Epcoritamab: Drug information

(For additional information see "Epcoritamab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

ALERT: US Boxed Warning

Cytokine release syndrome:

Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving epcoritamab. Initiate treatment with the epcoritamab step-up dosing schedule to reduce the 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 with epcoritamab. Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold epcoritamab until ICANS resolves or permanently discontinue based on severity.

Brand Names: US

Epkinly

Brand Names: Canada

Epkinly

Pharmacologic Category

Antineoplastic Agent, Anti-CD20;
Antineoplastic Agent, Anti-CD3;
Antineoplastic Agent, Bispecific T Cell Engager;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Note: Ensure patients are well-hydrated prior to epcoritamab initiation. Avoid administering epcoritamab to patients with active infection. Should only be administered by a qualified provider with appropriate medical support to manage severe reactions (eg, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome). The manufacturer recommends hospitalization for 24 hours following administration of the cycle 1 day 15 dosage (48 mg).

Premedication: Premedicate prior to each dose in cycle 1; if patient experienced grade 2 or 3 cytokine release syndrome (CRS) with the previous dose, administer premedication in cycle 2 and beyond until epcoritamab is tolerated without subsequent grade 2 or higher CRS. See "Epcoritamab Recommended Premedications" table below.

Prophylaxis: Provide prophylaxis for Pneumocystis jirovecii pneumonia prior to initiating epcoritamab. Consider initiating herpes virus prophylaxis prior to initiating epcoritamab to prevent herpes zoster reactivation. Consider prophylactic granulocyte colony-stimulating factor administration as appropriate.

Diffuse large B-cell lymphoma, relapsed or refractory

Diffuse large B-cell lymphoma, relapsed or refractory: SUBQ:

**Epcoritamab Dosing Schedule^a,b (28-day Treatment Cycles)**
Cycle number	Day of treatment	Epcoritamab dose^b
^a Continue until disease progression or unacceptable toxicity.
^b Manufacturer's labeling, Thieblemont 2023.
Cycle 1	Day 1	0.16 mg SUBQ (step up dose 1)
	Day 8	0.8 mg SUBQ (step up dose 2)
	Day 15	48 mg SUBQ (first full dose)
	Day 22	48 mg SUBQ
Cycles 2 and 3	Days 1, 8, 15, and 22	48 mg SUBQ
Cycles 4 to 9	Days 1 and 15	48 mg SUBQ
Cycles 10 and beyond^a	Day 1	48 mg SUBQ

**Recommendations for Restarting Epcoritamab After a Dosing Delay**
Last dose administered	Time since last dose	Action for next epcoritamab dose(s)^a
^a Administer premedications prior to epcoritamab dose and monitor appropriately.
Cycle 1, day 1 (0.16 mg)	>8 days	Repeat 0.16 mg SUBQ, then administer 0.8 mg SUBQ the following week, followed by 2 weekly doses of 48 mg SUBQ. Then resume the planned dosage schedule beginning with day 1 of the subsequent cycle.
Cycle 1, day 8 (0.8 mg)	≤14 days	Administer 48 mg SUBQ, then resume the recommended dosage schedule.
Cycle 1, day 8 (0.8 mg)	>14 days	Repeat 0.16 mg SUBQ, then administer 0.8 mg SUBQ the following week, followed by 2 weekly doses of 48 mg SUBQ. Then resume the planned dosage schedule beginning with day 1 of the subsequent cycle.
Cycle 1, day 15 and beyond (48 mg)	≤6 weeks	Administer 48 mg SUBQ, then resume the recommended dosage schedule.
Cycle 1, day 15 and beyond (48 mg)	>6 weeks	Repeat 0.16 mg SUBQ, then administer 0.8 mg SUBQ the following week, followed by 2 weekly doses of 48 mg SUBQ. Then resume the planned dosage schedule beginning with day 1 of the subsequent cycle.

**Epcoritamab Recommended Premedications**
Cycle	Patients requiring premedication	Premedication	Administration schedule
^aEpcoritamab should be permanently discontinued if grade 4 CRS occurs.
^b CRS = cytokine release syndrome.
Cycle 1	All patients	Dexamethasone 15 mg oral or IV or prednisolone 100 mg oral or IV (or equivalent)	30 to 120 minutes prior to each weekly epcoritamab dose and for 3 consecutive days following each weekly epcoritamab dose in cycle 1
		Diphenhydramine 50 mg (or equivalent) orally or IV	30 to 120 minutes prior to each weekly epcoritamab dose
		Acetaminophen 650 to 1,000 mg orally	30 to 120 minutes prior to each weekly epcoritamab dose
Cycle 2 and beyond	Patients who experienced grade 2 or 3^a CRS^b with the previous dose	Dexamethasone 15 mg oral or IV or prednisolone 100 mg oral or IV (or equivalent)	30 to 120 minutes prior to the next epcoritamab dose after a grade 2 or 3^a CRS event and for 3 consecutive days following the next epcoritamab dose until epcoritamab is administered and tolerated without subsequent ≥ grade 2 CRS.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function estimated using the Cockcroft-Gault equation.

