CD20 monoclonal antibodies
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Epkinly Dosage

Drug Detail:Epkinly (Epcoritamab-bysp)

Generic Name: epcoritamab 48mg in 0.8mL

Dosage Form: injection, solution

Drug Class: CD20 monoclonal antibodies

Contents
Uses Warnings Before Taking Dosage Side effects Interactions

Important Dosing Information

  • Administer EPKINLY to well-hydrated patients.
  • Premedicate before each dose in Cycle 1 [see Dosage and Administration (2.4)].
  • EPKINLY should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) [see Warnings and Precautions (5.1, 5.2)].
  • Administer EPKINLY subcutaneously according to the dosage schedule in Table 1 to reduce the incidence and severity of CRS. Due to the risk of CRS and ICANS, patients should be hospitalized for 24 hours after administration of the Cycle 1 Day 15 dosage of 48 mg [see Dosage and Administration (2.2) and Warnings and Precautions (5.1, 5.2)].

Recommended Dosage

EPKINLY is for subcutaneous injection only.

The recommended dosage schedule for EPKINLY is provided in Table 1. Administer EPKINLY in 28-day cycles until disease progression or unacceptable toxicity.

Table 1: EPKINLY Dosage Schedule
Cycle of treatment* Day of treatment Dose of EPKINLY
*
Cycle = 28 days
Cycle 1 1 Step-up dose 1 0.16 mg
8 Step-up dose 2 0.8 mg
15 First full dose 48 mg
22 48 mg
Cycles 2 and 3 1, 8, 15 and 22 48 mg
Cycles 4 to 9 1 and 15 48 mg
Cycle 10 and beyond 1 48 mg

Restarting EPKINLY after Dosage Delay

If a dose of EPKINLY is delayed, restart therapy based on the recommendations made in Table 2 and resume the treatment schedule accordingly [see Dosage and Administration (2.2)].

Table 2: Recommendations for Restarting Therapy with EPKINLY After Dosage Delay
Last Dose Administered Time Since the Last Dose Administered Action for Next Dose(s)*
*
Administer pretreatment medication prior to EPKINLY dose and monitor patients accordingly [see Dosage and Administration (2.4, 2.6)].
0.16 mg on Cycle 1 Day 1 More than 8 days Repeat 0.16 mg, then administer 0.8 mg the following week, followed by two weekly doses of 48 mg. Then resume the planned dosage schedule beginning with Day 1 of the subsequent cycle.
0.8 mg on Cycle 1 Day 8 14 days or less Administer 48 mg then resume the recommended dosage schedule.
More than 14 days Repeat 0.16 mg, then administer 0.8 mg the following week, followed by two weekly doses of 48 mg. Then resume the planned dosage schedule beginning with Day 1 of the subsequent cycle.
48 mg on Cycle 1 Day 15 onwards 6 weeks or less Administer 48 mg, then resume the recommended dosage schedule.
More than 6 weeks Repeat 0.16 mg, then administer 0.8 mg the following week, followed by two weekly doses of 48 mg. Then resume the planned dosage schedule beginning with Day 1 of the subsequent cycle.

Recommended Premedications

Administer premedications as outlined in Table 3 to reduce the risk of CRS [see Warnings and Precautions (5.1)].

Table 3: EPKINLY Premedications
Cycle Patients requiring premedication Premedication Administration
*
Patients will be permanently discontinued from EPKINLY after Grade 4 CRS.
Cycle 1 All patients
  • Prednisolone (100 mg oral or intravenous) or Dexamethasone (15 mg oral or intravenous) or equivalent
  • 30-120 minutes prior to each weekly administration of EPKINLY
  • And for three consecutive days following each weekly administration of EPKINLY in Cycle 1
  • Diphenhydramine (50 mg oral or intravenous) or equivalent
  • Acetaminophen (650 to 1,000 mg oral)
  • 30-120 minutes prior to each weekly administration of EPKINLY
Cycle 2+ Patients who experienced Grade 2 or 3* CRS with previous dose
  • Prednisolone (100 mg oral or intravenous) or Dexamethasone (15 mg oral or intravenous) or equivalent
  • 30-120 minutes prior to next administration of EPKINLY after a Grade 2 or 3* CRS event
  • And for three consecutive days following the next administration of EPKINLY until EPKINLY is given without subsequent CRS of Grade 2 or higher

Recommended Prophylaxis

Pneumocystis jirovecii pneumonia (PJP)

Provide PJP prophylaxis prior to starting treatment with EPKINLY.

