Sunitinib

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. Tell your doctor or nurse about the missed dose.

Sunitinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Sunitinib is used to treat certain types of advanced or progressive tumors of the digestive system, the pancreas, or the kidneys.

Sunitinib may also be used for purposes not listed in this medication guide.

Sunitinib can cause severe or fatal effects on your liver. You will need frequent blood tests to check your liver function during treatment. Call your doctor if you have any signs of a liver problem, such as upper stomach pain, itching, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

You should not use sunitinib if you are allergic to it.

To make sure sunitinib is safe for you, tell your doctor if you have:

• liver or kidney disease;
• heart disease, high blood pressure, heart rhythm disorder;
• diabetes (your diabetes medicine may need to be adjusted);
• seizures;
• a bleeding or blood-clotting disorder;
• a disorder of your thyroid or adrenal gland;
• a personal or family history of Long QT syndrome; or
• a history of stroke, heart attack, congestive heart failure, a blood clot, or coronary artery disease.

In rare cases, this medicine may cause bone loss (osteonecrosis) in the jaw. Symptoms include jaw pain or numbness, red or swollen gums, loose teeth, or slow healing after dental work.

Osteonecrosis of the jaw may be more likely if you have cancer or received chemotherapy, radiation, or steroids. Other risk factors include blood clotting disorders, anemia (low red blood cells), and a pre existing dental problem.

Do not use sunitinib if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether sunitinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using sunitinib.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Your blood pressure and liver function may need to be tested at the beginning of each 4-week treatment cycle.

Sunitinib is usually taken once per day. Sunitinib is sometimes taken for 4 weeks followed by 2 weeks off the drug. Your doctor will determine how many complete treatment cycles you need based on your condition.

You may take sunitinib with or without food.

Do not crush, chew, or open a sunitinib capsule. Swallow it whole. The medicine from a crushed or broken pill can be dangerous if it gets on your skin. If this occurs, wash your skin with soap and water and rinse thoroughly.

To be sure this medicine is not causing harmful effects, you will need frequent blood and urine tests. Your heart function may also need to be tested with an electrocardiogram (ECG or EKG) on a regular basis, and you may also need frequent dental exams. Do not miss any follow-up visits to your doctor.

If you need surgery or a dental procedure, tell the surgeon or dentist ahead of time that you are using sunitinib. You may need to stop using the medicine for a short time.

Store at room temperature away from moisture and heat.

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

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Sunitinib may be found in some form under the following brand names:

• Sutent

Serious side effects have been reported with sunitinib including the following:

• Liver problems, including death (see Black Box Warning). Tell your healthcare provider right away if you develop any of the following signs and symptoms of liver problems during treatment with sunitinib:
  • itching
  • yellow eyes or skin,
  • dark urine, and
  • pain or discomfort in the right upper stomach area.
    • Your healthcare provider should do blood tests to check your liver function before you start taking sunitinib and during treatment.
• Heart problems. Heart problems may include heart failure and heart muscle problems (cardiomyopathy) that can lead to death. Tell your healthcare provider if you feel very tired, are short of breath, or have swollen feet and ankles. 
• Abnormal heart rhythm changes. Your healthcare provider may do electrocardiograms and blood tests to watch for these problems during your treatment with sunitinib. Tell your healthcare provider if you feel dizzy, faint, or have abnormal heartbeats while taking sunitinib. 
• High blood pressure. Your healthcare provider may check your blood pressure during treatment with sunitinib. Your healthcare provider may prescribe medicine for you to treat high blood pressure, if needed.
• Bleeding sometimes leading to death. Tell your healthcare provider right away if you have any of these symptoms or a serious bleeding problem during treatment with sunitinib.
  • painful, swollen stomach (abdomen) 
  • vomiting blood 
  • black, sticky stools 
  • bloody urine 
  • headache or change in your mental status

• Hormone problems, including thyroid and adrenal gland problems. Your healthcare provider may do tests to check your thyroid and adrenal gland function during sunitinib treatment. Tell your doctor if you have any of the following signs and symptoms during treatment with sunitinib:
  • tiredness that worsens and does not go away 
  • loss of appetite 
  • heat intolerance 
  • feeling nervous or agitated, tremors 
  • sweating 
  • nausea or vomiting 
  • diarrhea 
  • fast heart rate 
  • weight gain or weight loss 
  • feeling depressed 
  • irregular menstrual periods or no menstrual periods 
  • headache 
  • hair loss

Do not take sunitinib if you are allergic to any of its ingredients.

