Pazopanib

(pah-zoe-puh-nib)

Trade/Other Name(s): Votrient

Why would this drug be used?

Pazopanib is used to treat kidney cancer and soft tissue sarcoma. It is also being studied for use against other types of cancer.

How does this drug work?

This drug is a type of targeted therapy known as a known as a kinase inhibitor. Kinases are proteins on or near the surface of a cell that transmit signals to the cell's control center. Pazopanib inhibits several kinase proteins (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-A, PDGFR-B, FGFR-1, FGFR-3, Kit, Itk, Lck, and c-Fms). These proteins either prompt tumor cells to grow and divide or help form new blood vessels (angiogenesis) that feed the tumor. By blocking these proteins, pazopanib may help stop the growth of cancer cells.

Before taking this medicine

Tell your doctor…

• If you are allergic to anything, including medicines, dyes, additives, or foods.
• If you have high blood pressure. Pazopanib may raise blood pressure. Your doctor will likely want to monitor this closely during treatment.
• If you have any type of liver disease (including hepatitis). This drug can cause severe liver damage in some people. Your doctor may need to reduce your dose of this drug, and will monitor lab tests of liver function closely while you are on this drug. Some patients with liver problems may not be able to take this drug at all.
• If you have any type of heart disease. Pazopanib can cause problems with the heart, especially in patients with underlying heart problems.
• If you have long Q-T interval or irregular heart rhythm. This drug can make it worse.
• If you have ever had a hole or tear (perforation) in your stomach or intestine, or if you have ever had a fistula (abnormal connection between 2 parts of the intestine).
• If you have had any unusual bleeding in the past 6 months, such as coughing up blood or having blood in your stools. This drug may make bleeding worse, which in some cases may even be life threatening.
• If you are planning to have surgery soon. This drug may affect wound healing, so it should be stopped at least a week before any surgery.
• If you have any other medical conditions such as kidney disease, diabetes, gout, or infections. These conditions may require that your medicine dose, regimen, or timing be changed.
• If you are pregnant, trying to get pregnant, or if there is any chance of pregnancy. This drug can cause problems with the fetus if taken at the time of conception or during pregnancy. Men and women who are taking this drug should use some kind of birth control during and for at least 2 weeks after finishing treatment. It is important to check with your doctor about what kinds of birth control can be used with this medicine. In pregnant women, treatment with this drug should be used only if the potential benefit to the mother outweighs the risk to the fetus.
• If you are breast-feeding. While no studies have been done, this drug may pass into breast milk and affect the baby. Breast-feeding is not recommended during treatment with this drug.
• About any other prescription or over-the-counter medicines you are taking, including vitamins and herbs. In fact, keeping a written list of each of these medicines (including the doses of each and when you take them) with you in case of emergency may help prevent complications if you get sick.

Interactions with other drugs

Certain medicines can interfere with the breakdown (metabolism) of pazopanib, leading to an increase in serious side effects. These include:

• Anti-fungal medications such as ketoconazole, itraconazole, and voriconazole
• Antiviral medications that are used to treat HIV infection, such as atazanavir, saquinavir, ritonavir, amprenavir, indinavir, nelfinavir, and delaviridine
• Antibiotics such as clarithromycin, erythromycin, and telithromycin
• Nefazodone, an antidepressant
• Simvastatin (Zocor) raises the risk of liver damage when used with pazopanib. It is unclear whether other cholesterol-lowering drugs in the statin family such as atorvastatin (Lipitor), lovastatin (Mevacor), pravastatin (Pravachol), or rosuvastatin (Crestor) have similar effects; talk with your doctor or pharmacist

Other drugs can lower blood levels of pazopanib, so that it is less likely to work against the cancer. These are:

• Dexamethasone
• Phenytoin (Dilantin)
• Carbamazepine (Tegretol)
• Phenobarbital
• Rifampin, rifampicin, and rifabutin (used to treat TB and other unusual infections)

St. John's Wort, an herbal supplement, can also decrease pazopanib levels (this would make it less likely to work against the cancer).

Other drugs that affect the heart’s rhythm or electrical impulses, such as amiodorone (Cordarone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn), flecainide (Rhythmol), ibutilide (Corvert), procainamide (Procan, Pronestyl), propafenone (Tambocor), quinidine (Quinidex, Cardioquin), or sotalol (Betapace) can worsen the effects of this drug on the heart.

Interactions with foods

Grapefruit or grapefruit juice may cause the level of pazopanib in your blood to become high, which can lead to increased side effects and toxicity. Avoid grapefruit while you take this medicine.

Do not take pazopanib with food. It affects the way the drug is absorbed.

Tell all the doctors, dentists, nurses, and pharmacists you visit that you are taking this drug.

How is this drug taken or given?

