation or ulceration of the mouth mucosa.
• Hair loss.
• Dizziness.
• Headache.
• Weakness.
• Lack of coordination.
• Lack of appetite.

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

• Blood alterations (decrease in the number of white blood cells, red blood cells, and/or platelets).
• Allergic reactions.
• Skin rashes, including hand-foot syndrome (numbness, pain, swelling, or redness in the hands and feet).
• Gastritis.
• Duodenal ulcer, gastrointestinal bleeding.

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

• Disorientation.
• Somnolence.
• Euphoria.
• Changes in tests that indicate liver function (bilirubin, alkaline phosphatase).
• Chest pain.
• Thrombosis in arteries or veins.
• Infection due to decreased defenses.
• Double vision.
• Uncontrolled and involuntary eye movements.
• Light intolerance.
• Changes in tests that indicate blood coagulation function.

In addition to the above 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 blood cells, 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 like these, talk to your doctor. He/she will indicate whether you should stop treatment for a while or change the dose.
• Nausea, mouth ulcers, anorexia, and abdominal pain.
• Feeling of weakness.
• Increased blood 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, abnormal sensation of touch (hypoesthesia), tingling, or loss of sensation in the hands or feet.
• Tearing, eye inflammation (conjunctivitis).
• Constipation, flatulence, indigestion, dry mouth, belching, intestinal obstruction.
• Desquamation, skin discoloration, itching, sweating, dry skin, and nail changes.
• Muscle pain, back pain, joint pain.
• Fever, swelling, discomfort, chills, and pain.
• Weight loss.

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

• Infection, sepsis.
• Blood coagulation problems.
• Irregular heartbeat, heart failure, infarction, and cardiac arrest.
• Circulatory collapse.
• Pulmonary embolism (blood clot in the veins inside and around 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 1,000 people):

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

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

• Pneumonia.
• Various alterations of blood cells (hemolytic anemia, agranulocytosis, myelodysplastic syndrome, acute myeloid leukemia, acute leukemia), and disseminated intravascular coagulation.
• Memory loss, speech disorders, abnormally decreased sensitivity to touch (hypoesthesia).
• Pancreatitis, stomach or intestinal ulcers, paralysis of the large intestine (paralytic ileus), fluid in the abdomen (ascites), ischemic colitis.
• Liver cirrhosis, severe and rapidly progressive liver inflammation (fulminant hepatitis).
• Skin changes similar to lupus erythematosus, other skin changes including blisters, urticaria with hives, severe skin reaction with blisters (Stevens-Johnson syndrome).
• Acute kidney 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 to feel a side effect. Your doctor may advise you to lower the dose and/or temporarily stop taking Utefos. Your doctor may advise you to resume treatment with a lower dose. This will help reduce the likelihood that the side effect will continue or become serious.

Reporting of 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 Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Utefos

Store below 30°C.

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 packaging, after CAD or EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicine in the pharmacy's SIGRE collection point. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Utefos

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

The other ingredients (excipients) are: magnesium stearate, corn starch, anhydrous lactose, and colloidal silica.

The components of the capsule shell are: titanium dioxide (E-171), indigo carmine (E-132), and gelatin

Appearance of the Product and Package Contents

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

Packages containing 20 or 60 hard capsules.

Marketing Authorization Holder

Mylan Pharmaceuticals, S.L.

C/Plom 2-4, 5th floor

08038 – Barcelona

Spain

Manufacturer

Prasfarma, S.L.

C/ Sant Joan, 11-15

08560 - Manlleu (Barcelona)

Spain

Date of the Last Revision of this Leaflet:September 2020

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/