ENFIERA (RITUXIMAB) 500MG 50ML VIAL

ENFIERA contains rituximab, a chimeric monoclonal antibody that specifically targets CD20 — a phosphoprotein expressed on the surface of pre-B and mature B lymphocytes (but not on plasma cells or haematopoietic stem cells).

Rituximab binds CD20 and depletes B cells through multiple mechanisms: complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and induction of apoptosis.

Rituximab is used for:

·       Non-Hodgkin's Lymphoma (NHL) — including diffuse large B-cell lymphoma (DLBCL),

·       follicular lymphoma, and other CD20-positive B-cell NHLs;

·       Chronic Lymphocytic Leukaemia (CLL) — in combination with chemotherapy;

·       Rheumatoid Arthritis (RA) — in combination with methotrexate in adults with severe active RA who have failed anti-TNF therapy;

·       Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA); and pemphigus vulgaris.

ENFIERA is a biosimilar or branded rituximab preparation. The mechanism, efficacy, and safety profile are the same as the reference rituximab product (MabThera/Rituxan). Biosimilar rituximab products undergo rigorous regulatory evaluation to confirm comparability.

ENFIERA must be administered as an intravenous infusion by trained healthcare professionals in a facility equipped to manage severe infusion reactions. It must never be given as an IV bolus or direct injection.

Pre-medication (Mandatory)

•       Antihistamine (e.g., diphenhydramine or chlorpheniramine) IV or oral, 30–60 minutes before infusion.

•       Antipyretic (paracetamol 1g oral) 30–60 minutes before infusion.

•       Corticosteroid (prednisolone or methylprednisolone IV) — especially for the first infusion and in patients with high circulating lymphocyte counts or tumour burden.

NHL Dosing

•       375 mg/m2 body surface area per cycle, typically given on day 1 of each chemotherapy cycle (e.g., R-CHOP, R-CVP, R-FC).

RA / Autoimmune Dosing

•       1000 mg IV on day 1 and day 15 (two infusions per course, 2 weeks apart).

Infusion Reactions (Very Common — First Infusion)

•       Fever, chills, rigors, urticaria, angioedema, nausea, vomiting, flushing.

•       Hypotension, bronchospasm — may require temporary infusion interruption.

•       Severe cytokine release syndrome (CRS) — can be fatal; highest risk in first infusion in patients with high tumour burden.

Infectious Complications

•       Serious bacterial, viral, and fungal infections — B-cell depletion impairs humoral immunity for 6–12 months.

•       Hepatitis B virus reactivation — can be fatal; screen all patients before starting rituximab.

•       Progressive Multifocal Leukoencephalopathy (PML) — caused by JC virus reactivation; rare but potentially fatal. Symptoms: confusion, motor deficits, vision changes.

Haematological

•       Neutropenia (including late-onset neutropenia), thrombocytopenia, anaemia.

Other

•       Tumour lysis syndrome (TLS) in high-burden lymphoma — prevent with adequate hydration, allopurinol, and monitoring.

•       Cardiac arrhythmias during infusion.

•       Hypogammaglobulinaemia with prolonged use.

Hepatitis B Screening — Mandatory Before Every Course

All patients must be screened for hepatitis B infection (HBsAg, anti-HBc) before starting rituximab. HBsAg-positive patients must receive antiviral prophylaxis (lamivudine or tenofovir) before and during rituximab and for at least 12 months after treatment. Anti-HBc-positive/HBsAg-negative patients should be monitored for HBV DNA reactivation.

PML Risk

JC virus reactivation causing PML is rare but reported. Inform patients about the symptoms (neurological changes, cognitive decline, visual loss) and advise them to report these immediately. PML requires immediate cessation of rituximab and specialist neurology involvement.

Tumour Lysis Syndrome (TLS)

Patients with high-burden CLL or NHL (high white cell count, large tumour mass) are at risk of TLS. Pre-treat with allopurinol 300 mg daily for 48 hours before the first infusion. Ensure adequate IV hydration. Monitor electrolytes, uric acid, renal function during and after infusion.

