Sunitinib is a medication used in the treatment of certain types of cancer. It belongs to a class of drugs known as tyrosine kinase inhibitors (TKIs). Sunitinib works by inhibiting the activity of specific proteins called tyrosine kinases, which are involved in the growth and spread of cancer cells.

Sunitinib is primarily used in the treatment of advanced renal cell carcinoma (a type of kidney cancer) and gastrointestinal stromal tumors (GISTs), a rare type of cancer that affects the digestive tract. It may also be prescribed for other types of cancer, such as pancreatic neuroendocrine tumors and advanced soft tissue sarcoma.

Sunitinib (Sutent) Uses:

• Gastrointestinal stromal tumor:
  • Sunitinib is approved for the treatment of advanced GIST after disease progression on or intolerance to imatinib. It has shown efficacy in controlling the growth of GIST tumors and prolonging progression-free survival in patients who have become resistant to or cannot tolerate imatinib.
• Advanced pancreatic neuroendocrine tumors:
  • Treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with non-resectable locally advanced or metastatic disease.
• Renal cell carcinoma:
  • Adjuvant treatment of adult patients at high risk of recurrent renal cell carcinoma (RCC) after nephrectomy;
  • Treatment of advanced RCC.
• Off Label Use of Sunitinib in Adult
  • Thyroid cancer;
  • Soft tissue sarcoma (non-GIST)

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Sunitinib (Sutent) Dose in Adults

Sunitinib (Sutent) Dose in the treatment of gastrointestinal stromal tumor (GIST):

Sunitinib Dosing for Gastrointestinal Stromal Tumor (GIST):

• Standard Dosing (Demetri 2006):
  • Take Sunitinib orally (by mouth).
  • The recommended dose is 50 mg once daily.
  • Treatment is given in a 6-week cycle.
  • For the first 4 weeks of the cycle, take the medication daily.
  • After the initial 4 weeks, take a break for 2 weeks (no medication).
  • Repeat the cycle with 4 weeks on and 2 weeks off.
• Off-Label Dosing for GIST (George 2009a):
  • This dosing regimen is not part of the approved label but has been used in clinical practice.
  • Take Sunitinib orally (by mouth).
  • The recommended dose is 37.5 mg once daily.
  • Continuous daily dosing is followed without any treatment breaks.

Please note that these dosing regimens are based on studies by Demetri in 2006 and George in 2009.

Sunitinib (Sutent) Dose in the treatment of advanced pancreatic neuroendocrine tumors, (PNET):

Sunitinib Dosing for Advanced Pancreatic Neuroendocrine Tumors (PNET):

• Take Sunitinib orally (by mouth).
• The recommended dose is 37.5 mg once daily.
• Continuous daily dosing is followed without any treatment breaks.
• This dosing regimen was described in a study by Raymond in 2011, and the maximum daily dose used in clinical trials was 50 mg.

Sunitinib (Sutent) Dose in the treatment of the adjuvant treatment of Renal cell cancer:

Sunitinib Dosing for Adjuvant Treatment of Renal Cell Cancer:

• Take Sunitinib orally (by mouth).
• The recommended dose is 50 mg once daily.
• Treatment is given in a 6-week cycle.
• For the first 4 weeks of the cycle, take the medication daily.
• After the initial 4 weeks, take a break for 2 weeks (no medication).
• This cycle is repeated for a total of 9 cycles.
• This dosing regimen was described in a study by Ravaud in 2016.
• The minimum daily dose used in clinical trials was 37.5 mg.

Sunitinib (Sutent) Dose in the Treatment of Advanced Renal cell cancer:

Sunitinib Dosing for Advanced Renal Cell Cancer:

• Take Sunitinib orally (by mouth).
• The recommended dose is 50 mg once daily.
• Treatment is given in a 6-week cycle.
• For the first 4 weeks of the cycle, take the medication daily.
• After the initial 4 weeks, take a break for 2 weeks (no medication).
• This dosing regimen was described in studies conducted by Motzer in 2006a, 2006b, and 2009.

