Prospect: information for the patient

Fotivda 890microgram hard capsules

Fotivda 1340microgram hard capsules

tivozanib

Read this prospect carefully before starting to take this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospect. See section 4.

1.What is Fotivda and for what it is used

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

3.How to take Fotivda

4.Adverse effects

5.Storage of Fotivda

6.Contents of the package and additional information

The active ingredient of Fotivda is tivozanib, which is a protein kinase inhibitor. Tivozanib reduces blood supply to the cancer, thereby slowing the growth and spread of cancer cells. It acts by blocking the action of a protein called vascular endothelial growth factor (VEGF). The blockade of VEGF action prevents the formation of new blood vessels.

Fotivda is used to treat adults with advanced kidney cancer. It is used when other treatments such as interferon-alpha or interleukin-2 have not been used yet or have not been effective in stopping their disease.

Do not take Fotivda:

• If you are allergic to tivozanib or any of the other ingredients of this medicine (listed in section 6).
• If you are taking St. John's Wort (also known asHypericum perforatum, a herbal medicine used for the treatment of depression and anxiety).

Warnings and precautions

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

• If you havehigh blood pressure.

Fotivda may increase your blood pressure. Your doctor will monitor your blood pressure periodically and, if it is too high, may give you a medicine to reduce it or decide to reduce your dose of Fotivda. However, if your blood pressure remains too high, your doctor may decide to interrupt or stop treatment with Fotivda. If you are already taking a medicine to treat high blood pressure and your doctor reduces your dose of Fotivda or interrupts or stops treatment, you will be monitored periodically for low blood pressure.

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

• If you have had problems withblood clots.

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

• If you have or have had any of these symptoms or are being treated for heart failure:
• • Shortness of breath (dyspnoea) when exercising or when lying down
  • Feeling weak and tired
  • Swelling (oedema) of the legs, ankles and feet
  • Reduction in ability to exercise
  • Cough or wheezing persistently with mucus of white or pink colour tinged with blood

Your doctor will monitor signs and symptoms of heart failure while you are receiving your medicine. If necessary, your doctor may reduce your dose of Fotivda or interrupt or stop treatment with Fotivda.

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

• If you haveliver problems.

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

• If you haveproblems with your thyroid glandorare taking medicines to treat thyroid disease.The treatment with Fotivda may make your thyroid gland work less well than usual. Your doctor will monitor your thyroid gland function periodically before and during treatment with Fotivda (e.g., with blood tests).

Consult your doctor, pharmacist or nurse while taking Fotivda:

• If you haveshortness 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 the severity, may reduce your dose of Fotivda or interrupt or stop treatment with Fotivda.
• If you have had problems withbleeding.
  Treatment with Fotivda may increase the risk of bleeding. If you develop bleeding problems (with painful swelling of the stomach (abdomen), vomiting blood, coughing up blood, black stools, blood in the urine, headache or changes in mental state), inform your doctor immediately. It may be necessary to temporarily stop treatment with Fotivda.

• If blood tests show that there areproteins in the urine.
  Your doctor will monitor you at the start and during your treatment. Depending on the results, your doctor may reduce your dose of Fotivda or interrupt or stop treatment.

• If you have a brain disease calledreversible posterior leukoencephalopathy syndrome (RPLS).
  Inform your doctor immediately if you have symptoms such as headache, seizures, lack of energy, confusion, blindness or other visual and neurological changes such as weakness in an arm or leg. If you are diagnosed with RPLS, your doctor will stop treatment with Fotivda.

• If theskin on the palms of your hands and the soles of your feetbecomes dry, with cracks, scales or peeling or you have itching or tingling sensations
• These may be symptoms of a condition called hand-foot syndrome. Your doctor will treat the problem and, depending on the severity, may reduce your dose of Fotivda or interrupt or stop treatment with Fotivda.

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

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

• If you need to undergosurgery or other forms of surgery.
  Your doctor may recommend that you temporarily stop taking Fotivda if you undergo surgery or other forms of surgery, as it may affect wound healing.

Children and adolescents

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

Other medicines and Fotivda

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine. This includes herbal medicines and other medicines that you have bought without a prescription.

Fotivda may work less well when taken with some medicines. Inform your doctor if you are taking any of the following medicines; your doctor may decide to change your medication:

• dexamethasone (a corticosteroid to reduce inflammation and treat immune system disorders);
• rosuvastatin (a medicine used to help reduce blood cholesterol levels);
• phenobarbital, phenytoin, carbamazepine (used to treat epilepsy);
• nafcillin, rifampicin, rifabutin, rifapentine (antibiotics);
• St. John's Wort (also known asHypericum perforatum, a herbal medicine used for the treatment of depression and anxiety), as this herbal medicine should 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 child.

• You and your partner shoulduse effective contraceptive methods.If you or your partner are taking hormonal contraceptives (the pill, an implant or a patch)you should use an additional barrier methodduring treatment and for another month after stopping treatment.

• Stop 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 plan to have a baby, as Fotivda may affectfertilityin men and women.

Driving and using machines

Fotivda may have side effects that may affect your ability to drive or use machines. 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 in the 890 microgram Fotivda capsule contains tartrazine (E102), which may cause allergic reactions.

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

Recommended dose

The recommended dose is one capsule ofFotivda 1340micrograms, taken once a day for 21days (3weeks), followed by a 7-dayperiod when no capsules are taken.

This regimen is repeated in cycles of 4 weeks.

Your doctor will check on you periodically and will normally continue taking Fotivda as long as it works and you do not experience unacceptable side effects.

Reduced dose

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

One capsule ofFotivda 890micrograms, taken once a day for 21days (3weeks), followed by a 7-dayperiod when no capsules are taken.

This regimen is repeated in cycles of 4 weeks.

Liver problems

If you haveliver problems, your doctor may reduce the frequency with which your dose is taken to alternate days (this is, one capsule of 1340micrograms on alternate days).

Use of Fotivda with food and drinks

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 break 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 1 capsule a day.

Taking too much Fotivda may make side effects more likely or more intense, especially high blood pressure. Getimmediate medical helpif you experience confusion, changes in your mental state or headaches. These are all symptoms of high blood pressure.

If you forgot to take Fotivda

If you have forgotten to take a capsule,do nottake a capsule to make up for it. Continue taking the next dose at the scheduled time.

Do nottake a double dose to make up for a missed capsule.

If you vomit after taking Fotivda,do nottake a capsule to make up for it. Continue taking the next dose at the scheduled time.

If you interrupt treatment with Fotivda

Do not stop taking this medication unless your doctor tells you to. If you stop taking the capsules, your condition may worsen.

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

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

Severe side effects

Hypertensionis the most severe and very common side effect (also see section 2“Warnings and precautions”).

Inform your doctor immediatelyif you think you havehigh 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 medication to treat hypertension, reduce your dose of Fotivda, or stop treatment with Fotivda.

Other side 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, in the limbs, sides of the body, groin, tumor)
• Mouth inflammation; mild pain or discomfort in the mouth; feeling sick; stomach pain, discomfort, and pressure
• Palmar-plantar syndrome with skin redness, swelling, numbness, and peeling of the skin on the palms and soles of the feet
• Back pain
• Fatigue and lack of energy

Common(may affect up to 1 in 10 people)

• Low thyroid activity, which can cause symptoms such as fatigue, lethargy, muscle weakness, slow heart rate, weight gain
• Insomnia
• Neurological damage, including numbness, tingling, skin sensitivity, or numbness and weakness in arms and legs
• Visual problems, including blurred vision
• Fast heart rate; 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 difficulty breathing, or coughing up blood
• Blood clot in a deep vein, such as in the leg
• Very high blood pressure leading to a stroke; red skin
• Nasal bleeding; runny nose; nasal congestion
• Flatulence; heartburn; difficulty and pain swallowing; throat pain; swollen and painful tongue; painful and/or bleeding gums
• Changes in taste or loss of taste
• Dizziness; ringing in the ears; dizziness and feeling that the environment is spinning (vertigo)
• Bleeding, e.g., in the brain, mouth, gums, lungs, stomach, intestinal ulcers, female genitalia, anus, adrenal gland
• Blood in the cough; vomiting blood
• Pale skin and fatigue due to excessive bleeding
• Feeling sick; indigestion; constipation; dry mouth
• Itching skin; rash; general itching; skin peeling; dry skin; hair loss; red skin, including hands and body; acne
• Fever; chest pain; swelling of feet and legs; chills and low body temperature
• Joint pain; muscle pain
• Increased protein in the urine
• Abnormal blood test results for the liver, pancreas, kidneys, and thyroid
• Pancreatitis that causes intense stomach pain that can spread to the back

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

• Posterior reversible encephalopathy syndrome (PRES). Symptoms include headache, seizures, fatigue, confusion, blindness, or other visual and neurological changes.

Unknown frequency(cannot be estimated from available data)

• Increased and weakened wall of a blood vessel or tearing of the wall of a blood vessel (aneurysms and arterial dissections)

Reporting side effects

If you experience side effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this leaflet.You can also report them directly through thenational notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and the bottle after CAD. The expiration date is the last day of the month indicated.

Keep the bottle perfectly closed to protect it from moisture.

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Product Content

Fotivda 890hard capsules

The active ingredient is tivozanib. Each hard capsule contains tivozanib hydrochloride monohydrate equivalent to 890micrograms of tivozanib.

The other components are:

• Hard capsule content: mannitol, magnesium stearate.
• Hard capsule coating: gelatin, titanium dioxide (E171), indigo carmine (E132), iron oxide yellow (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 1340micrograms hard capsules

The active ingredient is tivozanib. Each capsule contains tivozanib hydrochloride monohydrate equivalent to 1340micrograms of tivozanib.

The other components are:

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

Appearance of the product and contents of the pack

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

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

Fotivda 890micrograms and Fotivda 1340micrograms are available in HDPE bottles with child-resistant closures containing 21capsules.

Marketing Authorisation Holder

Recordati Netherlands B.V.Beechavenue 54,

1119PW Schiphol-Rijk

Netherlands

Manufacturer

ALMAC PHARMA SERVICES (IRELAND) LIMITED

Finnabair Industrial Estate

Dundalk

Co. Louth

A91 P9KD

Ireland

Last update of this leaflet: 07/2023

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