CrCl 30 to <90 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in epcoritamab pharmacokinetics was observed based on CrCl 30 to <90 mL/minute.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effects on epcoritamab pharmacokinetics are unknown).

Dosing: Hepatic Impairment: Adult

Mild impairment (total bilirubin ≤ ULN with AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in epcoritamab pharmacokinetics was observed based on mild hepatic impairment.

Moderate or severe impairment (total bilirubin >1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (effects on epcoritamab pharmacokinetics are unknown).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m²: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m² experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).

Dosing: Adjustment for Toxicity: Adult

Refer to "Dosing: Adult" for recommendations on restarting epcoritamab after dose delays.

Cytokine release syndrome: If cytokine release syndrome (CRS) is suspected, interrupt epcoritamab until CRS resolves; manage according to the table below and per clinical practice guidelines. Supportive therapy for CRS may include intensive care for severe or life-threatening CRS. Identify CRS based on the clinical presentation. Evaluate for other causes (eg, fever, hypotension, hypoxia) and manage appropriately.

**Epcoritamab-Related CRS Management^d**
CRS grade	Presenting symptoms	Actions
^aFever may be masked by premedications; if clinical presentation is consistent with CRS, follow CRS management recommendations.
^bRefer to "Dosing: Adult" for recommendations for restarting epcoritamab after a dosing delay.
^cIf grade 2 or 3 CRS occurs with the second full epcoritamab dose (48 mg) or beyond, administer CRS premedications with each subsequent dose until an epcoritamab dose is administered without subsequent ≥ grade 2 CRS. Refer to "Dosing: Adult" for recommended premedications.
^d CRS = cytokine release syndrome; CPAP = continuous positive airway pressure; BiPAP = bilevel positive airway pressure.
Grade 1	Temperature ≥38°C (100.4°F)^a, attributed to CRS.	Withhold epcoritamab and manage per practice guidelines. Ensure CRS symptoms are resolved prior to the next epcoritamab dose^b.
Grade 2	Temperature ≥38°C (100.4°F)^awith: Hypotension not requiring vasopressors and/or Hypoxia requiring low-flow oxygen (<6 L/minute) via nasal cannula or blow-by.	Withhold epcoritamab and manage per practice guidelines. Ensure CRS symptoms are resolved prior to the next epcoritamab dose^b. Administer premedication^c prior to the next epcoritamab dose. For the next dose, monitor more frequently and consider hospitalization.
Grade 3	Temperature ≥38°C (100.4°F)^a with: Hypotension requiring a vasopressor (with or without vasopressin) and/or Hypoxia requiring high-flow oxygen (≥6 L/minute) via nasal cannula, face mask, non-rebreather mask, or Venturi mask.	Withhold epcoritamab and manage per practice guidelines, which may include intensive care. Ensure CRS symptoms are resolved prior to the next epcoritamab dose^b. Administer premedication^c prior to the next epcoritamab dose. Hospitalize for the next epcoritamab dose.
Grade 3, recurrent		Permanently discontinue epcoritamab. Manage CRS per practice guidelines and provide supportive therapy, which may include intensive care.
Grade 4	Temperature ≥38°C (100.4°F)^a with: Hypotension requiring multiple vasopressors (excluding vasopressin) and/or Hypoxia requiring oxygen via positive pressure (eg, CPAP, BiPAP, intubation, mechanical ventilation).	Permanently discontinue epcoritamab. Manage CRS per practice guidelines and provide supportive therapy, which may include intensive care.

Immune effector cell-associated neurotoxicity syndrome: Monitor for signs/symptoms of immune effector cell-associated neurotoxicity syndrome (ICANS). Interrupt epcoritamab at the first sign of neurologic toxicity, including ICANS, and consider neurology evaluation. Rule out other causes of neurologic symptoms. Manage ICANS according to the table below and consider further management according to current practice guidelines.

**Epcoritamab-Related ICANS Management^e**
Grade	Presenting symptoms^a	Actions
^aManagement is determined by the most severe event (not attributable to any other cause).
^bIf patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) assessment: Orientation (oriented to year, month, city, hospital = 4 points) Naming (name 3 objects, eg, point to clock, pen, button = 3 points) Following commands (eg, “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point) Writing (ability to write a standard sentence = 1 point) Attention (count backwards from 100 by 10 = 1 point) If unarousable and unable to perform ICE assessment (grade 4 ICANS = 0 points).
^cNot attributable to any other cause.
^dRefer to "Dosing: Adult" for recommendations for restarting epcoritamab after a dosing delay.
^e ICANS = immune effector cell-associated neurotoxicity syndrome.
Grade 1	ICE score 7 to 9^b, or depressed level of consciousness^c(awakens spontaneously)	Withhold epcoritamab until ICANS resolves^d. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (eg, consideration for initiating seizure prophylaxis with nonsedating, antiseizure medication).
Grade 2	ICE score 3 to 6^b, or depressed level of consciousness^c (awakens to voice)	Withhold epcoritamab until ICANS resolves^d. Administer dexamethasone 10 mg IV every 6 hours (or equivalent); continue dexamethasone until resolution to ≤ grade 1, then taper. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (including consideration for initiating seizure prophylaxis with nonsedating, antiseizure medication).
Grade 3	ICE score 0 to 2^b, or depressed level of consciousness^c (awakens only to tactile stimulus), or seizures^c (either any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on EEG that resolve with intervention), or raised intracranial pressure (focal/local edema on neuroimaging^c)	First occurrence of grade 3 ICANS: Withhold epcoritamab until ICANS resolves^d. Administer dexamethasone 10 mg IV every 6 hours (or equivalent); continue dexamethasone until resolution to ≤ grade 1, then taper. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (including consideration for initiating seizure prophylaxis with nonsedating, antiseizure medication). Provide supportive therapy as clinically appropriate (may include intensive care).
Grade 3		Recurrent grade 3 ICANS: Permanently discontinue epcoritamab. Administer dexamethasone 10 mg IV every 6 hours (or equivalent); continue dexamethasone until resolution to ≤ grade 1, then taper. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (including consideration for initiating seizure prophylaxis with nonsedating, antiseizure medication). Provide supportive therapy as clinically appropriate (may include intensive care).
Grade 4	ICE score 0^b, or depressed level of consciousness^c (either unarousable or requires vigorous/repetitive tactile stimuli to arouse, or stupor or coma), or seizures^c (either life-threatening prolonged seizure >5 minutes, or repetitive clinical or electrical seizures without return to baseline in between), or motor findings^c (deep focal motor weakness such as hemiparesis or paraparesis), or raised intracranial pressure/cerebral edema^c, with signs/symptoms such as diffuse cerebral edema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilledema, or Cushing triad	Permanently discontinue epcoritamab. Administer dexamethasone 10 mg IV every 6 hours (or equivalent); continue dexamethasone until resolution to ≤ grade 1, then taper. Alternatively, consider methylprednisolone 1,000 mg IV daily for ≥2 days. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (including consideration for initiating seizure prophylaxis with nonsedating, antiseizure medication). Provide supportive therapy as clinically appropriate (may include intensive care).

**Recom** **mended Epcoritamab Dosage Modifications for Other Adverse Reactions**
Adverse reaction	Severity	Actions
^aRefer to "Dosing: Adult" for recommendations for restarting epcoritamab after a dosing delay.
Hematologic toxicity	ANC <500/mm³	Withhold epcoritamab until ANC is ≥500/mm³.^a Consider prophylactic granulocyte colony-stimulating factor administration as appropriate.
	Platelets <50,000/mm³	Withhold epcoritamab until platelets are ≥50,000/mm³.^a
	Other cytopenias	Withhold or discontinue epcoritamab based on the severity.
Infections	Grades 1 to 4	Withhold epcoritamab or consider permanently discontinuing based on severity. Manage infection appropriately and as clinically indicated. Withhold epcoritamab in patients with active infection until infection resolves.^a For grade 4 infection, consider permanently discontinuing epcoritamab.
Other adverse reactions	Grade 3 or higher	Withhold epcoritamab until adverse reaction resolves to grade 1 or baseline.^a

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.

