Epcoritamab Dosage

Medically reviewed by Drugs.com. Last updated on Nov 17, 2023.

Usual Adult Dose for B-Cell Lymphoma

Cycle 1:

• Day 1 (step-up dose 1): 0.16 mg subcutaneously
• Day 8 (step-up dose 2): 0.8 mg subcutaneously
• Day 15 (first full dose): 48 mg subcutaneously
• Day 22: 48 mg subcutaneously

Cycles 2 and 3:

• Days 1, 8, 15, and 22: 48 mg subcutaneously

Cycles 4 to 9:

• Days 1 and 15: 48 mg subcutaneously

Cycle 10 and beyond:

• Day 1: 48 mg subcutaneously

Duration of Therapy: Until disease progression or unacceptable toxicity

Restarting Therapy After Dosage Delay:
If last dose administered was 0.16 mg (e.g., on Cycle 1 Day 1):

• If more than 8 days since the last dose: Repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg); following the repeat of Cycle 1 schedule, resume the planned treatment schedule.

If last dose administered was 0.8 mg (e.g., on Cycle 1 Day 8):

• If 14 days or less since the last dose: Administer 48 mg, then resume the planned treatment schedule.
• If more than 14 days since the last dose: Repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg); following the repeat of Cycle 1 schedule, resume the planned treatment schedule.

If last dose administered was 48 mg (e.g., on Cycle 1 Day 15 onwards):

• If 6 weeks or less since the last dose: Administer 48 mg, then resume the planned treatment schedule.
• If more than 6 weeks since the last dose: Repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg); following the repeat of Cycle 1 schedule, resume the planned treatment schedule.

Comments:

• A cycle is 28 days.

Uses: For the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade lymphoma after at least 2 lines of systemic therapy

Usual Adult Dose for Follicular Lymphoma

Cycle 1:

• Day 1 (step-up dose 1): 0.16 mg subcutaneously
• Day 8 (step-up dose 2): 0.8 mg subcutaneously
• Day 15 (step-up dose 3): 3 mg subcutaneously
• Day 22 (first full dose): 48 mg subcutaneously

Cycles 2 and 3:

• Days 1, 8, 15, and 22: 48 mg subcutaneously

Cycles 4 to 9:

• Days 1 and 15: 48 mg subcutaneously

Cycle 10 and beyond:

• Day 1: 48 mg subcutaneously

Duration of Therapy: Until disease progression or unacceptable toxicity

Restarting Therapy After Dosage Delay:
If last dose administered was 0.16 mg (e.g., on Cycle 1 Day 1):

• If more than 8 days since the last dose: Repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg); following the repeat of Cycle 1 schedule, resume the planned treatment schedule.

If last dose administered was 0.8 mg (e.g., on Cycle 1 Day 8):

• If more than 8 days since the last dose: Repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg); following the repeat of Cycle 1 schedule, resume the planned treatment schedule.

If last dose administered was 3 mg (e.g., on Cycle 1 Day 15):

• If 14 days or less since the last dose: Administer 48 mg, then resume the planned treatment schedule.
• If more than 14 days since the last dose: Repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg); following the repeat of Cycle 1 schedule, resume the planned treatment schedule.

If last dose administered was 48 mg (e.g., on Cycle 1 Day 22 onwards):

• If 6 weeks or less since the last dose: Administer 48 mg, then resume the planned treatment schedule.
• If more than 6 weeks since the last dose: Repeat Cycle 1 schedule starting at step-up dose 1 (0.16 mg); following the repeat of Cycle 1 schedule, resume the planned treatment schedule.

Comments:

• A cycle is 28 days.

Use: For the treatment of patients with relapsed/refractory follicular lymphoma after at least 2 lines of systemic therapy

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

CYTOKINE RELEASE SYNDROME (CRS):
Identify CRS based on clinical presentation; evaluate for and treat other causes of fever, hypotension, and hypoxia.

• Premedication may mask fever; therefore, if clinical presentation is consistent with CRS, the management guidelines should be followed.

If CRS is suspected: Withhold this drug until CRS resolves.

• Manage according to recommendations below and consider further management according to current practice guidelines.
• Administer supportive therapy for CRS, which may include intensive care for severe/life-threatening CRS.

Recommendations for Management of CRS:
Grade 1 (temperature at least 38C [100.4F]): Withhold this drug and manage per current practice guidelines; ensure CRS symptoms are resolved before the next dose of this drug.

Grade 2 (temperature at least 38C [100.4F] with: hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen [defined as oxygen delivered at less than 6 L/min] by nasal cannula or blow-by): Withhold this drug and manage per current practice guidelines; ensure CRS symptoms are resolved before the next dose of this drug.

• Administer premedication before the next dose of this drug.
• If grade 2 CRS occurs with the second full dose (48 mg) or beyond, administer CRS pre- and post-administration medications with each subsequent dose until a dose is given without subsequent CRS of grade 2 or higher.
• For the next dose of this drug, monitor more frequently and consider hospitalization.

