PRESCRIBING INFORMATION (PI) FOR NORTHERN IRELAND

TEPKINLY (epcoritamab) 4mg/0.8ml concentrate for solution for injection; and 48mg/0.8ml solution for injection

Refer to Summary of Product Characteristics (SmPC) before prescribing.

PRESENTATIONS: Concentrate for solution for injection: each 0.8 ml single-use vial contains 4 mg of epcoritamab at a concentration of 5 mg/mL. Solution for injection: each 0.8 ml single-use vial contains 48 mg of epcoritamab at a concentration of 60 mg/mL.

INDICATION: Monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy.

DOSAGE and ADMINISTRATION: Posology: Prior to epcoritamab administration: Measures to prevent and reduce the risk of cytokine release syndrome (CRS) prophylaxis should be followed. Epcoritamab administration: For subcutaneous injection only. Patients should be adequately hydrated. Must only be administered under the supervision of a healthcare professional qualified in use of anti-cancer therapies. At least 1 dose of tocilizumab for use in the event of CRS should be available prior to epcoritamab administration for Cycle 1. Access to an additional dose of tocilizumab within 8 hours of use of the previous tocilizumab dose should be available. Priming (0.16 mg) and intermediate (0.8 mg) dose require dilution. Administer epcoritamab in 28-day cycles until disease progression or unacceptable toxicity. During Cycle 1, administer weekly on Day 1 (priming dose of 0.16 mg), Day 8 (intermediate dose of 0.8 mg), Day 15 (first full dose of 48 mg), and Day 22 (48 mg). Administer 48 mg during subsequent cycles. For Cycles 2 and 3, administer on Day 1, 8, 15 and 22. For Cycles 4 to 9, administer on Day 1 and 15. For Cycles 10 and beyond, administer on Day 1. Prophylaxis against Pneumocystis jirovecii pneumonia and herpes virus infections is strongly recommended especially during concurrent steroid use. Patients at an increased risk for clinical tumour lysis syndrome (CTLS) are recommended to receive hydration and prophylactic treatment with a uric acid lowering agent. Missed or delayed dose: A re-priming Cycle (identical to Cycle 1 with standard CRS prophylaxis) is required if there are more than 8 days between priming and intermediate dose, or if there are more than 14 days between intermediate dose and first full dose of 48 mg, or if there are more than 6 weeks between full doses of 48 mg. After a re-priming Cycle, patients should resume treatment with Day 1 of the next planned treatment cycle. Dose modification and management for CRS: At the first signs or symptoms of CRS, provide supportive care such as antipyretics and intravenous hydration and, dependent on grade, initiate treatment with anti-cytokine therapy such as tocilizumab and/or corticosteroids as indicated in the SmPC. Permanently discontinue epcoritamab in the event of Grade 4 CRS, Grade 3 CRS lasting longer than 72 hours, or if more than 2 separate events of Grade 3 CRS, even if each event resolved to Grade 2 within 72 hours. Dose modification and management for immune effector cell associated neurotoxicity syndrome (ICANS): At the first signs or symptoms of ICANS, initiate treatment with corticosteroids and consider non-sedating anti-seizure medication. See SmPC. Delay or discontinue epcoritamab as recommended. Permanently discontinue epcoritamab after a Grade 3 or 4 ICANS event. Dose modification for other adverse reactions: Infections (Grade 1-4): Withhold epcoritamab in patients with active infection, until the infection resolves. For Grade 4, consider permanent discontinuation of epcoritamab. Neutropenia or Febrile neutropenia (Absolute neutrophil count less than 0.5 x 10⁹/L): Withhold epcoritamab until absolute neutrophil count is 0.5 x 10⁹/L or higher. Thrombocytopenia (Platelet count less than 50 x 10⁹/L): Withhold epcoritamab until platelet count is 50 x 10⁹/L or higher. Other Adverse Reactions (Grade 3 or higher): Withhold epcoritamab until the toxicity resolves to Grade 1 or baseline. Special populations: Renal impairment: No dosage adjustment is necessary for patients with mild or moderate renal impairment. No data available in patients with severe renal impairment to end-stage renal disease. Hepatic impairment: No dosage adjustment is necessary for patients with mild hepatic impairment. Limited or no data available in patients with moderate to severe hepatic impairment. Paediatric population: The safety and efficacy in children aged less than 18 years of age have not yet been established. Elderly: No dose adjustment is necessary in patients ≥65 years.

CONTRAINDICATIONS: Hypersensitivity to the active substance or to excipients.

