Dosing & Uses
Dosage Forms & Strengths H3
injectable solution, single-dose vial
- 4mg/0.8mL (dilute before use)
- 48mg/0.8 mL
B-Cell Lymphoma
Indicated for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥2 lines of systemic therapy
Each cycle is 28 days
See Administration for recommended premedications
Cycle 1
- Day 1 (step-up dose 1): 0.16 mg SC x 1 dose
- Day 8 (step-up dose 2): 0.8 mg SC x 1 dose
- Day 15 (first full dose): 48 mg SC x 1 dose (hospitalize patient for 24 hr during first 48-mg dose)
- Day 22: 48 mg SC x 1 dose
Cycles 2 and 3
- Days 1, 8, 15, and 22: 48 mg SC x 1 dose
Cycles 4-9
- Days 1 and 15: 48 mg SC x 1 dose
Cycle 10 and thereafter
- Day 1: 48 mg SC x 1 dose
- Continue until disease progression or unacceptable toxicity
Dosage Modifications
Cytokine release syndrome (CRS)
- If CRS suspected, withhold until CRS resolves
- Identify CRS based on clinical presentation; evaluate for and treat other causes of fever, hypotension, and hypoxia
- Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS
- NOTE: Premedication may mask fever; therefore, if clinical presentation is consistent with CRS, follow these management guidelines
Grade 1
- Defined as temperature ≥100.4ºF (38ºC)
- Withhold epcoritamab and manage per current practice guidelines, ensure CRS symptoms have resolved before next dose
-
Grade 2
- Defined as 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 epcoritamab and manage per current practice guidelines
- Ensure CRS symptoms have resolved before next dose
- Premedicate before next dose
- For next dose, monitor more frequently and consider hospitalization
-
Grade 3 (first occurrence)
- Defined as temperature ≥100.4ºF (38ºC) with hypotension requiring a vasopressor (with or without vasopressin) and/or hypoxia requiring high-flow oxygen by nasal cannula, face mask, nonrebreather mask, or Venturi mask
- Withhold epcoritamab and manage per current practice guidelines, which may include intensive care
- Ensure CRS symptoms have resolved before next dose
- Premedicate before next dose
- Hospitalize for next dose
- If Grade 2 or 3 CRS occurs with second full dose (48 mg) or beyond, administer CRS premedications with each subsequent dose until a dose is given without subsequent CRS of Grade 2 or higher
-
Grade 4 or recurrent Grade 3
- Grade 4 defined as temperature ≥100.4°F (38°C) with hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring oxygen by positive pressure (eg, continuous positive airway pressure [CPAP], bi-level positive airway pressure [BiPAP], intubation and mechanical ventilation)
- Permanently discontinue
- Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care
Immune effector cell–associated neurotoxicity syndrome (ICANS)
- Monitor for signs and symptoms of ICANS
- At first sign, withhold epcoritamab and consider neurology evaluation
- Rule out other causes of neurologic symptoms
- Provide supportive therapy, which may include intensive care, for ICANS
-
Grade 1
- Defined as immune effector cell–associated encephalopathy (ICE) score 7-9, or depressed level of consciousness (awakens spontaneously)
- Withhold epcoritamab until ICANS resolves
- Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management (eg, consider starting nonsedating antiseizure medications for seizure prophylaxis)
-
Grade 2
- Defined as ICE score 3-6, or depressed level of consciousness: awakens to voice
- Withhold epcoritamab until ICANS resolves
- Administer dexamethasone 10 mg IV q6hr; continue until resolution to Grade ≤1, then taper
- Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management (eg, consider starting nonsedating antiseizure medications for seizure prophylaxis)
-
Grade 3 (first occurrence)
- Defined as 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 nonconvulsive seizures on electroencephalogram (EEG) that resolve with intervention, OR
- Raised intracranial pressure: focal/local edema on neuroimaging
- Withhold epcoritamab until ICANS resolves
- Administer dexamethasone 10 mg IV q6hr; continue until resolution to Grade ≤1, then taper
- Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management (eg, consider starting nonsedating antiseizure medications for seizure prophylaxis)
- Provide supportive therapy, which may include intensive care
-
Grade 4 or recurrent Grade 3
- Defined as ICE score 0, OR
- Depressed level of consciousness: Patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, OR
- Stupor, coma OR
- Seizures: 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, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing’s triad
- Permanently discontinue