Sunitinib (Sutent) Dose in the treatment of Soft tissue sarcoma, non-GIST (off-label):

Sunitinib Dosing for Soft Tissue Sarcoma (Non-GIST) (Off-label use):

• Take Sunitinib orally (by mouth).
• The recommended dose is 37.5 mg once daily.
• Continuous daily dosing is followed without any treatment breaks.
• This dosing regimen for soft tissue sarcoma, non-GIST, is considered off-label and was mentioned in a study by George in 2009b.

Sunitinib (Sutent) Dose in the treatment of Thyroid cancer, refractory (off-label):

Sunitinib Dosing for Refractory Thyroid Cancer (Off-label use):

• Take Sunitinib orally (by mouth).
• The recommended dose is 50 mg once daily.
• Treatment is given in a 6-week cycle.
• For the first 4 weeks of the cycle, take the medication daily.
• After the initial 4 weeks, take a break for 2 weeks (no medication).
• This dosing regimen for refractory thyroid cancer is considered off-label.
• The dosing information is based on studies conducted by Cohen in 2008 and Ravaud in 2008.

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Dosage Adjustment with Concurrent Strong CYP3A4 Inhibitor:

If you are taking a strong CYP3A4 inhibitor, such as ketoconazole, alongside sunitinib, it is generally advised to avoid concomitant administration. However, if concomitant administration with a strong CYP3A4 inhibitor cannot be avoided, a dose reduction of sunitinib should be considered.

The recommended reduced doses are as follows:

• For Gastrointestinal Stromal Tumor (GIST) and Renal Cell Carcinoma (RCC): A minimum dose of 37.5 mg/day is recommended.
• For Pancreatic Neuroendocrine Tumor (PNET): A minimum dose of 25 mg/day is recommended.

Dosage Adjustment with Concurrent CYP3A4 Inducer:

If you are taking a CYP3A4 inducer, such as rifampin, alongside sunitinib, it is generally advised to avoid concomitant administration. However, if concomitant administration with a CYP3A4 inducer cannot be avoided, a dosage increase of sunitinib may be considered.

The recommended increased doses are as follows:

• For Gastrointestinal Stromal Tumor (GIST) and Renal Cell Carcinoma (RCC): A maximum dose of 87.5 mg/day is recommended.
• For Pancreatic Neuroendocrine Tumor (PNET): A maximum dose of 62.5 mg/day is recommended.

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Use in Children:

Not indicated.

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Sunitinib (Sutent) Pregnancy Risk Category: D

• Sunitinib may harm a developing fetus if given to a pregnant woman, based on studies done in animals and how it works in the body.
• This is because it can interfere with the growth of blood vessels, which are important for fetal development.
• Women who may become pregnant should take a pregnancy test before starting treatment and use effective birth control during treatment and for at least 4 weeks after the last dose.
• Men who have female partners who could become pregnant should also use effective birth control during treatment and for 7 weeks after the last dose.
• Sunitinib may also affect the fertility of both men and women.

Sunitinib can be used during breastfeeding

• The presence of sunitinib in human milk is not well-established.
• As a precautionary measure, the manufacturer does not recommend breastfeeding during treatment with sunitinib and for at least 4 weeks after the last dose.
• This is because there is a possibility of serious adverse reactions in the breastfed infant.
• It is important to consult with your healthcare professional for guidance on alternative feeding options and to weigh the potential risks and benefits in your specific situation.

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Sunitinib (Sutent) Dose in Kidney Disease:

• For patients with a creatinine clearance (CrCl) of at least 30 mL/minute, no initial adjustment of sunitinib dosage is required. However, subsequent dosage adjustments may be necessary based on the safety and tolerance of the medication.
• For patients with a CrCl less than 30 mL/minute (but not on hemodialysis), no initial adjustment of sunitinib dosage is needed. However, subsequent adjustments may be required based on safety and tolerance.
• For patients with end-stage renal disease (ESRD) who are undergoing hemodialysis, no initial adjustment of sunitinib dosage is necessary. However, subsequent dosage increases of up to twofold may be required due to the reduced exposure to the medication (approximately 47%).