This drug is given in pill form once a day. Tablets should be swallowed whole and not broken or crushed. The most common starting dose is 800 mg (as two 400 mg tablets) once a day. This drug should be taken on an empty stomach, at least an hour before or 2 hours after eating.

Precautions

Pazopanib can cause liver damage, which in some cases may be life threatening. This drug should be used at a lower dose (or not at all) in patients with known liver problems. Lab tests of liver function should be checked before treatment is started, and then again periodically as long as treatment continues. Tell your doctor right away if you notice your skin or the whites of your eyes turning yellow, pain in the right upper part of the belly, or if your urine becomes dark. These can be signs of liver damage.

This drug can cause a heart rhythm problem known as "prolonged QT syndrome," which in some cases may be life threatening. If you have heart problems, your doctor may check your heart rhythm with an EKG (electrocardiogram) before treatment is started and again periodically as long as treatment continues. Call your doctor right away if you notice irregular or fast heartbeat or fainting.

Problems with bleeding from the stomach, lungs, and brain have been seen in some patients taking pazopanib. This bleeding was fatal in a few cases. This drug should not be given to patients who have had recent problems with severe bleeding from these areas. Speak with your doctor before taking any drugs or supplements that might affect your body's ability to stop bleeding, such as aspirin or aspirin-containing medicines, warfarin (Coumadin), or vitamin E. Tell your doctor right away if you have unusual bruising, or bleeding such as nosebleeds, bleeding gums when you brush your teeth, or black, tarry stools.

Patients taking pazopanib have an increased risk of certain problems caused by blood clots, such as heart attack, chest pain, pulmonary embolus (blood clot in the lungs), stroke, and transient ischemic attack (TIA). This drug should be used with caution in patients who already have a high risk of these problems, and it should not be used at all in patients who have had any of these problems recently (within the past 6 months). Get help right away if you have chest pain, trouble breathing, trouble moving or speaking, dizziness, or other serious symptoms.

This drug can cause problems with wound healing and should be stopped at least a week before any planned surgery. This drug can slow the healing of ulcers in the stomach and intestine. This can lead to the ulcer growing through the wall (of the stomach or intestine), a condition called perforation.

Pazopanib can cause high blood pressure. Patients should have normal blood pressure before starting this drug, and blood pressure should be checked regularly while the patient is taking pazopanib. Get help if you have severe chest pain, severe headache, shortness of breath, seizures, or loss of consciousness (passing out)

This drug may cause the thyroid gland to become underactive, a condition called hypothyroidism. Symptoms of hypothyroidism include fatigue and tiredness, weight gain, feeling cold, and constipation. The diagnosis can be made with a simple blood test, and it can easily be treated with medicine. Patients on pazopanib should be watch for signs and symptoms of hypothyroidism.

Pazopanib can cause damage to the kidneys leading to the finding of protein in the urine. The drug should be stopped if this becomes severe.

Rarely, pazopanib can cause holes (perforations) in the digestive tract, which can be life-threatening. Tell your doctor or nurse right away if you have any severe stomach (abdominal) pain, especially if you also have nausea, vomiting, constipation, fever, or any other symptom.

In rare cases, pazopanib can cause the heart to pump less effectively, allowing fluid to back up in the lungs and make it hard to breathe. It can also cause swelling of the feet, ankles and legs, along with sudden weight gain due to fluid buildup.

Possible side effects

Common

• Diarrhea
• Nausea
• Headache
• Changes in hair or skin color
• Low blood counts
• Abnormal blood tests suggesting drug may be affecting the liver (Your doctor will discuss the importance of this finding, if any.)*
• High blood pressure*

Less common

• Abdominal pain
• Vomiting
• Loss of appetite
• Feeling tired
• Feeling weak
• Hair loss (may include body and facial hair)
• Taste disturbance or loss of taste
• Minor bleeding* (such as nosebleed, blood in urine, blood in stool)
• Protein in urine* (a sign of kidney damage)
• Hand-foot syndrome (redness and pain in the palms of the hands and the soles of the feet)

Rare

• Liver failure*
• Hypothyroidism*
• Severe bleeding (from the kidneys/bladder, stomach/intestine, or lungs)*
• Problem with heart rhythm*
• Angina (chest pain)*
• Heart attack*
• Congestive heart failure*
• Stroke*
• Transient ischemic attack (sometimes called a "mini-stroke") *
• Death from liver failure, bleeding, heart attack, blood clots, or other problem

There are some other side effects not listed above that can also occur in some patients. Tell your doctor or nurse if you develop these or any other problems.

FDA approval

Yes - first approved October 2009

Disclaimer: This information does not cover all possible uses, actions, precautions, side effects, or interactions. It is not intended as medical advice, and should not be relied upon as a substitute for talking with your doctor, who is familiar with your medical needs.