Adult: Patient with T315I mutation, resistant or intolerant to tyrosine kinase inhibitors (e.g. dasatinib, nilotinib) and for whom subsequent treatment with imatinib is not clinically appropriate: Initially, 45 mg once daily. Continue treatment until disease progression or unacceptable toxicity occurs. May reduce dose in patients with chronic or accelerated phase who have achieved a major cytogenetic response. Discontinue treatment if no response is achieved after 3 months. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Mild to severe (Child-Pugh class A, B or C): Initially, 30 mg once daily.
May be taken with or without food. Swallow whole. Do not crush/dissolve tab.
Patients with history of cardiac disease, ischaemia, hypertension, diabetes, hyperlipidaemia, hepatitis B infection, history of MI or stroke, pancreatitis, alcohol abuse. Not recommended for treatment of newly diagnosed chronic phase myeloid leukaemia. Renal (CrCl <50 mL/min or ESRD) and hepatic impairment. Elderly. Pregnancy. Patient taking strong CYP3A inhibitors.
This drug may cause dizziness, lethargy or blurred vision, if affected, do not drive or operate machinery.
Assess CV status prior and during therapy. Monitor CBC with differential and platelets every 2 weeks for the 1st 3 months and monthly thereafter or as indicated; LFT at baseline and monthly thereafter or as clinically indicated; serum lipase every 2 weeks for the 1st 2 months then monthly thereafter. Perform ocular exam at baseline and periodically. Monitor cardiac function, blood pressure, serum electrolytes, uric acid. Monitor for signs and symptoms of arterial or venous occlusion or thromboembolism, hepatotoxicity (e.g. jaundice, anorexia, bleeding, bruising), haemorrhage, fluid retention, pancreatitis, gastrointestinal perforation, neuropathy.
Increased ponatinib serum concentration with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, indinavir, nefazodone, nelfinavir, saquinavir, boceprevir, telaprevir). Decreased ponatinib serum concentration with strong CYP3A4 inducers (e.g. rifampin, carbamazepine, phenobarbital, phenytoin). May increase plasma concentrations of substrates of P-glycoprotein (e.g. digoxin, dabigatran, colchicine, pravastatin) or breast cancer resistance protein (e.g. methotrexate, rosuvastatin, sulfasalazine).
Increased ponatinib serum concentration with grapefruit juice. Decreased ponatinib serum concentration with St. John’s Wort.
Description: Ponatinib is a tyrosine kinase inhibitor that blocks the activity of cells expressing native or mutant BCR-ABL including T315I. It also inhibits the activities of VEGFR, FGFR, PDGFR, EPH, SRC kinases, KIT, RET, TIE2 and FLT3. Pharmacokinetics: Absorption: Time to peak plasma concentration: ≤6 hours. Distribution: Volume of distribution: 1,223 L. Plasma protein binding: >99%. Metabolism: Undergoes phase I metabolism in the liver mainly by CYP3A4, and to a lesser extent by CYP2C8, CYP2D6 and CYP3A5; phase II metabolism by esterases and or/amidases. Excretion: Via faeces (approx 87%); urine (approx 5%). Elimination half-life: Approx 24 hours (range: 12-66 hours).
L01EA05 - ponatinib ; Belongs to the class of BCR-ABL tyrosine kinase inhibitors. Used in the treatment of cancer.
Anon. Ponatinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 17/12/2019.Buckingham R (ed). Ponatinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/12/2019.Iclusig Tablets (Millennium Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 17/12/2019.Joint Formulary Committee. Ponatinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/01/2020.