EPKINLY SOLUTION FOR INJECTION 48MG/0.8ML [SIN17106P]

Product Info

EPKINLY SOLUTION FOR INJECTION 48MG/0.8ML

[SIN17106P]

Indication

2. INDICATION

2.1 Diffuse Large B-Cell Lymphoma
EPKINLY is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

2.2 Follicular Lymphoma

EPKINLY is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.

Dosing

3. DOSAGE AND ADMINISTRATION

3.1 Recommended dosage and premedications

Epcoritamab is for subcutaneous (SC) injection only. Epcoritamab should be administered by a licensed healthcare professional.

Administered epcoritamab according to the following step-up dosage (SUD) schedule in 28-day cycles which is outlined in Table 1 for patients with diffuse large B-cell lymphoma and Table 2 for patients with follicular lymphoma.

Administer epcoritamab until disease progression or unacceptable toxicity.

Premedications and Prophylaxis

Epcoritamab should be administered to adequately hydrated patients.

Details on recommended premedication for CRS is shown in Table 3.

Prophylaxis against Pneumocystis jirovecii pneumonia (PCP) and herpes virus infections is strongly recommended especially during concurrent use of steroids.

Monitor patients for potential CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) and manage per practice guidelines following EPKINLY administrations during Cycle 1 and in subsequent cycles as needed at the physician’s discretion. Counsel patients on the signs and symptoms associated with CRS and ICANS and on seeking immediate medical attention should signs or symptoms occur at any time [see Warnings and Precautions (5.1 and 5.2) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

Patients should remain within close proximity to a healthcare facility that can assess and manage potential CRS and /or ICANS for 24 hours following administration of the first full dose.

3.2 Missed or Delayed Dose

Diffuse Large B-Cell Lymphoma

A re-priming Cycle (identical to Cycle 1 with standard CRS prophylaxis) is required:

• If there are more than 8 days between the priming dose (0.16 mg) and intermediate dose (0.8 mg), or

• If there are more than 14 days between the intermediate dose (0.8 mg) and first full dose (48 mg), or

• If there are more than 6 weeks between full doses (48 mg)

After the re-priming cycle, the patient should resume treatment with Day 1 of the next planned treatment cycle (subsequent to the cycle during which the dose was delayed).

Follicular Lymphoma

A re-priming Cycle (identical to Cycle 1 with standard CRS prophylaxis) is required:

• If there are more than 8 days between the priming dose (0.16 mg) and intermediate dose (0.8 mg), or

• If there are more than 8 days between the intermediate dose (0.8 mg) and the second intermediate dose (3 mg), or

• If there are more than 14 days between the second intermediate dose (3 mg) and first full dose (48 mg), or

• If there are more than 6 weeks between full doses (48 mg)

After the re-priming cycle, the patient should resume treatment with Day 1 of the next planned treatment cycle (subsequent to the cycle during which the dose was delayed).

3.3 Dosage Modifications and Management of Adverse Reactions

Cytokine Release Syndrome (CRS)

Patients treated with EPKINLY may develop CRS.
Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 4. Patients who experience CRS should be monitored more frequently during next scheduled EPKINLY administrations.

Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)
Monitor patients for signs and symptoms of ICANS. Rule out other causes of neurologic symptoms. If ICANS is suspected, manage according to the recommendations in Table 5.

3.4 Preparation and Administration

3.4.1 Preparation of Diluted EPKINLY using the Vial Method

Read this entire section carefully before preparation of EPKINLY. Certain doses of EPKINLY require dilution prior to administration. Follow the preparation instructions provided below, as improper preparation may lead to improper dose. This section describes preparation of diluted EPKINLY using empty sterile vial method. For preparation using sterile syringe method, see subsection 3.4.2 [see Dosage and Administration (3.4.2)].

Epcoritamab should be prepared and administered by a healthcare provider as a subcutaneous injection (SC). Each vial of epcoritamab is intended for single dose only.

The administration of EPKINLY takes place over the course of 28-day cycles, following the step-up dosage schedule in Section 3.1.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Use aseptic technique to prepare EPKINLY. Filtration of the diluted solution is not required.