- Administer dexamethasone 10 mg IV q6hr; continue until resolution to Grade ≤1, then taper
- Note for Grade 4 only: Alternatively, consider administration of methylprednisolone 1,000 mg/day IV for ≥2 days
- Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management (eg, consider starting nonsedating antiseizure medications for seizure prophylaxis)
- Provide supportive therapy, which may include intensive care
Infections
- Grade 1-3: Withhold epcoritamab in patients with active infection, until infection resolves
- Grade 4: Consider permanent discontinue
Neutropenia
- Defined as absolute neutrophil count (ANC) <0.5 x 109/L
- Withhold epcoritamab until ANC ≥0.5 x 109/L
Thrombocytopenia
- Defined as platelet count <50 x 109/L
- Withhold epcoritamab until platelet count ≥50 x 109/L
Other adverse reactions Grade 3 or more
- Withhold epcoritamab until Grade <1
Renal impairment
- Mild-to-moderate (creatinine clearance [CrCl] 30 to < 90 mL/min): No dosage adjustment necessary
- Severe and end-stage renal disease (CrCl <30 mL/min): Pharmacokinetics are unknown
Hepatic impairment
- Mild (total bilirubin ≤1.5x ULN and any AST): No dosage adjustment necessary
- Moderate-to-severe (total bilirubin >1.5x ULN and any AST): Pharmacokinetics are unknown
Dosing Considerations
- Verify pregnancy status in females of reproductive potential before initiating
- Administer to well-hydrated patients
-
Prophylaxis
- Provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis before starting treatment
- Consider initiating prophylaxis against herpes virus before initiating to prevent herpes zoster reactivation
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (1)
- ublituximab
ublituximab and epcoritamab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Each drug is an anti-CD20 monoclonal antibody indicated for multiple sclerosis.
Monitor Closely (50)
- alfentanil
epcoritamab, alfentanil. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- alosetron
epcoritamab, alosetron. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- bendamustine
epcoritamab, bendamustine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- carbamazepine
epcoritamab, carbamazepine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- clomipramine
epcoritamab, clomipramine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- clonidine
epcoritamab, clonidine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- clozapine
epcoritamab, clozapine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- cyclosporine
epcoritamab, cyclosporine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- dihydroergotamine
epcoritamab, dihydroergotamine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- dihydroergotamine inhaled
epcoritamab, dihydroergotamine inhaled. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- dihydroergotamine intranasal
epcoritamab, dihydroergotamine intranasal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- disopyramide
epcoritamab, disopyramide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- divalproex sodium
epcoritamab, divalproex sodium. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- duloxetine
epcoritamab, duloxetine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- ergotamine
epcoritamab, ergotamine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- ethosuximide
epcoritamab, ethosuximide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- everolimus
epcoritamab, everolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- fentanyl
epcoritamab, fentanyl. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- fentanyl intranasal
epcoritamab, fentanyl intranasal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- fentanyl iontophoretic transdermal system
epcoritamab, fentanyl iontophoretic transdermal system. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- fentanyl transdermal
epcoritamab, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- fluvoxamine
epcoritamab, fluvoxamine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- mexiletine
epcoritamab, mexiletine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- midazolam
epcoritamab, midazolam. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- midazolam intranasal
epcoritamab, midazolam intranasal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- olanzapine
epcoritamab, olanzapine. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- pacritinib
epcoritamab, pacritinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- phenobarbital
epcoritamab, phenobarbital. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- phenytoin
