Fotivda 890 micrograms hard capsules

Package Leaflet: Information for the User

Introduction

Package Leaflet: Information for the Patient

Fotivda 890 micrograms hard capsules

Fotivda 1340 micrograms hard capsules

tivozanib

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What Fotivda is and what it is used for

The active substance in Fotivda is tivozanib, which is a kinase inhibitor. Tivozanib reduces blood supply to the cancer, thereby delaying the growth and spread of cancer cells. It works by blocking the action of a protein called vascular endothelial growth factor (VEGF). By inhibiting VEGF activity, it prevents the formation of new blood vessels.

Fotivda is used to treat adults with advanced renal cell cancer. It is used when other treatments, such as interferon-alpha or interleukin-2, have not yet been used or have not been effective in controlling the disease.

2. What you need to know before taking Fotivda

Do not take Fotivda:

• If you are allergic to tivozanib or any of the other components of this medicine (listed in section 6).
• If you are taking St. John’s wort (also known as Hypericum perforatum, a herbal medicine used to treat depression and anxiety).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to take Fotivda:

• If you have high blood pressure.

Fotivda can increase your blood pressure. Your doctor will monitor your blood pressure periodically, and if it becomes too high, may prescribe medication to lower it or decide to reduce your Fotivda dose. However, if your blood pressure remains too high, your doctor may decide to interrupt or stop treatment with Fotivda. If you are already taking medication for high blood pressure and your doctor reduces your Fotivda dose or interrupts or stops treatment, you will be monitored periodically for low blood pressure.

• If you have or have had an aneurysm (a bulge and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.

• If you have had blood clotting problems.

Treatment with Fotivda may increase the risk of developing a blood clot (thrombus) in your blood vessels, which could break loose and travel through the bloodstream to block another blood vessel. Inform your doctor if you have ever had any of the following conditions:

• a blood clot in the lungs (with cough, chest pain, sudden shortness of breath, or coughing up blood)

• a blood clot in the legs or arms, eye, or brain (with pain or swelling in hands or feet, reduced vision, or changes in mental state)

• a stroke or signs and symptoms of a "mini-stroke" (transient ischemic attack)

• a heart attack

• high blood pressure

• diabetes

• major surgery

• multiple injuries, such as broken bones and internal organ damage

• inability to move for a prolonged period

• heart failure that may cause shortness of breath or swelling of the ankles

• difficulty breathing, bluish skin, fingertips, or lips, restlessness, anxiety, confusion, altered consciousness or level of consciousness, rapid and shallow breathing, rapid heartbeat, or excessive sweating

• If you have or have had any of these symptoms or are being treated for heart failure:

  • Shortness of breath (dyspnea) during exercise or when lying down
  • Feeling weak and tired
  • Swelling (edema) in the legs, ankles, and feet
  • Reduced ability to exercise
  • Persistent cough or wheezing with white or pink, blood-tinged sputum

Signs and symptoms of heart failure will be monitored while you are receiving this medicine. If necessary, your doctor may reduce your Fotivda dose or interrupt or stop this treatment.

• If you have or have been treated for a heart rhythm disorder (arrhythmia). Your doctor will monitor the effect of Fotivda on your heart by recording the electrical activity (electrocardiogram) or measuring blood levels of calcium, magnesium, and potassium during treatment.

• If you have liver problems.

Your doctor will periodically monitor how well your liver is functioning before and during treatment with Fotivda (e.g., through blood tests), and if necessary, may have to reduce the frequency with which you take Fotivda.

• If you have thyroid gland problems or are taking medications to treat thyroid disease. Treatment with Fotivda may cause your thyroid gland to function worse than usual. Your doctor will periodically monitor how well your thyroid gland is working before and during treatment with Fotivda (e.g., through blood tests).

Talk to your doctor, pharmacist, or nurse while taking Fotivda:

• If you have shortness of breath or swelling of the ankles. Inform your doctor immediately, as these may be symptoms of heart failure. Your doctor will monitor you and, depending on severity, may reduce your Fotivda dose or interrupt or stop treatment with Fotivda.

