Cabozantinib


Thông tin thuốc gốc
Chỉ định và Liều dùng
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.
Cách dùng
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.
Chống chỉ định
History of haemorrhage or haemoptysis. Lactation.
Thận trọng
Patient with hypertension, wound healing complications. Renal and hepatic impairment. Pregnancy.
Phản ứng phụ
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).
Thông tin tư vấn bệnh nhân
Do not substitute tablets with capsules.
MonitoringParameters
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).
Tương tác
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.
Tác dụng
Description: 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).
Đặc tính

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)

Bảo quản
Store between 20-25°C. Protect from moisture.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
Phân loại MIMS
Phân loại ATC
L01XE26 - cabozantinib ; Belongs to the class of protein kinase inhibitors, other antineoplastic agents. 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.

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