Votrient (Pazopanib)

Safety and efficacy of VOTRIENT have not been established in children less than 18 years of age. VOTRIENT must not be used in children under two years of age.

BEFORE you use VOTRIENT talk to your doctor or pharmacist:

• If you have or had heart disease, heart failure or heart attack

• If you have or have had a heart rhythm disorder such as irregular heartbeat, prolongation of the QT interval or any risk factors for Torsade de Pointes (dangerous rapid fluttering of the heart) such as diabetes, low potassium, magnesium or calcium levels, or a history of low heart rate, fainting, or loss of consciousness

• If you have high blood pressure

• If you have liver disease

• If you have problems with bleeding

• If you have gastrointestinal problems

• If you have or had a blood clot in a vein or in a lung

• If you have had prior collapse of a lung

• If you have a kidney problem

• If you have thyroid problems

• If you are going to have a surgical or dental procedure, or if you have had either recently

While you are taking VOTRIENT your doctor will take blood samples to check for any liver problems. You should report any signs or symptoms of liver injury including jaundice (yellowing of whites of eyes or skin), unusual darkening of the urine, anorexia (loss of appetite), nausea, fatigue, right upper abdominal discomfort and vomiting. Your doctor will also take urine samples to check for any kidney problems. You will also have your blood pressure checked. Your doctor will periodically record your electrocardiogram (ECG) to check your heart's electrical conduction.

Your doctor will also check on any recent surgical or dental procedures to see if you are healing properly.

Use a reliable method of contraception to avoid becoming pregnant while you’re taking VOTRIENT and for up to 8 weeks after you stop treatment with VOTRIENT. If you are pregnant or think you could be, talk to your doctor about the risks and benefits to you and your baby while taking VOTRIENT. Your doctor may recommend that you don't take VOTRIENT while you are pregnant.

Breastfeeding is not recommended during treatment with VOTRIENT. Ask your doctor for advice.

Like all medicines, VOTRIENT can cause side effects.

Very common side effects—these may affect more than 1 in 10 people:

• diarrhea (which can be severe; e.g. with fever or 3 or more times a day)
• feeling or being sick (nausea or vomiting)
• loss of appetite
• stomach pain or discomfort
• high blood pressure
• headache
• loss of strength
• lack of energy
• weakness
• changes in hair colour
• weight loss
• problems with taste
• skin rash
• a skin reaction or pain on the palms of the hands or soles of the feet (including tingling, numbness, pain, swelling or reddening)
• dizziness
• cough
• shortness of breath
• chest pain
• swelling of hands, ankles or feet
• muscle pain
• pain in the bones, muscles, ligaments, joints and tendons
• mouth sores
• unusual hair loss or thinning
• loss of skin pigment
• slow heart rate

Very common side effect that may show up in your blood tests:

• increase in some substances (enzymes) produced by the liver

Common side effects—these may affect up to 1 in 10 people:

• temporary reduction in blood supply to the brain (mini-stroke)
• reduction of blood supply to the heart (angina)
• changes in the heart's electrical conduction (QT-prolongation) which may cause irregular heartbeat
• heart attack
• severe bleeding in the lung
• under-active thyroid gland
• abnormal liver function (which can be severe and may cause yellowing of the skin or the whites of the eyes (jaundice), unusual darkening of the urine, unusual tiredness, or right upper stomach area pain)
• indigestion
• flatulence
• nosebleeds
• dry skin
• nail disorder
• hoarseness
• blurred vision
• chills
• urinary tract infection
• blood in the urine
• painful urination
• sudden collapse of a lung
• heart becomes less effective at pumping blood (cardiac dysfunction)
• excessive sweating
• atypical prickling or crawling sensations on the skin
• sore mouth or mouth ulcers
• blood clot in your body (you might feel chest pain, shortness of breath, leg pain, and swelling of the legs/feet). Such blood clots can break off and travel to your lungs which may be life-threatening or even fatal
• muscle spasms

Common side effects that may show up in your blood or urine tests:

• a decrease in the number of cells involved in blood clotting (thrombocytopenia)
• low white blood cell count (neutropenia, leucopenia, lymphopenia)
• protein in urine
• increase in bilirubin (a substance produced by the liver)
• decrease in albumin (a protein found in the blood)
• increase in lipase (an enzyme from the pancreas)
• increased potassium in the blood

