Pemindr Pralsetinib capsule

I. Drug Name

Generic Name: Pralsetinib Capsules

English Name: Pralsetinib Capsules

Brand Name: GAVRETO, Pujihua

Dosage Form: Oral Capsules

Specification: 100 mg/capsule; 60 capsules/box

Manufacturer: INDAR Pharmaceuticals Pvt Ltd

II. Indications and Usage

This product is a highly selective RET (Rearranged during Transfection) tyrosine kinase inhibitor, indicated for the treatment of:

1. Metastatic RET-fusion-positive Non-Small Cell Lung Cancer (NSCLC): Indicated for adult patients with metastatic NSCLC whose tumors have been confirmed to harbor a RET gene fusion using an FDA-approved test.

2. Advanced or Metastatic RET-mutant Medullary Thyroid Cancer (MTC): Indicated for adult and pediatric patients aged 12 years and older with advanced or metastatic MTC whose tumors have been confirmed to harbor a RET gene mutation using an FDA-approved test, and who require systemic therapy.

3. Advanced or Metastatic RET-fusion-positive Thyroid Cancer (TC): Indicated for adult and pediatric patients aged 12 years and older with advanced or metastatic TC whose tumors have been confirmed to harbor a RET gene fusion using an FDA-approved test, who require systemic therapy, and who are radioactive iodine-refractory (if applicable).

III. Dosage and Administration

Recommended Dosage: 400 mg orally once daily (i.e., four 100 mg capsules), taken on an empty stomach (at least 2 hours before a meal or at least 1 hour after a meal).

Administration Method: Swallow capsules whole; do not crush, chew, or dissolve.

Dosage Adjustment: Detailed dosage adjustment guidelines are provided for adverse reactions such as interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, and hemorrhagic events (involving dose reduction to 300 mg or 200 mg following interruption, or permanent discontinuation).

Pre-treatment Testing: Confirmation of the presence of a RET gene alteration (fusion or mutation) using an approved test method is required.

IV. Contraindications

Patients with severe hypersensitivity to pralsetinib or to any of the excipients.

V. Warnings and Precautions

1. Interstitial Lung Disease/Pneumonitis: Occurs in approximately 10% of patients, with Grade 3 or 4 events occurring in approximately 3.3%. If new or worsening symptoms such as dyspnea, cough, or fever occur, discontinue the medication immediately and conduct an assessment, including imaging studies. Once a diagnosis is confirmed, either temporarily suspend or permanently discontinue the medication based on the severity of the condition.

2.  **Hypertension:** Blood pressure should be controlled prior to initiating treatment. During the first 2 months of treatment, monitor blood pressure every 2 weeks; thereafter, monitor at least once monthly. For Grade 3 hypertension, suspend the medication until blood pressure is controlled; for a hypertensive crisis, permanently discontinue the medication.

3.  **Hepatotoxicity:** Monitor ALT/AST and bilirubin levels prior to treatment and every 2 weeks during the first 3 months of treatment; thereafter, monitor periodically. For Grade 3–4 hepatotoxicity, suspend, reduce the dose, or permanently discontinue the medication.

4.  **Hemorrhagic Events:** Serious, and potentially fatal, bleeding events may occur. Use with caution in patients at risk of bleeding. Permanently discontinue the medication in the event of serious or life-threatening hemorrhage.

5.  **Risk of Impaired Wound Healing:** Discontinue the medication at least 5 days prior to elective surgery; resume treatment post-operatively based on the status of wound healing.

6.  **Embryo-Fetal Toxicity:** May cause harm to the fetus. Women and men of reproductive potential should use effective contraception during treatment and for a period of time following the discontinuation of the medication.

**VI. Adverse Reactions**

Based on clinical trial data, common adverse reactions (incidence ≥25%) include:

**Very Common:** Musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, fever, cough.

**Laboratory Abnormalities:** Increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased blood phosphorus, decreased blood sodium, decreased blood calcium, increased alkaline phosphatase, decreased lymphocyte count.

