Sunitinib

About Sunitinib

• On August 10, 2005, Pfizer submitted Sunitinib malate for FDA review. FDA approved the medicine on January 26, 2006, for gastrointestinal stromal tumors (GIST) and advanced renal cell carcinoma (RCC). 
• Further approval came on May 20, 2011, for rare pancreatic cancer treatment. Finally, on November 16, 2017, the FDA approved the medicine for adjuvant treatment in high-risk recurrent RCC patients.
• Sunitinib is a kinase inhibitor indicated for several conditions. It is used in adult patients with gastrointestinal stromal tumors (GIST) after disease progression or intolerance to imatinib mesylate. Additionally, it is prescribed for adult patients with advanced renal cell carcinoma (RCC). 
• It is also approved for adjuvant treatment in adult patients at high risk of recurrent RCC following nephrectomy. 
• Furthermore, it is indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in adult patients with unresectable locally advanced or metastatic disease.
• Sunitinib  acts as a kinase inhibitor, blocking multiple receptor tyrosine kinases (RTKs) involved in tumor growth, angiogenesis, and metastasis. 
• It targets vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), stem cell factor receptors (KIT), FMSlike tyrosine kinase 3 (FLT3), colony-stimulating factor receptor type 1 (CSF1R), and RET proto-oncogene.
• This action disrupts tumor cell proliferation, angiogenesis, and metastasis, halting cancer progression.

Strength: 

Sunitinib malate capsules are available in strengths of 312.5 mg, 25 mg, 37.5 mg, and 50 mg. 

Recommended Dosage:

Follow your healthcare provider’s instructions precisely for taking the Sunitinib capsule, whether it’s once daily with or without food. Treatment cycles for GIST or RCC typically involve a 4-week on, 2-week off regimen, while for pNET, continue daily until otherwise directed. Avoid grapefruit or grapefruit juice during treatment to prevent increased levels. Regular blood tests are essential to monitor for side effects.

If a dose is missed by less than 12 hours, take it promptly, but if it’s more than 12 hours, skip it and take the next dose as scheduled, informing your healthcare provider of any missed doses. In the event of an accidental overdose, contact your healthcare provider immediately.

The recommended dosage varies depending on the indication:

• For gastrointestinal stromal tumor (GIST) and advanced renal cell carcinoma (RCC), the recommended dose is 50 mg taken orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2) until disease progression or unacceptable toxicity. Sunitinib can be taken with or without food.
• For the adjuvant treatment of RCC, the recommended dose is also 50 mg taken orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2), for nine 6-week cycles. It may be taken with or without food.
• For pancreatic neuroendocrine tumors (pNET), the recommended dose is 37.5 mg taken orally once daily until disease progression or unacceptable toxicity. It can be taken with or without food.

Important:

Dose adjustments for adverse reactions with Sunitinib involve interrupting or modifying doses in 12.5 mg increments or decrements based on individual safety and tolerability. The maximum dose used in the pNET study was 50 mg daily, while the minimum dose in the adjuvant RCC study was 37.5 mg daily. These modifications aim to ensure patient safety and treatment efficacy.

Warnings & Precaution:

• Hepatotoxicity (Fatal liver failure) has occurred in patients treated with the medicine. Monitoring of liver function tests is crucial at baseline, during each treatment cycle, and as clinically indicated. Treatment interruption is advised for Grade 3 or 4 hepatotoxicity, with consideration of discontinuation if resolution is not observed.
• Reports of myocardial ischemia, myocardial infarction, heart failure, and other cardiac complications necessitate vigilant monitoring. Assessment of left ventricular ejection fraction (LVEF) at baseline and periodically during treatment is recommended. Discontinuation of the capsule should be considered for clinical signs of heart failure.
• Close monitoring, including electrocardiograms and electrolyte monitoring as appropriate, is essential for patients at higher risk of QT interval prolongation and Torsade de Pointes.
• Regular blood pressure monitoring is advised for hypertension, with initiation or adjustment of antihypertensive therapy as needed.
• Serial complete blood counts and physical examinations are necessary due to the risk of tumor-related hemorrhage and viscus perforation in patients experiencing hemorrhagic events.
• Monitoring and appropriate treatment are required for Tumor Lysis Syndrome (TLS), especially in patients with renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GIST).
• Discontinuation of the medicine is recommended for Thrombotic Microangiopathy (TMA), necessitating vigilant monitoring due to its potential for renal failure or a fatal outcome. 
• Additionally, regular monitoring of urine protein levels is advised for Proteinuria, with treatment interruption for significant episodes. Immediate discontinuation of the medicine is essential in cases of serious skin reactions like necrotizing fasciitis and Stevens-Johnson syndrome. 
• Careful monitoring and treatment interruption until resolution are necessary for Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Regular monitoring of thyroid function is recommended, with appropriate therapy adjustments as needed for Thyroid Dysfunction. 
• Furthermore, regular blood glucose monitoring is advised for Hypoglycemia, with adjustment of antidiabetic drug doses as necessary. The medicine should be withheld before invasive dental procedures and for developing Osteonecrosis of the Jaw (ONJ) until complete resolution. 
• Likewise, the treatment should be withheld before elective surgery and not resumed until adequate wound healing, with the safety of resuming the medicine after wound healing complications remaining unestablished. 
• Patients should be informed of the potential risk to a fetus and advised to use effective contraception during treatment with the medicine for embryo-fetal toxicity.

Common Sunitinib Side Effects:

•  Fatigue/asthenia
•  Diarrhea
•  Mucositis/stomatitis
•  Nausea
•  Decreased appetite/anorexia
•  Vomiting
•  Abdominal pain
•  Hand-foot syndrome
•  Hypertension
•  Bleeding events
•  Dysgeusia/altered taste
•  Dyspepsia
•  Thrombocytopenia

Use in Specific Population

• Sunitinib, based on animal reproduction studies and its mechanism of action, can potentially cause fetal harm when administered to pregnant women. There is currently no information available regarding the medicine and its metabolites in human milk. 
• Therefore, it is advised that females of reproductive potential use effective contraception during treatment with the medicine and for at least 4 weeks after the last dose. 
• Males with female partners of reproductive potential should also use effective contraception during the treatment and for 7 weeks after the last dose, as indicated by findings in animal reproduction studies. 
• Additionally, the medicine may impair male and female fertility based on animal studies. 
• The safety and effectiveness of the medicine in pediatric patients have not been established. 
• No overall differences in safety or effectiveness were observed between these patients and younger patients. 
• No dose adjustment is required in patients with mild or moderate hepatic impairment. 
• The medicine was not studied in patients with severe hepatic impairment. Regarding renal impairment, no dose adjustment is recommended for patients with mild to severe renal impairment who are not on dialysis, or for patients with end-stage renal disease (ESRD) on hemodialysis. 
• Due to the potential for serious adverse reactions in breastfed infants, women are advised not to breastfeed during treatment with the medicine and for at least 4 weeks after the last dose.

Storage and Handling 

Store Sunitinib capsules within a temperature range of 20°C to 25°C (68°F to 77°F), with excursions allowed between 15°C and 30°C (59°F and 86°F). Properly dispose of any medication that has expired or is no longer required. 

• 2.5 mg capsules, 25 mg, 37.5 mg, and 50 mg in bottles of 28 capsules
• Keep the capsules away from pets and children.