• If you have had bleeding problems. Treatment with Fotivda may increase the risk of bleeding. If you develop bleeding problems (with painful abdominal swelling, vomiting blood, coughing up blood, black stools, blood in urine, headache, or changes in mental state), inform your doctor immediately. Temporary interruption of Fotivda treatment may be necessary.

• If laboratory tests show protein in your urine. Your doctor will monitor you at the beginning and during your treatment. Depending on the results, your doctor may reduce your Fotivda dose or interrupt or stop this treatment.

• If you have a brain disorder called posterior reversible encephalopathy syndrome (PRES). Inform your doctor immediately if you experience symptoms such as headache, seizures, lack of energy, confusion, blindness, or other visual or neurological disturbances such as weakness in one arm or leg. If PRES is diagnosed, your doctor will stop treatment with Fotivda.

• If the skin on the palms of your hands and soles of your feet becomes dry, cracked, scaly, peeling, itchy, or tingly.

• These could be symptoms of a condition called hand-foot skin reaction. Your doctor will manage the condition and, depending on severity, may reduce your Fotivda dose or interrupt or stop treatment with Fotivda.

• If you have symptoms of gastrointestinal perforation or fistula formation (developing a hole in the stomach or intestine or abnormal connections between parts of the intestine), such as severe stomach pain, chills, fever, nausea, vomiting, painful intestinal obstruction, diarrhea, or rectal bleeding.

Your doctor will monitor you periodically for these symptoms during treatment with Fotivda.

• If you need to undergo surgery or another surgical procedure. Your doctor may recommend temporarily stopping Fotivda if you are undergoing surgery, as it may affect wound healing.

Children and adolescents

Do not give Fotivda to children and adolescents under 18 years of age. This medicine has not been studied in children and adolescents.

Other medicines and Fotivda

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This includes herbal medicines and other medicines you have purchased without a prescription.

Fotivda may be less effective when taken with certain medicines. Inform your doctor if you are taking any of the following medicines; they may decide to change your medication:

• dexamethasone (a corticosteroid to reduce inflammation and treat immune system disorders);
• rosuvastatin (a medicine used to help lower blood cholesterol levels);
• phenobarbital, phenytoin, carbamazepine (used to treat epilepsy);
• nafcillin, rifampicin, rifabutin, rifapentine (antibiotics);
• St. John’s wort (also known as Hypericum perforatum, a herbal medicine used to treat depression and anxiety), as this herbal medicine must not be used at the same time as Fotivda.

Pregnancy, breastfeeding, and fertility

• Do not take Fotivda if you are pregnant. Inform your doctor, who will discuss with you the risks of taking Fotivda for you and your unborn child.

• Both you and your partner must use effective contraception. If you or your partner are using hormonal contraceptives (pill, implant, or patch), you must use an additional barrier method throughout treatment and for one month after stopping treatment.

• Interrupt breastfeeding during treatment with Fotivda, as it is unknown whether the active ingredient of Fotivda passes into breast milk. Talk to your doctor if you are already breastfeeding your child.

• Talk to your doctor if you are planning to have a baby, as Fotivda may affect fertility in both men and women.

Driving and using machines

Fotivda may cause side effects that could affect your ability to drive or operate machinery. Do not drive or use machines if you feel weak, tired, or dizzy. See also section 4 “Possible side effects”.

Fotivda contains tartrazine (E102)

The printing ink used on the 890 microgram Fotivda capsule contains tartrazine (E102), which may cause allergic reactions.

3. How to take Fotivda

Follow exactly the instructions for administering this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

Recommended dose

The recommended dose is one Fotivda 1340 microgram capsule, taken once daily for 21 days (3 weeks), followed by a 7-day period (1 week) when no capsules are taken.

This regimen is repeated in 4-week cycles.