Uncommon side effects—these may affect up to 1 in 100 people:

• stroke
• severe bleeding in digestive tract (stomach and intestine) and brain
• a dangerous rapid fluttering of the heart (Torsades de Pointes)
• hole (perforation) in digestive tract
• abnormal connection between parts of the digestive tract (fistula)
• a sudden and severe rise in blood pressure which may be life-threatening
• liver failure

Other side effects that have occurred at an uncommon rate:

• infections, with or without changes in white blood cells (cells that fight infection)
• inflammation of the pancreas
• separation or tear of the lining of the back part of the eye (retinal detachment or tear). This can result in trouble seeing (blurry or impaired vision).

Other side effects that have occurred rarely—these may affect up to 1 in 1000 people:

• blood clots accompanied by a decrease in red blood cells and cells involved in clotting. These clots may harm organs such as the brain and kidneys.

Side Effects with Unknown Frequency:

• Interstitial lung disease, a form of lung scarring or inflammation, can have a fatal outcome in some cases. If you develop symptoms such as sudden difficulty of breathing associated with cough or fever contact your doctor immediately.
• reversible swelling in the rear part of the brain that can be associated with high blood pressure and can lead to headache, loss of speech or vision, abnormal drowsiness, confusion and/or seizure (Posterior Reversible Encephalopathy Syndrome or Reversible Posterior Leukoencephalopathy Syndrome)

Tell your doctor or pharmacist if you are taking, or have recently taken any other medicines including any medicines you bought without a prescription. This includes herbal medicines.

Some medicines may affect the way VOTRIENT works or VOTRIENT may affect how other medicines work. These include:

• clarithromycin, ketoconazole, itraconazole, telithromycin, voriconazole (used to treat infections)
• atazanavir, indinavir, nelfinavir, ritonavir, saquinavir (used to treat HIV)
• dextromethorphan (used in cough medicines)
• simvastatin and possibly other statins (used to treat high cholesterol levels)
• medicines that reduce stomach acid (e.g. esomeprazole, ranitidine, magnesium hydroxide)

Also, the following list includes some, but not all, of the drugs that may interact with VOTRIENT to affect the electrical activity of your heart:

• Antiarrhythmics (drugs that stabilize the heart rhythm function, such as quinidine, procainamide, amiodarone, sotalol, etc.)
• Antidepressants (mood disorder drugs)
• Antipsychotics (drugs used to stabilize thinking and behaviour)
• Opioids (e.g. methadone)
• Macrolide antibiotics (such as erythromycin, clarithromycin)
• Fluoroquinolone antibiotics (such as moxifloxacin, levofloxacin, ciprofloxacin)
• Antifungals (such as fluconazole, voriconazole)
• Antimalarials (e.g. quinine)
• Antinauseants (e.g. granisetron, ondansetron, dolasetron)
• Anti-asthmatics (e.g. salmeterol, formoterol)
• Tacrolimus (used after organ transplant to prevent rejection)
• Certain anticancer treatments (e.g. sunitinib, nilotinib, lapatinib, sorafenib, vorinostat)

VOTRIENT is affected by food intake. You should not drink grapefruit juice or eat grapefruit while you are being treated with VOTRIENT as this may increase the chance of side effects.

Always take VOTRIENT exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Usual dose:

The usual dose is 800 mg VOTRIENT, taken once a day.

Do not take more than 800 mg VOTRIENT a day.

Swallow the tablets whole with water, one after the other, at about the same time each day. Do not break or crush the tablets as it affects the way the medicine is absorbed and may increase the chance of side effects.

It is important that you take VOTRIENT either at least one hour before or at least two hours after food.

Depending on your response to treatment, your doctor may recommend adjusting your dose or temporarily stopping your treatment.

Overdose:

If you have accidentally taken more VOTRIENT tablets than you should, contact your doctor, or poison control centre, or go to the emergency room of the nearest hospital even if there are no symptoms.

Missed dose:

If you forget to take VOTRIENT, do not take a double dose to make up for a missed dose. Take the next dose at the scheduled time.