ALIPEMETINIB Pemigatinib Tablets 4.5mg

I. Drug Name

Generic Name: Pemigatinib Tablets

English Name: Pemigatinib Tablets

Brand Names: PEMAZYRE, Dabotan, ALIPEMETINIB

Dosage Form: Oral Tablets

Specification: 4.5 mg per tablet; 14 tablets per box

Target: FGFR1/2/3 kinase inhibitor (IC50 < 2 nM); exhibits weaker inhibition of FGFR4.

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Lao National Drug Administration Approval No.: 09L 1383/25

II. Indications and Usage

This product is a selective fibroblast growth factor receptor inhibitor indicated for the treatment of:

1.  Cholangiocarcinoma: Indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements.

2.  Myeloid/Lymphoid Neoplasms: Indicated for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements.

Key Prerequisite: Prior to use, the presence of the corresponding FGFR gene alteration must be confirmed using an approved diagnostic test.

III. Dosage and Administration

Recommended Dosage:

"2 Weeks On, 1 Week Off" Schedule: 13.5 mg orally once daily on Days 1 through 14 of each 21-day cycle. No drug is taken on Days 15 through 21.

Continuous Dosing Schedule (for specific situations or following adjustment): 13.5 mg orally once daily, taken continuously until disease progression or unacceptable toxicity occurs.

Administration Method: May be taken with or without food. Tablets should be swallowed whole; do not crush, chew, or dissolve. If a dose is missed or vomiting occurs, do not take a missed dose; resume dosing with the next scheduled dose.

Dosage Adjustment: Detailed dosage adjustment guidelines are provided for hyperphosphatemia, ocular toxicity, and other adverse reactions (involving dose reduction to 9 mg or 4.5 mg, or temporary/permanent discontinuation).

IV. Contraindications

Patients with severe hypersensitivity to Pemigatinib Tablets or to any of the excipients. V. Warnings and Precautions

1.  **Ocular Toxicity:** The most common manifestations are central serous retinopathy and retinal pigment epithelial detachment. Patients should undergo a comprehensive ophthalmologic examination—including Optical Coherence Tomography (OCT)—prior to treatment, at 1 month after initiating treatment, every 3 months thereafter, and immediately upon the onset of any visual symptoms. If Grade 2 or higher retinal toxicity occurs, the drug should be temporarily withheld and restarted at a reduced dose upon resolution; if Grade 4 retinal toxicity occurs, the drug should be permanently discontinued.

2.  **Hyperphosphatemia and Soft Tissue Mineralization:** Hyperphosphatemia is a pharmacodynamic effect with an incidence rate of >90%. Serum phosphate levels must be monitored regularly. For persistent or recurrent Grade 2 (>5.5–7.0 mg/dL) or higher hyperphosphatemia, phosphate-lowering agents (e.g., phosphate binders) should be initiated, and dose adjustments should be made based on serum phosphate levels and the severity of mineralization-related adverse reactions.

3.  **Embryo-Fetal Toxicity:** This drug may cause fetal harm. Patients of reproductive potential must use effective contraception.

VI. Adverse Reactions

Based on clinical trial data, common adverse reactions (incidence ≥20%) include:

Hyperphosphatemia (incidence >90%), nail toxicity, alopecia, diarrhea, fatigue, nausea, constipation, stomatitis, abdominal pain, dry mouth, dry skin, decreased appetite, vomiting, arthralgia, dysgeusia, and back pain.

Laboratory Abnormalities: Increased serum creatinine, increased serum phosphate, decreased serum calcium, decreased serum sodium, increased alkaline phosphatase, and lymphopenia.

VII. Drug Interactions

**Strong CYP3A4 Inducers** (e.g., rifampin, phenytoin, carbamazepine, St. John's wort): These agents significantly decrease the plasma concentration of pemigatinib tablets, thereby compromising efficacy; concomitant use should be avoided.

**Strong CYP3A4 Inhibitors** (e.g., itraconazole, clarithromycin): These agents may increase the plasma concentration of pemigatinib tablets, thereby increasing the risk of adverse reactions. When used concomitantly, consideration should be given to reducing the dose of Pemigatinib tablets to 9 mg once daily (intermittent regimen).

VIII. Use in Specific Populations

Hepatic Impairment: No dose adjustment is required for mild hepatic impairment. For patients with moderate hepatic impairment, the recommended dose is 9 mg once daily (intermittent regimen). Use is not recommended in patients with severe hepatic impairment.

Renal Impairment: No dose adjustment is required for mild to moderate renal impairment. For patients with severe renal impairment or end-stage renal disease (CLcr < 30 mL/min), the recommended dose is 9 mg once daily (intermittent regimen).

Pediatric Use: Safety and efficacy have not been established.

Geriatric Use: No specific adjustment to the starting dose is required.

IX. Pharmacological Actions

Pharmacologic Class: Selective FGFR 1, 2, and 3 tyrosine kinase inhibitor.

Mechanism of Action: Pemigatinib tablets inhibit the proliferation, survival, and migration of tumor cells harboring FGFR gene alterations by selectively inhibiting the activity of FGFR1-3 and blocking downstream signaling pathways.

X. Storage

Store at room temperature between 20°C and 25°C; excursions between 15°C and 30°C are permitted during short-term transport.

Keep the medication in its original packaging to protect it from moisture.

Keep out of reach of children.

Important Notice:

This package insert is not a substitute for professional medical advice. Before using Pemigatinib tablets, patients must undergo a comprehensive evaluation by a specialist physician and strictly adhere to the detailed medication instructions provided by their physician and pharmacist. FGFR gene testing must be performed prior to initiating treatment. During treatment, regular ophthalmologic examinations, monitoring of serum phosphate levels, and management of adverse reactions are mandatory.