Sunitinib (Sutent) Dose in Liver Disease:

Sunitinib in Pre-existing Hepatic Impairment:

• Mild-to-moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment is necessary.
• Severe hepatic impairment (Child-Pugh class C): Sunitinib has not been studied in patients with severe hepatic impairment. Therefore, its use in this population is not recommended.
• The clinical trials excluded patients with ALT or AST levels greater than 2.5 times the upper limit of normal (ULN), or if liver metastases were present, ALT or AST levels greater than 5 times the ULN.

Hepatotoxicity during Treatment:

• If hepatic adverse events reach grade 3 or 4 (severe), treatment with sunitinib should be withheld.
• If the hepatotoxicity does not resolve, sunitinib should be permanently discontinued.
• In patients with severe changes in liver function tests or other signs/symptoms of liver failure, reinitiating sunitinib treatment is not recommended.

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Common Side Effects of Sunitinib (Sutent):

• Cardiovascular:
  • Increased Serum Creatine Kinase
  • Hypertension
  • Peripheral Edema
  • Decreased Left Ventricular Ejection Fraction
  • Chest Pain
• Central Nervous System:
  • Fatigue
  • Headache
  • Insomnia
  • Chills
  • Mouth Pain
  • Depression
  • Dizziness
• Dermatologic:
  • Palmar-Plantar Erythrodysesthesia
  • Skin Discoloration
  • Skin Rash
  • Hair Discoloration
  • Xeroderma
  • Alopecia
  • Erythema Of Skin
  • Pruritus
• Endocrine & Metabolic:
  • Increased Uric Acid
  • Decreased Serum Calcium
  • Decreased Serum Albumin
  • Decreased Serum Phosphate
  • Hypothyroidism
  • Increased Thyroid Stimulating Hormone Level
  • Decreased Serum Potassium
  • Decreased Serum Sodium
  • Decreased Serum Magnesium
  • Weight Loss
  • Increased Serum Calcium
  • Increased Serum Sodium
• Gastrointestinal:
  • Diarrhea
  • Stomatitis
  • Nausea
  • Increased Serum Lipase
  • Anorexia
  • Dysgeusia
  • Abdominal Pain
  • Vomiting
  • Increased Serum Amylase
  • Dyspepsia
  • Constipation
  • Decreased Appetite
  • Flatulence
  • Xerostomia
  • Gastroesophageal Reflux Disease
  • Glossalgia
• Hematologic & Oncologic:
  • Decreased Hemoglobin
  • Lymphocytopenia
  • Hemorrhage
  • Neutropenia
• Hepatic:
  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Increased Serum Bilirubin
  • Increased Indirect Serum Bilirubin
• Local:
  • Localized Edema
• Neuromuscular & Skeletal:
  • Asthenia
  • Limb Pain
  • Arthralgia
  • Back Pain
  • Myalgia
• Renal:
  • Increased Serum Creatinine
• Respiratory:
  • Cough
  • Dyspnea
  • Epistaxis
  • Nasopharyngitis
  • Oropharyngeal Pain
  • Upper Respiratory Tract Infection
• Miscellaneous:
  • Fever

Less Common Side Effects Of Sunitinib (Sutent):

• Cardiovascular:
  • Edema
  • Venous Thromboembolism
  • Cardiac Failure
• Endocrine & Metabolic:
  • Hypoglycemia
  • Hyperglycemia
  • Hyperkalemia
• Gastrointestinal:
  • Hemorrhoids
  • Pancreatitis
• Hematologic & Oncologic:
  • Thrombocytopenia
  • Leukopenia
• Respiratory:
  • Flu-Like Symptoms

Side effects of Sunitinib (Sutent) Frequency Not Defined:

• Gastrointestinal:
  • Aphthous Stomatitis
  • Dry Mucous Membranes
  • Gingival Pain
  • Gingivitis
  • Glossitis
  • Hematemesis
  • Hematochezia
  • Melena
  • Oral Discomfort
  • Oral Mucosal Ulcer
  • Tongue Ulcer
• Genitourinary:
  • Abnormal Uterine Bleeding
• Hematologic & Oncologic:
  • Hematoma
• Respiratory:
  • Hemoptysis

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Contraindications to Sunitinib (Sutent):

Based on the manufacturer's US labeling, there are no specific contraindications listed for sunitinib.

