Pazopanib pharmascience

Package leaflet: Information for the patient

Pazopanib Pharmascience, 200 mg, film-coated tablets
Pazopanib Pharmascience, 400 mg, film-coated tablets
Pazopanibum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• Consult your doctor or pharmacist if you have any doubts.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

1. What Pazopanib Pharmascience is and what it is used for
2. Important information before taking Pazopanib Pharmascience
3. How to take Pazopanib Pharmascience
4. Possible side effects
5. How to store Pazopanib Pharmascience
6. Contents of the pack and other information

1. What Pazopanib Pharmascience is and what it is used for

Pazopanib Pharmascience belongs to a group of medicines called protein kinase inhibitors.
It works by inhibiting the activity of proteins involved in the growth and spread of cancer cells.
Pazopanib Pharmascience is used in adult patients for the treatment of:

• advanced or metastatic renal cell carcinoma (kidney cancer),
• certain types of soft tissue sarcoma, which is a type of tumour affecting the body's connective tissues. It may occur in muscles, blood vessels, fatty tissue, or other tissues that support, surround, and protect internal organs.

2. Important information before using Pazopanib Pharmascience

When not to use Pazopanib Pharmascience

• if the patient is allergic to pazopanib or to any of the other ingredients of this medicine (listed in section 6). Consult a doctor if the patient thinks the above applies.

Warnings and precautions
Before starting treatment with Pazopanib Pharmascience, discuss with the doctor if:

• the patient has heart disease,
• the patient has liver disease,
• the patient has had heart failure or heart attack,
• the patient has a history of pneumothorax (collapsed lung),
• the patient has bleeding, blood clots, or arterial stenosis,
• the patient has had stomach or intestinal disorders, such as perforation (a hole) or fistula (abnormal connections between parts of the intestines),
• the patient has thyroid disorders,
• the patient has impaired kidney function,
• the patient has or has previously had an aneurysm (enlargement and weakening of a blood vessel wall) or arterial dissection. Inform the doctor if any of these conditions apply. The doctor will decide whether Pazopanib Pharmascience is suitable. Additional tests may be required to assess proper functioning of the kidneys, heart, and liver.

High blood pressure and use of Pazopanib Pharmascience
Pazopanib Pharmascience may increase blood pressure. Blood pressure will be monitored before starting and during treatment. If the patient develops high blood pressure, the doctor will prescribe antihypertensive medications.

• Inform the doctor if the patient has high blood pressure.

If surgery is planned
The doctor will advise stopping Pazopanib Pharmascience at least 7 days before surgery, as the drug may affect postoperative wound healing. Treatment will be resumed once the wound has healed.

Conditions requiring special attention
Pazopanib Pharmascience may worsen certain conditions or cause serious adverse effects. During treatment with Pazopanib Pharmascience, particular attention should be paid to certain symptoms to reduce the risk of adverse effects. See section 4.

Children and adolescents
Pazopanib Pharmascience is not recommended for patients under 18 years of age. The effect of pazopanib in this patient group has not been established. For safety reasons, the medicine should not be used in children under 2 years of age.

Pazopanib Pharmascience and other medicines
Inform the doctor or pharmacist about all medicines currently used, recently taken, or planned for use, including herbal products and other medicines available without a prescription.

Some medicines may affect the action of Pazopanib Pharmascience or increase the risk of adverse reactions. Pazopanib Pharmascience may also affect the action of other medicines. These include:

• clarithromycin, ketoconazole, itraconazole, rifampicin, telithromycin, voriconazole (used to treat infections),
• atazanavir, indinavir, nelfinavir, ritonavir, saquinavir (used to treat HIV infection),
• nefazodone (used to treat depression),
• simvastatin and possibly other statins (used to treat elevated blood cholesterol),
• medicines reducing gastric acid secretion. Medicines taken to reduce stomach acid (e.g. proton pump inhibitors, H-receptor antagonists, or antacids) may affect pazopanib absorption. Consult a doctor or nurse for advice.

