Sunitinib

Sunitinib Uses, Dosage, Side Effects, Food Interaction and all others data.

Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases (RTKs).

These include all receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), which play a role in both tumor angiogenesis and tumor cell proliferation. The simultaneous inhibition of these targets therefore reduces tumor vascularization and triggers cancer cell apoptosis and thus results in tumor shrinkage.

Sunitinib also inhibits CD117 (c-KIT), the receptor tyrosine kinase that (when improperly activated by mutation) drives the majority of gastrointestinal stromal cell tumors. It has been recommended as a second-line therapy for patients whose tumors develop mutations in c-KIT that make them resistant to imatinib, or who the cannot tolerate the drug.

In addition, sunitinib binds other receptors. These include: RET, CD114, CD135. The fact that sunitinib targets many different receptors, leads to many of its side effects such as the classic hand-foot syndrome, stomatitis, and other dermatologic toxicities.

Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006.

Trade Name Sunitinib
Availability Prescription only
Generic Sunitinib
Sunitinib Other Names Sunitinib, Sunitinibum
Related Drugs Keytruda, pembrolizumab, fluorouracil, Avastin, imatinib, bevacizumab, Opdivo, Gleevec, gemcitabine, everolimus
Weight 12.5mg, 25mg, 37.5mg, 50mg
Type Oral capsule
Formula C22H27FN4O2
Weight Average: 398.4738
Monoisotopic: 398.211804333
Protein binding

Binding of sunitinib and its primary metabolite to human plasma protein in vitro was 95% and 90%, respectively.

Groups Approved, Investigational
Therapeutic Class Targeted Cancer Therapy
Manufacturer
Available Country United States
Last Updated: September 19, 2023 at 7:00 am
Sunitinib
Sunitinib

Uses

Gastrointestinal Stromal Tumor (GIST): Sunitinib is used for the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate.

Advanced Renal Cell Carcinoma (RCC): Sunitinib is used for the treatment of advanced renal cell carcinoma.

Advanced Pancreatic Neuroendocrine Tumors (pNET): Sunitinib is used for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease.

Sunitinib is also used to associated treatment for these conditions: Advanced Renal Cell Carcinoma, Soft Tissue Sarcoma (STS), Thyroid Cancers, Metastatic Pancreatic Neuroendocrine Tumors, Refractory Gastrointestinal stromal tumor, Unresectable, locally advanced Pancreatic Neuroendocrine Tumors

How Sunitinib works

Sunitinib is a small molecule that inhibits multiple RTKs, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRa and PDGFRb), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.

Dosage

Sunitinib dosage

Recommended Dose For GIST And RCC:The recommended dose of Sunitinib for gastrointestinal stromal tumor (GIST) and advancedrenal 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.

Recommended Dose For pNET: 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.

Dose Modification: Dose interruption and/or dose modification in 12.5 mg increments or decrements is recommended based on individual safety and tolerability. The maximum dose administered in the Phase 3 pNET study was 50 mg daily.

Strong CYP3A4 inhibitors such as ketoconazole may increas e sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential is recommended. A dose reduction for Sunitinib to a minimum of 37.5 mg (GIST and RCC) or 25 mg (pNET) daily should be considered if Sunitinib must be co-administered with a strong CYP3A4 inhibitor

CYP3A4 inducers such as rifampin may decreas e sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme induction potential is recommended. A dose increase for Sunitinib to a maximum of 87.5 mg (GIST and RCC) or 62.5 mg (pNET) daily should be considered if Sunitinib must be co-administered with a CYP3A4 inducer. If dose is increased, the patient should be monitored carefully for toxicity

Side Effects

Fatigue, GI disorders, skin discoloration, rash, palmar-plantar erythrodysesthesia, dry skin, hair color changes, mucosal inflammation, asthenia, dysguesia, anorexia, HTN, neutropenia.

Toxicity

The maximally tolerated dose for rat, mouse, and dog when given orally is greater than 500 mg/kg. The maximally tolerated dose of a non-human primate is greater 1200 mg/kg.

Interaction

Increased plasma cone with strong CYP3A4 inhibitors (eg ketoconazole, ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice). Decreased plasma cone with strong CYP3A4 inducers [eg rifampin, dexamethasone, phenytoin, carbamazepine, phenobarb, St. John's wort (Hypericum perforatum)]. Anticoagulants eg warfarin, acenocoumarol (periodically monitor platelets, prothrombin time/INR & physical exam).

Food Interaction

  • Avoid grapefruit products. Grapefruit may reduce the CYP3A4 metabolism of sunitinib.
  • Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of sunitinib.
  • Take with or without food.

[Moderate] GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during sunitinib therapy may increase the plasma concentrations of sunitinib.

The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of large amounts of grapefruit or grapefruit juice during sunitinib therapy.

Sunitinib Hypertension interaction

[Moderate] The use of sunitinib has been associated with hypertension and it should be used with caution in patients with elevated blood pressure.

Therapy with sunitinib should be withheld in case of severe hypertension and appropriate measures should be taken to correct the blood pressure to acceptable readings.

Close monitoring of blood pressure is recommended.