**VII. Drug Interactions**

**Strong and Moderate CYP3A Inhibitors** (e.g., ketoconazole, clarithromycin, fluconazole, grapefruit juice): May increase plasma concentrations of pralsetinib, thereby increasing the risk of adverse reactions. Concomitant use should be avoided; if unavoidable, the dose of pralsetinib must be reduced.

**Strong and Moderate CYP3A Inducers** (e.g., rifampin, carbamazepine, St. John's wort): May significantly decrease plasma concentrations of pralsetinib, potentially compromising efficacy. Co-administration should be avoided.

P-gp and BCRP Inhibitors: May increase pratinib exposure; monitoring for adverse reactions is required.

VIII. Use in Specific Populations

Hepatic Impairment: No dose adjustment is required for mild hepatic impairment. For patients with moderate hepatic impairment, the dose should be reduced to 300 mg once daily. The recommended dose for patients with severe hepatic impairment is 200 mg once daily.

Renal Impairment: No dose adjustment is required for mild to moderate renal impairment. The recommended dose for patients with severe renal impairment or end-stage renal disease is 300 mg once daily.

Pediatric Use: Approved for use in patients aged 12 years and older with RET-mutant MTC and RET-fusion-positive TC.

Geriatric Use: Elderly patients (≥65 years) may be at a higher risk of experiencing adverse reactions (e.g., hypertension, fatigue, edema, diarrhea).

IX. Pharmacological Actions

Pharmacological Class: Selective RET tyrosine kinase inhibitor.

Mechanism of Action: Pratinib is a potent, highly selective RET inhibitor capable of inhibiting native RET signaling as well as various RET mutations that confer resistance. It inhibits tumor cell proliferation by blocking abnormal signaling pathways driven by RET fusion and mutant proteins.

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 Note:

This package insert is not a substitute for professional medical advice. Before using pratinib, patients must undergo a comprehensive evaluation by a specialist and strictly adhere to the detailed dosing instructions provided by their physician and pharmacist. RET gene testing must be performed prior to initiating treatment. Regular monitoring and follow-up are required throughout the course of treatment. Product Specifications

Product Name: Pralsetinib Capsules 100 mg * 60 Capsules/Box (Pemindr)

Common Name: Pralsetinib Capsules

Composition: Pralsetinib

Dosage Form: Oral Capsules

Specification: 100 mg/capsule; 60 capsules/box

Manufacturer: INDAR Pharmaceuticals Pvt Ltd

Indications: This product is a highly selective RET (Rearranged during Transfection) tyrosine kinase inhibitor, indicated for the treatment of:

1. Metastatic RET-fusion-positive Non-Small Cell Lung Cancer (NSCLC): Indicated for adult patients with metastatic NSCLC whose tumors have been confirmed to harbor a RET gene fusion using an FDA-approved test.

2. Advanced or Metastatic RET-mutant Medullary Thyroid Cancer (MTC): Indicated for adult and pediatric patients (aged 12 years and older) with advanced or metastatic MTC requiring systemic therapy, whose tumors have been confirmed to harbor a RET gene mutation using an FDA-approved test.

3. Advanced or Metastatic RET-fusion-positive Thyroid Cancer (TC): Indicated for adult and pediatric patients (aged 12 years and older) with advanced or metastatic TC requiring systemic therapy—and who are radioactive iodine-refractory (if applicable)—whose tumors have been confirmed to harbor a RET gene fusion using an FDA-approved test.

Dosage and Administration: Recommended Dosage: 400 mg orally once daily (i.e., four 100 mg capsules), taken on an empty stomach (at least 2 hours before a meal or at least 1 hour after a meal).

Administration Method: Swallow capsules whole; do not crush, chew, or dissolve.

Dosage Adjustments: Detailed dosage adjustment guidelines are provided for adverse reactions such as interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, and hemorrhagic events (involving temporary suspension followed by dose reduction to 300 mg or 200 mg, or permanent discontinuation).

Pre-treatment Testing: Confirmation of the presence of a RET gene alteration (fusion or mutation) using an approved test method is required.