Fotivda

Основна информация

  • Търговско наименование:
  • Fotivda
  • Използвай за:
  • Хората
  • Вид на лекарството:
  • алопатични наркотици

Документи

Локализация

  • Предлага се в:
  • Fotivda
    Европейски съюз
  • Език:
  • английски

Терапевтична информация

  • Терапевтична група:
  • Antineoplastic agents,
  • Терапевтична област:
  • Carcinoma, Renal Cell
  • Терапевтични показания:
  • Fotivda is indicated for the first line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced RCC.Treatment of advanced renal cell carcinoma.
  • Каталог на резюме:
  • Revision: 4

Състояние

  • Източник:
  • EMA - European Medicines Agency
  • Статус Оторизация:
  • Authorised
  • Номер на разрешението:
  • EMEA/H/C/004131
  • Дата Оторизация:
  • 24-08-2017
  • EMEA код:
  • EMEA/H/C/004131
  • Последна актуализация:
  • 06-05-2020

Доклад обществена оценка

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© European Medicines Agency, 2017. Reproduction is authorised provided the source is acknowledged.

EMA/427397/2017

EMEA/H/C/004131

EPAR summary for the public

Fotivda

tivozanib

This is a summary of the European public assessment report (EPAR) for Fotivda. It explains how the

Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is

not intended to provide practical advice on how to use Fotivda.

For practical information about using Fotivda, patients should read the package leaflet or contact their

doctor or pharmacist.

What is Fotivda and what is it used for?

Fotivda is a medicine for treating adults with advanced renal cell carcinoma (a kidney cancer).

Fotivda may be used in previously untreated patients or in those whose disease has got worse despite

treatment with another medicine working in a different way.

It contains the active substance tivozanib.

How is Fotivda used?

Fotivda is available as capsules (890 and 1,340 micrograms). The usual dose is one 1,340-microgram

capsule once a day for three weeks, followed by a week when the patient does not take any capsules.

The patients should continue repeating this 4-week course for as long as the disease does not get

worse or until side effects become unacceptable. If the patient has troublesome side effects, the doctor

may decide to switch to the lower-strength 890-microgram capsules or interrupt treatment.

Fotivda can only be obtained with a prescription, and treatment should be supervised by a doctor with

experience of treating cancers. For further information, see the package leaflet.

Fotivda

EMA/427397/2017

Page 2/2

How does Fotivda work?

The active substance in Fotivda, tivozanib, works by blocking the activity of proteins known as VEGF,

which stimulate the formation of new blood vessels. By blocking this protein, tivozanib stops the

formation of new blood vessels that the tumour needs, thereby cutting off its blood supply and

reducing the growth of the cancer.

What benefits of Fotivda have been shown in studies?

A main study of 517 patients with advanced renal cell carcinoma that had either come back or spread

to other parts of the body has shown that Fotivda can help stop the disease from getting worse. In this

study, patients taking Fotivda lived for longer without their disease worsening (12 months) than those

given another approved medicine sorafenib (9 months).

What are the risks associated with Fotivda?

The most important serious side effect with Fotivda is high blood pressure. The most common side

effects are high blood pressure (which occurs in almost half of patients) and voice changes, tiredness

and diarrhoea (which occur in about a quarter of patients). For the full list of all side effects, see the

package leaflet.

Patients must not take St John’s wort (a herbal remedy for depression) during treatment with Fotivda.

For the full list of restrictions, see the package leaflet.

Why is Fotivda approved?

A main study showed that Fotivda increased the time it took for the disease to get worse by almost 3

months when compared with another approved medicine sorafenib. The most common side effects with

Fotivda are considered manageable, although they may affect the patient’s quality of life. On the

whole, its side effects are in line with what is expected of a medicine of its class (VEGF inhibitors).

The European Medicines Agency therefore concluded that the benefits of Fotivda outweighed its risk

and recommended that it be granted authorisation in the EU.

What measures are being taken to ensure the safe and effective use of

Fotivda?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe

and effective use of Fotivda have been included in the summary of product characteristics and the

package leaflet.

Other information about Fotivda

The European Commission granted a marketing authorisation valid throughout the European Union for

Fotivda on 24 August 2017.

The full EPAR for Fotivda can be found on the Agency’s website:

ema.europa.eu/Find medicine/Human

medicines/European public assessment reports. For more information about treatment with Fotivda,

read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 08-2017.

Листовка за пациента: състав, показания, Нежелани лекарствени реакции, дозиране, взаимодействия, бременност, кърмене

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Fotivda 890 microgram hard capsules

Fotivda 1340 microgram hard capsules

tivozanib

This medicine is subject to additional monitoring. This will allow quick identification of new

safety information. You can help by reporting any side effects you may get. See the end of section 4

for how to report side effects.