Your doctor will review you periodically and will normally continue Fotivda treatment as long as it is effective and you do not experience unacceptable side effects.

Reduced dose

If you experience severe adverse effects, your doctor may decide to interrupt treatment with Fotivda and/or reduce your dose to:

One Fotivda 890 microgram capsule, taken once daily for 21 days (3 weeks), followed by a 7-day period (1 week) when no capsules are taken.

This regimen is repeated in 4-week cycles.

Liver problems

If you have liver problems, your doctor may reduce the frequency of your dose to alternate days (i.e., one 1340 microgram capsule on alternate days).

Use of Fotivda with food and drink

Fotivda should be taken with a glass of water and may be taken with or without food. Swallow the capsule whole. Do not chew, dissolve, or open the capsule before swallowing.

If you take more Fotivda than you should

Inform your doctor immediately if you have taken more than the prescribed dose of one capsule per day.

Taking too much Fotivda may make adverse effects more likely or more severe, especially high blood pressure. Seek immediate medical help if you experience confusion, changes in mental status, or headaches. These are all symptoms of high blood pressure.

If you forget to take Fotivda

If you forget to take a capsule, do not take a capsule to make up for it. Continue taking the next dose at the scheduled time.

Do not take a double dose to make up for a missed capsule.

If you vomit after taking Fotivda, do not take a capsule to replace it. Continue taking the next dose at the scheduled time.

If you stop taking Fotivda

Do not stop taking this medicine unless instructed by your doctor. If you stop taking the capsules, your condition may worsen.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody gets them.

Serious adverse effects

Hypertension is the most serious and very common adverse effect (see also section 2, “Warnings and precautions”).

Tell your doctor immediately if you think you have high blood pressure. Symptoms include severe headaches, blurred vision, shortness of breath, changes in your mental state, such as feeling anxious, confused, or disoriented.

Your doctor will check your blood pressure periodically during treatment with Fotivda. If you develop high blood pressure, your doctor may prescribe a medicine to treat the hypertension, reduce your dose of Fotivda, or stop your treatment with Fotivda.

Other adverse effects

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

• Difficulty speaking
• Diarrhea
• Loss of appetite; weight loss
• Headache
• Difficulty breathing; shortness of breath during exercise; cough
• Fatigue; unusual weakness; pain (oral, bone, limb, flank, groin, tumor-related)
• Mouth inflammation; mild mouth pain or discomfort; feeling unwell; stomach pain, discomfort, and pressure
• Palmar-plantar syndrome with redness of the skin, swelling, numbness, and peeling of the skin on the palms and soles of the feet
• Back pain
• Tiredness and lack of energy

Common (may affect up to 1 in 10 people)

• Underactive thyroid gland, which may cause symptoms such as fatigue, sluggishness, muscle weakness, slow heart rate, weight gain
• Insomnia
• Nerve damage, including numbness, tingling, sensitive skin, or numbness and weakness in arms and legs
• Vision problems, including blurred vision
• Rapid heartbeat; chest tightness; heart attack/reduced blood flow to the heart; blood clot in an artery (blood vessel)
• Blood clot in the lung. Symptoms include cough, chest pain, sudden shortness of breath, or coughing up blood
• Blood clot in a deep vein, such as in the leg
• Very high blood pressure leading to stroke; red skin
• Nosebleeds; runny nose; nasal congestion
• Flatulence; acid reflux; difficulty and pain when swallowing; sore throat; bloated stomach; swollen and painful tongue; painful and/or bleeding gums
• Changes in taste sensation or loss of taste
• Dizziness; ringing in the ears; dizziness and sensation that the surroundings are spinning (vertigo)
• Bleeding, e.g., in the brain, mouth, gums, lungs, stomach, intestinal ulcers, female genital organs, anus, adrenal gland
• Blood in cough; vomiting blood
• Paleness and fatigue due to excessive bleeding
• Feeling unwell; indigestion; constipation; dry mouth
• Itching of the skin; rash; generalized itching; skin peeling; dry skin; hair loss; redness of the skin, including hands and body; acne
• Fever; chest pain; swelling of feet and legs; chills and low body temperature
• Joint pain; muscle pain
• Increased amount of protein in urine
• Abnormal blood test results for liver, pancreas, kidneys, and thyroid
• Pancreatitis causing severe stomach pain that may spread to the back

