Description

COMPOSITION 

CABOXEN 20 capsule: Each capsule contains Cabozantinib (S)-malate INN equivalent to 20 mg Cabozantinib. 

CABOXEN 80 capsule: Each capsule contains Cabozantinib (S)-malate INN equivalent to 80 mg Cabozantinib.

 

Product Features

Product Name	:	Caboxen
Generic Name	:	Cabozantinib
Formulation	:	Capsule
Available Pack Size	:	90’s Pot
Available Strength	:	20 mg
Registrations	:	Export Only
Manufacture	:	Everest Pharmaceuticals Ltd

 

Cabozantinib Mechanism of Action

Cabozantinib works by blocking the activity of several proteins called receptor tyrosine kinases. These proteins, including MET, VEGFR-1, VEGFR-2, VEGFR-3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2, play roles in various cellular functions and disease processes like cancer growth, spread, blood vessel formation around tumors, resistance to drugs, and maintaining the environment around tumors. Cabozantinib’s action helps in interfering with these processes, which is beneficial in treating certain types of cancer.

 

Dosage and Administration

The recommended daily dose of Cabozantinib is 140 mg, consisting of one 80-mg capsule and three 20-mg capsules. When taking Caboxen, it’s important to do so on an empty stomach. Also avoid eating for at least 2 hours before and after taking the medication. This helps ensure optimal absorption and effectiveness of the medicine. Treatment should be continued until disease progression or unacceptable side effects occur.

Do not substitute Cabozantinib capsules with tablets and to swallow them whole without opening.

If a dose is missed, it should not be taken within 12 hours of the next scheduled dose.

Patients should also avoid consuming foods or supplements known to inhibit cytochrome P450 while taking Cabozantinib. In cases of hepatic impairment, the starting dose is usually reduced to 80 mg.

 

Dosage Modifications For Adverse Reactions

Cabozantinib treatment should be withheld for severe adverse reactions, including Grade 4 hematologic adverse reactions, Grade 3 or greater non-hematologic adverse reactions, or intolerable Grade 2 adverse reactions. Upon resolution or improvement of the adverse reaction, the dose should be adjusted as follows:

• If previously receiving a 140 mg daily dose, resume treatment at 100 mg daily (one 80-mg and one 20-mg capsule).
• If previously receiving a 100 mg daily dose, resume treatment at 60 mg daily (three 20-mg capsules).
• If previously receiving a 60 mg daily dose, resume at 60 mg if tolerated; otherwise, discontinue Cabozantinib permanently.

 

Cabozantinib should be permanently discontinued for the following conditions:

• Development of visceral perforation or fistula formation.
• Severe hemorrhage.
• Serious arterial thromboembolic event (e.g., myocardial infarction, cerebral infarction).
• Nephrotic syndrome.
• Malignant hypertension, hypertensive crisis, persistent uncontrolled hypertension despite optimal medical management.
• Osteonecrosis of the jaw.
• Reversible posterior leukoencephalopathy syndrome.

Dosage Adjustment with CYP3A4 Inhibitors and Inducers:

If patients taking a strong CYP3A4 inhibitor, Cabozantinib dose should be reduced by 40 mg.

If patients taking a strong CYP3A4 inducer, Cabozantinib dose should be increased by 40 mg, as tolerated. For better dose modification consult with your doctor.

 

Overdose 

If you overdose on Caboxen, seek immediate medical attention.

 

Cabozantinib Side Effects

Common Side Effects of Cabozantinib

• Diarrhea
• Stomatitis (inflammation of the mouth and lips)
• Palmar-plantar erythrodysesthesia syndrome (PPES) – also known as hand-foot syndrome, causing redness, swelling, and pain on the palms of the hands and/or soles of the feet
• Decreased weight
• Decreased appetite
• Nausea
• Fatigue
• Oral pain
• Hair color changes
• Dysgeusia (changes in taste perception)
• Hypertension (high blood pressure)
• Abdominal pain
• Constipation

 

Common Laboratory Abnormalities

• Increased AST (aspartate aminotransferase)
• Increased ALT (alanine aminotransferase)
• Lymphopenia (reduced white blood cell count)
• Increased ALP (alkaline phosphatase)
• Hypocalcemia (low calcium levels)
• Neutropenia (reduced neutrophil count)
• Thrombocytopenia (reduced platelet count)
• Hypophosphatemia (low phosphate levels)
• Hyperbilirubinemia (high bilirubin levels)

Grade 3-4 Adverse Reactions

• Diarrhea
• PPES
• Lymphopenia
• Hypocalcemia
• Fatigue
• Hypertension
• Asthenia (weakness)
• Increased ALT
• Decreased weight
• Stomatitis
• Decreased appetite
• Nausea

 

These side effects and laboratory abnormalities should be monitored closely during treatment with Cabozantinib, and healthcare providers should be informed if any symptoms or changes occur.

 

Warnings and Precautions

Perforations and Fistulas

Gastrointestinal (GI) perforations and fistulas occurred in 3% and 1% of patients treated with Cabozantinib, respectively. All instances were serious, with one GI fistula resulting in fatality (< 1%). Non-GI fistulas, including tracheal/esophageal, were reported in 4% of patients treated with Cabozantinib, with two (1%) fatalities. It is crucial to monitor patients for symptoms of perforations and fistulas, including abscesses, and discontinue Cabozantinib for patients experiencing such complications.

 

Hemorrhage

Serious and occasionally fatal hemorrhages have been associated with Cabozantinib treatment. Grade ≥ 3 hemorrhagic events were more frequent in Cabozantinib-treated patients compared to those receiving placebo (3% vs. 1%). Cabozantinib should not be administered to patients with a recent history of hemorrhage or hemoptysis.

 

Thrombotic Events

The use of Cabozantinib has been linked to an increased incidence of thrombotic events, including venous thromboembolism (6% vs. 3%) and arterial thromboembolism (2% vs. 0%) in Cabozantinib-treated and placebo-treated patients, respectively. Discontinuation of Cabozantinib is recommended for patients experiencing acute myocardial infarction or any other clinically significant arterial thromboembolic complications.

 

Wound Complications

Wound complications have been reported with Cabozantinib use. Treatment with Cabozantinib should be ceased at least 28 days prior to scheduled surgery. Resumption of Cabozantinib therapy after surgery should be based on clinical judgment regarding adequate wound healing. Cabozantinib should be withheld in patients with wound healing complications requiring medical intervention.

 

Hypertension

Cabozantinib treatment is associated with an increased incidence of treatment-emergent hypertension, with 61% of Cabozantinib-treated patients exhibiting Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (modified JNC criteria) stage 1 or 2 hypertension, compared to 30% of placebo-treated patients. Blood pressure should be monitored before initiation of Cabozantinib and regularly during treatment. Cabozantinib should be withheld for uncontrolled hypertension and discontinued for severe hypertension that cannot be managed with antihypertensive therapy.

 

Osteonecrosis of the Jaw

Osteonecrosis of the jaw (ONJ) occurred in 1% of patients treated with Cabozantinib. ONJ can present with various symptoms including jaw pain, osteomyelitis, and tooth or periodontal infections. Cabozantinib should be discontinued for ONJ. Prior to initiation of Cabozantinib and periodically during therapy, patients should undergo oral examinations, and they should be advised on good oral hygiene practices.

 

Palmar-Plantar Erythrodysesthesia Syndrome

Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 50% of patients treated with Cabozantinib, with 13% experiencing severe (Grade 3) PPES. Cabozantinib should be withheld in patients with Grade 2 or 3 PPES until improvement to Grade 1, after which it can be resumed at a reduced dose.

 

Proteinuria

Proteinuria was observed in 2% of patients receiving Cabozantinib, including one case of nephrotic syndrome. Patients should be monitored for urine protein regularly during Cabozantinib treatment, and the drug should be discontinued in those who develop nephrotic syndrome.

 

Reversible Posterior Leukoencephalopathy Syndrome

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) occurred in one (<1%) patient. Evaluation for RPLS is warranted in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Cabozantinib should be discontinued in patients who develop RPLS.

 

Embryo-Fetal Toxicity

Cabozantinib can cause fetal harm when administered to pregnant women, as indicated by data from animal studies. Pregnant women should be advised of the potential risk to the fetus. Females of reproductive potential should use effective contraception during Cabozantinib treatment and for 4 months after the last dose.

 

Use in Specific Populations

Pregnancy

Cabozantinib poses a risk of fetal harm when administered to pregnant women, as evidenced by animal studies. No data is available in pregnant women to quantify the associated risk. Administration of Cabozantinib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal lethality and structural anomalies at exposures below those occurring clinically at the recommended dose. Women of childbearing potential should be informed of the potential hazard to a fetus.

 

Breastfeeding

No information is available regarding the presence of Cabozantinib or its metabolites in human milk or their effects on the breastfed infant or milk production. Due to the potential for serious adverse reactions in breastfed infants, lactating women should refrain from breastfeeding during Cabozantinib treatment and for 4 months after the final dose.

 

Fertility

Data on human fertility is lacking. Based on non-clinical safety findings, both male and female fertility may be compromised by Cabozantinib treatment. Therefore, individuals of reproductive potential should seek advice and consider fertility preservation before initiating treatment.

 

Contraception for Females and Males of Reproductive Potential

Cabozantinib can cause fetal harm during pregnancy. Females of reproductive potential should use effective contraception during Cabozantinib treatment and for 4 months after the final dose.

 

Infertility

Both females and males may experience impaired fertility due to Cabozantinib, based on animal findings.

 

Pediatric Use

The safety and efficacy of Cabozantinib in pediatric patients have not been studied.

 

Geriatric Use

Clinical studies did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients.

 

Hepatic Impairment

Patients with mild to moderate hepatic impairment exhibit increased exposure to Cabozantinib. The starting dose should be reduced in patients with mild (Child-Pugh score (C-P) A) or moderate (C-P B) hepatic impairment. Cabozantinib is not recommended for use in patients with severe hepatic impairment.

 

Renal Impairment

No dosage adjustment is necessary in patients with mild or moderate renal impairment. However, there is no experience with Cabozantinib in patients with severe renal impairment.

 

Storage Conditions 

Store Cabozantinib 20 mg below 25°C. Keep out of the sight & reach of children. Protect from moisture & light. 

 

How supplied 

CABOXEN 20 capsule: Each HDPE container contains 90 capsules each of which contains Cabozantinib 20 mg. 

CABOXEN 80 capsule: Each HDPE container contains 30 capsules each of which contains Cabozantinib 80 mg. 

 

Countries where our service provided

Delivering worldwide including United State (USA), United Kingdom (UK), Saudi Arabia, Dubai, Kuwait, Qatar, Philippines, Nepal, Malaysia, Indonesia, Thailand, Poland, Peru, South Korea, New Zealand, Netherlands, Georgia, France, Egypt, Australia, Germany, Canada, Uzbekistan, Lebanon, Mexico, Singapore, Vietnam,  Pakistan, Russia, Ukraine, Bangladesh, India

 

Note: The descriptions provided above are taken from the prescription information for Caboxen (Cabozantinib), as provided by Everest Pharmaceuticals Ltd.  Full prescription