epcoritamab, phenytoin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- pimozide
epcoritamab, pimozide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- pirfenidone
epcoritamab, pirfenidone. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- pomalidomide
epcoritamab, pomalidomide. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- primidone
epcoritamab, primidone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- quinidine
epcoritamab, quinidine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- quinine
epcoritamab, quinine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- ramelteon
epcoritamab, ramelteon. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- rasagiline
epcoritamab, rasagiline. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- repaglinide
epcoritamab, repaglinide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- riluzole
epcoritamab, riluzole. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- ropinirole
epcoritamab, ropinirole. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- sirolimus
epcoritamab, sirolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- sirolimus intravitreal
epcoritamab, sirolimus intravitreal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- tacrolimus
epcoritamab, tacrolimus. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- tasimelteon
epcoritamab, tasimelteon. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- theophylline
epcoritamab, theophylline. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- thioridazine
epcoritamab, thioridazine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- tizanidine
epcoritamab, tizanidine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- triazolam
epcoritamab, triazolam. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- valproic acid
epcoritamab, valproic acid. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- warfarin
epcoritamab, warfarin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
Minor (0)
Adverse Effects
>10%
All grades
- Lymphocyte count decreased (87%)
- Hemoglobin decreased (62%)
- Sodium decreased (56%)
- Phosphate decreased (56%)
- White blood cell count decreased (53%)
- Cytokine release syndrome (51%)
- Neutrophil count decreased (50%)
- Platelet count decreased (48%)
- AST increased (48%)
- ALT increased (45%)
- Potassium decreased (34%)
- Magnesium decreased (31%)
- Fatigue (29%)
- Musculoskeletal pain (28%)
- Injection site reactions (27%)
- Pyrexia (24%)
- Creatinine increased (24%)
- Abdominal pain (23%)
- Potassium increased (21%)
- Diarrhea (20%)
- Nausea (20%)
- Rash (15%)
- Edema (14%)
- Headache (13%)
- Decreased appetite (12%)
- Vomiting (12%)
Grade 3 or 4
- Lymphocyte count decreased (77%)
- Neutrophil count decreased (32%)
- White blood cell count decreased (22%)
- Platelet count decreased (12%)
- Hemoglobin decreased (12%)
1-10%
All grades
- Cardiac arrhythmias (10%)
- Grade 3 or 4 H4
- ALT increased (5.3%)
- Potassium decreased (5.3%)
- AST increased (4.6%)
- Creatinine increased (3.3%)
- Sodium decreased (2.6%)
- Cytokine release syndrome (2.5%)
- Fatigue (2.5%)
- Edema (1.9%)
- Abdominal pain (1.9%)
- Nausea (1.3%)
- Musculoskeletal pain (1.3%)
- Potassium increased (1.3%)
<1%
Grade 3 or 4
- Vomiting (0.6%)
- Rash (0.6%)
- Headache (0.6%)
- Decreased appetite (0.6%)
- Cardiac arrhythmias (0.6%)
Warnings
Black Box Warnings
Cytokine release syndrome
- Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur
- Initiate treatment with step-up dosing schedule to reduce incidence and severity of CRS
- Withhold epcoritamab until CRS resolves or permanently discontinue based on severity
Immune effector cell-associated neurotoxicity syndrome
- Immune effector cell-associated neurotoxicity syndrome (ICANS), including life-threatening and fatal reactions, can occur
- Monitor for neurological signs or symptoms of ICANS during treatment
- Withhold epcoritamab until ICANS resolves or permanently discontinue based on severity
Contraindications
None
Cautions
Serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia reported; based on the severity of cytopenias, temporarily withhold or permanently discontinue therapy; consider prophylactic granulocyte colony-stimulating factor administration as applicable
Based on its mechanism of action, fetal harm may occur when administered to pregnant females
Cytokine release syndrome
- Can cause CRS, including serious or life-threatening reactions
- Signs and symptoms include pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia
- Concurrent neurologic adverse reactions associated with CRS include headache, confusional state, tremors, dizziness, and ataxia