Grade 3 (temperature at least 38C [100.4F] with: hypotension requiring a vasopressor [with or without vasopressin] and/or hypoxia requiring high-flow oxygen [defined as oxygen delivered at 6 L/min or greater] by nasal cannula, face mask, nonrebreather mask, or Venturi mask): Withhold this drug and manage per current practice guidelines, which may include intensive care; ensure CRS symptoms are resolved before the next dose of this drug.

• Administer premedication before the next dose of this drug.
• If grade 3 CRS occurs with the second full dose (48 mg) or beyond, administer CRS pre- and post-administration medications with each subsequent dose until a dose is given without subsequent CRS of grade 2 or higher.
• Hospitalize for the next dose of this drug.

Grade 4 (temperature at least 38C [100.4F] with: hypotension requiring multiple vasopressors [excluding vasopressin] and/or hypoxia requiring oxygen by positive pressure [e.g., continuous positive airway pressure, bilevel positive airway pressure, intubation, mechanical ventilation]) OR recurrent grade 3: Permanently discontinue this drug; 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/symptoms of ICANS. At first sign of ICANS, withhold this drug and consider neurology evaluation; rule out other causes of neurologic symptoms.
• Consult the manufacturer product information for immune effector cell-associated encephalopathy (ICE) assessment.
• Provide supportive therapy, which may include intensive care, for ICANS.
• Manage ICANS according to recommendations below and consider further management according to current practice guidelines.
• Management is determined by the most severe event (e.g., depressed level of consciousness, seizures, raised intracranial pressure/cerebral edema, motor findings), not attributable to any other cause.

Recommendations for Management of ICANS:
Grade 1 (ICE score 7 to 9 or depressed level of consciousness [awakens spontaneously]): Withhold this drug until ICANS resolves.

• Monitor neurologic symptoms and consider consulting neurologist and other specialists for further evaluation and management; consider starting nonsedating, antiseizure drugs for seizure prophylaxis.

Grade 2 (ICE score 3 to 6 or depressed level of consciousness [awakens to voice]): Withhold this drug until ICANS resolves.

• Administer dexamethasone (10 mg IV every 6 hours) or equivalent; continue dexamethasone use until resolution to grade 1 or lower, then taper.
• Monitor neurologic symptoms and consider consulting neurologist and other specialists for further evaluation and management; consider starting nonsedating, antiseizure drugs for seizure prophylaxis.

Grade 3 ICANS (ICE score 0 to 2 or depressed level of consciousness [awakens only to tactile stimulus], or seizures [either any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on electroencephalogram that resolve with intervention], or raised intracranial pressure [focal/local edema on neuroimaging]):

• First occurrence of grade 3 ICANS: Withhold this drug until ICANS resolves.
• Administer dexamethasone (10 mg IV every 6 hours) or equivalent; continue dexamethasone use until resolution to grade 1 or lower, then taper.
• Monitor neurologic symptoms and consider consulting neurologist and other specialists for further evaluation and management; consider starting nonsedating, antiseizure drugs for seizure prophylaxis.
• Provide supportive therapy, which may include intensive care.
• Recurrent grade 3 ICANS: Permanently discontinue this drug.
• Administer dexamethasone (10 mg IV every 6 hours) or equivalent; continue dexamethasone use until resolution to grade 1 or lower, then taper.
• Monitor neurologic symptoms and consider consulting neurologist and other specialists for further evaluation and management; consider starting nonsedating, antiseizure drugs for seizure prophylaxis.
• Provide supportive therapy, which may include intensive care.

Grade 4 ICANS (ICE score 0 or depressed level of consciousness [either patient is unarousable or requires vigorous/repetitive tactile stimuli to arouse, or stupor/coma], or seizures [either life-threatening prolonged seizure (greater than 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 [e.g., diffuse cerebral edema on neuroimaging, decerebrate/decorticate posturing, cranial nerve VI palsy, papilledema, Cushing's triad]): Permanently discontinue this drug.

• Administer dexamethasone (10 mg IV every 6 hours) or equivalent; continue dexamethasone use until resolution to grade 1 or lower, then taper.
• Alternatively, consider administration of methylprednisolone (1000 mg/day IV); continue methylprednisolone for at least 2 more days.
• Monitor neurologic symptoms and consider consulting neurologist and other specialists for further evaluation and management; consider starting nonsedating, antiseizure drugs for seizure prophylaxis.
• Provide supportive therapy, which may include intensive care.

Recommendations for Other Adverse Reactions:
Infections:

• Grades 1 to 4: Withhold this drug in patients with active infection until the infection resolves.
• For grade 4: Consider permanent discontinuation of this drug.

Neutropenia:

• Absolute neutrophil count (ANC) less than 0.5 x 10(9)/L: Withhold this drug until ANC is at least 0.5 x 10(9)/L.

Thrombocytopenia:

• Platelet count less than 50 x 10(9)/L: Withhold this drug until platelet count is at least 50 x 10(9)/L.

Other adverse reactions:

• Grade 3 or higher: Withhold this drug until toxicity resolves to grade 1 or baseline.