>10%:

Cardiovascular: Edema (14%)

Dermatologic: Skin rash (15%)

Endocrine & metabolic: Decreased serum magnesium (31%), decreased serum phosphate (56%), decreased serum potassium (34%), decreased serum sodium (56%), increased serum potassium (21%)

Gastrointestinal: Abdominal pain (23%), decreased appetite (12%), diarrhea (20%), nausea (20%; grades 3/4: 1%), vomiting (12%; grades 3/4: <1%)

Hematologic & oncologic: Decreased hemoglobin (62%; grades 3/4: 12%), decreased neutrophils (50%; grades 3/4: 32%), decreased platelet count (48%; grades 3/4: 12%), decreased white blood cell count (53%; grades 3/4: 22%), lymphocytopenia (87%; grades 3/4: 77%)

Hepatic: Increased serum alanine aminotransferase (45%), increased serum aspartate aminotransferase (48%)

Hypersensitivity: Cytokine release syndrome (51%)

Infection: Serious infection (15%; including opportunistic infection, pneumonia, sepsis, upper respiratory tract infection, and urinary track infection)

Local: Injection-site reaction (27%)

Nervous system: Fatigue (29%), headache (13%), severe neurotoxicity (immune effector cell-associated neurotoxicity syndrome [ICANS]: 6%)

Neuromuscular & skeletal: Musculoskeletal pain (28%)

Renal: Increased serum creatinine (24%)

Miscellaneous: Fever (24%)

1% to 10%:

Cardiovascular: Cardiac arrhythmia (10%)

Hematologic & oncologic: Febrile neutropenia, tumor flare, tumor lysis syndrome

Respiratory: Pleural effusion

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to epcoritamab or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Cytokine release syndrome: Epcoritamab may cause cytokine release syndrome (CRS); may be serious or life-threatening. CRS occurred in over half of patients who received epcoritamab at the recommended dose. Grades 1, 2, and 3 CRS were reported. Recurrent CRS was also reported. Most CRS events occurred during cycle 1, predominantly with the cycle 1, day 15 dose, although CRS also occurred with day 1, 8, and 22 doses. The median time to onset of CRS across all doses was 24 hours (range: up to 10 days) and the median time to CRS onset after the first full 48 mg dose was 21 hours (range: up to 7 days). CRS resolved in most patients and the median duration of CRS events was 2 days (range: 1 to 27 days). Signs/symptoms of CRS included pyrexia, chills, hypotension, hypoxia, dyspnea, and tachycardia. Concurrent neurological adverse reactions associated with CRS occurred in a small percentage of patients and included headache, confusion, tremors, dizziness, and ataxia. Patients who experience CRS (and/or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

• Cytopenias: Epcoritamab may cause serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia. Grade 3 and 4 cytopenias and neutropenic fever have occurred.

• Immune effector cell-associated neurotoxicity syndrome:Epcoritamab may cause immune effector cell-associated neurotoxicity syndrome (ICANS), including life-threatening and fatal reactions. ICANS occurred in a small percentage of patients who received epcoritamab at the recommended dose. Grade 1 and 2 ICANS have been reported, along with one fatal ICANS case. Most ICANS events occurred during cycle 1 of epcoritamab treatment, with a median time to onset of ICANS of 16.5 days (range: 8 to 141 days) from the start of treatment in cycle 1. The median time to ICANS onset across all doses was 3 days (range: 1 to 13 days). The median duration of ICANS was 4 days (range: up to 8 days) with ICANS resolving with supportive care in most patients. Clinical manifestations of ICANS included (although not limited to) confusion, lethargy, tremor, dysgraphia, aphasia, and nonconvulsive status epilepticus. The onset of ICANS may be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Patients who experience signs/symptoms of ICANS or any other adverse reactions impairing cognition or consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

• Infection: Epcoritamab may cause serious and fatal infections. Serious infections (≥ grade 3), including opportunistic infections have been reported with the recommended epcoritamab dose. The most common ≥ grade 3 infections were sepsis, COVID-19, urinary tract infection, pneumonia, and upper respiratory tract infection.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Epkinly: Epcoritamab-bysp 4 mg/0.8 mL (0.8 mL); Epcoritamab-bysp 48 mg/0.8 mL (0.8 mL) [contains polysorbate 80]

Generic Equivalent Available: US

Pricing: US

Solution (Epkinly Subcutaneous)

4 mg/0.8 mL (per 0.8 mL): $1,545.40

48 mg/0.8 mL (per 0.8 mL): $18,544.75

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Epkinly: Epcoritamab-bysp 4 mg/0.8 mL (0.8 mL); Epcoritamab-bysp 48 mg/0.8 mL (0.8 mL) [contains polysorbate 80]

Prescribing and Access Restrictions

Epcoritamab is available through specialty distributors. Distribution information is available at https://www.epkinlyhcp.com/order.

