Ponatinib is a kinase inhibitor indicated for the:
- Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.
- Treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
Tyrosine Kinase Inhibitor
Ponatinib is a kinase inhibitor. Ponatinib inhibited the in vitro tyrosine kinase activity of ABL and T315I mutant ABL with IC 50 concentrations of 0.4 nM and 2.0 nM, respectively. Ponatinib inhibited the in vitro activity of additional kinases with IC 50 concentrations between 0.1 nM and 20 nM, including members of the VEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3. Ponatinib inhibited the in vitro viability of cells expressing native or mutant BCR-ABL, including T315I. In mice, treatment with ponatinib reduced the size of tumors expressing native or T315I mutant BCR-ABL when compared to controls.
Recommended dose: 45 mg taken orally once daily with or without food
Hepatic Impairment: 30 mg orally once daily. Modify or interrupt dosing for hematologic and non-hematologic toxicity
CYP3A inhibitors: Ponatinix is metabolized by CYP3A4. Caution should be exercised and a reduction of the starting dose of ponatinib to 30 mg should be considered with concurrent use of strong CYP3A inhibitors such as clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit juice.
Substances that may decrease ponatinib serum concentrations CYP3A inducers: Co-administration of strong CYP3A4 inducers such as carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin, and St. John's Wort with ponatinib should be avoided, and alternatives to the CYP3A4 inducer should be sought, unless the benefit
outweighs the possible risk of ponatinib underexposure.
The most common non-hematologic adverse reactions (≥20%) were, abdominal pain, rash, constipation, headache, dry skin, arterial occlusion, fatigue, hypertension, pyrexia, arthralgia, nausea, diarrhea, lipase increased, vomiting, myalgia and pain in extremity.
Based on its mechanism of action and findings in animals, Ponatinib can cause fetal harm when administered to a pregnant woman. There are no available data on Ponatinib use in pregnant women. In animal reproduction studies, oral administration of ponatinib to pregnant rats during organogenesis caused adverse developmental effects at doses lower than human exposures at the recommended human dose. Advise pregnant women of the potential risk to a fetus.
There is no data on the presence of ponatinib in human milk, the effects on the breastfed infant or on milk production.
Overdoses with ponatinib were reported in clinical trials. One patient was accidentally administered the entire contents of a bottle of study medication via nasogastric tube. The investigator estimated that the patient received 540 mg of ponatinib. Two hours after the overdose, the patient had an uncorrected QT interval of 520 ms. Subsequent ECGs showed normal sinus rhythm with uncorrected QT intervals of 480 ms and 400 ms. The patient died 9 days after the overdose from pneumonia and sepsis. Another patient accidentally self-administered 165 mg on Cycle 1 Day 2. The patient experienced fatigue and non-cardiac chest pain on Day 3. Multiple doses of 90 mg per day for 12 days in a patient resulted in pneumonia, systemic inflammatory response, atrial fibrillation, and a moderate pericardial effusion. In the event of an overdose of ponatinib, stop ponatinib, observe the patient and provide appropriate supportive treatment.
Store Ponatinib at room temperature between 20° C to 25° C
Ponatinib Hydrochloride (15mg, 45mg)
.png&w=384&q=75)