However, in Canadian labeling, two contraindications are mentioned:

• Hypersensitivity to sunitinib or any component of the formulation: If an individual has a known severe allergic reaction or hypersensitivity to sunitinib or any of its ingredients, the use of sunitinib is contraindicated.
• Pregnancy: Sunitinib is contraindicated during pregnancy. Due to the potential for fetal harm based on animal studies and the drug's mechanism of action, sunitinib should not be used by pregnant women.

Warnings and precautions

Cardiovascular events

• Sunitinib may cause heart problems, some of which can be fatal.
• Patients without heart problems should have their heart function checked before starting treatment and be closely monitored for signs of heart failure during treatment.
• Treatment should be stopped if there are signs of heart failure.
• If heart function decreases during treatment, the dose may need to be decreased or treatment may need to be stopped.
• Patients who have had heart events in the past 12 months or have been treated with certain other medications or radiation that can harm the heart were not included in clinical trials, so it is not known if they have an increased risk of heart problems with sunitinib.

Dermatologic toxicities

• Sunitinib can cause severe skin reactions, some of which can be life-threatening. These include erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).
• If you experience progressive skin rash, blisters, or mucosal lesions, it may be a sign of EM, SJS, or TEN. In such cases, sunitinib should be discontinued, and treatment should not be restarted if SJS or TEN is suspected.
• Necrotizing fasciitis, a serious skin infection that can be fatal, has been reported in some patients taking sunitinib.
• This includes cases of perineum necrotizing fasciitis and fasciitis secondary to fistula formation. If necrotizing fasciitis is diagnosed, sunitinib should be discontinued.
• Sunitinib can also cause depigmentation or discoloration of the skin and/or hair. These changes in pigmentation are known side effects of the medication.

Complications of the gastrointestinal tract:

• Sunitinib can cause serious and sometimes fatal problems in the digestive system, including perforation (a hole) in the stomach or intestines.
• This is rare and mostly happens in patients with abdominal cancer.
• In RCC patients, pancreatitis (inflammation of the pancreas) has been observed.

Reaction to skin on the hand-foot:

• Hand-foot skin reaction (HFSR) is a skin problem that can occur with tyrosine kinase inhibitors (TKIs) like sunitinib.
• It is different from the hand-foot syndrome associated with traditional chemotherapy agents.
• HFSR with TKIs causes specific changes on the palms and soles, such as thickened skin with defined rough patches.
• Symptoms may include a burning sensation, altered sensation, tingling, or discomfort in the palms and soles.
• HFSR usually occurs within the first few weeks of treatment.
• Blisters, dry and cracked skin, swelling, redness, peeling, and increased thickness of the skin can also develop, especially in areas under pressure or with frequent bending.

To help manage HFSR and alleviate symptoms, certain measures can be taken:

• Before starting treatment, a pedicure is recommended to remove any thickened areas of skin or calluses that may increase the risk of developing HFSR.
• Avoid vigorous exercise or activities that can put stress on the hands or feet.
• Minimize exposure to hot water, as it can worsen HFSR symptoms.
• Avoid tight-fitting footwear and excessive friction on the affected areas.
• Wear thick cotton gloves or socks and use shoes with padded insoles for added comfort.

Treatment options for HFSR depend on its severity:

• For grade 1 HFSR (mild), moisturizing creams, cotton gloves, and socks worn overnight can help. Keratolytic creams containing urea (20% to 40%) or salicylic acid (6%) can also be used to soften the thickened skin.
• Grade 2 HFSR (moderate) may require the application of a topical steroid like clobetasol ointment twice daily to areas of redness. Topical anaesthetics such as lidocaine (2%) and systemic pain relievers may be used if needed for pain control.
• As acute redness resolves, the affected areas may become thickened and calloused. These areas can be softened with keratolytic agents.

