Drug reference

Ponatinib

Tyrosine Kinase Inhibitor · Antineoplastic

Also known as Ponatinib hydrochloride, Iclusig

Tyrosine Kinase InhibitorAntineoplastic

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Avoid—toxicity in animal studies. See also

FDA category + note

Top interactionssee all 12 →

AbciximabSevereDatabaseDDInter
AcalabrutinibSevereDatabaseDDInter
AdalimumabSevereDatabaseDDInter
AlteplaseSevereDatabaseDDInter

Mechanism

Inhibits Bcr-Abl tyrosine kinase and retains activity in imatinib-resistant Bcr-Abl mutations including the T315I gatekeeper mutation. It also inhibits other tyrosine kinases, including VEGFR, PDGFR, FGFR, Flt3, Src family kinases, Kit, Ret, and EPH.

Indications

Chronic myeloid leukaemia (chronic-, accelerated- or blast-phase) in adults when resistant to dasatinib or nilotinibChronic myeloid leukaemia (chronic-, accelerated- or blast-phase) in adults when intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriateChronic myeloid leukaemia (chronic-, accelerated- or blast-phase) in adults when the T315I gene mutation is presentPhiladelphia-chromosome-positive acute lymphoblastic leukaemia in adults when resistant to dasatinibPhiladelphia-chromosome-positive acute lymphoblastic leukaemia in adults when intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriatePhiladelphia-chromosome-positive acute lymphoblastic leukaemia in adults when the T315I gene mutation is presentresistant CMLPh+ ALLT315I mutationFailure of ≥2 tyrosine kinase inhibitors

Dosing

Adult: l INDICATIONS AND DOSE Treatment of chronic, accelerated, or blast phase chronic myeloid leukaemia in patients who have the T315I mutation or who have resistance to or intolerance of dasatinib or nilotinib, and for whom subsequent treatment with imatinib is not clinically appropriate | Treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia in patients who have the T315I mutati…

Pharmacokinetics

Peak effect

within 6 h

Half-life

about 24 h

Bioavailability

altered by drugs affecting gastric pH

Protein binding

99% (highly bound to plasma proteins)

Metabolism

CYP3A4 (primarily), CYPs 2C8, 2D6, and 3A511 (to a lesser extent); esterases; and amidases

Excretion

primarily in the feces (87%), small portion in urine (5%)

Contraindications

Vascular occlusion
Thromboembolism
Myocardial ischaemia
Myocardial infarction
Hypertensive crisis
Major surgical procedures (due to impaired wound healing risk)
Predisposition to bleeding

Side effects

Common

HypertensionSkin rashskin rashes (10–20%)pancreatitis (10%)elevations of amylase/lipase (10%)systemic hypertension (10–15%; severe in 20%)

Serious

Hepatotoxicity
Bleeding complications
Arterial thromboembolic events
Cardiac arrhythmias
Fluid retention
Gastrointestinal perforation
Wound healing complications
Vascular occlusion
Thromboembolism
Myocardial ischaemia
Myocardial infarction
Hypertensive crisis
arterial thrombosis
elevated lipase and amylase levels
pancreatitis
arterio-occlusive events (cardiovascular, cerebrovascular, and peripheral arterial) (10-20%, highest incidence among TKIs)
vasospastic or vaso-occlusive events