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Indications and Dosage
Oral
Advanced renal cell carcinoma Adult: Initially, 5 mg bid (given approx 12 hrly), may be increased further to 7 mg bid, then 10 mg bid, if the initial dose is tolerated (patients w/ no AR above grade 2, w/ normal BP, and are not receiving antihypertensive therapy) for at least 2 consecutive wk. If dosage reduction is needed due to AR, 5 mg bid dose may be reduced to 3 mg bid and further to 2 mg bid.
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Special Patient Group
Patients taking strong CYP3A4/5 inhibitors: Reduce to approx 50% of the usual initial dose (e.g. 5 mg bid reduced to 2 mg bid), w/ further adjustments according to response.
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Hepatic Impairment
Moderate (Child-Pugh Class B): Reduce to approx 50% of the usual initial dose (e.g. 5 mg bid reduced to 2 mg bid), w/ further adjustments according to response. Severe (Child-Pugh Class C): Contraindicated.
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Administration
May be taken with or without food.
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Contraindications
Recent active GI bleeding, untreated brain metastases. Severe hepatic impairment (Child-Pugh Class C). Lactation.
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Special Precautions
Patient w/ HTN, cardiac disease, history of or risk for thrombosis. Patients taking strong CYP3A4 inhibitors. Withhold treatment at least 24 hr prior to scheduled surgery. Moderate hepatic impairment (Child-Pugh Class B). Pregnancy.
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Adverse Reactions
Significant: HTN, posterior reversible leukoencephalopathy syndrome, proteinuria, thyroid dysfunction, increased Hb or haematocrit, impaired wound healing.
Nervous: Headache, fatigue, asthenia. GI: GI disturbance, decreased appetite, nausea, vomiting, oral mucositis, taste disturbance, vocal changes, dysphonia, abdominal pain, dyspepsia, diarrhoea, constipation. Hepatic: Increased hepatic enzymes and bilirubin. Endocrine: Wt loss. Musculoskeletal: Arthralgia, myalgia. Dermatologic: Palmar-plantar erythrodysaesthesia, rash, dry skin, itch, erythema, alopecia. Others: Electrolyte disturbance. Potentially Fatal: Cardiac failure, arterial thrombotic events (e.g. MI, TIA, CVA, retinal artery exclusion), venous thrombotic events (e.g. DVT, pulmonary embolism, retinal vein occlusion or thrombosis), hypertensive crisis, haemorrhagic events (e.g. GI or cerebral haemorrhage, haemoptysis, haematuria, melaena), GI perforation and fistula formation. |
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Patient Counseling Information
This drug may cause dizziness and fatigue, if affected, do not drive or operate machinery.
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Monitoring Parameters
Monitor BP, Hb or haematocrit, LFT, thyroid function, and urinalysis (for proteinuria) prior to and during treatment.
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Overdosage
Symptoms: Dizziness, HTN, seizures, haemoptysis. Management: Supportive treatment.
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Drug Interactions
Plasma concentration is increased by strong CYP3A4/5 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin) and decreased by strong CYP3A4/5 inducers (e.g. rifampicin, phenytoin, carbamazepine). May enhance adverse effects (e.g. osteonecrosis of the jaw) of bisphosphonate derivatives.
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Food Interaction
Increased plasma concentrations w/ grapefruit or grapefruit juice. Reduced plasma concentrations w/ St John’s wort.
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Action
Description:
Mechanism of Action: Axitinib, a selective 2nd generation tyrosine kinase inhibitor, blocks angiogenesis, tumour growth, and cancer progression by inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3). Pharmacokinetics: Absorption: Rapidly absorbed from the GI tract. Bioavailability: Approx 58%. Time to peak plasma concentration: 2.5-4 hr. Distribution: Volume of distribution: 160 L. Plasma protein binding: >99%, mainly to albumin and α1-acid glycoprotein. Metabolism: Metabolised in the liver mainly by CYP3A4/5, and to a lesser extent by CYP1A2, CYP2C19, and UGT1A1. Excretion: Via faeces (approx 41%, 12% as unchanged drug) and urine (approx 23%, as metabolites). Elimination half-life: 2.5-6.1 hr. |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Database. Axitinib, CID=6450551, https://pubchem.ncbi.nlm.nih.gov/compound/Axitinib (accessed on Jan. 21, 2020) |
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Storage
Store between 20-25°C.
This is a cytotoxic drug. Use appropriate personal protective equipment (e.g. gloves) for receiving, handling, admin, and disposal. Any unused portions should be disposed of in accordance w/ local requirements. |
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MIMS Class
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ATC Classification
L01EK01 - axitinib ; Belongs to the class of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors. Used in the treatment of cancer.
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References
Anon. Axitinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/05/2017 . Buckingham R (ed). Axitinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/05/2017 . Inlyta Tablet, Film Coated (Pfizer Laboratories Div, Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/05/2017 . Joint Formulary Committee. Axitinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/05/2017 . McEvoy GK, Snow EK, Miller J et al (eds). Axitinib. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 03/05/2017 .
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