sunitinib

Action and Spectrum

Actions and Spectrum: 

sunitinib is a tyrosine kinase inhibitor (TKI) medication that works by inhibiting the activity of multiple receptor tyrosine kinases involved in tumor growth, angiogenesis (the formation of new blood vessels to supply the tumor), and metastasis (the spread of cancer cells to other parts of the body). 

sunitinib has a broad spectrum of action, and it is approved for the treatment of several types of cancer, including: 

• Advanced renal cell carcinoma (kidney cancer) 
• Gastrointestinal stromal tumors (GIST) 
• Pancreatic neuroendocrine tumors (PNET) 
• Progressive, well-differentiated pancreatic islet cell tumors (pancreatic NET) 

sunitinib’s broad spectrum of action is due to its ability to target multiple tyrosine kinase receptors, including vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), stem cell factor receptor (c-KIT), and fms-like tyrosine kinase 3 (FLT3). 

By inhibiting these receptors, sunitinib reduces the growth and spread of cancer cells, and it also inhibits the formation of new blood vessels that supply tumors with nutrients and oxygen. This makes sunitinib an effective medication for slowing the progression of cancer and improving survival rates in patients with advanced-stage cancer. 

Drug Interaction

Adverse Reaction

Frequency defined: 

>10% 

Dyspepsia  

Altered taste  

Fatigue  

Diarrhea  

Rash 

Vomiting  

Constipation  

Skin discoloration  

Abdominal pain  

Nausea  

Anorexia  

Mucositis/stomatitis  

Dyspnea  

Arthralgia  

Bleeding  

Headache  

Asthenia  

Lymphopenia  

Fever  

Limb pain  

Back pain  

Myalgia  

Cough  

Dry skin  

Hair color changes  

Neutropenia  

Alopecia  

Hand-foot syndrome  

Dehydration  

1-10% 

Venous thrombotic events 

Hemorrhoids 

Pancreatitis 

Flu-like syndrome 

<1% 

Acute renal failure 

Adrenal dysfunction 

Hepatotoxicity 

Black Box Warning

Black Box Warning: 

sunitinib has a black box warning, which is the most serious type of warning that the US Food and Drug Administration (FDA) can require for a prescription medication. The black box warning for sunitinib is related to the risk of severe and sometimes fatal liver toxicity, including liver failure.  

In addition to liver toxicity, the black box warning for sunitinib also includes information about the risk of heart failure, arterial thromboembolic events, and gastrointestinal perforation. Healthcare providers are advised to carefully evaluate the benefits and risks of sunitinib before prescribing it and to closely monitor patients for signs and symptoms of these potential adverse effects. 

Contraindication / Caution

Contraindication/Caution: 

• Hypersensitivity: sunitinib is contraindicated in patients who have a known hypersensitivity to sunitinib or any of its components. 
• Cardiovascular conditions: sunitinib may increase the risk of cardiovascular events, such as heart attack or stroke, especially in patients with preexisting cardiovascular conditions. It is therefore recommended to closely monitor patients with a history of cardiovascular disease or those who are at high risk for developing cardiovascular disease. 
• Liver and kidney function: sunitinib is metabolized in the liver and excreted through the kidneys. Patients with impaired liver or kidney function may require a lower dose of sunitinib or more frequent monitoring. 
• Bleeding: sunitinib may increase the risk of bleeding, especially in patients who are taking anticoagulants or have a history of bleeding disorders. It is recommended to closely monitor patients for signs of bleeding during treatment with sunitinib. 
• Pregnancy and breastfeeding: sunitinib can cause harm to a developing fetus and should not be used during pregnancy. It is also not known whether sunitinib is excreted in breast milk, so women should avoid breastfeeding while taking sunitinib. 

Pregnancy / Lactation

Pregnancy consideration: The drug is toxic and unsafe for pregnant women and the developing fetus.  

Breastfeeding warnings: No data on the excretion of sunitinib in breast milk is available. Because of possible serious effects, women are advised to breastfeed four weeks after the last dose of sunitinib. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no affirmation of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a product in humans; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits. The drug is not for pregnant women. 
• Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

sunitinib is a targeted cancer therapy that belongs to a class of medications known as tyrosine kinase inhibitors (TKIs). It works by inhibiting several different receptors on the surface of cancer cells, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and stem cell factor receptor (KIT). By blocking these receptors, sunitinib can help to slow or stop the growth and spread of cancer cells. 

VEGFR and PDGFR are involved in the formation of new blood vessels that supply nutrients and oxygen to cancer cells. By inhibiting these receptors, sunitinib can reduce the blood supply to tumors, which can help to slow their growth. KIT is a receptor that is involved in the growth and survival of certain types of cancer cells. By inhibiting KIT, sunitinib can help to reduce the growth and spread of these cancer cells. 

Pharmacodynamics: 

The pharmacodynamics of sunitinib are dose-dependent, meaning that higher doses of the medication may have stronger effects on RTK inhibition and tumor growth. However, higher doses may also be associated with increased side effects. 

The pharmacodynamics of sunitinib involve its ability to inhibit key molecular targets involved in tumor growth and angiogenesis, which can help to slow the growth and spread of cancer cells. 

Pharmacokinetics: 

Absorption 

The steady-state concentrations of sunitinib is achieved in 10-14 hours 

The peak plasma concentration is obtained in 6-12 hours 

Distribution 

The volume of distribution is 2,230 L 

The bound protein is 95% for sunitinib and 90% for active metabolites 

Metabolism 

The drug is primarily metabolized to its active metabolite by CYP3A4  

Elimination and Excretion 

The rate of clearance is 34-62 L/hr 

The half-life for single-oral dose is around 40-60 hours. For active metabolites it is 80-110 hours 

The drug is excreted 61% in feces and 16% in urine 

Adminstartion

Administration: 

sunitinib is a prescription medication used to treat several types of cancer, including kidney cancer, gastrointestinal stromal tumors (GIST), and pancreatic neuroendocrine tumors (PNET). It works by inhibiting the growth and spread of cancer cells in the body. 

sunitinib is available in the form of oral capsules and should be taken once a day, preferably at the same time each day. The capsules should be swallowed whole with a glass of water and can be taken with or without food. 

The dosage of sunitinib prescribed will depend on a variety of factors, including the patient’s age, weight, overall health, and the type and stage of their cancer. Your healthcare provider will determine the appropriate dose and duration of treatment for you. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sunitinib (Rx) 

Pronounced: soo-NIT-in-ib 

Why do we use sunitinib? 

sunitinib is a medication used to treat certain types of cancer, including advanced kidney cancer (renal cell carcinoma), gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. sunitinib is a type of targeted therapy that works by inhibiting the activity of certain proteins in cancer cells, which can slow or stop the growth and spread of the cancer. 

sunitinib is typically prescribed after other treatments have been tried or if the cancer has spread to other parts of the body. It is usually taken orally, in the form of capsules, once a day. 

sunitinib is a powerful medication and can cause a range of side effects, including fatigue, nausea, vomiting, diarrhea, and skin discoloration. Patients taking sunitinib should be carefully monitored by their healthcare providers and report any side effects they experience.