Inform the doctor or pharmacist if the patient is taking any of these medicines.

Pazopanib Pharmascience with food and drink

Do not take Pazopanib Pharmascience with food, as this affects drug absorption. The medicine should be taken at least two hours after a meal or one hour before a meal (see section 3).

While taking Pazopanib Pharmascience, do not drink grapefruit juice, as it may increase the risk of adverse reactions.

Pregnancy, breastfeeding, and effects on fertility

Pazopanib Pharmascience is not recommended during pregnancy. It is unknown how this medicine affects pregnancy.

• Inform the doctor if the patient is pregnant or planning to become pregnant. During treatment with Pazopanib Pharmascience and for at least 2 weeks after stopping treatment, an effective method of contraception must be used to prevent pregnancy.
• Inform the doctor if the patient becomes pregnant while taking Pazopanib Pharmascience.

Breastfeeding must not be undertaken during treatment with Pazopanib Pharmascience. It is unknown whether the active substance passes into human milk. Discuss this with the treating doctor.

Men (including men who have had a vasectomy), whose partners are pregnant or may become pregnant (including women using other contraceptive methods), should use condoms during sexual intercourse while taking Pazopanib Pharmascience and for at least 2 weeks after the last dose.

Treatment with Pazopanib Pharmascience may affect fertility. Discuss this with the treating doctor.

Driving and operating machinery
Adverse reactions associated with Pazopanib Pharmascience may impair the ability to drive or operate machinery.

• Avoid driving and operating machinery if the patient experiences dizziness, fatigue, weakness, or low energy levels.

Pazopanib Pharmascience contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per coated tablet, meaning the medicine is considered "sodium-free".

3. How to use Pazopanib Pharmascience

This medicine should always be taken as directed by the doctor. If in doubt, consult the doctor or pharmacist.
How many tablets to take
Pazopanib Pharmascience, 200 mg
The usual dose of Pazopanib Pharmascience, 200 mg is four tablets (800 mg of pazopanib) once daily. This is the maximum daily dose. The doctor may recommend reducing the dose if the patient experiences adverse effects.
Pazopanib Pharmascience, 400 mg
The usual dose of Pazopanib Pharmascience, 400 mg is two tablets (800 mg of pazopanib) once daily. This is the maximum daily dose. The doctor may recommend reducing the dose if the patient experiences adverse effects.
When to take the medicine
Do not take Pazopanib Pharmascience with food. The medicine should be taken at least two hours after a meal or one hour before a meal. For example, the medicine may be taken two hours after breakfast or one hour before lunch. Pazopanib Pharmascience should be taken at the same time each day.
The tablets should be swallowed whole, one after another, with water. Do not break or crush the tablets, as this affects the absorption of the medicine and may increase the risk of adverse effects.
Taking more Pazopanib Pharmascience than prescribed
If the patient takes too many tablets, seek advice from a doctor or pharmacist immediately. If possible, show the medicine packaging or this leaflet.
If a dose of Pazopanib Pharmascience is missed
Do not take a double dose to make up for a missed dose. Take the next dose at the usual time.
Do not stop taking Pazopanib Pharmascience without medical advice
Continue taking Pazopanib Pharmascience for as long as the doctor prescribes. Do not discontinue treatment unless instructed by the doctor.

4. Possible side effects

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

Possible serious side effects

Brain swelling (reversible posterior leukoencephalopathy syndrome)
Rarely, Pazopanib Pharmascience may cause brain swelling, which can be life-threatening.
Symptoms include:

• loss of speech
• vision disturbances
• seizures
• disorientation
• high blood pressure. Stop taking Pazopanib Pharmascience and seek immediate medical help if any of these symptoms occur, or if you experience headache accompanied by any of these symptoms.

