Sunicent50 mg

FDA-Approved Indications

• Advanced Renal Cell Carcinoma (RCC): Sunicent is indicated for the treatment of advanced renal cell carcinoma.
• Adjuvant Treatment of Renal Cell Carcinoma: Sunicent is indicated for the adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy.
• Gastrointestinal Stromal Tumor (GIST): Sunicent is indicated for the treatment of GIST after disease progression on, or intolerance to, imatinib mesylate.
• Pancreatic Neuroendocrine Tumors (pNET): Sunicent is indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease.

Sunicent is used as monotherapy in each of these settings. Use of Sunicent outside these approved settings (off-label) should only occur under specialist oncology supervision.

Each capsule contains Sunitinib (as sunitinib malate) equivalent to 12.5 mg, 25 mg, 37.5 mg, or 50 mg of Sunitinib base.

Sunicent is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor (TKI) used in the treatment of certain advanced cancers, including renal cell carcinoma, gastrointestinal stromal tumor, and pancreatic neuroendocrine tumors. By blocking multiple receptor tyrosine kinases involved in tumor growth and angiogenesis, Sunicent helps slow or stop the growth and spread of susceptible tumors.

Sunicent is a specialist oncology medicine and must only be prescribed and monitored by, or in close consultation with, an oncologist experienced in its use.

Multi-targeted receptor tyrosine kinase inhibitor (antineoplastic agent); Sunicent belongs to this class.

Mechanism of Action

Sunitinib inhibits multiple receptor tyrosine kinases (RTKs), several of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib inhibits vascular endothelial growth factor receptors (VEGFR1, VEGFR2, VEGFR3), platelet-derived growth factor receptors (PDGFR-alpha and PDGFR-beta), stem cell factor receptor (KIT), FMS-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor type 1 (CSF-1R), and the RET receptor.

Pharmacokinetics

Sunitinib is absorbed orally, with peak plasma concentrations typically occurring 6 to 12 hours after dosing; absorption is not significantly affected by food. It is extensively metabolized in the liver, primarily by the CYP3A4 enzyme, to an active primary metabolite with similar potency. The combined half-life of Sunitinib and its active metabolite is approximately 40-60 hours, supporting once-daily dosing. Elimination is predominantly via feces, with a smaller portion excreted in urine.

Take Sunicent capsules by mouth, swallowed whole with a glass of water, with or without food, at about the same time every day. Do not open, crush, or chew the Sunicent capsule unless specifically advised by your physician. Avoid grapefruit and grapefruit juice while taking Sunicent. If a dose is missed, do not take a double dose - simply resume the regular schedule at the next scheduled time. Continue taking Sunicent for as long as your oncologist prescribes it, and do not stop without medical advice.

CYP3A4 Interactions

Sunicent is metabolized primarily by CYP3A4. Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) can substantially increase Sunicent plasma concentrations and toxicity; such combinations should be avoided, or the Sunicent dose reduced if co-administration is unavoidable. Concomitant use with strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort) can significantly decrease Sunicent exposure and reduce efficacy; these combinations should also be avoided, or the Sunicent dose increased with careful monitoring if unavoidable.

QT-Prolonging Drugs

Combining Sunicent with other drugs that prolong the QT interval may increase the risk of ventricular arrhythmia; use with caution and monitor ECG/electrolytes when co-administration is necessary.

Anticoagulants and Antiplatelet Agents

Sunicent may increase the risk of bleeding when combined with warfarin, other anticoagulants, or antiplatelet drugs; more frequent monitoring of coagulation parameters and clinical status is advised. See Precautions and Warnings for bleeding risk.

Very Common / Common Side Effects

• Fatigue and asthenia
• Diarrhea, nausea, vomiting, and stomatitis/mucosal inflammation
• Decreased appetite and taste alteration
• Hand-foot syndrome (palmar-plantar erythrodysesthesia) and other skin rashes
• Yellow skin discoloration and hair depigmentation
• Hypertension
• Hypothyroidism
• Myelosuppression (neutropenia, thrombocytopenia, anemia)
• Bleeding events (e.g., epistaxis)

Serious Side Effects

See Precautions and Warnings for detailed discussion of hepatotoxicity, cardiotoxicity, QT prolongation, severe hypertension, hemorrhage, thrombotic microangiopathy, adrenal insufficiency, gastrointestinal perforation/fistula, osteonecrosis of the jaw, and impaired wound healing associated with Sunicent.

Sunicent can cause fetal harm based on its mechanism of action and animal reproduction studies (see Pregnancy Category). Sunicent should not be used during pregnancy unless the potential benefit to the mother clearly justifies the potential risk to the fetus; women of reproductive potential should use effective contraception during treatment with Sunicent and for a period after the last dose, as advised by their physician.