Precautions

US BOXED WARNINGS:

• CYTOKINE RELEASE SYNDROME (CRS): CRS, including serious or life-threatening reactions, can occur in patients receiving this drug. Therapy should be started with the step-up dosage schedule to reduce the incidence and severity of CRS. This drug should be withheld until CRS resolves or permanently discontinued based on severity.
• IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS): ICANS, including life-threatening and fatal reactions, can occur with this drug. Patients should be monitored for neurological signs/symptoms of ICANS during therapy. This drug should be withheld until ICANS resolves or permanently discontinued based on severity.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Before starting this drug, provide Pneumocystis jirovecii pneumonia prophylaxis; consider starting prophylaxis against herpes virus before starting this drug to prevent herpes zoster reactivation.
• This drug should only be administered by a qualified health care professional with appropriate medical support to manage severe reactions (e.g., CRS, ICANS).
• For subcutaneous injection only; administration occurs over the course of 28-day cycles, after the step-up dosage schedule.
• Administer to well-hydrated patients.
• Premedicate before each dose in Cycle 1.
• When restarting therapy after dosage delay: Administer pretreatment medication before the dose of this drug and monitor patients accordingly.
• Administer subcutaneously according to the appropriate step-up schedule (based on indication) to reduce the incidence and severity of CRS.
• To minimize injection pain, allow the solution to equilibrate to room temperature for no longer than 1 hour before administration.
• Inject the required volume of this drug into the subcutaneous tissue of the lower part of the abdomen (preferred injection site) or the thigh.
• Change the site of injection from the left or right side or vice versa, especially during weekly administrations (Cycles 1 to 3); do not inject into tattoos, scars, or areas where skin is red/bruised/tender/hard/not intact.
• Monitor all patients for signs/symptoms (due to the risk of CRS and ICANS).
• For patients with DLBCL or high-grade B-cell lymphoma: Hospitalize patients for 24 hours after administration of the Cycle 1 Day 15 dosage of 48 mg.

Pre- and Post-Administration Medications (to reduce the risk of CRS):

• Cycle 1 (all patients):
• Dexamethasone (preferred [when available]; 15 mg IV or oral) or prednisolone (100 mg IV or oral) or equivalent: Administer 30 to 120 minutes before each weekly administration of this drug and for 3 consecutive days after each weekly administration of this drug in Cycle 1.
• Diphenhydramine (50 mg IV or oral) or equivalent: Administer 30 to 120 minutes before each weekly administration of this drug.
• Acetaminophen (650 to 1000 mg oral): Administer 30 to 120 minutes before each weekly administration of this drug.
• Cycle 2 onwards (patients who had grade 2 or 3 CRS with previous dose [permanently discontinue this drug after grade 4 CRS event]):
• Dexamethasone (preferred [when available]; 15 mg IV or oral) or prednisolone (100 mg IV or oral) or equivalent: Administer 30 to 120 minutes before next administration of this drug after a grade 2 or 3 CRS event and for 3 consecutive days after the next administration of this drug until it is given without subsequent CRS of grade 2 or higher.

Storage requirements:

• Vials: Store refrigerated at 2C to 8C (36F to 46F), in original carton to protect from light; do not freeze or shake.
• Solution in the syringe: If immediate use is not possible, store refrigerated at 2C to 8C (36F to 46F) for up to 24 hours or at room temperature at 20C to 25C (68F to 77F) for up to 12 hours.
• Total storage time from start of dose preparation to administration should not exceed 24 hours; discard unused solution beyond the allowable storage time.
• Protect from direct sunlight.

Reconstitution/preparation techniques:

• This drug is prepared by a health care provider.
• Certain doses require dilution before administration; 2 methods are available for dilution of this drug:
• Empty sterile vial method
• Sterile syringe method
• Preparation of 3 mg and 48 mg doses do not require dilution.
• The manufacturer product information should be consulted.

General:

• The indications are approved under accelerated approval based on response rate and durability; continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial(s).

Monitoring:

• Hematologic: CBC counts (throughout therapy)
• Immunologic: For potential CRS (after administration)
• Infections/Infestations: For signs/symptoms of infection (before and during therapy)
• Nervous System: For potential ICANS (after administration)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Immediately contact your health care provider if signs/symptoms associated with CRS (e.g., pyrexia, hypotension, hypoxia, chills, tachycardia, headache, dyspnea) occur at any time.
• Immediately contact your health care provider if signs/symptoms associated with ICANS (manifesting as [for example] confusional state, lethargy, tremor, dysgraphia, aphasia, nonconvulsive status epilepticus) occur; onset of events may be delayed.
• If symptoms of CRS or ICANS that impair consciousness occur, do not drive or operate heavy/potentially hazardous machinery until such events resolve.
• Contact your health care professional for signs/symptoms of serious infection.
• Patients of childbearing potential: Inform your health care provider if you are or become pregnant; use effective contraception during therapy and for 4 months after the last dose.
• Do not breastfeed during therapy and for 4 months after the last dose.

See also:

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer