Votrient

Votrient is a prescription medication used to treat kidney cancer and soft tissue sarcoma. Votrient belongs to a group of drugs called kinase inhibitors which work by slowing or stopping the growth of cancer cells.

This medication comes in tablet form and is taken once daily, on an empty stomach.

Common side effects of Votrient include diarrhea, change in hair color, nausea, and vomiting.

• Glaxo SmithKline Pharmaceuticals

• GlaxoSmithKline LLC

Votrient may cause serious side effects including. See “Drug Precautions”

The most common side effects in people who take Votrient include:

• diarrhea
• change in hair color
• nausea or vomiting
• loss of appetite

Other common side effects in people with advanced soft tissue sarcoma who take Votrient include:

• feeling tired
• decreased weight
• tumor pain
• muscle or bone pain
• headache
• taste changes
• trouble breathing
• change in skin color

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Votrient. For more information, ask your healthcare provider or pharmacist.

Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Votrient may affect the way other medicines work and other medicines may affect how Votrient works.

Especially, tell your healthcare provider if you:

• take medicines that can affect how your liver enzymes work such as:
  • certain antibiotics (used to treat infections)
  • certain medicines used to treat HIV
  • certain medicines used to treat depression
  • medicines used to treat irregular heart beats
• take a medicine that contains simvastatin to treat high cholesterol levels
• drink grapefruit juice

Ask your healthcare provider if you are not sure if your medicine is one that is listed above.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

Take Votrient exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. 

Oral:

The recommended starting dose of Votrient is 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). The dose of Votrient should not exceed 800 mg.

If you take too much Votrient, call your local Poison Control Center or seek emergency medical attention right away.

You should not use pazopanib if you are allergic to it, or if you have severe liver disease.

To make sure pazopanib is safe for you, tell your doctor if you have ever had:

• liver disease;

• heart disease, heart rhythm disorder, long QT syndrome;

• high blood pressure;

• a blood clot or stroke;

• a thyroid disorder;

• headaches, seizures, or vision problems;

• a perforation (a hole or tear) in your stomach or intestines;

• a fistula (an abnormal passageway) within your stomach or intestines;

• stomach or intestinal bleeding within the past 6 months; or

• a surgery within the past 7 days.

Do not use pazopanib if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 2 weeks after your last dose.

You may need to have a negative pregnancy test before starting this treatment.

It is not known whether pazopanib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using pazopanib, and for at least 2 weeks after your last dose.

Renal Cell Carcinoma

Treatment of advanced renal cell carcinoma.1 2

Contraindications

• No known contraindications.1

Warnings/Precautions

Warnings

Severe or fatal hepatotoxicity, manifested as increases in concentrations of aminotransferases (ALT, AST) and bilirubin, reported.1 Most (92.5%) cases of aminotransferase elevations (of any grade) occurred during first 18 weeks of therapy.1

Because pazopanib inhibits UGT1A1 (an enzyme that catalyzes the glucuronidation of bilirubin for elimination), mild elevations in indirect (unconjugated) bilirubin may occur in patients with deficient glucuronidation of bilirubin (i.e., Gilbert's syndrome).1 8

Perform liver function tests prior to initiation of therapy, at least once every 4 weeks for at least the first 4 months or as clinically indicated, and periodically thereafter.1

If hepatotoxicity occurs, interrupt therapy, reduce dosage, or discontinue pazopanib permanently.1 (See Hepatotoxicity under Dosage and Administration.)

Other Warnings and Precautions

Prolongation of QT interval and torsades de pointes reported.1

Use with caution in patients with history of QT interval prolongation, patients receiving antiarrhythmic agents or other drugs known to cause prolongation of the QT interval, and patients with relevant preexisting cardiac disease.1

Monitor ECG prior to initiation of pazopanib and periodically during therapy; maintain serum electrolytes (e.g., calcium, magnesium, potassium) within normal range.1

Hemorrhage, sometimes severe or fatal, reported.1 Most common hemorrhagic events reported include hematuria, epistaxis, hemoptysis, and rectal hemorrhage; severe hemorrhagic events reported include pulmonary, GI, GU, and cerebral/intracranial hemorrhage.1

Not evaluated in patients with history of hemoptysis or patients with cerebral or GI hemorrhage within the past 6 months; avoid use in such patients.1

Arterial thromboembolic events (e.g., myocardial infarction/ischemia, angina, cerebrovascular accident, TIA, ischemic stroke), sometimes severe or fatal, reported.1