Hypertensive crisis (sudden and severe increase in blood pressure)
Pazopanib Pharmascience may occasionally cause a sudden and severe rise in blood pressure.
This condition is known as a hypertensive crisis. Your doctor will monitor your blood pressure during treatment with Pazopanib Pharmascience. Symptoms of a hypertensive crisis may include:

• severe chest pain
• severe headache
• blurred vision
• disorientation
• nausea
• vomiting
• severe restlessness
• shortness of breath
• seizures
• fainting. Stop taking Pazopanib Pharmascience and seek immediate medical help if a hypertensive crisis occurs.

Heart problems
The risk of these problems may be higher in people with existing heart disease or those taking other medicines. While taking Pazopanib Pharmascience, patients will be monitored for heart problems.

Heart rhythm disorders/heart failure, heart attack
Pazopanib Pharmascience may affect the heart's ability to pump blood or may increase the risk of heart attack. Symptoms include:

• irregular or rapid heartbeat
• fast palpitations
• fainting
• pain or pressure in the chest
• pain in the arms, back, neck, or jaw
• shortness of breath
• swelling of the legs. Seek immediate medical help if any of these symptoms occur.

Changes in heart rhythm (QT interval prolongation)
Pazopanib Pharmascience may affect heart rhythm, which in some people may lead to a serious arrhythmia called torsade de pointes. This may cause a very rapid heartbeat and may result in sudden loss of consciousness.
Inform your doctor if you experience changes in heart rhythm, such as a heartbeat that is too fast or too slow.

Stroke
Pazopanib Pharmascience may increase the risk of stroke. Symptoms of stroke may include:

• numbness or weakness on one side of the body
• difficulty speaking
• headache
• dizziness. Seek immediate medical help if any of these symptoms occur.

Bleeding
Pazopanib Pharmascience may cause severe bleeding from the gastrointestinal tract (from the stomach, oesophagus, rectum, or intestines) or from the lungs, kidneys, mouth, vagina, or bleeding into the brain, although this is not common. Symptoms of bleeding include:

• presence of blood in stool or black-coloured stool
• blood in urine
• abdominal pain
• coughing up blood or vomiting blood.
  Seek immediate medical help if any of these symptoms occur.

Perforation and fistula
Pazopanib Pharmascience may cause a tear (perforation) in the wall of the stomach or intestine or the formation of an abnormal connection between two parts of the gastrointestinal tract (fistula). Symptoms may include:

• severe abdominal pain
• nausea and (or) vomiting
• fever
• development of an opening (perforation) in the stomach, large intestine, or small intestine, from which blood-stained or foul-smelling pus leaks. Seek immediate medical help if any of these symptoms occur.

Liver problems
Pazopanib Pharmascience may cause liver problems, which may progress to serious symptoms such as impaired liver function or liver failure, which may be fatal. Your doctor will monitor liver enzyme activity during treatment with this medicine.
Symptoms indicating impaired liver function may include:

• yellowing of the skin or whites of the eyes (jaundice)
• dark-coloured urine
• feeling tired
• nausea
• vomiting
• loss of appetite
• pain on the right side of the abdomen
• easy bruising. Seek immediate medical help if any of these symptoms occur.

Blood clots
Deep vein thrombosis and pulmonary embolism
Pazopanib Pharmascience may cause blood clots in the veins, especially in the legs (deep vein thrombosis), which may travel to the lungs (pulmonary embolism). Symptoms may include:

• sudden chest pain
• shortness of breath
• rapid breathing
• leg pain
• swelling of arms and hands or hands and feet.

Thrombotic microangiopathy
Pazopanib Pharmascience may cause blood clots in small blood vessels in the kidneys and brain, associated with a decrease in red blood cells and platelets (thrombotic microangiopathy). Symptoms may include:

• easy bruising
• high blood pressure
• fever
• disorientation
• drowsiness
• seizures
• reduced urine output. Seek immediate medical help if any of these symptoms occur.