Before taking sunitinib tell your healthcare provider if you:

• have any heart problems 
• have high blood pressure 
• have thyroid problems 
• plan to have surgery 
• have kidney function problems (other than cancer) 
• have liver problems 
• have any bleeding problem 
• have seizures 
• have any other medical conditions 
• if you are having surgery (including dental surgery)
• are pregnant, could be pregnant or plan to become pregnant. Sunitinib may harm an unborn baby. You should not become pregnant while taking sunitinib. Tell your healthcare provider right away if you become pregnant while taking sunitinib. 
• are breastfeeding or plan to breastfeed. You and your healthcare provider should decide if you will take sunitinib or breastfeed. You should not do both.


Tell your healthcare provider about all the medicines you take, including prescription medicines and non-prescription medicines, vitamins, and herbal supplements. Using sunitinib with certain other medicines can cause serious side effects. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. Talk with your healthcare provider before starting any new medicines.

• Take sunitinib exactly the way your healthcare provider tells you. 
• Take sunitinib 1 time each day with or without food. 
• If you take sunitinib for GIST or RCC, you will usually take your medicine for 4 weeks (28 days) and then stop for 2 weeks (14 days). This is 1 cycle of treatment. You will repeat this cycle for as long as your healthcare provider tells you to. 
• If you take sunitinib for pNET, take it one time each day until your healthcare provider tells you to stop. 
• Do not open the sunitinib capsules. 
• Do not drink grapefruit juice or eat grapefruit during your treatment with sunitinib. They may cause you to have too much sunitinib in your body. 
• Your healthcare provider may do blood tests before each cycle of treatment. 
• If you miss a dose, take it as soon as you remember. Do not take it if it is close to your next dose. Just take the next dose at your regular time. Do not take more than 1 dose of sunitinib at a time. Tell your healthcare provider about any missed dose. 
• Call your healthcare provider right away, if you take too much sunitinib.

Take sunitinib exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. Your doctor will determine the best dose for you.

The recommended dose of sunitinib for gastrointestinal stromal tumor (GIST) and advanced renal cell carcinoma (RCC) is one 50 mg oral dose taken once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2). Sunitinib may be taken with or without food.

The recommended dose of sunitinib for pancreatic neuroendocrine tumors (pNET) is 37.5 mg taken orally once daily continuously without a scheduled off-treatment period. Sunitinib may be taken with or without food.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Grapefruit and grapefruit juice may interact with sunitinib and lead to unwanted side effects. Avoid the use of grapefruit products while taking sunitinib.

Your doctor will tell you how much of sunitinib to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to.

sunitinib comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

You may take sunitinib with or without food. Do not open the capsules.

Grapefruit and grapefruit juice may cause you to have too much of sunitinib in the blood. You should not eat grapefruit or drink grapefruit juice while you are taking sunitinib.

Dosing

The dose of sunitinib will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of sunitinib. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For the treatment of GIST and kidney cancer:
    • Adults—50 milligrams (mg) once a day for 4 weeks. This is followed by 2 weeks without medicine. Your doctor may tell you to repeat this cycle.
    • Children—Use and dose must be determined by your doctor.
  • For the treatment of advanced pancreatic cancer or pancreatic neuroendocrine tumor (pNET):
    • Adults—37.5 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 50 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

sunitinib needs to be given on a fixed schedule. If you miss a dose, call your doctor, home health caregiver, or treatment clinic for instructions.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• If you have an allergy to sunitinib 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 are taking St. John's wort. Do not take St. John's wort with sunitinib. This medicine may not work as well.

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 sunitinib with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Dosage modifications should be done in increments or decrements of 12.5 mg; individualize based on safety and tolerability.