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, pharmacist or nurse.

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, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

What Fotivda is and what it is used for

What you need to know before you take Fotivda

How to take Fotivda

Possible side effects

How to store Fotivda

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 protein kinase inhibitor. Tivozanib reduces the

supply of blood to the cancer, which slows down the growth and spread of cancer cells. It works by

blocking the action of a protein called vascular endothelial growth factor (VEGF). Blocking the action

of VEGF prevents the formation of new blood vessels.

Fotivda is used to treat adults with advanced kidney cancer. It is used where other treatments such as

interferon-alpha or interleukin-2 have either not yet been used or have not helped to stop your disease.

2.

What you need to know before you take 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

for treatment of depression and anxiety).

Warnings and precautions

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

if you have

high blood pressure

Fotivda can increase your blood pressure. Your doctor will monitor your blood pressure

regularly and, if it is too high, may either give you a medicine to lower it, or reduce your dose of

Fotivda. However, if your blood pressure remains too high, your doctor may decide to interrupt

or to stop treatment with Fotivda. If you are already taking a medicine to treat high blood

pressure, and your doctor reduces the dose of Fotivda or interrupts or stops treatment, you will

be regularly checked for low blood pressure.

if you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a

tear in a blood vessel wall.

if you have had problems with

blood clots

Treatment with Fotivda may raise the risk of developing a blood clot (thrombus) in your blood

vessels that could break loose and be carried by the blood stream to block another blood vessel.

Tell your doctor if you have ever had one of the following:

a blood clot in your lungs (with cough, chest pain, sudden shortness of breath or coughing

up blood),

blood clot in your legs or arms, eye, or brain (with pain or swelling in your hands or feet,

reduced vision, or changes in your mental state)

a stroke, or signs and symptoms of a ‘mini-stroke’ (transient ischaemic attack)

a heart attack

high blood pressure

diabetes

major surgery

multiple injuries such as broken bones and damage to internal organs

inability to move for a long period

heart failure which can cause shortness of breath or ankle swelling

inability to breathe, bluish colour on your skin, fingertips or lips, restlessness, anxiety,

confusion, altered consciousness or sense of awareness, rapid, shallow breathing, a racing

heart or excessive sweating.

if you suffer or have suffered from any of these symptoms or are treated for heart failure:

Shortness of breath (dyspnoea) when you exert yourself or when you lie down

Feeling weak and tired

Swelling (oedema) in your legs, ankles and feet

Reduced ability to exercise

Persistent cough or wheezing with white or pink blood-tinged phlegm

Signs and symptoms of heart failure will be monitored whilst you are taking your medicine. If

necessary, your doctor may reduce your dose of Fotivda, or interrupt or stop this treatment.

If you have or are treated for an

abnormal rate and rhythm of the heartbeat (arrhythmia)

Your doctor will monitor the effect of Fotivda on your heart by recording the electrical activity

of your heart (an electrocardiogram) or by measuring your blood calcium, magnesium and

potassium levels during your treatment.

if you have

problems with your liver

Your doctor will regularly monitor how well your liver is working before and during treatment

with Fotivda (e.g. with blood tests), and if necessary may need to reduce how often you take

Fotivda.

if you have

problems with your thyroid gland

use medicines to treat thyroid disease

Treatment with Fotivda may cause your thyroid gland to work less well than usual. Your doctor

will regularly monitor how well your thyroid gland is working before and during treatment with

Fotivda (e.g. with blood tests).

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

if you get

shortness of breath or ankle swelling

Tell your doctor right away as these may be symptoms of heart failure. Your doctor will

monitor this, and depending on the severity may reduce your dose of Fotivda, or interrupt or

stop treatment with Fotivda.

if you have had problems with

bleeding

Treatment with Fotivda may increase the risk of bleeding. If you get bleeding problems (with

painful swollen stomach (abdomen), vomiting blood, coughing up blood, black stools, blood in

your urine, headache or changes in your mental state), tell your doctor right away. Treatment

with Fotivda may need to be temporarily stopped.

if laboratory tests show that there is

protein in your urine

Your doctor will monitor this at the beginning and during your treatment. Depending on the

results, your doctor may reduce your dose of Fotivda, or interrupt or stop this treatment.

if you suffer from a disease of the brain, called

posterior reversible encephalopathy

syndrome (PRES)

Tell your doctor right away if you have symptoms such as headache, seizure (fit), lack of energy,

confusion, blindness or other visual and neurologic disturbances such as weakness in an arm or

a leg. If PRES is diagnosed, your doctor will stop treatment with Fotivda.

if the

skin on the palms of your hands and the soles of your feet

become dry, cracked,

scaling, or peeling, or is stinging or tingling

These may be symptoms of a condition called hand foot skin reaction. Your doctor will treat the

condition and, depending on the severity, the doctor may reduce your dose of Fotivda, or

interrupt or stop this treatment.

if you have symptoms of

gastrointestinal perforation or fistula

formation (developing a hole

in the stomach or intestine or abnormal passages forming between parts of the intestine) such as

severe stomach pain, chills, fever, nausea, vomiting or painful bowel obstruction, diarrhoea or

rectal bleeding.