Tumour lysis syndrome
Pazopanib Pharmascience may cause rapid breakdown of tumour cells, leading to tumour lysis syndrome, which may be fatal in some patients. Symptoms may include irregular heartbeat, seizures, confusion, muscle cramps, or reduced urine output. Seek immediate medical help if any of these symptoms occur.

Infections
Infections occurring during treatment with Pazopanib Pharmascience may become severe.
Symptoms of infection may include:

• fever
• flu-like symptoms such as cough, fatigue, and body aches that do not go away
• shortness of breath and (or) wheezing
• pain when urinating
• cuts, scratches, or wounds that are red, warm, swollen, or painful. Seek immediate medical help if any of these symptoms occur.

Lung inflammation
Pazopanib Pharmascience may rarely cause lung inflammation (interstitial lung disease, pneumonia), which may be fatal in some patients.
Symptoms include shortness of breath or persistent cough. During treatment, patients will be monitored for any lung function abnormalities. Seek immediate medical help if any of these symptoms occur.

Thyroid disorders
Pazopanib Pharmascience may reduce the production of thyroid hormones in the body.
This may lead to weight gain and fatigue. During treatment with this medicine, your doctor will monitor your thyroid hormone levels.
Inform your doctor if you notice significant weight gain or fatigue.

Blurred vision or visual disturbances
Pazopanib Pharmascience may cause detachment or tearing of the membrane at the back of the eye (retinal detachment or tear). This may lead to blurred vision or visual disturbances.
Inform your doctor if you notice any visual disturbances.

Possible side effects (including possible serious side effects in appropriate frequency categories)

Very common side effects (may affect more than 1 in 10 patients):

• high blood pressure
• diarrhoea
• nausea or vomiting
• abdominal pain
• loss of appetite
• weight loss
• taste disturbances or loss of taste
• mouth pain
• headache
• tumour pain
• lack of energy, feeling weak or tired
• changes in hair colour
• excessive hair loss or thinning
• skin discolouration
• skin rash with possible skin peeling
• redness and swelling of the palms or soles of the feet. Inform your doctor or pharmacist if any of these symptoms become bothersome.

Very common side effects that may be detected in blood or urine tests:

• increased liver enzyme activity
• decreased blood albumin levels
• protein in the urine
• decreased platelet count (blood component responsible for clotting)
• decreased white blood cell count.

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

• indigestion, bloating, flatulence
• nosebleeds
• dry mouth or mouth ulcers
• infections
• excessive drowsiness
• sleep disturbances
• chest pain, shortness of breath, leg pain, and swelling of legs or feet. These may be symptoms of blood clots forming in the body (thromboembolism). If a clot detaches, it may travel to the lungs, which may be life-threatening or even fatal
• reduced ability of the heart to pump blood to the whole body (heart dysfunction)
• slow heartbeat
• bleeding from the mouth, rectum, or lungs
• dizziness
• blurred vision
• hot flushes
• swelling of the face, hands, legs around the ankles, feet, or eyelids due to fluid accumulation
• tingling, weakness, or numbness in the hands, arms, legs, or feet
• skin disorders, redness, itching, dry skin
• nail disorders
• burning, stinging, itching, or tingling sensation of the skin
• feeling cold with chills
• excessive sweating
• dehydration
• muscle, joint, tendon, or chest pain, muscle cramps
• hoarseness
• shortness of breath
• cough
• haemoptysis
• hiccups
• lung collapse with air trapped between the lung and chest wall, often causing shortness of breath (pneumothorax). Inform your doctor or pharmacist if any of these symptoms become bothersome.

Common side effects that may be detected in blood or urine tests:

• hypothyroidism
• abnormal liver function
• increased bilirubin levels (a substance produced by the liver)
• increased lipase activity (an enzyme involved in digestion)
• increased creatinine levels (a substance produced in muscles)
• changes in concentration/activity of various other substances/enzymes in the blood. Your doctor will inform you about blood test results.