Volume of Distribution

  • 2230 L (apparent volume of distribution, Vd/F)

Elimination Route

Maximum plasma concentrations (Cmax) of sunitinib are generally observed between 6 and 12 hours (Tmax) following oral administration. Food has no effect on the bioavailability of sunitinib. Sunitinib may be taken with or without food. The pharmacokinetics were similar in healthy volunteers and in the solid tumor patient populations tested, including patients with GIST and RCC.

Half Life

Following administration of a single oral dose in healthy volunteers, the terminal half-lives of sunitinib and its primary active metabolite are approximately 40 to 60 hours and 80 to 110 hours, respectively.

Clearance

  • 34 - 62 L/h [Total oral clearance]

Elimination Route

Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4. Elimination is primarily via feces. In a human mass balance study of [14C]sunitinib, 61% of the dose was eliminated in feces, with renal elimination accounting for 16% of the administered dose.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Contraindication

Hypersensitivity, Renal impairment

Acute Overdose

Treatment of overdose with Sunitinib should consist of general supportive measures. There is no specific antidote for overdosage with Sunitinib. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage. Cases of accidental overdose have been reported; these cases were associated with adverse reactions consistent with the known safety profile of Sunitinib, or without adverse reactions. A case of intentional overdose involving the ingestion of 1,500 mg of Sunitinib in an attempted suicide was reported without adverse reaction. In non-clinical studies mortality was observed following as few as 5 daily doses of 500 mg/kg (3000 mg/m²) in rats. At this dose, signs of toxicity included impaired muscle coordination, head shakes, hypoactivity, ocular discharge, piloerection and gastrointestinal distress. Mortality and similar signs of toxicity were observed at lower doses when administered for longer durations.

Innovators Monograph

You find simplified version here Sunitinib

Sunitinib contains Sunitinib see full prescribing information from innovator Sunitinib Monograph, Sunitinib MSDS, Sunitinib FDA label

FAQ

What is Sunitinib used for?

Sunitinib Sunitinib used for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST).

How safe is Sunitinib?

Individualised Sunitinib therapy is feasible, safe and an effective method to manage toxicity with one of the best efficacy seen for oral vascular endothelial growth factor inhibitors in metastatic renal cell carcinom.

How does Sunitinib work?

By blocking a particular enzyme from working, this medication can slow the growth of cancer cells.

What are the common side effects of Sunitinib?

Common side effects of Sunitinib are include:

  • Fatigue.
  • Diarrhea.
  • Nausea and vomiting.
  • Heartburn.
  • Taste changes.
  • Hypertension (high blood pressure)
  • Low blood counts. ...
  • Skin discoloration (possibly due to the drug color - yellow)

Is Sunitinib safe during pregnancy?

Use should be avoided. If used during pregnancy or if pregnancy occurs, apprise the patient of potential hazard to the fetus. As angiogenesis is a critical component of embryonic and fetal development, this drug is expected to cause fetal harm if administered to pregnant women.

Is Sunitinib safe during breastfeeding?

A decision should be made to discontinue breastfeeding or discontinue the Sunitinib, taking into account the importance of the Sunitinib to the mother.

Can I drink alcohol with Sunitinib?

The drinking of alcohol (in small amounts) does not appear to affect the safety or usefulness of Sunitinib.

How to take Sunitinib?

Sunitinib is usually taken once a day.Take Sunitinib at around the same time every day.

How long can I take Sunitinib?

Sunitinib is taken once every day for 4 weeks (28 days), then it is stopped for 2 weeks (14 days). This is 1 cycle of treatment. This cycle is repeated for as long as your doctor tells you to.

How long does Sunitinib stay in my system?

One dose of Sunitinib takes between 8 and 12 days before most (96%) of it to leave your body. Some of the Sunitinib is broken down by the body into an active metabolite which takes between 16 and 23 days for most (96%) to be removed from the body.

Does Sunitinib cause hair loss?

Hair loss may not be serious but may cause concern.

Who should not take Sunitinib?

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 right-sided upper stomach pain, itching, dark urine, or jaundice (yellowing of the skin or eyes).

What happens if I miss a dose?

Use the medicine as soon as you can, but skip the missed dose if you are more than 12 hours late for the dose. Do not use two doses at one time.

Does Sunitinib cause high blood pressure?

Many patients taking Sunitinib experience hypertension (high blood pressure) as a side effect.

Can Sunitinib cause stomach pain?

Bleeding is common with Sunitinib, but can also cause severe bleeding problems that can lead to death.

Is Sunitinib cytotoxic?

In pancreatic neuroendocrine tumours, sunitinib is taken continuously. Targeted therapies are not cytotoxic and do not require cytotoxic handling precautions.

Can I take overdose of Sunitinib?

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

Is there any food or drink I need to avoid when taking Sunitinib?

Grapefruit and grapefruit juice may interact with Sunitinib and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

How is Sunitinib eliminated from the body??

Sunitinib is primarily eliminated with the feces , with renal elimination accounting for only 16% of the administered dose.

*** Taking medicines without doctor's advice can cause long-term problems.
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