It is not known whether Sunicent passes into human breast milk; because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment with Sunicent and for a period after the last dose. Consult a physician before breastfeeding.

Boxed Warning: Hepatotoxicity

Hepatotoxicity has been observed with Sunicent and may be severe, and in rare cases, fatal. Liver function tests (ALT, AST, bilirubin) should be monitored at baseline and periodically during Sunicent treatment. Sunicent should be interrupted for severe or worsening liver function abnormalities and discontinued if hepatic failure is confirmed.

Cardiotoxicity

Decreases in left ventricular ejection fraction (LVEF) and congestive heart failure, sometimes fatal, have been reported with Sunicent. Cardiac function should be assessed at baseline and monitored periodically, particularly in patients with cardiac risk factors.

QT Prolongation

Sunicent can prolong the QT interval and has been associated with torsades de pointes. Use with caution in patients with a history of QT prolongation, electrolyte abnormalities, or concomitant use of QT-prolonging drugs; correct electrolyte disturbances before starting Sunicent.

Hypertension

Hypertension, sometimes severe, is common with Sunicent. Blood pressure should be monitored and controlled with standard antihypertensive therapy; Sunicent should be interrupted for severe or persistent hypertension.

Hemorrhagic Events

Serious, sometimes fatal, hemorrhagic events (including tumor-related bleeding) have occurred with Sunicent. Use Sunicent with caution in patients at risk of bleeding.

Thrombotic Microangiopathy

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, have been reported with Sunicent; discontinue Sunicent if this occurs.

Adrenal Function

Adrenal insufficiency has been reported with Sunicent; adrenal function should be monitored, especially during periods of acute stress such as surgery, trauma, or severe infection.

Osteonecrosis of the Jaw

Osteonecrosis of the jaw has been reported with Sunicent, particularly with concomitant or prior use of bisphosphonates. A dental examination is recommended before starting Sunicent in patients with risk factors.

Gastrointestinal Perforation and Fistula

Serious, sometimes fatal, gastrointestinal perforation and fistula formation have been reported with Sunicent; discontinue Sunicent in patients who develop these complications.

Thyroid Dysfunction

Hypothyroidism and, less commonly, hyperthyroidism can occur with Sunicent. Thyroid function should be monitored at baseline and periodically during treatment.

Impaired Wound Healing

Sunicent may impair wound healing. Treatment should be temporarily discontinued in patients undergoing major surgery and resumed only after adequate wound healing is confirmed.

Specialist Monitoring

Sunicent is a specialist oncology medicine and must be prescribed and monitored only by, or in close consultation with, an oncologist familiar with its use and toxicity profile; it is not intended for general-practice initiation or unsupervised use.

There is no specific antidote for Sunicent overdose. Reported cases of overdose with Sunicent have been associated with adverse reactions consistent with the known safety profile, including worsening of typical side effects. If overdose with Sunicent is suspected, seek immediate medical attention or contact emergency services/a poison control center right away; treatment should consist of general supportive measures under close medical supervision, including cardiac monitoring.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

Safety and efficacy of Sunicent have not been established in pediatric patients; Sunicent is not recommended for use in children.

Elderly

No overall differences in safety or efficacy of Sunicent have been reported between elderly and younger adult patients, but greater sensitivity in some older individuals cannot be ruled out; use with routine monitoring.

Hepatic Impairment

See Dosage and Administration for guidance on Sunicent use in mild-to-moderate hepatic impairment; Sunicent is not recommended in severe hepatic impairment.

Renal Impairment

See Dosage and Administration; use Sunicent with caution and close monitoring in patients with significant renal impairment or on dialysis.

Sunicent is generally continued for as long as clinical benefit is observed and toxicity remains acceptable, i.e., until disease progression or unacceptable toxicity occurs, as determined by the treating oncologist. In the adjuvant renal cell carcinoma setting, Sunicent treatment is typically planned for a defined course of approximately 9 treatment cycles unless discontinued earlier for recurrence or toxicity.

Tyrosine kinase inhibitors; antineoplastic agents; VEGFR/PDGFR/KIT inhibitors - Sunitinib belongs to these classes.

Sunitinib works by inhibiting multiple receptor tyrosine kinases (including VEGFR1-3, PDGFR-alpha/beta, KIT, FLT3, CSF-1R, and RET) that drive tumor cell proliferation and the formation of new blood vessels (angiogenesis) that tumors need to grow and spread. By blocking these signaling pathways, Sunitinib helps inhibit tumor growth and vascularization.

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The safety and efficacy of Sunicent have not been established in pediatric patients. Sunicent is intended for use in adults only and is not recommended for children or adolescents outside of a clinical trial setting.