Use with caution in patients who are at increased risk or who have a history of arterial thromboembolic events.1 Not evaluated in patients with history of an arterial thromboembolic event within the past 6 months; avoid use in such patients.1

GI perforation or fistula, sometimes fatal, reported.1

Use with caution in patients at increased risk for GI perforation or fistula formation.1

Monitor for manifestations of GI perforation or fistula formation during therapy.1

Hypertension (SBP ≥150 mm Hg or DBP ≥100 mm Hg) reported.1 Most (88%) cases occurred during first 18 weeks of therapy.1 Majority of cases were managed with antihypertensive therapy or by reduction in pazopanib dosage.1 Hypertensive crisis reported rarely.1

Monitor BP and treat hypertension with standard antihypertensive therapy as needed.1 If hypertension persists despite use of antihypertensive therapy, reduce pazopanib dosage1 (i.e., by 400 mg daily initially, then by 200 mg daily, depending on individual patient tolerability).15 If hypertension is severe or persists despite use of antihypertensive therapy and pazopanib dosage reduction, discontinue pazopanib.1

Effect on wound healing not established.1

Inhibitors of vascular endothelial growth factor receptor (VEGFR), including pazopanib, may impair wound healing; discontinue pazopanib ≥7 days prior to scheduled surgery.1 Decision to resume therapy should be based on clinical assessment of adequacy of wound healing.1

Discontinue pazopanib if wound dehiscence occurs.1

Hypothyroidism reported.1

Proactive monitoring of thyroid function tests is recommended.1

Proteinuria reported.1

Perform urinalysis prior to initiation of pazopanib and periodically during therapy; discontinue pazopanib if grade 4 proteinuria occurs.1

May cause fetal harm; teratogenicity, embryotoxicity, fetotoxicity, and abortifacient effects demonstrated in animals.1 Avoid pregnancy during therapy.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1

Monitor liver function tests, ECG, electrolytes, BP, and urinalysis prior to initiation of pazopanib and periodically during therapy.1 Proactive monitoring of thyroid function tests is recommended.1

Specific Populations

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Not known whether pazopanib is distributed into human milk.1 Discontinue nursing or the drug.1

Safety and efficacy not established in children <18 years of age.1

No substantial differences in safety and efficacy relative to younger patients, but increased sensitivity cannot be ruled out.1 Patients >60 years of age may be at greater risk of hepatotoxicity (i.e., serum ALT concentration >3 times ULN).1

Decreased pazopanib clearance in patients with moderate hepatic impairment (total serum bilirubin concentration >1.5 times but ≤3 times ULN and any concentration of ALT15 ); dosage reduction necessary.1 (See Hepatic Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Safety and pharmacokinetics not established in patients with severe hepatic impairment; use not recommended.1

Renal impairment unlikely to affect pharmacokinetics (e.g., exposure) of pazopanib; no dosage adjustment necessary in patients with renal impairment.1 (See Special Populations under Pharmacokinetics.)

Pharmacokinetic profile not established in patients with severe renal impairment (Clcr <30 mL/minute) or in patients undergoing peritoneal dialysis or hemodialysis.1

Common Adverse Effects

Diarrhea,1 hypertension,1 hair color changes (depigmentation),1 nausea,1 anorexia,1 vomiting,1 fatigue,1 asthenia,1 abdominal pain,1 headache.1

Laboratory abnormalities: Increased ALT,1 AST,1 and bilirubin1 concentrations; increased or decreased glucose concentrations;1 cytopenias (leukopenia,1 neutropenia,1 thrombocytopenia,1 lymphocytopenia1 ); decreased sodium,1 magnesium,1 and phosphorus1 concentrations.