SPECIAL WARNINGS AND PRECAUTIONS: Traceability: Name and batch number of the administered product should be clearly recorded. CRS: Most CRS events occurred in Cycle 1 and were associated with the first full dose of 48 mg. Monitor patients for potential CRS following epcoritamab administration during Cycle 1 and in subsequent cycles as needed. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of CRS. Counsel patients on the signs and symptoms associated with CRS and instruct patients to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. ICANS: Majority of ICANS cases occurred within Cycle 1, however, some occurred with delayed onset. Monitor patients for signs and symptoms of ICANS following epcoritamab administration during Cycle 1 and in subsequent cycles as needed at the physician’s discretion. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of ICANS. Counsel patients on the signs and symptoms of ICANS and that the onset of events may be delayed. Instruct patients to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Serious infections: Avoid administration in patients with clinically significant active systemic infections. As appropriate, administer prophylactic antimicrobials prior to and during treatment with epcoritamab. Patients should be monitored for signs and symptoms of infection before and after epcoritamab administration and treated appropriately. In the event of febrile neutropenia, patients should be evaluated for infection and managed with antibiotics, fluids and other supportive care, according to local guidelines. Tumour Lysis Syndrome (TLS): Patients at an increased risk for TLS are recommended to receive hydration and prophylactic treatment with a uric acid lowering agent. Patients should be monitored for signs or symptoms of TLS. Patients should be monitored for blood chemistries and abnormalities should be managed promptly. Tumour flare: Manifestations could include localised pain and swelling. There are no specific risk factors for tumour flare that have been identified; however, there is a heightened risk of compromise and morbidity due to mass effect secondary to tumour flare in patients with bulky tumours located in close proximity to airways and/or a vital organ. Patients treated with epcoritamab should be monitored and evaluated for tumour flare at critical anatomical sites. CD20-negative disease: There are limited data available on patients with CD20-negative DLBCL treated with epcoritamab, and it is possible that patients with CD20-negative DLBCL may have less benefit compared to patients with CD20-positive DLBCL. Patient card: The doctor must inform the patient of the risk of CRS and ICANS and any signs and symptoms of CRS and ICANS. Patients must be instructed to seek immediate medical attention if they experience signs and symptoms of CRS and/or ICANS and to carry the patient card at all times. Immunisation: Live and/or live-attenuated vaccines should not be given concurrently during treatment with epcoritamab.

INTERACTIONS: On initiation of epcoritamab therapy in patients being treated with CYP450 substrates with a narrow therapeutic index, therapeutic monitoring should be considered.

FERTILITY, PREGNANCY AND LACTATION: Women of childbearing potential/Contraception in females: Use effective contraception during treatment with epcoritamab and for at least 4 months after the last dose. Verify pregnancy status in females of reproductive potential prior to initiating epcoritamab treatment. Pregnancy: There are no data on the use of epcoritamab in pregnant women. Epcoritamab is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding: It is not known whether epcoritamab is excreted in human milk or its effect on milk production. Breast-feeding should be discontinued during treatment with epcoritamab and for at least 4 months after the last dose. Fertility: No fertility studies have been conducted. The effect on male and female fertility is unknown.

ABILITY TO DRIVE AND USE MACHINES: Epcoritamab has minor influence on the ability to drive and use machines. Due to potential for ICANS, patients should be advised to exercise caution while (or avoid if symptomatic) driving, cycling or using heavy or potentially dangerous machines.

UNDESIRABLE EFFECTS:

See SmPC for full list of adverse events.

Very common (≥1/10): Viral infection, pneumonia, neutropenia (including grade 3-4), anaemia (including grade 3-4), thrombocytopenia, CRS, decreased appetite, headache, cardiac arrhythmias, abdominal pain, nausea, diarrhoea, vomiting, musculoskeletal pain, fatigue, injection site reactions, pyrexia, oedema.

Common (≥1/100 to <1/10): Grade 3-4 viral infection, grade 3-4 pneumonia, upper respiratory tract infection (including grade 3-4), fungal infections, sepsis (including grade 3-4), cellulitus (including grade 3-4), tumour flare, grade 3-4 thrombocytopenia, lymphopenia (including grade 3-4), febrile neutropenia (including grade 3-4), grade 3-4 CRS, hypophosphatemia (including grade 3-4), hypokalemia, hypomagnesemia, TLS (including grade 3-4), ICANS, grade 3-4 cardiac arrhythmias, pleural effusion (including grade 3-4), grade 3-4 abdominal pain, grade 3-4 nausea, rash, pruritus, grade 3-4 musculoskeletal pain, grade 3-4 fatigue, grade 3-4 oedema, alanine aminotransferase increased, aspartate aminotransferase increased (including grade 3-4), blood creatinine increased, blood sodium decreased, alkaline phosphatase increased.

Serious (≥10%): CRS.

MARKETING AUTHORISATION NUMBERS / PRESENTATIONS / NHS LIST PRICES: One 4mg/0.8ml concentrate for solution for injection in each carton, Northern Ireland (NI) EU/1/23/1759/001, £547.33 / One 48mg/0.8ml solution for injection in each carton, NI EU/1/23/1759/002 £6,568.

LEGAL CLASSIFICATION: POM

MA HOLDER: Further information available from Abbvie Ltd, Maidenhead, SL6 4UB.

DATE OF REVISION: December 2023

DOCUMENT NUMBER: EPCO-UK-00009-C

 
TEPKINLY has a conditional marketing authorisation – further data is awaited.

UK-EPCOR-230173. Date of preparation: March 2024.