Cabozantinib

Oral
Metastatic medullary thyroid carcinoma, Unresectable locally advanced medullary thyroid carcinoma

Oral
Advanced renal cell carcinoma, Hepatocellular carcinoma

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.

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.

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

History of haemorrhage or haemoptysis. Lactation.

Patient with hypertension, wound healing complications. Renal and hepatic impairment. Pregnancy.

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).

Do not substitute tablets with capsules.

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).

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).

May increase serum concentration with grapefruit or grapefruit juice. May decrease serum concentration with St. John’s wort.

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).

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

Store between 20-25°C. Protect from moisture.
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.

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.