0.16 mg Priming Dose Preparation Instructions – (2 dilutions required) – Empty Sterile Vial Method
Use an appropriately sized syringe, vial, and needle for each transfer step.

Discard the vial and any unused portion of EPKINLY in accordance with local requirements.

0.8 mg Intermediate Dose Preparation Instructions – (1 dilution required) –Empty Sterile Vial Method
Use an appropriately sized syringe, vial, and needle for each transfer step.

Discard the vial and any unused portion of EPKINLY in accordance with local requirements.

3.4.2 Preparation of Diluted EPKINLY using the Syringe Method

Read this entire section carefully before preparation of EPKINLY. Certain doses of EPKINLY require dilution prior to administration. Follow the preparation instructions provided below, as improper preparation may lead to improper dose. This section describes preparation of diluted EPKINLY using the empty sterile syringe method. For preparation using sterile vial method, see subsection 3.4.1 [see Dosage and Administration (3.4.1)].

EPKINLY should be prepared and administered by a healthcare provider as a subcutaneous injection. Each vial of epcoritamab is intended for single dose only. The administration of EPKINLY takes place over the course of 28-day cycles, following the step-up dosage schedule in Section 3.1.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Use aseptic technique to prepare EPKINLY. Filtration of the diluted solution is not required.

0.16 mg Priming Dose Preparation Instructions (2 dilutions required) – Sterile Syringe Method
Use an appropriately sized syringe and needle for each transfer step.

Discard the vial containing unused EPKINLY.

0.8 mg Intermediate Dose Preparation Instructions (1 dilution required) – Sterile Syringe Method
Use an appropriately sized syringe and needle for each transfer step.

Discard the vial containing unused EPKINLY.

3.4.3. Preparation of 3 mg and 48 mg EPKINLY Doses

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Each vial of epcoritamab is intended for single dose only.

Use aseptic technique to prepare EPKINLY.

3 mg Second Intermediate Dose Preparation Instructions (No dilution required)

EPKINLY 3 mg second intermediate dose is required for FL patients only [see Dosage and Administration (3.1)].

Discard the vial and any unused portion of EPKINLY in accordance with local requirements.

48 mg Full Dose Preparation Instructions (No dilution required)
EPKINLY 48mg/0.8mL vial is supplied as ready-to-use solution that does not need dilution prior to administration.

Discard the vial and any unused portion of EPKINLY in accordance with local requirements.

3.4. 4. Storage of EPKINLY Solution in the Syringe

Chemical and physical in-use stability has been demonstrated for 24 hours at 2 °C to 8 °C including up to 12 hours at room temperature (20–25 °C).

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

Minimise exposure to daylight. Allow EPKINLY solution to equilibrate to room temperature before administration. Discard unused EPKINLY solution beyond the allowable storage time.

3.4.5 Site Administration
The injection site should be preferably in the lower part of abdomen or the thigh. Change of injection site from left or right side or vice versa is recommended especially during the weekly administration (Cycles 1–3).

3.5 Dosing in Special Populations

3.5.1 Pediatrics
The safety and efficacy of epcoritamab in children aged less than 18 years of age have not yet been established.

3.5.2 Geriatric
In patients with LBCL in EPCORE NHL-1, 48 (31%) were ≥65 to <75 years of age and 29 (18%) were ≥75 years of age. No clinically meaningful differences in safety or efficacy were observed between patients ≥65 years of age compared with younger adult patients.

In patients with FL in EPCORE NHL-1, 50 (39%) were ≥65 to <75 years of age and 17 (13%) were ≥75 years of age.

3.5.3 Renal impairment
Dose adjustments are not considered necessary in patients with mild to moderate renal impairment. No dose recommendations can be made for patients with severe renal impairment to end-stage renal disease.

3.5.4 Hepatic impairment
Dose adjustments are not considered necessary in patients with mild hepatic impairment. No dose recommendations can be made for patients with moderate to severe hepatic impairment.

Contraindications

4. CONTRAINDICATIONS

Hypersensitivity to the active substance or to any of the excipients listed in section 15.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.