Hemorrhage

• Hemorrhage means bleeding, and it can happen when taking sunitinib. It can be very serious, even fatal.
• Bleeding events have been reported in different parts of the body, such as the gastrointestinal tract, respiratory system, urinary tract, and brain.
• Epistaxis, which means nosebleeds, is the most common bleeding event.
• Gastrointestinal bleeding is the most severe bleeding event.
• In some cases, tumors can cause bleeding, which can happen suddenly and be life-threatening.
• In patients with lung tumors, severe and life-threatening coughing up blood or bleeding in the lungs can occur, which can be fatal. It is important to monitor for signs and symptoms of bleeding, and to get blood tests if needed.

Hepatotoxicity: [US Boxed Warning]

• Hepatotoxicity refers to liver damage, which can be severe and even fatal.
• It has been observed in clinical trials and reported after the drug was approved.
• To monitor liver function, liver function tests should be done before starting treatment, at each treatment cycle, and if there are any signs or symptoms of liver problems.
• Signs of liver failure may include yellowing of the skin or eyes (jaundice), elevated liver enzymes (transaminases), and/or high levels of bilirubin in the blood.
• Liver failure can also be accompanied by symptoms such as confusion (encephalopathy), problems with blood clotting (coagulopathy), and kidney failure.
• If there is grade 3 or 4 hepatotoxicity (severe liver damage), treatment with sunitinib should be stopped temporarily or permanently depending on the situation.
• It is not recommended to restart treatment in patients with severe liver function test changes or other signs of liver failure.
• Sunitinib has not been studied in patients with liver enzyme levels (ALT or AST) more than 2.5 times the upper limit of normal (ULN) or more than 5 times ULN if the increase is due to cancer that has spread to the liver.

Hypertension

• Sunitinib can cause high blood pressure (hypertension).
• If the hypertension becomes severe, treatment with sunitinib should be temporarily stopped until the blood pressure is under control.
• It is important to regularly monitor blood pressure during treatment with sunitinib.
• If the blood pressure is high, appropriate antihypertensive treatment should be started to reduce the risk of heart problems.

Hypoglycemia

• Sunitinib can sometimes cause low blood sugar levels (hypoglycemia), which can lead to symptoms such as dizziness, confusion, or even loss of consciousness.
• In some cases, hospitalization may be required.
• Hypoglycemia is not very common in patients with renal cell cancer or gastrointestinal stromal tumors, but it occurs more frequently (around 10%) in patients with pancreatic neuroendocrine tumors.
• It's important to note that pre-existing problems with glucose regulation are not always present in patients who experience hypoglycemia with pancreatic neuroendocrine tumors.
• Regular monitoring of blood sugar levels is necessary during treatment with sunitinib, and adjustments to antidiabetic medications may be needed to reduce the risk of hypoglycemia.

Osteonecrosis in the jaw:

• Osteonecrosis of the jaw (ONJ), also known as medication-related osteonecrosis of the jaw (MRONJ), is a rare side effect associated with sunitinib.
• The risk of developing ONJ may increase if sunitinib is used together with bisphosphonates or if the patient has existing dental problems.
• According to experts, ONJ has been seen with the use of bisphosphonates, antiresorptive agents, and antiangiogenic agents like sunitinib, which are used for treating osteoporosis or cancer.
• The risk of ONJ is higher when antiangiogenic agents and antiresorptive agents are used together.
• Other factors that increase the risk of MRONJ include dental surgeries like tooth extraction or dental implants, existing dental issues, and the use of corticosteroids.
• It is recommended to have a dental examination and preventive dental care before starting sunitinib and throughout the treatment.
• If possible, invasive dental procedures should be avoided in patients who have received bisphosphonates, especially intravenous (IV) bisphosphonates.
• The experts suggest that if antiangiogenic therapy for cancer is planned, it's best to wait until the patient has optimal dental health.
• If extractions are necessary, antiangiogenetic therapy should be delayed until the extraction site has healed.
• If a patient develops ONJ during treatment, they should seek care from an oral surgeon who specializes in these cases.