Uncommon (may affect up to 1 in 100 people)

• Pus-filled rashes; fungal infections
• Easy bruising, bleeding into the skin
• Overactive thyroid gland (which may cause symptoms such as increased appetite, weight loss, heat intolerance, increased sweating, tremors, rapid heartbeat); enlarged thyroid gland
• Increased red blood cell count
• Memory loss
• Transient reduction in blood flow to the brain
• Watery eyes
• Ear blockage
• Lack of blood flow through the blood vessels of the heart
• Peptic ulcer in the small intestine
• Redness, swelling, and pain in the skin; skin blisters; excessive sweating; hives
• Muscle weakness
• Swelling or irritation of mucous membranes
• Fast and/or irregular heartbeat
• Heart failure. Symptoms include shortness of breath or ankle swelling. Lung swelling due to fluid accumulation

Rare (may affect up to 1 in 1,000 people)

• Posterior reversible encephalopathy syndrome (PRES). Symptoms include headache, seizures, lack of energy, confusion, blindness, or other visual and neurological disturbances.

Frequency not known (cannot be estimated from available data)

• Enlargement and weakening of a blood vessel wall or tearing of a blood vessel wall (arterial aneurysms and dissections)

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Fotivda

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

Do not use this medicine after the expiry date stated on the carton and vial after EXP. The expiry date refers to the last day of the month indicated.

Keep the vial tightly closed to protect it from moisture.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Contents of Fotivda

Fotivda 890 micrograms hard capsules

The active substance is tivozanib. Each hard capsule contains tivozanib monohydrochloride monohydrate equivalent to 890 micrograms of tivozanib.

The other components are:

• Capsule contents: mannitol, magnesium stearate.
• Capsule shell: gelatin, titanium dioxide (E171), indigo carmine (E132), yellow iron oxide (E172).
• Yellow printing ink: shellac, propylene glycol, strong ammonia solution, titanium dioxide (E171), aluminium lake of tartrazine (E102) (see section 2 “Fotivda contains tartrazine (E102)”).
• Blue printing ink: shellac, propylene glycol, strong ammonia solution, aluminium lake of indigo carmine (E132).

Fotivda 1340 micrograms hard capsules

The active substance is tivozanib. Each capsule contains tivozanib monohydrochloride monohydrate equivalent to 1340 micrograms of tivozanib.

The other components are:

• Capsule contents: mannitol, magnesium stearate.
• Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172).
• Blue printing ink: shellac, propylene glycol, strong ammonia solution, aluminium lake of indigo carmine (E132).

Nature and contents of the container

Fotivda 890 micrograms hard capsules have an opaque dark blue cap and a bright yellow opaque body, with “TIVZ” printed on the cap in yellow ink and “LD” on the body in dark blue ink.

Fotivda 1340 micrograms hard capsules have a bright yellow opaque cap and a bright yellow opaque body, with “TIVZ” printed on the cap in dark blue ink and “SD” on the body in dark blue ink.

Fotivda 890 micrograms and Fotivda 1340 micrograms are available in packs of 21 capsules in HDPE bottles with child-resistant closure.

Marketing Authorisation Holder

Recordati Netherlands B.V.
Beechavenue 54,
1119PW Schiphol-Rijk
The Netherlands

Manufacturer

ALMAC PHARMA SERVICES (IRELAND) LIMITED
Finnabair Industrial Estate
Dundalk
Co. Louth
A91 P9KD
Ireland

Date of the most recent revision of this leaflet: 07/2023

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