Pregnancy and Contraception

Rituximab must not be used during pregnancy. Women of childbearing potential must use effective contraception during and for 12 months after the last dose. Rituximab crosses the placenta and depletes B cells in neonates of mothers who received it in the 2nd or 3rd trimester.

Live Vaccines

Avoid live attenuated vaccines (BCG, yellow fever, MMR, chickenpox) during and for at least 12 months after rituximab. Ideally, complete vaccination schedules before starting treatment.

•       Antihypertensive medications — rituximab can cause hypotension during infusion; consider temporarily withholding antihypertensives on infusion days.

•       Cisplatin and other nephrotoxic agents — concurrent use associated with renal toxicity.

•       Live vaccines — absolute contraindication during B-cell depletion period.

•       Other immunosuppressants (methotrexate, azathioprine, leflunomide, corticosteroids) — additive immunosuppression; increased infection risk.

•       Biologic DMARDs (anti-TNF, abatacept, JAK inhibitors) — do not combine; wash-out periods required when switching between biologics.

•       Store in a refrigerator at 2–8 degrees Celsius. Do not freeze.

•       Keep in the original outer carton to protect from light.

•       Prepared infusion solutions (diluted in 0.9% NaCl or 5% glucose) are stable for 24 hours at 2–8 degrees Celsius, or 12 hours at room temperature.

•       Single-use vial — discard any unused portion.

•       Keep out of reach of children.

ENFIERA is a prescription-only medicine (POM) in Kenya, classified as a specialist oncology and rheumatology biologic. It must be prescribed by a consultant oncologist, haematologist, or rheumatologist with appropriate expertise.

Administration must take place in a hospital or specialist infusion unit with resuscitation facilities available.

Pre-treatment Screening Checklist

•       HBsAg, anti-HBc, HBV DNA — hepatitis B screen.

•       HIV status (if not known).

•       Full blood count, renal and liver function.

•       Baseline immunoglobulin levels (IgG, IgM, IgA).

•       Echocardiogram or cardiac assessment if significant cardiac history.

•       Vaccination history and update any non-live vaccines before starting.

Infusion Reaction Management

Grade 1–2 reactions (flush, fever, mild urticaria): slow infusion rate by 50%. Resume at slower rate after symptoms resolve. Grade 3 reactions (angioedema, significant bronchospasm): stop infusion; administer adrenaline 0.3–0.5 mg IM, IV antihistamine, IV corticosteroid; resume at 50% rate only after full resolution. Grade 4 (anaphylaxis): stop permanently; manage as anaphylaxis with adrenaline, airway support.

Immunoglobulin Monitoring

Monitor IgG levels before each rituximab course. If IgG falls below 5 g/L or patient develops recurrent serious infections, consider IVIg replacement therapy. Hypogammaglobulinaemia can be persistent and requires long-term management.

Why do I need to wait in the hospital for hours during each rituximab infusion?

Rituximab infusions are given slowly over several hours to minimise the risk of infusion reactions. The first infusion is given most slowly because the risk is highest when the drug is given for the first time. If reactions occur, the infusion can be slowed or paused. The monitoring during and after infusion ensures your safety.

How long will my immune system be weakened after rituximab?

B cells (the immune cells depleted by rituximab) typically take 6–12 months to recover after treatment. During this time, you are more susceptible to infections, particularly viral infections and pneumocystis pneumonia. Your doctor may prescribe prophylactic antibiotics (co-trimoxazole) during the recovery period.

Will rituximab affect my hepatitis B?

Rituximab can reactivate the hepatitis B virus in patients who have been previously infected, even if the infection appeared to be resolved. This is why all patients must be tested for hepatitis B before starting treatment. Those at risk will be given antiviral medication (prophylaxis) to prevent reactivation throughout treatment and for 12 months after.