Ponatinib Hydrochloride (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ICLUSIG
- PONATINIB HYDROCHLORIDE
Indications and Usage
ICLUSIG® is indicated for the treatment of adult patients with: Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Newly diagnosed Ph+ ALL in combination with chemotherapy. This indication is approved under accelerated approval based on minimal residual disease (MRD)-negative complete remission (CR) at the end of induction [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s). As monotherapy in Ph+ ALL for whom no other kinase inhibitors are indicated or T315I-positive Ph+ ALL. Chronic Myeloid Leukemia (CML) Chronic phase (CP) CML with resistance or intolerance to at least two prior kinase inhibitors. Accelerated phase (AP) or blast phase (BP) CML for whom no other kinase inhibitors are indicated. T315I-positive CML (chronic phase, accelerated phase, or blast phase).
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Arterial Occlusive Events [see Warnings and Precautions (5.1)] Venous Thromboembolic Events [see Warnings and Precautions (5.2)] Heart Failure [see Warnings and Precautions (5.3)] Hepatotoxicity [see Warnings and Precautions (5.4)] Hypertension [see Warnings and Precautions (5.5)] Pancreatitis [see Warnings and Precautions (5.6)] Neuropathy [see Warnings and Precautions (5.8)] Ocular Toxicity [see Warnings and Precautions (5.9)] Hemorrhage [see Warnings and Precautions (5.10)] Fluid Retention [see Warnings and Precautions (5.11)] Cardiac Arrhythmias [see Warnings and Precautions (5.12)] Myelosuppression [see Warnings and Precautions (5.13)] Tumor Lysis Syndrome [see Warnings and Precautions (5.14)] Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.15)] Impaired Wound Healing and Gastrointestinal Perforation [see Warnings and Precautions (5.16)]
Mechanism of Action
Ponatinib is a kinase inhibitor. Ponatinib inhibited the in vitro tyrosine kinase activity of ABL and T315I mutant ABL with IC50 concentrations of 0.4 nM and 2.0 nM, respectively. Ponatinib inhibited the in vitro activity of additional kinases with IC50 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.
Overdosage
Overdoses with ICLUSIG were reported in clinical trials. One patient was estimated to have been administered 540 mg via nasogastric tube. Two hours after the overdosage, 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 overdosage from pneumonia and sepsis. Another patient 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 overdosage, stop ICLUSIG, observe the patient and provide supportive treatment as appropriate.