Herpes virus

Consider initiating prophylaxis against herpes virus prior to starting EPKINLY to prevent herpes zoster reactivation.

Dosage Modifications and Management of Adverse Reactions

See Tables 4 and 5 for recommended actions for adverse reactions of CRS and ICANS, respectively. See Table 6 for recommended actions for other adverse reactions following administration of EPKINLY.

Cytokine Release Syndrome (CRS)

Identify CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes of fever, hypotension, and hypoxia.

If CRS is suspected, withhold EPKINLY until CRS resolves. Manage according to the recommendations in Table 4 and consider further management per current practice guidelines. Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS.

Table 4: Recommendations for Management of Cytokine Release Syndrome
Grade* Presenting Symptoms Actions
*
Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for CRS.
†
Premedication may mask fever, therefore if clinical presentation is consistent with CRS, follow these management guidelines.
‡
Refer to Table 2 for information on restarting EPKINLY after dosage delays [see Dosage and Administration (2.3)].
§
Low-flow oxygen defined as oxygen delivered at < 6L/minute; high-flow oxygen defined as oxygen delivered at ≥ 6 L/minute.
If Grade 2 or 3 CRS occurs with the second full dose (48 mg) or beyond, administer CRS premedications with each subsequent dose until a EPKINLY dose is given without subsequent CRS of Grade 2 or higher. Refer to Table 3 for additional information on premedication.
Grade 1 Temperature ≥ 100.4°F (38°C)†
  • Withhold EPKINLY and manage per current practice guidelines.
  • Ensure CRS symptoms are resolved prior to next dose of EPKINLY.‡
Grade 2 Temperature ≥ 100.4°F (38°C)† with:
Hypotension not requiring vasopressors
and/or
Hypoxia requiring low-flow oxygen§ by nasal cannula or blow-by.
  • Withhold EPKINLY and manage per current practice guidelines.
  • Ensure CRS symptoms are resolved prior to next dose of EPKINLY.‡
  • Administer premedication¶ prior to next dose of EPKINLY.
  • For the next dose of EPKINLY, monitor more frequently and consider hospitalization.
Grade 3 Temperature ≥ 100.4°F (38°C)† with:
Hypotension requiring a vasopressor (with or without vasopressin)
and/or
Hypoxia requiring high-flow oxygen§ by nasal cannula, face mask, non-rebreather mask, or Venturi mask.
  • Withhold EPKINLY and manage per current practice guidelines, which may include intensive care.
  • Ensure CRS symptoms are resolved prior to the next dose of EPKINLY.‡
  • Administer premedication¶ prior to next dose of EPKINLY.
  • Hospitalize for the next dose of EPKINLY.
Recurrent Grade 3 CRS
  • Permanently discontinue EPKINLY.
  • Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care.
Grade 4 Temperature ≥ 100.4°F (38°C)† with:
Hypotension requiring multiple vasopressors (excluding vasopressin)
and/or
Hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation and mechanical ventilation).
  • Permanently discontinue EPKINLY.
  • Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care.

Immune Effector Cell-Associated Neurological Toxicity Syndrome (ICANS)

Monitor patients for signs and symptoms of ICANS [see Warnings and Precautions (5.2)]. At the first sign of ICANS, withhold EPKINLY and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for ICANS [see Warnings and Precautions (5.2)]. Manage ICANS according to the recommendations in Table 5 and consider further management per current practice guidelines.