Cardiac toxicity:

Ejection fraction <50% and >20% below baseline without evidence of CHF: Interrupt treatment and/or reduce dose.

LV dysfunction with CHF clinical manifestations: Discontinue treatment.

Dermatologic toxicity:

Signs/symptoms of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), including progressive skin rash, often with blisters or mucosal lesions: Discontinue sunitinib; do not restart treatment if SJS or TEN are suspected.

Necrotizing fasciitis: Discontinue sunitinib.

Hypertension, severe: Temporarily interrupt treatment until hypertension is controlled.

Nephrotic syndrome: Discontinue treatment.

Pancreatitis: Discontinue treatment.

Proteinuria:

Urine protein ≥3 g/24 hours: Interrupt treatment and reduce the dose.

Persistent urine protein ≥3 g/24 hours despite dose reductions: Discontinue treatment.

Reversible posterior leukoencephalopathy (RPLS): Temporarily withhold treatment; after resolution, may resume with discretion.

Thrombotic microangiopathy: Discontinue treatment.

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May increase the serum concentration of SUNItinib. Applicable Isavuconazonium considerations are addressed in separate monographs. Management: Consider a reduced dose of sunitinib (minimum of 37.5 mg daily) during concomitant use. Concurrent use with itraconazole is not recommended per itraconazole labeling. Exceptions: Isavuconazonium Sulfate. Consider therapy modification

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bevacizumab: SUNItinib may enhance the adverse/toxic effect of Bevacizumab. Specifically, the risk for a specific form of anemia, microangiopathic hemolytic anemia (MAHA), may be increased. Bevacizumab may enhance the hypertensive effect of SUNItinib. Avoid combination

Bisphosphonate Derivatives: Systemic Angiogenesis Inhibitors may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing sunitinib dose and monitor clinical response and toxicity closely. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dexamethasone (Systemic): May decrease the serum concentration of SUNItinib. Consider therapy modification

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Grapefruit Juice: May increase the serum concentration of SUNItinib. Management: Advise patients to avoid consuming grapefruit and grapefruit juice during sunitinib treatment. Consider therapy modification

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

NiCARdipine: May increase the serum concentration of SUNItinib. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

St John's Wort: May decrease the serum concentration of SUNItinib. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Temsirolimus: May enhance the adverse/toxic effect of SUNItinib. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Commonly reported side effects of sunitinib include: oral candidiasis, asthenia, decreased left ventricular ejection fraction, diarrhea, hypokalemia, lymphocytopenia, mucositis, neutropenia, vomiting, and hypertension. Other side effects include: severe hypertension. See below for a comprehensive list of adverse effects.

50 mg orally once daily on a schedule of 4 weeks on treatment followed by 2 weeks off

Comment: May be taken with or without food.

Uses:
-For the treatment of advanced renal cell carcinoma (RCC)
-For the treatment of gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib.

Administration Advice:
-May be taken with or without food
-Do not open capsules
-If dose is missed, may take as soon as remembered if not too close to next dose. If close to next dose, take next dose at your scheduled time. Do not take more than 1 dose at a time.

General:
Therapy should be initiated by a physician experienced in the administration of anti-cancer agents.

Monitoring:
-Baseline monitoring should include a CBC with platelet count, serum chemistry including phosphate, liver function tests (ALT, AST, bilirubin), assessment of thyroid function, and urinalyses.
-Consider baseline LVEF evaluation in all patients, and an ECG in patients at risk for QT prolongation.
-Repeat CBC, serum chemistry, and liver function tests with each treatment cycle; repeat all other monitoring as clinically indicated.

Patient Advice:
-Advise patient to contact healthcare provider if they experience cardiac symptoms, hypertension, bleeding, skin or mouth reactions including jaw-bone problems, hormone (thyroid or adrenal) problems, or symptoms suggestive of tumor lysis syndrome.
-Advise patient to use effective contraception during therapy; if pregnancy is suspected, patients should seek medical advice and counseling.
-Advise patients with diabetes that it may affect blood glucose levels.