Administration: Adult

SUBQ: Inject required dose volume into the tissue of the lower part of the abdomen (preferred site) or the thigh. Rotate injection site from left to right (or vice versa), particularly during the weekly administrations (in cycles 1 to 3). Do not inject into tattoos or scars, or areas where the skin is red, bruised, tender, hard, or not intact.

Epcoritamab should be prepared and administered by a health care provider. If refrigerated, allow epcoritamab solution to equilibrate to room temperature for no more than 1 hour before administration. Discard unused epcoritamab solution beyond the allowable storage time.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Epkinly: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761324s000lbl.pdf#page=26

Use: Labeled Indications

Diffuse large B-cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma in adults after 2 or more lines of systemic therapy.

Medication Safety Issues

Sound-alike/look-alike issues:

Epcoritamab may be confused with elotuzumab, mosunetuzumab, teclistamab.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Antithymocyte Globulin (Equine): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of anti-CD20 B-cell depleting therapy is reduced. Anti-CD20 B-Cell Depleting Therapies may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chikungunya Vaccine (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccines: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of COVID-19 Vaccines. Management: Administer COVID-19 vaccine 2 to 4 weeks prior to the next scheduled dose of anti-CD20 therapy, if used chronically for the treatment of autoimmune disease. Revaccinate 6 months after completion of anti-CD20 therapy if used over a limited period. Risk D: Consider therapy modification

CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Epcoritamab may increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines 2 weeks prior to starting anti-CD20 B-cell depleting therapies. Vaccination of patients treated with these agents in the past 6 months is not recommended. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Poliovirus Vaccine (Live/Trivalent/Oral): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation or 6 months after anti-CD20 B-cell depleting therapies. If vaccinated prior to B cell recovery, consider assessing immune response to vaccination. Risk D: Consider therapy modification

Vaccines (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Verify pregnancy status prior to treatment initiation in patients who could become pregnant.

Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last epcoritamab dose.

Pregnancy Considerations

Epcoritamab is a humanized bispecific antibody (IgG₁). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to epcoritamab may cause fetal harm. In addition, newborns exposed to epcoritamab in utero may develop B-cell lymphocytopenia.

Breastfeeding Considerations

It is not known if epcoritamab is present in breast milk.

Epcoritamab is a humanized bispecific antibody (IgG₁). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 4 months after the last epcoritamab dose.

Monitoring Parameters

CBC (throughout treatment). Verify pregnancy status prior to treatment (in patients who could become pregnant). Monitor for signs/symptoms of CRS (eg, pyrexia, chills, hypotension, hypoxia, dyspnea, tachycardia); at the first signs or symptoms, immediately evaluate patients for hospitalization. Monitor for neurological signs/symptoms of immune effector cell-associated neurotoxicity syndrome (ICANS) during treatment; evaluate patient immediately at the first signs/symptoms of ICANS. Monitor hydration status. Monitor for signs/symptoms of infection (including opportunistic infections) prior to and during epcoritamab treatment.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Epcoritamab is a bispecific T-cell engaging antibody that targets CD3 and CD20 (Thieblemont 2023). Epcoritamab binds to the CD3 receptor expressed on the surface of T-cells and CD20 expressed on the surface of lymphoma cells and healthy B-lineage cells. Epcoritamab activates T-cells resulting in the release of proinflammatory cytokines, and induces B-cell lysis.

Pharmacokinetics (Adult Data Unless Noted)

Onset: Circulating B cells decreased to undetectable levels (in patients who had detectable B cells at treatment initiation) following the approved recommended epcoritamab dose by cycle 1, day 15 (after the first full dose of 48 mg).

Duration: B cell depletion was sustained throughout treatment.

Distribution: V_d: 25.6 L.

Metabolism: Metabolized into small peptides via catabolic pathways.

Half-life elimination: ~22 days (after the end of cycle 3).

Time to peak: Following the first full (48 mg) dose in cycle 1: 4 days; following the end of cycle 3: 2.3 days.

Excretion: Clearance: 0.53 L/day (after the end of cycle 3).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Body weight: In patients who received the recommended epcoritamab dose, cycle 1 median average concentration was 13% lower in a group of patients weighing 85 to 144 kg and 37% higher in a group of patients weighing 39 to 65 kg, compared to patients weighing 65 to <85 kg.

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Topic 141559 Version 25.0

خرید پکیج

Epcoritamab: Drug information