Table 5: Recommendations for Management of Immune Effector Cell-Associated Neurotoxicity Syndrome
Grade* Presenting Symptoms† Actions
*
Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS.
†
Management is determined by the most severe event, not attributable to any other cause.
‡
If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (names 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., "show me 2 fingers" or "close your eyes and stick out your tongue" = 1 point); Writing (ability to write a standard sentence = 1 point); and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points.
§
Not attributable to any other cause.
See Table 2 for recommendations on restarting EPKINLY after dosage delays [see Dosage and Administration (2.3)].
#
All references to dexamethasone administration are dexamethasone or equivalent.
Grade 1 ICE score 7-9‡,
Or depressed level of consciousness§: awakens spontaneously.
  • Withhold EPKINLY until ICANS resolves.¶
  • Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis.
Grade 2 ICE score 3-6‡,
Or depressed level of consciousness§: awakens to voice.
  • Withhold EPKINLY until ICANS resolves.¶
  • Administer dexamethasone# 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.
  • Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis.
Grade 3 ICE score 0-2‡,
Or depressed level of consciousness§: awakens only to tactile stimulus,
Or seizures,§ either:
  • Any clinical seizure, focal or generalized, that resolves rapidly, or
  • Non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention,
Or raised intracranial pressure: focal/local edema on neuroimaging.§		 First Occurrence of Grade 3 ICANS
  • Withhold EPKINLY until ICANS resolves.¶
  • Administer dexamethasone# 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.
  • Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis.
  • Provide supportive therapy, which may include intensive care.
Recurrent Grade 3 ICANS
  • Permanently discontinue EPKINLY
  • Administer dexamethasone# 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.
  • Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis.
  • Provide supportive therapy, which may include intensive care.
Grade 4 ICE score 0‡,
Or depressed level of consciousness§: either:
  • Patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or
  • Stupor or coma
Or seizures,§ either:
  • Life-threatening prolonged seizure (> 5 minutes), or
  • Repetitive clinical or electrical seizures without return to baseline in between,
Or motor findings§:
  • Deep focal motor weakness, such as hemiparesis or paraparesis,
or raised intracranial pressure/cerebral edema,§ with signs/symptoms such as:
  • Diffuse cerebral edema on neuroimaging, or
  • Decerebrate or decorticate posturing, or
  • Cranial nerve VI palsy, or
  • Papilledema, or
  • Cushing's triad.
  • Permanently discontinue EPKINLY.
  • Administer dexamethasone# 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.
  • Alternatively, consider administration of methylprednisolone 1,000 mg per day intravenously and continue methylprednisolone 1,000 mg per day intravenously for 2 or more days.
  • Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis.
  • Provide supportive therapy, which may include intensive care.
Table 6: Recommended Dosage Modifications for Other Adverse Reactions
Adverse Reaction* Severity* Action
*
Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
†
See Table 2 for recommendations on restarting EPKINLY after dosage delays [see Dosage and Administration (2.3)].
Infections [see Warnings and Precautions (5.3)] Grades 1-4
  • Withhold EPKINLY in patients with active infection, until the infection resolves.†
  • For Grade 4, consider permanent discontinuation of EPKINLY.
Neutropenia [see Warnings and Precautions (5.4)] Absolute neutrophil count less than 0.5 × 109/L
  • Withhold EPKINLY until absolute neutrophil count is 0.5 × 109/L or higher.†
Thrombocytopenia [see Warnings and Precautions (5.4)] Platelet count less than 50 × 109/L
  • Withhold EPKINLY until platelet count is 50 × 109/L or higher.†
Other Adverse Reactions [see Adverse Reactions (6.1)] Grade 3 or higher
  • Withhold EPKINLY until the toxicity resolves to Grade 1 or baseline.†

Preparation and Administration

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.

EPKINLY is prepared and administered by a healthcare provider as a subcutaneous injection.

The administration of EPKINLY takes place over the course of 28-day cycles, following the dosage schedule in Section 2.2.

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

Preparation of EPKINLY

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

Preparation instructions for 0.16 mg and 0.8 mg dose of EPKINLY

0.16 mg Dose Preparation Instructions (2 dilutions required)

Use an appropriately sized syringe, vial, and needle for each transfer step.

