Cabozantinib


Generic Medicine Info
Indications and Dosage
Oral
Metastatic medullary thyroid carcinoma, Unresectable locally advanced medullary thyroid carcinoma
Adult: As cap: 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 (refer to detailed product guideline). This indication and dosage is specific for cap formulation. Do not use interchangeably with the tab formulation due to different bioequivalence.

Oral
Advanced renal cell carcinoma, Hepatocellular carcinoma
Adult: As tab: Initially, 60 mg once daily. Adjust dose in decrements of 20 mg daily, if necessary. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline). This indication and dosage is specific for tab formulation. Do not use interchangeably with the cap formulation due to different bioequivalence.
Special Patient Group
Patient taking strong CYP3A4 inhibitor (e.g. ketoconazole, itraconazole):
As tab: Reduce daily dose by 20 mg. As cap: Reduce daily dose by 40 mg. Resume normal dosing 2-3 days after discontinuation of the strong CYP3A4 inhibitor.

Patient taking strong CYP3A4 inducer (e.g. rifampin, phenobarbital, phenytoin, carbamazepine):
As tab: Increase daily dose by 20 mg. Max 80 mg daily. As cap: Increase daily dose by 40 mg. Max: 180 mg daily. Resume normal dosing 2-3 days after discontinuation of strong CYP3A4 inhibitor.
Hepatic Impairment
Unresectable locally advanced medullary thyroid carcinoma; Metastatic medullary thyroid carcinoma:
Mild to moderate impairment: As cap: Initially, 60 mg. Severe: Not recommended. 

Advanced renal cell carcinoma; Hepatocellular carcinoma:
Moderate: Initially, 40 mg. Severe: Not recommended.
Administration
Should be taken on an empty stomach. Swallow whole, do not crush.
Contraindications
History of haemorrhage or haemoptysis. Lactation.
Special Precautions
Patient with hypertension, wound healing complications. Renal and hepatic impairment. Pregnancy.
Adverse Reactions
Significant: Hypertension, reversible posterior leukoencephalopathy syndrome (RPLS), palmar-plantar erythrodysesthesia syndrome, diarrhoea, proteinuria. Rarely, osteonecrosis of the jaw, nephrotic syndrome, wound healing impairment.
Blood and lymphatic system disorders: Anaemia, thrombocytopenia, neutropenia.
Ear and labyrinth disorders: Tinnitus.
Endocrine disorders: Hypothyroidism.
Gastrointestinal disorders: Nausea, vomiting, stomatitis, constipation, abdominal pain, dyspepsia, GERD, haemorrhoids, oral pain, dry mouth.
General disorders and administration site conditions: Fatigue, asthenia, peripheral oedema.
Hepatobiliary disorders: Hepatic encephalopathy.
Infections and infestations: Abscess.
Investigations: Weight decrease; increased ALT, AST, alkaline phosphatase, creatinine, cholesterol, triglycerides, lipase; decreased WBC count.
Metabolism and nutrition disorders: Decreased appetite, hypomagnesaemia, hypokalaemia, dehydration, hyperglycaemia, hypoglycaemia, hypophosphataemia, hypoalbuminaemia, hyponatraemia, hyperkalaemia, hypocalcaemia, hyperbilirubinemia.
Musculoskeletal and connective tissue disorders: Limb pain, muscle spasms, arthralgia.
Nervous system disorders: Dysgeusia, headache, dizziness, peripheral sensory neuropathy.
Respiratory, thoracic and mediastinal disorders: Dysphonia, dyspnea, cough, pulmonary embolism.
Skin and subcutaneous tissue disorders: Rash, alopecia, dry skin, dermatitis acneiform, hair discolouration, erythema.
Potentially Fatal: Serious haemorrhage (e.g. haemoptysis, gastrointestinal bleeding), gastrointestinal perforations, and fistula, thromboembolic events (e.g. pulmonary embolism, arterial thromboembolism).
Patient Counseling Information
Do not substitute tablets with capsules.
Monitoring Parameters
Monitor blood pressure prior to therapy and regularly thereafter; platelet count, and urine protein regularly. Perform oral examinations prior to and periodically throughout the therapy. Monitor for signs and symptoms of RPLS (e.g. seizures, headache); thromboembolic events (e.g. acute MI).
Drug Interactions
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).
Food Interaction
May increase serum concentration with grapefruit or grapefruit juice. May decrease serum concentration with St. John’s wort.
Action
Description:
Mechanism of Action: Cabozantinib is a proinvasive receptor tyrokinases (RTKs) inhibitor. It acts by inducing apoptosis of cancer cells and suppresses tumour growth, metastasis, and angiogenesis.
Pharmacokinetics:
Absorption: Food, particularly high fat meal, increases rate and extent of absorption. Bioavailability: Tab formulation has a 19% increase in Max concentration compared to cap following a single 140 mg dose, and therefore are not bioequivalent. Time to peak plasma concentration: 2-5 hours (cap); 3-4 hours (tab).
Distribution: Volume of distribution: 349 L (cap); 319 L (tab). Plasma protein binding: >99.7%.
Metabolism: Metabolised in the liver by CYP3A4, and by CYP2C9 (minimal).
Excretion: Via faeces (approx 54%, 43% as unchanged drug); urine (approx 27%). Terminal half-life: 55 hours (cap); 99 hours (tab).
Chemical Structure

Chemical Structure Image
Cabozantinib

Source: National Center for Biotechnology Information. PubChem Database. Cabozantinib, CID=25102847, https://pubchem.ncbi.nlm.nih.gov/compound/Cabozantinib (accessed on Jan. 21, 2020)

Storage
Store between 20-25°C. Protect from moisture.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
MIMS Class
Targeted Cancer Therapy
ATC Classification
L01EX07 - cabozantinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.
References
Anon. Cabozantinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/03/2019.

Buckingham R (ed). Cabozantinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/03/2019.

Cabometyx Tablet (Exelixis, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 06/03/2019.

Cabozantinib. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com/. Accessed 05/03/2019.

Cometriq Capsule (Exelixis, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2019.

Joint Formulary Committee. Cabozantinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/03/2019.

Disclaimer: This information is independently developed by MIMS based on Cabozantinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2024 MIMS. All rights reserved. Powered by MIMS.com
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