Nephrotic Syndrome/proteinuria:

• Proteinuria, which is the presence of excess protein in the urine, and nephrotic syndrome, a condition characterized by high levels of protein in the urine along with other symptoms, have been reported in some patients taking sunitinib.
• In certain cases, these conditions have led to kidney failure and even fatal outcomes.
• It is important to monitor for the development or worsening of proteinuria by conducting urine tests before starting sunitinib and periodically during treatment.
• If proteinuria is detected, further evaluation with a 24-hour urine protein test may be necessary.
• If the amount of protein in the urine is equal to or greater than 3 grams per 24 hours, the treatment should be interrupted, and the dose may need to be reduced.
• If a patient develops nephrotic syndrome or if the proteinuria persists at a level of 3 grams or more despite dose reductions, sunitinib should be discontinued.
• The safety of continuing treatment with sunitinib in patients with moderate to severe proteinuria has not been adequately studied, so careful consideration is required in such cases.

Extension of QTc:

• Sunitinib may make the QTc interval in the heart longer, which can increase the risk of an abnormal heart rhythm called torsade de pointes.
• This risk is higher in patients with a history of QTc prolongation, those taking other medications that can increase sunitinib levels or prolong the QT interval, or those with pre-existing heart disease, slow heart rate, or electrolyte imbalance.
• To help prevent this, doctors may perform a baseline and periodic 12-lead electrocardiogram (ECG) and correct any electrolyte imbalances before and during treatment.

Reversible posterior Leukoencephalopathy Syndrome:

• In rare cases, a condition called reversible posterior leukoencephalopathy syndrome (RPLS) has been reported with sunitinib use, and it can sometimes be fatal.
• Symptoms of RPLS may include confusion, headache, high blood pressure, lethargy, seizures, visual changes, and other neurological problems.
• If these symptoms occur, treatment with sunitinib should be stopped and appropriate medical management should be initiated, including the management of high blood pressure.

Thyroid disorders

• Sunitinib can affect the function of the thyroid gland, leading to thyroid disorders such as hypothyroidism (underactive thyroid), hyperthyroidism (overactive thyroid), or thyroiditis (inflammation of the thyroid).
• Some patients may experience hyperthyroidism followed by hypothyroidism.
• It is important to monitor thyroid function at the beginning of treatment and regularly throughout the course of treatment.
• Patients who are not already receiving thyroid hormone replacement therapy should have their thyroid-stimulating hormone (TSH) levels checked every 4 weeks for the first 4 months, and then every 2 to 3 months.
• Patients who are already taking levothyroxine (thyroid hormone replacement) before starting sunitinib should have their TSH levels monitored every 4 weeks until the levels stabilize and the levothyroxine dose is adjusted accordingly.

Thrombotic microangiopathy

• Thrombotic microangiopathy, which includes conditions like thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, has been observed in some patients treated with sunitinib.
• This can occur when sunitinib is used alone or in combination with bevacizumab.
• Thrombotic microangiopathy can lead to renal failure or even be fatal.
• If thrombotic microangiopathy is detected, sunitinib should be discontinued.
• It's important to note that the effects of this condition may be reversible after discontinuing sunitinib.

Tumor lysis syndrome

• Tumor lysis syndrome (TLS), which can be a serious condition, has been observed in patients receiving sunitinib, particularly those with renal cell carcinoma (RCC) or gastrointestinal stromal tumors (GIST).
• Patients with a high tumor burden before starting treatment are at a higher risk of developing TLS.
• Close monitoring is important in such cases.
• It is essential to address any significant dehydration and manage elevated levels of uric acid before initiating sunitinib treatment.
• Taking these precautions helps reduce the risk and potential complications associated with tumor lysis syndrome.