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

• stroke
• transient reduction in blood flow to the brain (transient ischaemic attack)
• interruption of blood flow to part of the heart or heart attack (myocardial ischaemia)
• partial interruption of blood flow to part of the heart (myocardial ischaemia)
• blood clots associated with reduced red blood cells and platelets (thrombotic microangiopathy). This may damage organs such as the brain and kidneys
• increased red blood cell count
• sudden shortness of breath, especially if accompanied by acute chest pain and (or) rapid breathing (pulmonary embolism)
• severe bleeding from the gastrointestinal tract (from the stomach, oesophagus, or intestines), kidneys, vagina, or bleeding into the brain
• heart rhythm disorders (QT interval prolongation)
• perforation of the stomach or intestine
• formation of abnormal connections between different parts of the intestine (fistula)
• excessive, heavy, or irregular menstrual bleeding
• sudden, severe increase in blood pressure (hypertensive crisis)
• pancreatitis
• inflammation, abnormal function, or damage to the liver
• yellowing of the skin or whites of the eyes (jaundice)
• inflammation of the abdominal lining (peritonitis)
• watery nasal discharge
• rashes, which may be itchy or associated with inflammation (flat or raised spots or blisters)
• frequent bowel movements
• increased sensitivity of the skin to sunlight
• reduced sensation or sensitivity, especially of the skin
• skin wound that does not heal (skin ulcer).

Rare side effects (may affect up to 1 in 1000 patients):

• lung inflammation
• enlargement and weakening of a blood vessel wall or tearing of the blood vessel wall (aneurysm and arterial dissection).

Frequency not known (frequency cannot be estimated from available data):

• tumour lysis syndrome due to rapid breakdown of tumour cells
• liver failure.

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department for Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Pazopanib Pharmascience

The medicine should be stored out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the carton.
The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. These measures will help protect
the environment.

6. Contents of the pack and other information

What Pazopanib Pharmascience contains
Pazopanib Pharmascience, 200 mg, film-coated tablets:

• The active substance is pazopanib (as hydrochloride). Each film-coated tablet contains 200 mg of pazopanib. The other ingredients are:
  Tablet core: microcrystalline cellulose type 101, sodium carboxymethylstarch (type A), povidone (K-30), magnesium stearate.
  Tablet coating: hypromellose 6 mPa  s, titanium dioxide (E 171), polyethylene glycol 400, iron oxide red (E 172), polysorbate 80.

Pazopanib Pharmascience, 400 mg, film-coated tablets:

• The active substance is pazopanib (as hydrochloride). Each film-coated tablet contains 400 mg of pazopanib. The other ingredients are:
  Tablet core: microcrystalline cellulose type 101, sodium carboxymethylstarch (type A), povidone (K-30), magnesium stearate.
  Tablet coating: hypromellose (6 mPa  s), titanium dioxide (E 171), polyethylene glycol 400, polysorbate 80.

What Pazopanib Pharmascience looks like and contents of the pack
Pazopanib Pharmascience, 200 mg, film-coated tablets: pink, film-coated, capsule-shaped tablet measuring 14.3 mm x 5.7 mm ± 5%, with the imprint "200" on one side.
Cardboard boxes containing tablets in blisters made of Aluminium/PVC/PE/PVDC foil.
Pack sizes: 30, 60 and 90 tablets.
Pazopanib Pharmascience, 400 mg, film-coated tablets: white, film-coated, capsule-shaped tablet measuring 18.0 mm x 7.1 mm ± 5%, with the imprint "400" on one side.
Cardboard boxes containing tablets in blisters made of Aluminium/PVC/PE/PVDC foil.
Pack sizes: 30, 60 and 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pharmascience International Limited
Lampousas 1
1095 Nicosia
Cyprus

Manufacturer
Remedica Ltd.
Aharnon Street, Limassol Industrial Estate
3056 Limassol
Cyprus

PharOS MT Ltd.
HF62X, Hal Far Industrial Estate
Birzebbugia, BBG3000
Malta

This medicinal product is authorised in the EEA Member States under the following names: