FOTIVDA 890 MCG Hard capsule

Зміст інструкції

1. Fotivda 890 micrograms hard capsules, 1340 micrograms hard capsules
   1. What is Fotivda and what is it used for
   2. What you need to know before taking Fotivda
   3. How to take Fotivda
   4. Possible side effects
   5. How to store Fotivda
   6. Contents of the pack and other information

Fotivda 890 micrograms hard capsules, 1340 micrograms hard capsules

tivozanib

Read 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is Fotivda and what is it used for

The active substance contained in Fotivda is tivozanib, a protein kinase inhibitor. Tivozanib reduces
the blood supply to the tumor by slowing the growth and spread of cancer cells. It blocks
the action of a protein called vascular endothelial growth factor (VEGF). By blocking
the action of VEGF, it prevents the formation of new blood vessels.
Fotivda is used in the treatment of advanced kidney cancer in adults. It is used where
other treatments, such as alpha-interferon or interleukin-2, have not yet been used or have not
been able to stop 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 ingredients of this medicine (listed in section 6);
• if you are taking St John's Wort (also known as Hypericum perforatum, a herbal remedy used to treat depression and anxiety).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Fotivda:

• if you have high blood pressure. Fotivda may increase blood pressure. Your doctor will regularly monitor your blood pressure and, if it is too high, will prescribe you a medicine to lower it or reduce the dose of Fotivda. However, if your blood pressure remains too high, your doctor may decide to stop or suspend treatment with Fotivda. If you are already taking medicine for high blood pressure and your doctor reduces the dose of Fotivda or stops or suspends treatment, your blood pressure will be regularly checked.
• 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 problems with blood clots. Treatment with Fotivda may increase the risk of blood clots (thrombi) forming in blood vessels that can break off and be carried by the bloodstream and cause blockage of another blood vessel. Tell your doctor if you have had any of the following conditions: o a blood clot in the lungs (with cough, chest pain, sudden shortness of breath or coughing up blood) o a blood clot in the legs or arms, in the eyes or in the brain (with painful or swollen hands or feet, decreased vision or changes in your mental state) o stroke o signs and symptoms of a “mini-stroke” (transient ischemic attack) o heart attack o high blood pressure o diabetes o major surgery o multiple injuries such as bone fractures and injuries to internal organs o prolonged immobility o heart failure which can cause shortness of breath and swollen ankles o difficulty breathing, bluish discoloration of the skin, fingertips or lips, restlessness, anxiety, confusion, altered state of consciousness, rapid breathing, shallow breathing, rapid heartbeat or excessive sweating.
• if you suffer from or have suffered from any of these symptoms or if you are being treated for heart failure: o Shortness of breath (dyspnea) when you exert yourself or when you are lying down o Feeling tired and weak o Swelling (edema) of legs, ankles and feet o Decreased ability to perform physical activity o Persistent cough or wheezing with white or pink-tinged mucus. The signs and symptoms of heart failure will be monitored during the period you take the medicine. If necessary, your doctor may reduce the dose of Fotivda or stop or suspend treatment.
• If you have been or are undergoing treatment for heart rate and rhythm disorders(arrhythmia). Your doctor will monitor the effects of Fotivda on your heart by recording its electrical activity (electrocardiogram) or measuring levels of calcium, magnesium and potassium in your blood during therapy.
• if you have liver problems.Your doctor will regularly monitor liver function before and during treatment with Fotivda (e.g. by prescribing blood tests) and, if necessary, may reduce how often you take Fotivda.
• if you have thyroid problemsor are using medicines for the treatment of thyroid disease.Treatment with Fotivda may cause a decrease in normal thyroid gland activity. Your doctor will regularly monitor thyroid function before and during treatment with Fotivda (e.g. by prescribing blood tests).

Talk to your doctor, pharmacist or nurse during the intake of Fotivda:

• if you have shortness of breathor swollen ankles. Tell your doctor immediately as these may be symptoms of heart failure. Your doctor will monitor these symptoms and, depending on the severity, may reduce the dose of Fotivda or stop or suspend treatment with Fotivda.
• if you have had problems with bleeding. Treatment with Fotivda may increase the risk of bleeding. If you have bleeding problems (with a swollen and painful stomach (abdomen), if you vomit blood, cough up blood, if your stools are black, if you have blood in your urine, headache or changes in your mental state) tell your doctor immediately. Treatment with Fotivda may need to be temporarily interrupted.
• if laboratory tests indicate the presence of protein in your urine. Your doctor will monitor your condition at the beginning and during treatment. Depending on the results, your doctor may reduce the dose of Fotivda or stop or suspend this treatment.
• if you suffer from a brain disease, known as reversible posterior encephalopathy syndrome (PRES). Tell your doctor immediately if you notice symptoms such as headache, seizures (convulsions), lack of energy, confusion, blindness or other visual and neurological disturbances such as weakness in an arm or leg. If you are diagnosed with PRES, your doctor will stop treatment with Fotivda.
• if the skin on the palms of your hands and soles of your feetbecomes dry or cracked, peeling, flaking or if you experience a tingling or prickling sensation. These may be symptoms of a condition called hand-foot skin reaction. Your doctor will treat this condition and, depending on the severity, may reduce the dose of Fotivda or stop or suspend this treatment.
• if you experience symptoms of gastrointestinal perforation or fistula formation(development of a hole in the stomach or intestine or formation of abnormal passages between different parts of the intestine) such as severe stomach pain, chills, fever, nausea, vomiting or painful bowel obstruction, diarrhea or rectal bleeding. Your doctor will regularly monitor these symptoms during treatment with Fotivda.
• if you are to undergo surgery or other form of surgical procedure. Your doctor may advise you to temporarily stop taking Fotivda if you are to undergo surgery or a surgical procedure, as Fotivda may interfere with wound healing.

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

Other medicines and Fotivda
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines, including herbal remedies and other medicines purchased without a
prescription.
Fotivda may be less effective if taken in combination with other medicines. Tell your
doctor if you are taking any of the following medicines; your doctor may decide to
change your therapy:

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

Pregnancy, breastfeeding and fertility

• Do not take Fotivda if you are pregnant.Tell your doctor who will discuss with you the risks associated with taking Fotivda for you and your baby.
• You and your partner must both use effective contraceptive methods. If you and your partner are using hormonal contraceptives (pill, implant or patch), you must use an additional barrier method of contraceptionduring treatment and for one month after completing treatment.
• Do not breastfeed during treatment with Fotivda, as it is not known whether the active substance contained in Fotivda passes into breast milk. Tell your doctor if you are breastfeeding.
• Tell your doctor if you are planning a pregnancy, as Fotivda may affect male and female fertility.

Driving and using machines
Fotivda may have side effects that can impair your ability to drive or
operate machines. Avoid driving or operating 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 Fotivda 890 microgram capsule contains tartrazine (E102),
which may cause allergic reactions.

3. How to take Fotivda

Take this medicine following the instructions of your doctor exactly. If you have any doubts, consult your
doctor or pharmacist.

Recommended dose
The recommended dose is one Fotivda 1340 microgram capsule once daily for
21 days (3 weeks), followed by a 7-day (1 week) period without taking capsules.
This schedule should be repeated in 4-week cycles.

21 days(three weeks) 7 days(1 week)

One Fotivda capsuleNo capsuletaken

once a day
Your doctor will monitor you regularly and you will continue to take Fotivda as long as it remains
effective and as long as the side effects are acceptable.

Reduced dosage
If you experience serious side effects, your doctor may decide to discontinue
therapy with Fotivda and/or reduce the dosage to:
One Fotivda 890 microgram capsule once daily for 21 days (3 weeks), followed by
a 7-day (1 week) period without taking capsules.
This schedule should be repeated in 4-week cycles.

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

Fotivda with food and drink
Fotivda should be taken with a glass of water and can be taken with or without food. The
capsule must be swallowed whole. Do not chew, dissolve, or open the capsule before swallowing.

If you take more Fotivda than you should
Immediately inform your doctor if you have taken a dose higher than the prescribed dose corresponding to
1 capsule per day.
An overdose of Fotivda increases the possibility of developing or worsening side
effects, particularly high blood pressure. Seek immediate medical attentionif you experience
symptoms such as confusion, changes in mental status, or headache. These are all symptoms
of high blood pressure.

If you forget to take Fotivda
Donot take a double dose to make up for a missed capsule. Continue to take the
next dose at the usual frequency.

Donot take a double dose to make up for a missed capsule .
Donot take a replacement capsule if you have vomited after taking Fotivda. Continue to take the
next dose at the usual frequency.

If you stop taking Fotivda
Do not stop taking this medicine without your doctor's consent. If you stop taking the
capsules, your condition may worsen.
If you have any doubts about the use of this medicine, ask your doctor, pharmacist, or
nurse.

4. Possible side effects

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

Serious side effects
High blood pressureis the most serious and the most common side effect (see also paragraph 2
“ Warnings and Precautions”).

Tell your doctor immediatelyif you think you have high blood pressure.Symptoms include severe headache,
blurred vision, shortness of breath, changes in mental status, such as feeling anxious,
confusion or disorientation.
Your doctor will check your blood pressure regularly during treatment with Fotivda. If you have high
blood pressure, your doctor may prescribe medicine to treat high blood pressure, reduce the
dosage 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 physical activity, cough
• Fatigue, unusual weakness, pain (including pain in the mouth, bones, extremities, hips, goiter, tumor)
• Inflammation of the mouth, mild pain or discomfort in the mouth, feeling unwell, pain, discomfort and a feeling of tightness in the stomach
• Hand-foot syndrome with red skin, swelling, numbness and peeling on the palms of the hands and soles of the feet
• Back pain
• Fatigue and lack of energy

Common(may affect up to 1 in 10 people)

• Hypothyroidism which can cause symptoms such as fatigue, lethargy, muscle weakness, slowed heart rate, weight gain
• Difficulty sleeping
• Nerve damage including numbness, tingling, sensitive or insensitive skin and weakness of the arms and legs
• Vision problems including blurred vision
• Fast heartbeat, feeling of tightness in the chest, heart attack/reduced blood flow to the heart, blood clot in an artery (blood vessel)
• Blood clot in the lungs. 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 which can cause stroke, reddened skin
• Nosebleeds, runny nose, stuffy nose
• Flatulence, heartburn, difficulty swallowing and painful swallowing, sore throat, swollen stomach, swollen and painful tongue, inflamed, painful and/or bleeding gums
• Altered taste or loss of taste
• Dizziness, ringing in the ears, vertigo and a feeling of dizziness
• Bleeding, e.g. brain, mouth, gums, lungs, stomach, intestinal ulcer, female genitals, anus, adrenal gland
• Coughing up blood; vomiting blood
• Paleness and fatigue caused by excessive bleeding
• Vomiting, indigestion, constipation, dry mouth
• Itching, rash, itchy body, scaling, dry skin, hair loss, reddened skin including hands and body, acne
• Fever, chest pain, swollen feet and legs, chills and low body temperature
• Joint pain, muscle aches
• Increased protein in the urine
• Abnormal blood test results for liver, pancreas, kidneys and thyroid
• Inflammation of the pancreas causing severe stomach pain that can spread to the back.

Uncommon(may affect up to 1 in 100 people)

• Skin rashes with pus; fungal infections
• Easy bruising, bleeding under the skin, hyperthyroidism (which can cause symptoms such as increased appetite, weight loss, intolerance to heat, increased sweating, tremors, fast heartbeat), enlarged thyroid
• Increased number of red blood cells
• Memory loss
• Temporary reduced blood flow to the brain
• Watery eyes
• Blocked ears
• Lack of blood flow in the arteries
• Peptic ulcer in the small intestine
• Red, swollen and painful throat, blisters, excessive sweating, hives
• Muscle weakness
• Swelling or irritation of the mucous membranes
• Abnormal electrocardiogram (ECG), fast and/or irregular heartbeat
• Heart failure. Symptoms include shortness of breath or swelling of the ankles. Fluid buildup in the lungs caused by 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 or neurological disturbances.

Not known(frequency cannot be estimated based on available data)

• Dilation and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections).

Reporting of side effects
If you get any side effect, even if not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly
through the national reporting system listed in Annex V. By reporting side
effects you can help provide more information on the safety of this medicine.

5. How to store Fotivda

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 pack and the vial after
Exp. The expiry date refers to the last day of that month.
Keep the vial tightly closed to protect the medicine from moisture.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Fotivda contains
Fotivda 890 micrograms hard capsules
The active ingredient is tivozanib. Each capsule contains tivozanib hydrochloride monohydrate equivalent to
890 micrograms of tivozanib.
The other ingredients are:

• Capsule content:mannitol, magnesium stearate.
• Capsule shell:gelatin, titanium dioxide (E171), indigotine (E132), yellow iron oxide (E172).
• Printing ink, yellow:shellac, propylene glycol, strong ammonia solution, titanium dioxide (E171), tartrazine aluminium lake (E102) (see section 2 “Fotivda contains tartrazine (E102)”).
• Printing ink, blue:shellac, propylene glycol, strong ammonia solution, indigotine aluminium lake (E132).

Fotivda 1340 micrograms hard capsules
The active ingredient is tivozanib. Each capsule contains tivozanib hydrochloride monohydrate equivalent to
1340 micrograms of tivozanib.
The other ingredients are:

• Capsule content:mannitol, magnesium stearate.
• Capsule shell:gelatin, titanium dioxide (E171), yellow iron oxide (E172).
• Printing ink, blue:shellac, propylene glycol, strong ammonia solution, indigotine aluminium lake (E132).

Description of the appearance of Fotivda and contents of the pack
Fotivda 890 micrograms hard capsules with a dark blue opaque cap and a bright yellow opaque body, with the inscription “TIVZ” printed in yellow ink on the cap and “LD” on the body in
dark blue ink.
Fotivda 1340 micrograms hard capsules with a bright yellow opaque cap and body, with the inscription “TIVZ” printed in dark blue ink on the cap 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 a child-resistant closure.

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