Wound healing complications

• Impaired wound healing is a potential complication associated with sunitinib treatment.
• If a patient is scheduled to undergo a major surgical procedure, it is advisable to temporarily stop sunitinib treatment.
• The appropriate timing for resuming sunitinib after surgery has not been established, and it should be determined based on the individual's recovery progress as assessed by the healthcare provider.
• The decision to resume sunitinib treatment following a major surgical procedure should be made using clinical judgement and considering the patient's overall condition.

Insufficiency of the renal system:

• Patients with renal insufficiency, specifically with a creatinine clearance (CrCl) of 60 mL/minute or lower, may experience certain effects when receiving sunitinib for the treatment of renal cell cancer.
• Studies have shown an increased incidence of fatigue, thyroid dysfunction, and treatment-induced hypertension in these patients.
• It is important for healthcare providers to monitor these patients closely for these potential side effects and adjust the treatment as necessary to ensure their safety and well-being.

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Sunitinib (Sutent): Drug Interaction

Category C Drugs: Only monitoring is required when these drugs are given in combination with Sunitinib.

 

Sunitinib may increase the risk of hypoglycemia with these drugs:	Androgens (Except Danazol) Antidiabetics Herbs with hypoglycemic properties Maitake Monoamine oxidase inhibitors Pegvisomant Prothionamide Quinolones Salicylates SSRIs
Sunitinib may enhance the QT-prolonging effects of these drugs	Haloperidol QT-prolonging drugs
Sunitinib levels are decreased with	CYP3A4 Inducers (Moderate) Bosentan Deferasirox Erdafitinib Ivosidenib Sarilumab Siltuximab Tocilizumab
Sunitinib levels are increased with	CYP3A4 Inhibitors Aprepitant Clofazimine Duvelisib Fosaprepitant Fosnetupitant Larotrectinib Netupitant Nicardipine Palbociclib Simeprevir
Bone marrow suppression and immunosuppression may occur more frequently with concomitant	Chloramphenicol Clozapine Denosumab Mesalamine Ocrelizumab Promazine Siponimod Trastuzumab
Sunitinib may reduce the diagnostic efficacy of these tests	Coccidioides immitis Skin Test
Sunitinib may decrease the therapeutic effects of these drugs	Pidotimod Tertomotide
Sunitinib may increase the side effects of these drugs	Bisphosphonate derivatives (ONJ)

Risk Category D Drugs: Avoid combining but if not possible, then monitor closely for drug interactions

Sunitinib may increase the immunosuppressive effects of these drugs	Baricitinib	Avoid combining with potent immunosuppressants. If one can not avoid combining these, very strict monitoring is necessary
Sunitinib levels are decreased with	Dabrafenib Echinacea Lorlatinib Mitotane Strong CYP3A4 inducers Enzalutamide	Seek alternative medicines if possible. Monitor closely if not
Sunitinib levels are increased with	CYP3A4 Inhibitors (Moderate) Itraconazole Mifepristone Posaconazole Stiripentol Voriconazole Grapefruit juice	Decrease Sunitinib dose and monitor closely
Bone marrow suppression and immunosuppression may occur more frequently with concomitant	Baricitinib Deferiprone Fingolimod Leflunomide Nivolumab Roflumilast Tofacitinib	Avoid concomitant use if possible; Monitor absolute neutrophil count closely if combined usage is necessary
Sunitinib may decrease the therapeutic effects of these drugs	Sipuleucel-T Nivolumab Inactivated vaccines	Consider reducing the dose of Sunitinib or discontinuing it before starting Sipuleucel-T therapy
Sunitinib may reduce the therapeutic effects of inactivated vaccines	Inactivated vacccines	Administer age-appropriate vaccinations prior to immunosuppressant therapy; Consider revaccination after therapy

Risk Category X: Avoid Combining these drugs with Sunitinib:

Sunitinib may increase the side effects of these drugs:	Natalizumab Bevacizumab (MAHA, Hypertension) Live vaccines (Can administer live vaccines at least 3 months after the last dose.
Sunitinib levels are decreased with	Strong CYP3A4 Inducers St John's Wort Live vaccines
Sunitinib levels are increased with	Strong CYP3A4 Inhibitors Bitter orange Conivaptan Fusidic Acid (Systemic) Grapefruit Juice Idelalisib Saquinavir
Bone marrow suppression and immunosuppression may occur more frequently with concomitant	Cladribine Dipyrone Pimecrolimus Tacrolimus (Topical) Temsirolimus Upadacitinib
Sunitinib may decrease the therapeutic effects of these drugs	Intravesical BCG Live Vaccines (Live vaccines except for monkey pox and smallpox vaccines can be given after 3 months of the last dose.

Monitoring parameters:

Monitoring Recommendations for Sunitinib Treatment:

• Laboratory Testing:
  • CBC with differential and platelets (before to each treatment cycle and if indicated during treatment)
  • Liver function tests (baseline, with each cycle and if clinically indicated)
  • Serum chemistries including magnesium, phosphate, calcium, and potassium (before to each treatment cycle)
  • Blood glucose levels (regularly during and following discontinuation of treatment)
  • Urinalysis (for proteinuria development or worsening)
  • Pregnancy test (before to treatment in females of reproductive potential)

• Cardiac Monitoring:
  • LVEF at baseline (and periodic with cardiac risk factors)
  • Consider ECG (12-lead; baseline and periodic)
  • Monitor blood pressure routinely
  • Monitor for signs/symptoms of heart failure during treatment
  • Consider periodic LVEF evaluations

• Other Monitoring:
  • Consider dental exam before to treatment initiation
  • Monitor for symptoms of hypothyroidism, hyperthyroidism, or thyroiditis
  • Monitor for signs/symptoms of bleeding/hemorrhage, hypoglycemia, and dermatologic toxicity
  • Monitor adherence to treatment regimen

• Thyroid Function Testing (Hamnvik, 2011):
  • Pre-existing levothyroxine therapy: Obtain baseline TSH levels, then monitor every 4 weeks until levels and levothyroxine dose are stable, then monitor every 2 months
  • Without pre-existing thyroid hormone replacement: TSH at baseline, then every 4 weeks for 4 months, then every 2-3 months.

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How to administer Sunitinib (Sutent)?

Sunitinib can be taken with or without food.

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Mechanism of action of Sunitinib (Sutent):

• Sunitinib works as an anticancer medication by targeting and inhibiting several receptor tyrosine kinases.
• These include platelet-derived growth factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), FMS-like tyrosine kinase-3 (FLT3), colony stimulating factor type 1 receptor (CSF-1R), and glial cell-line-derived neurotrophic factor receptor (RET).
• By inhibiting these receptors, sunitinib hinders the growth of tumors and reduces the formation of new blood vessels, known as angiogenesis, which is important for tumor growth and spread.

Distribution:

• Volume of distribution (V/F): 2230 liters

Protein Binding:

• Sunitinib: 95%
• SU12662 (metabolite): 90%

Metabolism:

• Sunitinib is primarily metabolized in the liver.
• The main metabolic pathway involves the enzyme CYP3A4.
• It is converted into an active metabolite called SU12662 (N-desethyl metabolite).

Elimination:

• Terminal elimination half-life:
  • Sunitinib: 40 to 60 hours
  • SU12662: 80 to 110 hours

Time to Peak Concentration in Plasma:

• It takes approximately 6 to 12 hours for sunitinib to reach its highest concentration in the blood plasma.

Excretion:

• Sunitinib is eliminated from the body through both feces (61%) and urine (16%).

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International Brand Names of Sunitinib:

• Sutent
• Sunitix
• Sutene

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Sunitinib Brand Names in Pakistan:

Sunitinib Capsules 25 mg in Pakistan
Sutent	Pfizer Laboratories Ltd.

Sunitinib Capsules 50 mg in Pakistan
Sutent	Pfizer Laboratories Ltd.

Sunitinib Caps 12.5 mg in Pakistan
Sutent	Pfizer Laboratories Ltd.