Storage

Oral

25°C (may be exposed to 15–30°C).1

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of pazopanib in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of pazopanib in the elderly. However, elderly patients are more likely to have unwanted effects (eg, decreased appetite, high blood pressure, tiredness) and age-related liver problems, which may require caution and an adjustment in the dose for patients receiving pazopanib.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Atazanavir
• Bepridil
• Boceprevir
• Cisapride
• Cobicistat
• Dronedarone
• Fluconazole
• Ketoconazole
• Mesoridazine
• Nelfinavir
• Pimozide
• Piperaquine
• Posaconazole
• Saquinavir
• Sparfloxacin
• Telaprevir
• Terfenadine
• Thioridazine
• Tipranavir
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Alfuzosin
• Aluminum Carbonate, Basic
• Aluminum Hydroxide
• Aluminum Phosphate
• Amiodarone
• Amitriptyline
• Amoxapine
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Astemizole
• Azithromycin
• Bedaquiline
• Buserelin
• Calcium Carbonate
• Carbamazepine
• Ceritinib
• Chloroquine
• Chlorpromazine
• Cimetidine
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Dabrafenib
• Dasabuvir
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dexlansoprazole
• Dihydroergotamine
• Dihydroxyaluminum Aminoacetate
• Dihydroxyaluminum Sodium Carbonate
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Droperidol
• Ebastine
• Efavirenz
• Eliglustat
• Enzalutamide
• Ergotamine
• Eribulin
• Erythromycin
• Escitalopram
• Esomeprazole
• Famotidine
• Felbamate
• Fentanyl
• Fingolimod
• Flecainide
• Fluoxetine
• Foscarnet
• Fosphenytoin
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Idelalisib
• Iloperidone
• Imipramine
• Indinavir
• Itraconazole
• Ivabradine
• Lansoprazole
• Lapatinib
• Leuprolide
• Levofloxacin
• Lumefantrine
• Magaldrate
• Magnesium Carbonate
• Magnesium Hydroxide
• Magnesium Oxide
• Magnesium Trisilicate
• Mefloquine
• Methadone
• Metronidazole
• Mifepristone
• Mizolastine
• Moxifloxacin
• Nafarelin
• Nefazodone
• Nilotinib
• Nizatidine
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olanzapine
• Omeprazole
• Ondansetron
• Paclitaxel
• Paliperidone
• Panobinostat
• Pantoprazole
• Paroxetine
• Pasireotide
• Pentamidine
• Perphenazine
• Phenytoin
• Pimavanserin
• Pipamperone
• Pitolisant
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Rabeprazole
• Ranitidine
• Ranolazine
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Rilpivirine
• Risperidone
• Ritonavir
• Sertindole
• Sevoflurane
• Simvastatin
• Sirolimus
• Sodium Bicarbonate
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• St John's Wort
• Sulpiride
• Sunitinib
• Tacrolimus
• Tamoxifen
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Tolterodine
• Toremifene
• Trazodone
• Trifluoperazine
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vinflunine
• Voriconazole
• Vorinostat
• Zuclopenthixol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• food
• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Angina (severe chest pain), history of or
• Blood clotting problems (eg, pulmonary embolism, venous thrombosis), history of or
• Congestive heart failure or
• Gilbert syndrome (a genetic liver disease) or
• Heart attack, history of or
• Heart disease or
• Heart rhythm problems (eg, QT prolongation), history of or
• Hypertension (high blood pressure) or
• Hypothyroidism (underactive thyroid) or
• Lung problems (eg, interstitial lung disease, pneumonitis) or
• Stomach or bowel problems (eg, fistula, perforation, tear), history of or
• Stroke, history of or
• Transient ischemic attack, history of—Use with caution. May make these conditions worse.

• Infection—May decrease your body's ability to fight an infection.

• Liver disease, moderate—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• chest pain
• chills
• clay colored stools
• cloudy urine
• constipation
• cough
• coughing up blood
• dark urine
• decreased appetite
• depressed mood
• difficulty with breathing or swallowing
• dizziness
• dry skin and hair
• feeling cold
• fever
• hair loss
• headache
• hoarseness or husky voice
• increased menstrual flow or vaginal bleeding
• itching, skin rash
• loss of appetite
• lower back or side pain
• muscle cramps and stiffness
• nausea and vomiting
• nervousness
• nosebleeds
• painful or difficult urination
• pale skin
• paralysis
• pinpoint red spots on the skin
• pounding in the ears
• prolonged bleeding from cuts
• red or black, tarry stools
• red or dark brown urine
• redness, swelling, or pain of the skin
• scaling of the skin on the hands and feet
• slow or fast heartbeat
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stomach pain or tenderness
• swelling of the feet or lower legs
• swollen glands
• tingling of the hands and feet
• ulceration of the skin
• unusual bleeding or bruising
• unusual tiredness or weakness
• weight gain
• yellow eyes or skin

• Bleeding from the rectum or bloody stools
• bloody nose
• chest discomfort
• confusion
• fainting
• irregular or slow heart rate
• numbness or tingling in the face, arms, or legs
• pain or discomfort in the shoulders, arms, jaw, back, or neck
• sweating
• swelling or puffiness of the face
• trouble speaking, thinking, or walking

