Caboxen Capsule

Caboxen Capsule is used for: Advanced renal cell carcinoma, Hepatocellular carcinoma, Medullary thyroid carcinoma,

Oral Adult: As Tablet: Renal Cell Carcinoma Combination with nivolumab Indicated in combination with nivolumab for first-line treatment of advanced renal cell carcinoma (RCC) 40 mg orally, once daily, administered in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks Single agent Indicated for advanced RC 60 mg orally, once daily Continue until disease progression or unacceptable toxicity occurs Hepatocellular Carcinoma Adult: As Tablet: Indicated for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib 60 mg orally, once daily Continue until disease progression or unacceptable toxicity occurs This indication and dosage is specific for tab formulation. Do not use interchangeably with the cap formulation due to different bioequivalence. Adult: As Capsule: Metastatic medullary thyroid carcinoma, Unresectable locally advanced medullary thyroid carcinoma Initially, 140 mg once daily. Adjust dose in decrements of 40 mg daily, if necessary. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability. This indication and dosage is specific for cap formulation. Do not use interchangeably with the tab formulation due to different bioequivalence.

Child: As Tablet: Differentiated Thyroid Cancer Indicated for locally advanced or metastatic differentiated thyroid cancer (DTC) in pediatric patients aged >12 years who have progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible BSA <1.2 m2: 40 mg PO once daily. BSA >1.2 m2: 60 mg PO once daily. Continue until disease progression or unacceptable toxicity This indication and dosage is specific for tab formulation. Do not use interchangeably with the cap formulation due to different bioequivalence.

Renal impairment Mild-to-moderate (CrCl >30 mL/min): No dosage adjustment necessary Severe (CrCl <30 mL/min): No experience

Should be taken on an empty stomach. Take at least 1 hr before or at least 2 hr after meals. Swallow whole, do not crush.

History of haemorrhage or haemoptysis. Lactation.

Hemorrhage: Do not administer Cabozantinib if recent history of hemorrhage. Perforations and Fistulas: Monitor for symptoms. Discontinue Cabozantinib for Grade 4 fistula or perforation. Thrombotic Events: Discontinue Cabozantinib for myocardial infarction or serious venous or arterial thromboembolic events. Hypertension and Hypertensive Crisis: Monitor blood pressure regularly. Interrupt for hypertension that is not adequately controlled with anti-hypertensive therapy. Discontinue Cabozantinib for hypertensive crisis or severe hypertension that cannot be controlled with anti-hypertensive therapy. Diarrhea: May be severe. Interrupt Cabozantinib immediately until diarrhea resolves or decreases to Grade 1. Recommend standard antidiarrheal treatments. Palmar-Plantar Erythrodysesthesia (PPE): Interrupt Cabozantinib treatment until PPE resolves or decreases to Grade 1. Hepatotoxicity: When used in combination with nivolumab, higher frequencies of Grade 3 and 4 ALT and AST elevation may occur than with Cabozantinib alone. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider withholding Cabozantinib and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity. Adrenal Insufficiency: When used in combination with nivolumab, primary or secondary adrenal insufficiency may occur. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold Cabozantinib and/or nivolumab depending on severity. Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome. Osteonecrosis of the jaw (ONJ): Withhold Cabozantinib for at least 3 weeks prior to invasive dental procedures and for the development of ONJ. Impaired Wound Healing: Withhold Cabozantinib for at least 3 weeks before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of Cabozantinib after the resolution of wound healing complications has not been established. Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue Cabozantinib. Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. Monitoring Parameters Monitor liver enzymes before initiation of and periodically throughout treatment. Monitor urine protein regularly and discontinue if nephrotic syndrome develops. Monitor blood pressure regularly.

Pregnancy Based on its mechanism of action, can cause fetal harm when administered to pregnant women Verify pregnancy status of females of reproductive potential before initiation Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the final dose May impair male and female fertility Lactation Unknown whether distributed in breast milk Because of potential for serious adverse reactions in a breastfed infant from cabozantinib, advise females of reproductive potential to not breastfeed during treatment and for 4 months after the final dose

Increased plasma concentration with strong CYP3A4 enzyme inhibitors (e.g. ketoconazole, itraconazole). Decreased plasma concentration with strong CYP3A4 enzyme inducers (e.g. rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine). Contraindicated (0) Serious (55) apalutamide armodafinil atazanavir bosentan carbamazepine ceritinib chloramphenicol clarithromycin clobazam cobicistat conivaptan dabrafenib darunavir dexamethasone efavirenz elvitegravir/cobicistat/emtricitabine/tenofovir DF enzalutamide eslicarbazepine acetate etrasimod etravirine fexinidazole fosamprenavir fosphenytoin idelalisib imatinib isoniazid itraconazole ivosidenib ketoconazole levoketoconazole lonafarnib lopinavir lumacaftor/ivacaftor mitotane nafcillin nefazodone nelfinavir nevirapine nicardipine oxcarbazepine palifermin pentobarbital phenobarbital phenytoin posaconazole primidone quinidine rifabutin rifampin rifapentine ritonavir St John's Wort tipranavir tucatinib voriconazole

Side effects of Cabozantinib : >10% AST, ALT increased (86%) Diarrhea (63%) Hypertension, treatment-emergent (61%) Increased TSH (57%) Lymphopenia (53%) ALP increased (52%) Hypocalcemia (52%) Stomatitis (51%) Palmar-plantar erythrodysesthesia syndrome (50%) Weight decreased (48%) Appetite decreased (46%) Nausea (43%) Fatigue (41%) Oral pain (36%) Neutropenia (35%) Thrombocytopenia (35%) Dysgeusia (34%) Hair color changes, depigmentation, graying (34%) Hypertension (33%) Hypophosphatemia (28%) Constipation (27%) Abdominal pain (27%) Hypobilirubinemia (25%) Vomiting (24%) Asthenia (21%) Dysphonia (20%) Rash (19%) Dry skin (19%) Hypomagnesemia (19%) Hypokalemia (18%) Headache (18%) Alopecia (16%) Dizziness (14%) Arthralgia (14%) Palmar-plantar erythrodysesthesia syndrome, Grade 3 or 4 (13%) Dysphagia (13%) Muscle spasms (12%) Dyspepsia (11%) Erythema (11%) 1-10% Hyponatremia (10%) Hemorrhoids (9%) Musculoskeletal chest pain (9%) Anxiety (9%) Paresthesia (7%) Peripheral sensory neuropathy (7%) Dehydration (7%) Hyperkeratosis (7%) Hypotension (7%) Venous thromboembolism (6%) Peripheral neuropathy (5%) Non-GI fistula (4%) GI perforation (3%) Arterial thromboembolism (2%) Proteinuria (2%) GI fistula (1%) Osteonecrosis of the jaw (1%)

Tyrosine kinase inhibitor that targets RET, MET, VEGFR-1, -2, and -3, KIT, TrkB, FLT-3, AXL, and TIE-2 pathways; these tyrosine kinases are involved in both normal cellular function and pathologic processes (eg, oncogenesis, metastasis, tumor angiogenesis, and maintenance of tumor microenvironment).

Caboxen 80 mg Capsule manufactured by Everest Pharmaceuticals Ltd.. Its generic name is Cabozantinib. Caboxen is availble in Bangladesh. Farmaco BD drug index information on Caboxen Capsule is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.