1. Prepare EPKINLY vial
  1. Retrieve one 4 mg/0.8 mL EPKINLY vial from the refrigerator.
  2. Allow the vial to come to room temperature for no more than 1 hour.
  3. Gently swirl the EPKINLY vial.
DO NOT invert, vortex, or vigorously shake the vial.
2. Perform first dilution
  1. Label an appropriately sized empty vial as "Dilution A."
  2. Transfer 0.8 mL of EPKINLY into the Dilution A vial.
  3. Transfer 4.2 mL of 0.9% Sodium Chloride Injection, USP into the Dilution A vial.
    The initially diluted solution contains 0.8 mg/mL of EPKINLY.
  4. Gently swirl the Dilution A vial for 30 to 45 seconds.
3. Perform second dilution
  1. Label an appropriately sized empty vial as "Dilution B."
  2. Transfer 2 mL of solution from the Dilution A vial into the Dilution B vial. The Dilution A vial is no longer needed.
  3. Transfer 8 mL of 0.9% Sodium Chloride Injection, USP into the Dilution B vial to make a final concentration of 0.16 mg/mL.
  4. Gently swirl the Dilution B vial for 30 to 45 seconds.
4. Withdraw dose
  1. Withdraw 1 mL of the diluted EPKINLY from the Dilution B vial into a syringe.
5. Label syringe
  1. Label the syringe with the dose strength (0.16 mg) and the time of day.

Discard the vial containing unused EPKINLY.

0.8 mg Dose Preparation Instructions (1 dilution required)

Use an appropriately sized syringe, vial, and needle for each transfer step.

1. Prepare EPKINLY vial
  1. Retrieve one 4 mg/0.8 mL EPKINLY vial from the refrigerator.
  2. Allow the vial to come to room temperature for no more than 1 hour.
  3. Gently swirl the EPKINLY vial.
DO NOT invert, vortex, or vigorously shake the vial.
2. Perform dilution
  1. Label an appropriately sized empty vial as "Dilution A".
  2. Transfer 0.8 mL of EPKINLY into the Dilution A vial.
  3. Transfer 4.2 mL of 0.9% Sodium Chloride Injection, USP into the Dilution A vial to make a final concentration of 0.8 mg/mL.
  4. Gently swirl the Dilution A vial for 30 to 45 seconds.
3. Withdraw dose
  1. Withdraw 1 mL of the diluted EPKINLY from the Dilution A vial into a syringe.
4. Label syringe
  1. Label the syringe with the dose strength (0.8 mg) and the time of day.

Discard the vial containing unused EPKINLY.

48 mg Dose Preparation Instructions (No dilution required)

EPKINLY 48 mg/0.8 mL vial is supplied as ready-to-use solution that does not need dilution prior to administration.

1. Prepare EPKINLY vial
  1. Retrieve one 48 mg/0.8 mL EPKINLY vial from the refrigerator.
  2. Allow the vial to come to room temperature for no more than 1 hour.
  3. Gently swirl the EPKINLY vial.
DO NOT invert, vortex, or vigorously shake the vial.
2. Withdraw dose
  1. Withdraw 0.8 mL of EPKINLY into a syringe.
3. Label syringe
  1. Label the syringe with the dose strength (48 mg) and the time of day.

Discard the vial containing unused EPKINLY.

Diluted EPKINLY Storage

Use diluted EPKINLY solution immediately. If not used immediately, store the solution refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at room temperature at 20°C to 25°C (68°F to 77°F) for up to 12 hours. The total storage time from the start of dose preparation to administration should not exceed 24 hours. Protect from direct sunlight. Allow EPKINLY solution to equilibrate to room temperature for no more than 1 hour before administration. Discard unused EPKINLY solution beyond the allowable storage time.

Administration

Inject the required volume of EPKINLY into the subcutaneous tissue of the lower part of the abdomen (preferred injection site) or the thigh. Change of injection site from the left or right side or vice versa is recommended, especially during the weekly administrations (Cycles 1 to 3).

Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard, or not intact.

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