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Change in hair color
• change in taste
• decreased weight
• diarrhea
• hair loss
• lack or loss of strength
• loss of taste
• thinning of the hair
• weight loss

• Belching
• heartburn
• indigestion
• stomach discomfort, upset, or pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If you have an allergy to pazopanib or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have liver disease.
• If you are taking any of these drugs: Cimetidine, dexlansoprazole, esomeprazole, famotidine, lansoprazole, nizatidine, omeprazole, pantoprazole, rabeprazole, or ranitidine.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with Votrient, like certain drugs that are used for HIV, infections, or seizures. There are many drugs that must not be taken with this medicine.
• If you are breast-feeding. Do not breast-feed while you take Votrient and for 2 weeks after your last dose.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Votrient with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Votrient (pazopanib), please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Votrient. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Votrient.

Review Date: October 4, 2017

Votrient® is indicated for the treatment of patients with advanced renal cell carcinoma (RCC).

Votrient is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy.

Limitations of Use: The efficacy of Votrient for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated.

      Recommended Dosing

The recommended starting dose of Votrient is 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal) [see Clinical Pharmacology (12.3)]. The dose of Votrient should not exceed 800 mg.

Do not crush tablets due to the potential for increased rate of absorption which may affect systemic exposure [see Clinical Pharmacology (12.3)].

If a dose is missed, it should not be taken if it is less than 12 hours until the next dose.

      Dose Modification Guidelines

In RCC, the initial dose reduction should be 400 mg, and additional dose decrease or increase should be in 200-mg steps based on individual tolerability.

In STS, a decrease or increase should be in 200-mg steps based on individual tolerability.

Hepatic Impairment: No dose adjustment is required in patients with mild hepatic impairment. In patients with moderate hepatic impairment, alternatives to Votrient should be considered. If Votrient is used in patients with moderate hepatic impairment, the dose should be reduced to 200 mg per day. Votrient is not recommended in patients with severe hepatic impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Concomitant Strong CYP3A4 Inhibitors: The concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin) increases pazopanib concentrations and should be avoided. Consider an alternate concomitant medication with no or minimal potential to inhibit CYP3A4. If coadministration of a strong CYP3A4 inhibitor is warranted, reduce the dose of Votrient to 400 mg. Further dose reductions may be needed if adverse effects occur during therapy [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Concomitant Strong CYP3A4 Inducer: The concomitant use of strong CYP3A4 inducers (e.g., rifampin) may decrease pazopanib concentrations and should be avoided. Consider an alternate concomitant medication with no or minimal enzyme induction potential. Votrient should not be used in patients who cannot avoid chronic use of strong CYP3A4 inducers [see Drug Interactions (7.1)].

Votrient (pazopanib) is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Votrient is used to treat advanced renal cell carcinoma (kidney cancer).

Votrient is also used to treat soft tissue sarcoma (a tumor that can develop in or around muscles, tendons, joints, organs, or blood vessels).

Votrient is usually given after other cancer medications have been tried without successful treatment of soft tissue sarcoma.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Applies to pazopanib: oral tablet

Along with its needed effects, pazopanib (the active ingredient contained in Votrient) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking pazopanib:

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• chest pain
• chills
• clay colored stools
• cloudy urine
• constipation
• cough
• coughing up blood
• dark urine
• decreased appetite
• depressed mood
• difficulty with breathing or swallowing
• dizziness
• dry skin and hair
• feeling cold
• fever
• hair loss
• headache
• hoarseness or husky voice
• increased menstrual flow or vaginal bleeding
• itching, skin rash
• loss of appetite
• lower back or side pain
• muscle cramps and stiffness
• nausea and vomiting
• nervousness
• nosebleeds
• painful or difficult urination
• pale skin
• paralysis
• pinpoint red spots on the skin
• pounding in the ears
• prolonged bleeding from cuts
• red or black, tarry stools
• red or dark brown urine
• redness, swelling, or pain of the skin
• scaling of the skin on the hands and feet
• slow or fast heartbeat
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stomach pain or tenderness
• swelling of the feet or lower legs
• swollen glands
• tingling of the hands and feet
• ulceration of the skin
• unusual bleeding or bruising
• unusual tiredness or weakness
• weight gain
• yellow eyes or skin

• Bleeding from the rectum or bloody stools
• bloody nose
• chest discomfort
• confusion
• fainting
• irregular or slow heart rate
• numbness or tingling in the face, arms, or legs
• pain or discomfort in the shoulders, arms, jaw, back, or neck
• sweating
• swelling or puffiness of the face
• trouble speaking, thinking, or walking

Some side effects of pazopanib may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Change in hair color
• change in taste
• decreased weight
• diarrhea
• hair loss
• lack or loss of strength
• loss of taste
• thinning of the hair
• weight loss

• Belching
• heartburn
• indigestion
• stomach discomfort, upset, or pain

Votrient can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Food interactions

You shouldn’t eat grapefruit or drink grapefruit juice while you’re taking Votrient. Grapefruit can make it harder for your body to process this drug. This may increase your risk of side effects.

Medications that might interact with this drug

Do not take these drugs with Votrient. When used with Votrient, these drugs can cause dangerous effects in your body. Examples of these drugs include:

• Ketoconazole, ritonavir, and clarithromycin
  • These drugs can increase the amount of Votrient in your body. This may increase your risk of side effects from Votrient. Tell your doctor if you take any of these drugs before you use Votrient.
• Rifampin
  • This drug can decrease the amount of Votrient in your body. This means that Votrient may not work as well. You shouldn’t use Votrient if you need to take rifampin.
• Amiodarone, atorvastatin, carvedilol, tamoxifen, and verapamil
  • These drugs may increase the amount of Votrient in your body. This raises your risk of side effects from Votrient.

Side effects from other drugs: Taking Votrient with certain medications raises your risk of side effects from these drugs. Examples of these drugs include:

• Simvastatin
  • Taking these drugs together may increase your liver enzymes. Your doctor may switch you to another drug or have you stop taking simvastatin.
• Carbamazepine, cyclosporine, sirolimus, tacrolimus, or warfarin
  • Votrient may increase the amount of these drugs in your body. This could cause more side effects from these drugs.

When Votrient is less effective: When Votrient is used with certain drugs, it may not work as well to treat your condition. This is because the amount of Votrient in your body may be decreased. Examples of these drugs include:

• Drugs that increase the pH of your stomach, such as proton pump inhibitors, H2 receptor antagonists, and antacids
  • Examples of these drugs include omeprazole, lansoprazole, famotidine, ranitidine, and Tums.
  • These drugs may cause Votrient to be less effective. If you’re taking a proton pump inhibitor or H2 receptor antagonist, your doctor may switch you to an antacid. You should take the antacid and Votrient several hours apart. 

People with liver problems

If you have liver problems or a history of liver disease you may not be able to take this drug. This medication can decrease your liver function. This can make your liver problems worse. Ask your doctor if this drug is safe for you.

People with heart disease

This drug can lead to heart rhythm problems. These include QT prolongation and torsade de pointes. If you have a history of QT prolongation, heart rhythm problems, or heart disease, or you’re at higher risk of QT prolongation. You’re also at higher risk if you’re taking drugs that can affect heart rhythm. Ask your doctor if this drug is safe for you.

People with plans to have surgery

Tell your doctor about your plans to have surgery. You’ll need to stop taking this drug at least 7 days before your procedure. This medication may affect your healing after surgery.

Pregnant women

This drug is a category D pregnancy drug. That means two things:

1. Research in humans has shown adverse effects to the fetus when the mother takes the drug.
2. This drug should only be used during pregnancy in serious cases where it's needed to treat a dangerous condition in the mother.

Talk to your doctor if you’re pregnant or plan to become pregnant. Ask your doctor to tell you about the specific harm that may be done to the fetus. This drug should be only used if the potential risk to the fetus is acceptable given the drug’s potential benefit.

Women who are breast-feeding

This drug may pass into breast milk and cause side effects in a child who is breastfed.

Talk to your doctor about breastfeeding your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

If you’re over the age of 65 years, you may be at higher risk of developing severe liver problems while you’re on this drug.

For children

This medication hasn’t been studied in children. It shouldn’t be used in people younger than 18 years.

When to call the doctor

Call your doctor if you need to have surgery. Call your doctor right away if you become pregnant while taking this drug.

Allergies

This drug can cause a severe allergic reaction. Symptoms can include:

• trouble breathing
• swelling of your throat or tongue

If you have an allergic reaction, call your doctor or local poison control center right away. If your symptoms are severe, call 9-1-1 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).