[Key Drug Information]

Chinese Name: Ponatinib Tablets (Ponatinib Hydrochloride)

English Name: Ponatinib Hydrochloride

Brand Names: Iclusig, ALIPONATIB

Generic Name: Ponatinib Hydrochloride (also known as Panatinib)

Dosage Form: Oral Film-Coated Tablets

Specifications: 15 mg × 30 tablets/box; 45 mg × 30 tablets/box

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Approval Numbers (Lao National Drug Administration): 11L1416/25 / 11L 1417/25

Pharmacological Action: A potent, oral, multi-targeted tyrosine kinase inhibitor. It not only inhibits unmutated and all known mutated forms of the Bcr-Abl fusion protein (including the highly resistant T315I mutation) but also acts on multiple targets—such as VEGFR, PDGFR, FGFR, KIT, and RET—thereby exerting anti-angiogenic and anti-tumor effects.

[Indications]

Indicated for the treatment of the following conditions in adults, primarily for patients who are resistant to or intolerant of prior tyrosine kinase inhibitor therapies:

1. Chronic Myeloid Leukemia (CML): Including the chronic phase, accelerated phase, or blast phase.

2. Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL).

3. T315I-positive CML or Ph+ ALL.

> Note: This drug has been approved in the United States for use in combination with chemotherapy as a first-line treatment for Ph+ ALL. ...ALL, and was approved for marketing in China in 2024.

【Dosage and Administration】

Recommended Starting Dose: 45 mg, once daily, orally.

Method of Administration: May be taken with or without food. Tablets should be swallowed whole; do not crush, chew, or break them.

Important Dosage Adjustments: Clinically, a significant proportion of patients (e.g., 59%) require a dose reduction during treatment from 45 mg once daily to 30 mg or 15 mg once daily. Specifically, for patients with chronic-phase CML who have achieved a major cytogenetic response, a dose reduction to 15 mg once daily should be considered to mitigate the risk of adverse reactions. Specific dosage adjustments must be strictly determined by a physician based on the patient's tolerability and therapeutic response.

Missed Dose: If a dose is missed, do not take a double dose to make up for it; simply resume the regular dosing schedule with the next scheduled dose.

【Important Warnings and Precautions (Including Boxed Warnings)】

Ponatinib carries a Boxed Warning; particular attention must be paid to the following risks, which may be severe or even fatal:

Risk Category: Specific Risks and Monitoring Requirements

Vascular Occlusive Events: High incidence of arterial and venous thrombosis/occlusion (reaching 27% in studies), including myocardial infarction, stroke, peripheral vascular disease (potentially leading to amputation), venous thromboembolism, etc. Monitor for any associated symptoms.

Heart Failure: Fatal heart failure may occur. Cardiac function and symptoms of heart failure (e.g., shortness of breath, lower extremity edema) must be monitored during treatment.

Hepatotoxicity: May lead to liver injury, liver failure, or even death. Liver function must be monitored regularly prior to and during treatment.

Hypertension: High incidence (reaching 67% in studies). Blood pressure must be controlled prior to treatment, and monitored and managed regularly throughout treatment.

Pancreatitis: The incidence of clinical pancreatitis is 6%. Serum lipase levels must be monitored regularly during treatment.

Myelosuppression: Common; may lead to neutropenia, thrombocytopenia, and anemia. Complete blood counts must be monitored regularly.

Other Important Precautions:

Pre- and Post-Surgery: May impair wound healing. The drug should be discontinued 1 week prior to elective surgery, and for at least 2 [weeks] following major surgery... Resume medication only after the wound has healed well.

Risk of Infection: May increase the risk of infection.

Posterior Reversible Encephalopathy Syndrome (PRES): Rare but serious; seek immediate medical attention if symptoms such as headache, seizures, or confusion occur.

Avoid Concomitant Use: Avoid consuming grapefruit or drinking grapefruit juice.

[Adverse Reactions]

Very Common Adverse Reactions (high incidence): Hypertension, rash, abdominal pain, constipation, headache, fatigue, arthralgia, nausea.

Serious but Common Adverse Reactions: Thrombotic events, heart failure, liver injury, pancreatitis, myelosuppression.

Common Laboratory Abnormalities: Elevated transaminases, elevated lipase, thrombocytopenia, anemia.

[Drug Interactions]

Strong CYP3A4 Inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir): Significantly increase plasma concentrations of ponatinib. When co-administered, consider reducing the ponatinib dosage to 30 mg once daily.

Strong CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin (e.g., St. John's Wort): May reduce plasma concentrations of ponatinib, thereby compromising efficacy; concomitant use should be avoided.

Others: Potential interactions may also exist with certain antihypertensive agents, anticoagulants, lipid-lowering agents, and gastrointestinal medications (e.g., proton pump inhibitors). Patients must inform their physician of all medications they are currently taking prior to initiating treatment.

【Use in Specific Populations】

Pregnant Women: Contraindicated. Animal studies have demonstrated reproductive toxicity and a clear risk to the fetus. Women of childbearing potential and men must employ highly effective contraceptive measures during treatment and for at least 3 weeks following the final dose.

Breastfeeding Women: Contraindicated. Breastfeeding is not recommended during treatment and for at least 1 week following the final dose.

Children and Adolescents (<18 years): Safety and efficacy have not been established; contraindicated.

Elderly Patients: Should be used with caution, as the risk of adverse reactions may be higher.

Hepatic Impairment: Dose adjustment may be required for patients with mild to moderate impairment; use with caution in patients with severe impairment.

Renal Impairment: Dose adjustment is typically not required for patients with mild to moderate impairment, but close monitoring is necessary; data are limited for patients with severe impairment.

【Storage】

Store at room temperature (20–25°C) in the original packaging, protected from light and moisture.

【Important Note】

Ponatinib is a pivotal medication for overcoming drug resistance—particularly in cases of CML and Ph+ ALL harboring the T315I mutation—yet it is associated with significant vascular-related toxicities. Its initial dosing and dose reduction strategies (e.g., reducing the dose from 45 mg to 15 mg) are critical for balancing therapeutic efficacy with safety.

This package insert synthesizes global regulatory information, the latest clinical research findings, and patient guidelines; it is intended to serve as a comprehensive reference but does not substitute for the prescription and guidance of a qualified medical professional.

All treatment decisions must be made by an experienced hematologist following a thorough assessment of the individual patient's specific clinical circumstances.