Cabozantinib

Patients taking strong CYP3A4 inhibitors (e.g. ketoconazole):
As cap: Reduce daily dose by 40 mg. Resume normal dosing 2-3 days after discontinuation of the strong CYP3A4 inhibitor. As tab: Reduce daily dose by 20 mg.

Patients taking strong CYP3A4 inducer (e.g. rifampicin):
As cap: Increase daily dose by 40 mg. Max: 180 mg daily. Resume normal dosing 2-3 days after discontinuation of the strong CYP3A4 inducer. As tab: Increase daily dose by 20 mg.

Oral:
Metastatic medullary thyroid carcinoma:
As cap: Mild to moderate (Child-Pugh class A-B): 60 mg once daily. Alternatively, 80 mg once daily. Severe (Child-Pugh class C): Not recommended. Dosage recommendations may vary among countries and between individual products (refer to specific product or local guidelines). This indication and dosage are specific for cap formulation. Do not use interchangeably with the tab formulation due to different bioequivalence.

Advanced renal cell carcinoma:
As tab: Moderate (Child-Pugh class B): If initial dose is 60 mg once daily: Reduce dose to 40 mg once daily. If initial dose is 40 mg once daily: Reduce dose to 20 mg once daily. Severe (Child-Pugh class C): Not recommended. Dosage recommendations may vary among countries and between individual products (refer to specific product or local guidelines). This indication and dosage are specific for tab formulation. Do not use interchangeably with the cap formulation due to different bioequivalence.

Hepatocellular carcinoma; Differentiated thyroid cancer:
As tab: Moderate (Child-Pugh class B): Reduce dose to 40 mg once daily. Severe (Child-Pugh class C): Not recommended. Dosage recommendations may vary among countries and between individual products (refer to specific product or local guidelines). This indication and dosage are specific for tab formulation. Do not use interchangeably with the cap formulation due to different bioequivalence.

Cabozantinib Should be taken on an empty stomach. Swallow whole, do not crush.

Patient with inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, peritonitis, diverticulitis), tumour infiltration of trachea, bronchi or oesophagus, complications from prior gastrointestinal surgery (particularly when associated with delayed or incomplete healing) or radiation treatment to the thoracic cavity including mediastinum; serious haemorrhage, history of haemorrhage, haemoptysis, haematemesis, or melaena, history of or at risk for thromboembolic events; hypertension, history of aneurysm; history of QT interval prolongation. Patients undergoing surgery including dental surgery or invasive dental procedures; discontinue treatment 28 days before scheduled procedures. Cabozantinib is available as capsule and tablet that are approved for specific indications and are not bioequivalent; these preparations are not interchangeable. Hepatic impairment. Children. Pregnancy and lactation.

Significant: Hepatotoxicity (e.g. increased AST and/or ALT), palmar-plantar erythrodysesthesia syndrome, diarrhoea, hypertension (including hypertensive crisis), hypocalcaemia, proteinuria, endocrinopathy (e.g. hypothyroidism, hyperthyroidism, thyrotoxicosis, adrenocortical insufficiency), wound healing impairment, reversible posterior leucoencephalopathy. Rarely, osteonecrosis of the jaw, nephrotic syndrome.
Blood and lymphatic system disorders: Thrombocytopenia, lymphopenia, neutropenia.
Cardiac disorders: Atrial fibrillation.
Ear and labyrinth disorders: Ear pain, tinnitus.
Eye disorders: Blurred vision.
Gastrointestinal disorders: Nausea, vomiting, stomatitis, oral pain, constipation, abdominal pain, dyspepsia, dysphagia, glossodynia, cheilitis, pancreatitis, haemorrhoids, anal fissure, anal inflammation.
General disorders and administration site conditions: Fatigue, mucosal inflammation, asthenia, chills, face oedema.
Hepatobiliary disorders: Cholelithiasis.
Infections and infestations: Skin, tooth, or visceral abscess; genital, oral, or skin fungal infection.
Investigations: Decreased weight, increased alkaline phosphatase, blood LDH, TSH, creatinine, and lipase.
Metabolism and nutrition disorders: Decreased appetite, dehydration, hypokalaemia, hypomagnesaemia, hypoalbuminaemia, hyperbilirubinaemia, hypophosphataemia.
Musculoskeletal and connective tissue disorders: Arthralgia, muscle spasms, pain in extremity, musculoskeletal chest pain.
Nervous system disorders: Headache, dizziness, dysgeusia, cerebrovascular accident, peripheral neuropathy, paraesthesia, ageusia, tremor.
Psychiatric disorders: Anxiety, confusional state, depression.
Renal and urinary disorders: Dysuria, haematuria.
Respiratory, thoracic and mediastinal disorders: Pneumonia, dysphonia, oropharyngeal pain, pneumonia aspiration.
Skin and subcutaneous tissue disorders: Folliculitis, hair colour changes, rash, dry skin, alopecia, erythema, hyperkeratosis, acne, blister, abnormal hair growth, skin exfoliation, skin hypopigmentation.
Vascular disorders: Hypotension, pallor, peripheral coldness.
Potentially Fatal: Gastrointestinal perforations and fistulas, tracheal/oesophageal fistulas, haemorrhage (including haemoptysis and gastrointestinal haemorrhage), venous thromboembolism (including pulmonary embolism, arterial thromboembolism), aortic aneurysm rupture, aortic dissection.