- Initiate therapy according to step-up dosing schedule
- Administer premedications to reduce the risk of CRS and monitor for potential CRS following dose
- Following administration of first 48 mg dose, hospitalize patient for 24 hr
- At first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate
- Withhold or discontinue therapy based on the severity of CRS
ICANS
- May cause life-threatening and fatal ICANS
- Clinical manifestations include confusional state, lethargy, tremor, dysgraphia, aphasia, and nonconvulsive status epilepticus
- Onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS
- Monitor for potential ICANS following administration
- At first signs or symptoms of ICANS, immediately evaluate patient and provide supportive therapy based on severity
- Withhold or discontinue therapy per recommendations and consider further management per current practice guidelines
- Advise patients of increased risk, and to refrain from driving and from operating heavy or potentially dangerous machinery until resolution
Infections
- Serious and fatal infections reported; monitor for signs and symptoms of infection before and during treatment and treat appropriately; avoid administration in patients with active infections
- Provide Pneumocystis jirovecii pneumonia (PJP) and herpes virus prophylaxis before initiating
Drug interaction overview
- For certain cytochrome P450 (CYP) substrates, minimal changes in concentration may lead to serious adverse reactions
- Monitor for toxicity or drug concentrations of such CYP substrates when co-administered
- Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates
- Increased exposure of CYP substrates is more likely to occur after first dose (Cycle 1 Day 1) and up to 14 days after first 48-mg dose on Cycle 1 Day 15, and during and after CRS
Pregnancy & Lactation
Pregnancy
Based on mechanism of action, epcoritamab fetal harm when administered to pregnant females
There are no available data on use in pregnant females to evaluate for a drug-associated risk
No animal reproductive or developmental toxicity studies have been conducted with epcoritamab
Epcoritamab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance; based on expression of CD20 on B-cells and finding of B-cell depletion in nonpregnant animals, epcoritamab can cause B-cell lymphocytopenia in infants exposed to epcoritamab in utero
Human immunoglobulin G (IgG) is known to cross the placenta; therefore, epcoritamab has may be transmitted from mother to developing fetus. Advise women of the potential
Verify pregnancy status in females of reproductive potential before initiating
Contraception
- Advise females of reproductive potential to use effective contraception during treatment and for 4 months after last dose
Lactation
There is no information regarding presence of epcoritamab in human milk, effect on breastfed children, or milk production
Advise females not to breastfeed during treatment and for 4 months after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
IgG1-bispecific antibody designed to simultaneously bind to CD3 on T-cells and CD20 on B-cells, and induce T-cell mediated lysis of CD20+ cells
CD20 is expressed on B-cells and is a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia
Absorption
Trough plasma concentration
- First full 48-mg dose: 1.7 mcg/mL
- End of weekly dosing (end of Cycle 3): 8.4 mcg/mL
- End of every 2-week dosing (end of Cycle 9): 4.1 mcg/mL
- Steady state with every 4-week dosing: 1.2 mcg/mL
Peak plasma concentration
- First full 48-mg dose: 2.2 mcg/mL
- End of weekly dosing (end of Cycle 3): 10.8 mcg/mL
- End of every 2-week dosing (end of Cycle 9): 7.5 mcg/mL
- Steady state with every 4-week dosing: 4.8 mcg/mL
Peak plasma time
- First full 48-mg dose: 4 days
- End of the weekly dosing regimen (end of Cycle 3): 2.3 days
Distribution
- Vd=25.6 L
Metabolism
- Expected to be metabolized into small peptides by catabolic pathways
Elimination
Clearance: 0.53 L/day (after end of Cycle 3)
Half-life: 22 days (first full 48-mg dose)
Administration
SC Preparation
0.16 mg-Dose
- Retrieve one 4 mg/0.8 mL vial from refrigerator
- Allow vial to come to room temperature for ≤1 hour
- Gently swirl vial; DO NOT invert, vortex, or vigorously shake vial
-
First dilution
- Label an appropriately sized empty vial as “Dilution A”
- Transfer 0.8 mL of epcoritamab into Dilution A vial
- Transfer 4.2 mL of 0.9% NaCl into Dilution A vial; initial diluted solution contains 0.8 mg/mL of epcoritamab
- Gently swirl Dilution A vial for 30-45 seconds
-
Second dilution
- Label an appropriately sized empty vial as “Dilution B”
- Transfer 2 mL of solution from Dilution A vial into Dilution B vial; Dilution A vial is no longer needed
- Transfer 8 mL of 0.9% NaCl into the Dilution B vial; final concentration of 0.16 mg/mL
- Gently swirl the Dilution B vial for 30-45 seconds
- Withdraw 1 mL of the diluted from Dilution B vial into a syringe
- Label syringe 0.16 mg and the time of day
- Discard vial containing unused drug
0.8 mg-Dose
- Retrieve one 4 mg/0.8 mL vial from refrigerator
- Allow vial to come to room temperature for ≤1 hour
- Gently swirl vial; DO NOT invert, vortex, or vigorously shake vial
-
First dilution
- Label an appropriately sized empty vial as “Dilution A”
- Transfer 0.8 mL of epcoritamab into Dilution A vial
- Transfer 4.2 mL of 0.9% NaCl into Dilution A vial; initial diluted solution contains 0.8 mg/mL of epcoritamab
- Gently swirl Dilution A vial for 30-45 seconds
- Withdraw 1 mL of the diluted from Dilution B vial into a syringe
- Label syringe 0.8 mg and time of day
- Discard vial containing unused drug
48-mg dose
- No dilution required
- Retrieve one 48 mg/0.8 mL vial from refrigerator
- Allow vial to come to room temperature for ≤1 hour
- Gently swirl vial; DO NOT invert, vortex, or vigorously shake vial
- Withdraw 0.8 mL into syringe
- Label syringe with 48 mg and time of day
- Discard vial containing unused drug
Premedications
Premedicate to reduce CRS risk
Cycle 1 (all patients)
- Administer 30-120 minutes before each weekly administration
- Acetaminophen 650-1,000 mg PO, AND
- Diphenhydramine 50 mg PO/IV or equivalent, AND
- Prednisolone 100 mg PO/IV or dexamethasone 15 mg PO/IV or equivalent; continue for 3 consecutive days following each weekly administration in Cycle 1
Cycle 2 and thereafter (Grade 2 or 3 CRS experienced with previous dose)
- Prednisolone 100 mg PO/IV or dexamethasone 15 mg PO/IV or equivalent
- Administer 30-120 minutes before next administration after a Grade 2 or 3 CRS event, and for 3 consecutive days following next administration until dose is given without subsequent CRS of Grade ≥2
- Note: Permanently discontinue for Grade 4 CRS
Prophylaxis
- Provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis before starting treatment
- Consider initiating prophylaxis against herpes virus before initiating to prevent herpes zoster reactivation
SC Administration
Inject required drug volume in SC tissue of lower part of the abdomen (preferred injection site) or thigh
Change injection site from left or right side or vice versa recommended, especially during weekly administrations (Cycles 1-3)
Do not inject into tattoos, scars, or areas where skin is red, bruised, tender, hard, or not intact
Dose delay (based on last dose administered)
- Premedicate before each dose and monitor patients accordingly
-
0.16 mg on Cycle 1 Day 1 and >8 days elapsed
- Repeat 0.16 mg, THEN
- Administer 0.8 mg the following week, followed by 48 mg weekly x 2, THEN
- Resume planned dosage schedule beginning with Day 1 of subsequent cycle
-
0.8 mg on Cycle 1 Day 8 and ≤14 days elapsed
- Administer 48 mg, THEN
- Resume recommended dosage schedule
-
0.8 mg on Cycle 1 Day 8 and >14 days elapsed
- Repeat 0.16 mg, THEN
- Administer 0.8 mg the following week, followed by 48 mg weekly x 2, THEN
- Resume planned dosage schedule beginning with Day 1 of subsequent cycle
-
48 mg on Cycle 1 Day 15 onwards and ≤6 weeks elapsed
- Administer 48 mg, THEN
- Resume recommended dosage schedule
-
48 mg on Cycle 1 Day 15 onwards and >6 weeks
- Repeat 0.16 mg, THEN
- Administer 0.8 mg the following week, followed by 48 mg weekly x 2, THEN
- Resume planned dosage schedule beginning with Day 1 of subsequent cycle
Storage
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF)
- Keep in original carton to protect from light
- Do not freeze
- Do not shake
Diluted solution
- Use immediately
- If not used immediately, refrigerate at 2-8ºC (36-46ºF) for up to 24 hours or at room temperature at 20-25°C (68-77°F) for up to 12 hours
- Total storage time from the start of dose preparation to administration should not exceed 24 hours
- Protect from direct sunlight
- Allow solution to equilibrate to room temperature for no more than 1 hour before administration
- Discard unused solution beyond the allowable storage time
Images
Formulary
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- View the formulary and any restrictions for each plan.
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- Compare formulary status to other drugs in the same class.
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