Ponatinib


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Chronic phase chronic myeloid leukaemia; Accelerated phase chronic myeloid leukaemia; Blast phase chronic myeloid leukaemia; Philadelphia chromosome-positive acute lymphoblastic leukaemia 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: Initial: 45 mg once daily. Continue treatment until disease progression or unacceptable toxicity occurs. 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).
Dosage Details
Oral
Accelerated phase chronic myeloid leukaemia, Blast phase chronic myeloid leukaemia, Chronic phase chronic myeloid leukaemia, Philadelphia chromosome-positive acute lymphoblastic leukaemia
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).
Special Patient Group
Patient taking strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin, indinavir, nefazodone, nelfinavir, saquinavir, boceprevir, telaprevir, grapefruit juice): Initially, 30 mg once daily.
Hepatic Impairment
Mild to severe (Child-Pugh class A, B or C): Initially, 30 mg once daily.
Administration
May be taken with or without food. Swallow whole. Do not crush/dissolve tab.
Contraindications
Lactation.
Special Precautions
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.
Adverse Reactions
Significant: Myelosuppression (e.g. thrombocytopenia, neutropenia, anaemia), fluid retention (e.g. peripheral oedema, pleural and pericardial effusions, peripheral swelling), cardiac arrhythmias (e.g. atrial fibrillation, bradyarrhythmia, tachyarrhythmia), retinal arterial occlusions, renal artery stenosis, venous thromboembolism (e.g. DVT, pulmonary embolism, thrombophlebitis, retinal vein thrombosis), hypertension (e.g. symptomatic hypertension, hypertensive crisis), ocular toxicity (e.g. blindness, blurred vision, corneal erosion, dry eye, conjunctivitis), reversible posterior leucoencephalopathy syndrome (e.g. seizure, headache, neurological disturbances, altered mental status), pancreatitis, hyperuricaemia, neuropathy (e.g. peripheral neuropathy, paraesthesia, hypoesthesia, hyperesthesia, dysgeusia, muscular weakness), wound healing impairment. Rarely, gastrointestinal perforation (fistula), cranial neuropathy and tumour lysis syndrome.
Cardiac disorders: Angina pectoris, decreased ejection fraction, pericardial effusion, peripheral ischaemia, dyspnoea.
Eye disorders: Visual impairment, periorbital oedema, eyelid oedema, eye pain.
Endocrine disorders: Hypothyroidism.
Gastrointestinal disorders: Abdominal pain, diarrhoea, vomiting, constipation, nausea, stomatitis.
General disorders and administration site conditions: Lethargy, fatigue, pyrexia, chills.
Infections and infestations: Sepsis, folliculitis, cellulitis.
Investigations: Decreased weight; increased lipase, AST, ALT, bilirubin, alkaline phosphatase.
Metabolism and nutrition disorders: Decreased appetite, dehydration, hypocalcaemia, hyperglycaemia, hypophosphataemia, hypertriglyceridaemia, hypokalaemia, hyponatraemia.
Musculoskeletal and connective tissue disorders: Bone pain, back pain, arthralgia, myalgia, pain in extremity, muscle spasms, musculoskeletal pain, neck pain.
Nervous system disorders: Headache, dizziness, cerebrovascular accident, cerebral infarction, migraine.
Psychiatric disorders: Insomnia.
Reproductive system and breast disorders: Erectile dysfunction.
Respiratory, thoracic and mediastinal disorders: Cough, pneumonia, upper respiratory tract infection.
Skin and subcutaneous tissue disorders: Rash, dry skin, pruritus, erythema, alopecia.
Vascular disorders: Transient ischaemic attack, epistaxis.
Potentially Fatal: Arterial occlusion (e.g. MI, stroke), brain oedema, heart failure, left ventricular dysfunction, hepatic failure, severe haemorrhage (e.g. gastrointestinal haemorrhage, subdural haematoma), hepatitis B reactivation, peripheral arterial occlusive events (e.g. mesenteric artery occlusion, peripheral arterial disease).
Patient Counseling Information
This drug may cause dizziness, lethargy or blurred vision, if affected, do not drive or operate machinery.
MonitoringParameters
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.
Overdosage
Symptoms: Pneumonia, systemic inflammatory response, atrial fibrillation, and asymptomatic, moderate pericardial effusion. Management: Supportive treatment.
Drug Interactions
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).
Food Interaction
Increased ponatinib serum concentration with grapefruit juice. Decreased ponatinib serum concentration with St. John’s Wort.
Action
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).
Chemical Structure

Click on icon to see table/diagram/image
Storage
Store between 20-25°C.
ATC Classification
L01XE24 - ponatinib ; Belongs to the class of protein kinase inhibitors, other antineoplastic agents. Used in the treatment of cancer.
Disclaimer: This information is independently developed by MIMS based on Ponatinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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