Products
Ponatinib is commercially available in film-coated tablet form (Iclusig). It was approved in the EU in 2013 and in many countries in 2014.
Structure and properties
Ponatinib (C29H27F3N6O, Mr = 532.6 g/mol) is present in the drug as ponatinib hydrochloride, a white to yellow powder whose water solubility decreases with increasing pH. It is a fluorinated imidazopyridazine, a piperazine and benzdamide derivative. The triple bond is a special feature.
Effects
Ponatinib (ATC L01XE24) has antiproliferative and selective cytostatic properties. The effects are due to high-affinity binding to BCR-ABL kinase and inhibition of cell proliferation. Ponatinib is also effective against mutant variants of the kinase (particularly T315I mutation) and therefore can be used in cases of resistance to other BCR-ABL inhibitors. Ponatinib has a long half-life of approximately 22 hours.
Indications
- Chronic myeloid leukemia (for resistance or intolerance to dasatinib or nilotinib, for a T315I mutation).
- Philadelphia chromosome-positive acute lymphoblastic leukemia (for resistance or intolerance to dasatinib, for a T315I mutation).
Dosage
According to the professional information. The drug is taken once a day, regardless of meals.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Ponatinib is metabolized by CYP3A4 and corresponding drug-drug interactions with CYP inhibitors and inducers are possible. Drugs that increase gastric pH may reduce bioavailability (eg, PPIs).
Adverse effects
The most common possible adverse effects a decreased platelet count, rash, dry skin, and abdominal pain. Severe possible adverse effects include arterial thrombosis and liver toxicity.
