Ponatinib(Iclusig)

Ponatinib was first approved for marketing in the United States in December 2012. As a prescription drug acting on multiple targets including BCR-ABL (including T315I mutation), VEGFR, PDGFR, FGFR, EPH receptors, SRC family kinases, KIT, RET, TIE2 and FLT3, it must be used strictly in accordance with the doctor’s instructions.

Targets of Action

BCR-ABL (including T315I mutation), VEGFR, PDGFR, FGFR, EPH receptors, SRC family kinases, KIT, RET, TIE2, FLT3, etc.

Mechanism of Action

Ponatinib helps inhibit the production of cancer cells by the oncogenic BCR-ABL1 fusion protein. Studies have shown that Ponatinib remains effective even when the protein has mutations such as the T315I mutation.

Dosage and Administration

Route and Frequency of Administration for Ponatinib: One tablet once daily.

The dosage of Ponatinib shall be adjusted according to the patient's actual condition. For specific circumstances, patients should consult their doctors and strictly follow the medical advice.

Recommended Reading: Dosage and Administration of Ponatinib

Adverse Reactions

Major Risks and Warnings: Arterial occlusive events, venous thromboembolic events, heart failure and hepatotoxicity.

Severe Adverse Reactions: Vascular (arterial and venous) thrombosis or occlusion, cardiac disorders, hepatic disorders.

Reference Article: Adverse Reactions of Ponatinib

Use in Special Populations

Lactation: Women are advised not to breastfeed during Ponatinib treatment and within 1 week after the last dose.

Women and Men of Reproductive Potential: Before initiating Ponatinib treatment, it is necessary to confirm the pregnancy status of women of reproductive potential. Ponatinib may impair female fertility, and it is currently unclear whether this effect is reversible.

Pre-existing Hepatic Impairment:For patients receiving monotherapy for chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia (CP-CML), accelerated-phase Philadelphia chromosome-positive chronic myeloid leukemia (AP-CML), blast-phase Philadelphia chromosome-positive chronic myeloid leukemia (BP-CML), and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who have pre-existing hepatic impairment, the initial dose of Ponatinib should be adjusted to 30 mg orally once daily.For patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who only have mild hepatic impairment, no dosage adjustment is required when using Ponatinib.

Precautions for Daily Use

1. Patients are advised to swallow the Ponatinib tablets whole; do not cut, crush or dissolve the tablets. Patients should avoid drinking grapefruit juice or eating grapefruits, as these may increase the risk of adverse reactions to Ponatinib.

2. If a patient misses a dose of Ponatinib, the next dose should be taken at the regular time; do not take a double dose to make up for the missed one.

3. There is a risk of arterial occlusive events and venous thromboembolic events. If a patient experiences any symptoms suggestive of a thromboembolic event (such as chest pain or pressure, shortness of breath, unilateral numbness or weakness, speech disturbance, headache, vision changes, severe abdominal pain, leg pain or swelling, or pain in the arms, back, neck or jaw), the patient should seek medical attention immediately and contact the clinician.

FDA,2022.02