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

if you need to have an

operation or another form of surgery

Your doctor may recommend that you temporarily stop taking Fotivda if you have an operation

or surgery, as it could affect wound healing.

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

cause allergic reactions.

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 take any other

medicines. This includes herbal medicines and other medicines you have bought without a

prescription.

Fotivda may work less well when taken with some medicines. Tell 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 disorders of the immune

system);

rosuvastatin (a medicine used to help lower cholesterol levels in your blood);

phenobarbital, phenytoin, carbamazepine (used to treat

epilepsy);

nafcillin, rifampicin, rifabutin, rifapentin (antibiotics);

St. John’s Wort (also known as

Hypericum perforatum

, a herbal remedy used for treatment of

depression and anxiety) as this herbal remedy should not be used at the same time as Fotivda.

Pregnancy, breast-feeding and fertility

Do not take Fotivda if you are pregnant.

Tell your doctor who will discuss with you the risks

of taking Fotivda to you and your child.

Both you and your partner must

use effective contraception.

If you or your partner are taking

hormonal contraceptives (the pill, an implant or patch) you

must use an additional barrier

method

throughout treatment and for another month after completing treatment.

Do not breast-feed during treatment with Fotivda

, as it is not known whether the active

ingredient in Fotivda passes into breast-milk. Talk to your doctor if you are already breast-

feeding.

Talk to your doctor when planning a baby, as Fotivda may affect the

fertility

of men and

women.

Driving and using machines

Fotivda can have side effects that may affect your ability to drive or use machines. Avoid driving or

using machines if you feel weak, tired, or dizzy. See also Section 4 “Possible side effects”.

3.

How to take Fotivda

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist

if you are not sure.

Recommended dose

The recommended dose is one Fotivda 1340 microgram capsule, taken once daily for 21 days

(3 weeks), followed by a 7-day

(1-week) period when no capsules are taken.

This schedule is repeated in cycles of 4 weeks.

Your doctor will check you regularly, and you will normally continue to take Fotivda as long as it is

working, and you do not suffer unacceptable side effects.

Reduced dose

In case you experience severe side effects, your doctor may decide to interrupt Fotivda therapy and/or

lower the dose to:

One Fotivda 890 microgram capsule, taken once daily for 21 days (3 weeks), followed by a 7-day

(1-week) period when no capsules are taken.

This schedule is repeated in cycles of 4 weeks.

Liver problems

If you have

liver problems

, your doctor may reduce how often you take your dose to every other day

(i.e. one 1340 microgram capsule every other day).

Taking with food and drink

Fotivda must be taken with a glass of water and can be taken either 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

Tell your doctor straightaway if you have taken more than your prescribed dose of 1 capsule per day.

21 days

(three weeks)

One Fotivda capsule

taken

once daily

7 days

(1 week)

No capsules

are taken

Taking too much Fotivda makes side effects more likely or to become more severe, especially high

blood pressure. Get

medical help straightaway

if you experience confusion, changes in your mental

state or headaches. These are all symptoms of high blood pressure.

If you forget to take Fotivda

If you have missed taking a capsule do

not

take a replacement capsule. Continue to take your next

dose at the usual time.

Do not

take a double dose to make up for a forgotten capsule.

If you vomit after taking Fotivda, do

not

take a replacement capsule. Continue to take your next dose

at the usual time.

If you stop taking Fotivda

Do not stop taking this medicine unless your doctor tells you to. If you stop taking the capsules your

condition may get worse.

If you have any further questions on 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 everybody gets them.

Serious side effects

High blood pressure

is the most serious and a very common side effect (see also in 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 disorientated

Your doctor will check your blood pressure regularly during treatment with Fotivda. If you develop

high blood pressure, your doctor may prescribe a medicine to treat your high blood pressure, lower

your dose of Fotivda, or stop your treatment with Fotivda.

Other side effects

Very common

(may affect more than 1 in 10 people)

Difficulty speaking

Diarrhoea

Loss of appetite; weight loss.

Headache

Difficult breathing; shortness of breath during exercise; coughing.