This drug may cause fatigue and weakness, if affected, do not drive or operate machinery. Women of childbearing potential must use effective birth control methods (in addition to barrier method) during treatment and 4 months following the last dose. Discontinue breastfeeding during treatment and 4 months following the last dose. Maintain good oral hygiene during treatment.

Evaluate pregnancy status prior to treatment initiation in patients who could become pregnant. Conduct HBV screening, including HBsAg, hepatitis B core antibody, total Ig or IgG, and antibody to HBsAg before or at the beginning of systemic anticancer therapy. Perform ECG periodically during therapy; oral examination prior to treatment initiation and periodically during treatment. Monitor kidney function, liver function (at baseline and periodically), CBC with differential, urine protein/creatine ratio; serum electrolytes including calcium, urine protein, blood pressure (regularly during treatment), thyroid function testing (at baseline and as clinically indicated). Assess for signs and symptoms of gastrointestinal perforation or fistulas (including abscess and sepsis), haemorrhage, palmar-plantar erythrodysesthesia syndrome, reversible posterior leukoencephalopathy syndrome, osteonecrosis of the jaw, thyroid dysfunction, wound healing complications, diarrhoea, stomatitis, thromboembolic events, and adrenal insufficiency. Evaluate oral hygiene practices.

Decreased serum concentrations with strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital). Increased serum concentrations with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, atazanavir, nefazodone). Increased plasma levels with multidrug resistance protein 2 (MRP2) inhibitors (e.g. abacavir, ritonavir, furosemide, lamivudine, nevirapine, probenecid). Increased risk of osteonecrosis of the jaw with bisphosphonate derivatives. May increase the serum concentrations of P-glycoprotein (P-gp) substrates.

Increased serum concentrations with grapefruit or grapefruit juice. Decreased serum concentrations with St. John's wort.

Description:
Overview: Cabozantinib, a potent tyrosine kinase inhibitor, is an antineoplastic agent.
Mechanism of Action: Cabozantinib inhibits multiple receptor tyrosine kinases associated in both normal cellular function and pathologic processes (e.g. oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumour microenvironment).
Pharmacodynamics: Cabozantinib exhibits dose-related tumour growth inhibition, regression of tumour, and/or inhibition of metastasis in a broad range of preclinical tumour models. Efficacy of observed in medullary thyroid cancer patients with wild-type or mutant rearranged during transfection (RET).

The exposure-response and safety relationship of cabozantinib has not been fully established. In a randomised, double-blind, placebo-controlled study in patients with medullary thyroid carcinoma, cabozantinib was associated with a mild, non-clinically significant QT interval prolongation. No changes in cardiac waveform morphology or rhythm were observed, and no definitive concentration-QTc relationship was established.
Pharmacokinetics:
Absorption: Food, particularly high-fat meal, increases exposure. Time to peak plasma concentration: 2-5 hours (cap); 3-4 hours (tab).
Distribution: Volume of distribution: Approx 349 L (cap); approx 319 L (tab). Plasma protein binding: ≥99.7%.
Metabolism: Metabolised in the liver mainly by CYP3A4 and CYPC29 (minimal).
Excretion: Via faeces (approx 54%; 43% as unchanged drug); urine (approx 27%). Elimination half-life: Approx 55 hours (cap); approx 99 hours (tab).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 25102847, Cabozantinib. https://pubchem.ncbi.nlm.nih.gov/compound/Cabozantinib. Accessed Nov. 27, 2025.

Store between 15-30°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

Targeted Cancer Therapy

L01EX07 - cabozantinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

Brayfield A, Cadart C (eds). Cabozantinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/09/2025.

Cabometyx 20 mg, 40 mg, and 60 mg Film-coated Tablets (Zuellig Pharma Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 11/09/2025.

Cabometyx Tablet (Exelixis, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 11/09/2025.

Cabozantinib Ipsen 60 mg Film-coated Tablets (Ipsen Pharma). MHRA. https://products.mhra.gov.uk. Accessed 11/09/2025.

Cabozantinib S-malate. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 11/09/2025.

Cabozantinib. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 11/09/2025.

Cabozantinib. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 11/09/2025.

Cometriq 20 and 80 mg Hard Capsules (Ipsen Pharma). MHRA. https://products.mhra.gov.uk. Accessed 11/09/2025.

Cometriq Capsule (Exelixis, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 11/09/2025.

Joint Formulary Committee. Cabozantinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/09/2025.

Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. Cabometyx 20 mg, 40 mg, and 60 mg Film-coated Tablets data sheet 14 March. Medsafe. http://www.medsafe.govt.nz. Accessed 11/09/2025.