CABOZAN Cabozantinib

[Product Name] Cabozantinib Tablets

[English Name] Cabozantinib Tablets

[Other Names] XL184 / Cometriq

[Specification] 20 mg × 90 tablets/box

[Manufacturer] Lao Pharmaceutical Group Co., Ltd.

[Approval Number] (Lao National Drug Administration): 03 L 0957/23

[Overview]

Cabozantinib was developed by the U.S. biopharmaceutical company Exelixis. It is a multi-targeted, broad-spectrum anticancer drug capable of inhibiting at least nine distinct targets, including: MET, VEGFR1/2/3, ROS1, RET, AXL, NTRK, KIT, and others.

Currently, Cabozantinib has demonstrated significant therapeutic efficacy across a wide range of solid tumors, including kidney cancer, thyroid cancer, liver cancer, soft tissue sarcoma, non-small cell lung cancer (NSCLC), prostate cancer, breast cancer, ovarian cancer, and colorectal cancer. Its efficacy in controlling bone metastases is particularly outstanding. Due to its broad effectiveness against multiple types of cancer, Cabozantinib is often referred to as the "universal remedy" among targeted therapies. Its therapeutic targets include: KIT, PDGFR, FGFR, BRAF, BRAF V600, RAF-1, VEGFR1/2/3, TIE-1/-2, and RET.

[Indications]

1. Treatment of progressive, unresectable, locally advanced, or metastatic medullary thyroid cancer;

2. Advanced kidney cancer following failure of Sunitinib therapy;

3. Advanced non-small cell lung cancer (NSCLC) in patients with *c-MET* amplification;

4. Liver cancer in patients who have developed resistance to Sorafenib;

5. Advanced prostate cancer in patients with bone metastases.

[Dosage and Administration]

Administration Method:

Oral administration. Take on an empty stomach; avoid taking with food. Specifically, do not consume food for at least 2 hours before taking the medication and for at least 1 hour after taking it.

During treatment, avoid consuming foods (such as grapefruit or grapefruit juice) or nutritional supplements known to inhibit Cytochrome P450 enzymes. Recommended Dosage:

Medullary Thyroid Carcinoma: 140 mg orally once daily; for patients with mild to moderate hepatic impairment, the starting dose is 80 mg.

Renal Cell Carcinoma, Hepatocellular Carcinoma: 60 mg orally once daily.

Prostate Cancer with Bone Metastases: 40 mg orally once daily.

[Side Effects and Adverse Reactions]

The most common (incidence > 20%) side effects and adverse reactions associated with Cabozantinib include:

Diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), weight loss, decreased appetite, nausea, fatigue, oral pain, hair discoloration, dysgeusia, hypertension, abdominal pain, and constipation.

The most common (incidence > 25%) laboratory abnormalities associated with Cabozantinib include:

Elevated AST, elevated ALT, lymphopenia, elevated ALP, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

The most common (incidence > 5%) Grade 3 or 4 side effects and adverse reactions associated with Cabozantinib include:

Diarrhea, palmar-plantar erythrodysesthesia syndrome (PPES), lymphopenia, hypocalcemia, fatigue, hypertension, asthenia, elevated ALT, weight loss, stomatitis, and decreased appetite.

The most common side effects and adverse reactions leading to permanent discontinuation of Cabozantinib include:

Hypocalcemia, elevated lipase, palmar-plantar erythrodysesthesia syndrome (PPES), diarrhea, fatigue, hypertension, nausea, pancreatitis, tracheoesophageal fistula formation, and vomiting.

[Warnings and Precautions]

1. Cardiotoxicity

Cabozantinib carries a certain risk of cardiotoxicity, manifesting as chest tightness, palpitations, dyspnea, etc. Prophylactic cardioprotective agents—such as Coenzyme Q10—may be administered to help prevent these effects. Recommended Dosage for Coenzyme Q10: For general health maintenance in healthy individuals, the dosage is 30–60 mg per day; for individuals at high risk of cardiovascular disease—including those with hypertension—the dosage is 60–120 mg per day; for patients already suffering from heart failure or ischemic heart disease, the dosage may be increased to 200–400 mg per day. When taking doses exceeding 60 mg per day, the total daily amount may be divided into 2–3 separate doses.

2. Indications for Permanent Discontinuation

Permanent discontinuation of the medication is required if any of the following severe adverse events occur during treatment: severe hemorrhage, myocardial infarction, cerebral infarction, thromboembolism, hypertensive crisis, nephrotic syndrome, severe hepatitis, osteonecrosis of the jaw, gastrointestinal perforation, or fistula formation.

[Drug Interactions]

The use of the following medications should be avoided while taking Cabozantinib:

1. Strong CYP3A4 Inhibitors

Including, but not limited to: ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole.

2. Strong CYP3A4 Inducers

Including, but not limited to: dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort.

[Special Populations]

Elderly Patients:

In Phase 3 studies, 41% of patients treated with Cabozantinib were aged 65 years or older, and 8% were aged 75 years or older. No differences in safety or efficacy were observed between elderly patients and younger patients.

Patients with Hepatic Impairment:

Increased exposure to Cabozantinib has been observed in patients with mild to moderate hepatic impairment. A reduced dosage of Cabozantinib is recommended for patients with mild (Child-Pugh [C-P] Class A) or moderate (C-P Class B) hepatic impairment. The use of Cabozantinib is not recommended in patients with severe hepatic impairment. Patients with Renal Impairment:

No dose adjustment is required for patients with mild or moderate renal impairment; there is currently no experience with the use of cabozantinib in patients with severe renal impairment.

[Use in Pregnant and Lactating Women]

Pregnancy Risk:

Physicians should advise pregnant women or women of reproductive potential that cabozantinib poses a potential risk to the fetus.

Lactation Risk:

Lactating women should not breastfeed during treatment with cabozantinib and for 4 months after discontinuing the drug.

Contraception:

Males and females of reproductive potential should use effective contraception during treatment with cabozantinib and for 4 months after discontinuing the drug.

[Storage]

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).