Tiredness; unusual weakness; pain (including in the mouth, bone, extremities, side of the body,

groin, tumour).

Inflammation of the mouth; slight mouth pain or discomfort; feeling sick; pain, discomfort and

tightness in the stomach.

Hand-foot-syndrome with skin reddening, swelling, numbness and skin peeling on palms and

soles.

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 tiredness, lethargy, muscle

weakness, slow heart rate, weight gain.

Unable to sleep.

Nerve damage including numbness, pins and needles, sensitive skin or numbness and weakness

in the arms and legs.

Sight problems including blurred vision.

Rapid heart rate; tightness of the chest; heart attack/reduced blood flow to 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 a stroke; flushed skin.

Nose bleed; runny nose; blocked nose.

Flatulence; heartburn; difficult and painful swallowing; sore throat; bloated stomach; swollen

and painful tongue; inflamed painful and/or bleeding gums.

Taste changes or loss of taste.

Dizziness; ringing in the ears; dizziness and a spinning sensation (vertigo).

Bleeding, e.g. in the brain, from the mouth, gums, lungs, stomach, gut ulcers, female genitals,

anus, adrenal gland.

Coughing up blood; vomiting up blood.

Paleness and tiredness from excess bleeding.

Being sick; indigestion; constipation; dry mouth.

Itchy skin; rash; itching of the body; skin peeling; dry skin; hair loss; redness of the skin

including the 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 the urine.

Abnormal blood test results for liver, pancreas, kidney, and thyroid.

Inflammation of the pancreas causing severe stomach pain which may spread to your back.

Uncommon

(may affect up to 1 in 100 people)

Rashes with pus; fungal infections.

Bruising easily, bleeding into the skin.

overactive thyroid gland (which may cause symptoms like increased appetite, loss of weight,

intolerance to heat, increased sweating, tremors, rapid heart rate); enlarged thyroid gland.

Increase in number of red blood cells.

Memory loss.

Temporary reduced blood flow to the brain.

Watery eyes.

Blocked ears.

Lack of blood flow through the heart blood vessels.

Peptic ulcer in the small intestines.

Red, swollen and sore skin; blistering skin; excessive sweating; hives.

Muscle weakness.

Swelling or irritation of the mucous membranes.

Abnormal electrocardiogram (ECG), rapid and/or irregular heart beat.

Heart failure. Symptoms include shortness of breath or ankle swelling. Swelling in the lungs

caused by fluid build-up.

R

are

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

Posterior reversible encephalopathy syndrome (PRES). Symptoms include headache, seizure,

lack of energy, confusion, blindness or other visual and neurologic disturbances.

Not known

An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall

(aneurysms and artery dissections).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. You can also report side effects directly via the national reporting

system listed in Appendix 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 carton and bottle after EXP. The

expiry date refers to the last day of that month.

Keep the bottle tightly closed in order to protect from moisture.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Fotivda contains

Fotivda 890 microgram hard capsules

The active substance is tivozanib. Each capsule contains tivozanib hydrochloride monohydrate

equivalent to 890 microgram of tivozanib.

The other ingredients are:

Capsule content

: mannitol, magnesium stearate.

Capsule shell

: gelatin, titanium dioxide (E171), indigo carmine (E132), yellow iron oxide

(E172).

Printing ink, yellow

: shellac, propylene glycol, strong ammonia solution, titanium dioxide

(E171), tartrazine aluminium lake (E102).

Printing ink, blue

: shellac, propylene glycol, strong ammonia solution, indigo carmine

aluminium lake (E132).

Fotivda 1340 microgram hard capsules

The active substance is tivozanib. Each capsule contains tivozanib hydrochloride monohydrate

equivalent to 1340 microgram 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, indigo carmine

aluminium lake (E132).

What Fotivda looks like and contents of the pack

Fotivda 890 microgram hard capsules have a dark blue opaque cap and bright yellow opaque body,

printed with yellow ink “TIVZ” on the cap and with dark blue ink “LD” on the body.

Fotivda 1340 microgram hard capsules have a bright yellow opaque cap and bright yellow opaque

body, printed with dark blue ink “TIVZ” on the cap and with dark blue ink “SD” on the body.

Fotivda 890 microgram and Fotivda 1340 microgram are available as packs of 21 capsules in

HDPE-bottles with child-resistant closure.

Marketing Authorisation Holder

EUSA Pharma (Netherlands) B.V.

Johannes Vermeerplein 11

1071 DV

Amsterdam

Netherlands

Manufacturer

ALMAC PHARMA SERVICES (IRELAND) LIMITED

Finnabair Industrial Estate

Dundalk

Co. Louth

A91 P9KD

Ireland

This leaflet was last approved in

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu