Mabthera

FDA-Approved Indications:

• Non-Hodgkin’s Lymphoma (NHL):
• Relapsed or refractory, low-grade or follicular CD20-positive B-cell NHL
• Previously untreated follicular NHL in combination with chemotherapy
• Maintenance therapy for follicular NHL responding to induction therapy
• Chronic Lymphocytic Leukemia (CLL):
• CD20-positive CLL in combination with fludarabine and cyclophosphamide
• Rheumatoid Arthritis (RA):
• In combination with methotrexate for moderate-to-severe active RA in adults who have had an inadequate response to one or more TNF antagonists
• Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA):
• Used in combination with glucocorticoids for adult and pediatric patients 2 years of age and older
• Pemphigus Vulgaris:
• Moderate-to-severe cases in adult patients

Clinically Accepted Off-label Uses:

• Multiple Sclerosis (MS) – Relapsing-remitting and progressive forms
• Systemic Lupus Erythematosus (SLE)
• Immune Thrombocytopenic Purpura (ITP)
• Nephrotic Syndrome (e.g., in minimal change disease)
• Autoimmune Hemolytic Anemia
• Myasthenia Gravis (refractory cases)

Administration Route: Intravenous (IV) infusion only.

Non-Hodgkin's Lymphoma (Adult):

• Monotherapy: 375 mg/m² IV weekly for 4–8 doses.
• With chemotherapy: 375 mg/m² IV on day 1 of each chemotherapy cycle for up to 8 doses.

CLL (Adult):

• 375 mg/m² IV on day 1 of cycle 1, then 500 mg/m² IV on day 1 of cycles 2–6 in combination with chemotherapy every 28 days.

Rheumatoid Arthritis (Adult):

• 1000 mg IV on days 1 and 15 in combination with methotrexate. May repeat every 24 weeks based on clinical evaluation.

GPA/MPA (Adult & Pediatric ≥2 years):

• 375 mg/m² IV weekly × 4 doses for induction
• Maintenance: 500 mg IV on day 1 and 15, then every 6 months × 2 years

Pemphigus Vulgaris (Adult):

• 1000 mg IV on days 1 and 15
• Maintenance: 500 mg at months 12 and 18, then every 6 months or based on relapse

Special Populations:

• Renal/Hepatic Impairment: No dose adjustment guidelines established; caution advised.
• Elderly: Similar dosing as adults; monitor closely for adverse reactions.
• Pediatric (for GPA/MPA only): Dosing based on body surface area (375 mg/m²)

Premedication: Administer antihistamines and acetaminophen 30–60 minutes prior to infusion to reduce infusion-related reactions. Corticosteroids may be used in some cases.

Infusion Instructions:

• Initial infusion rate: 50 mg/hr, increasing by 50 mg/hr every 30 minutes to a max of 400 mg/hr.
• Subsequent infusions may start at 100 mg/hr.

Rituximab is a chimeric monoclonal antibody that specifically targets the CD20 antigen found on the surface of normal and malignant B lymphocytes. Upon binding to CD20, Rituximab initiates B-cell lysis through mechanisms including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and apoptosis. This targeted B-cell depletion leads to reduction in pathogenic B-cell populations responsible for malignant proliferation or autoimmune disease activity, thus achieving therapeutic effects in both hematologic malignancies and autoimmune disorders.

• Absorption: Administered IV; bioavailability 100%
• Distribution: Volume of distribution ~3.1 L; largely stays in the vascular and interstitial spaces
• Metabolism: Metabolized via non-specific proteolytic degradation pathways into peptides and amino acids
• Elimination: Elimination half-life varies by indication:
• NHL: 76 to 480 hours
• RA: ~18 days
• Clearance: Decreases with repeated doses due to B-cell depletion
• Steady-State: Reached after 4 doses (in RA and NHL)
• No active metabolites

• Pregnancy: Not assigned a formal FDA category. However, based on animal data and mechanism of action, Rituximab may cause B-cell depletion in the fetus. Use only if clearly needed; avoid during pregnancy unless benefits outweigh risks.
• Lactation: Unknown if excreted into human milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued during treatment and for at least 6 months after the last dose.
• Fertility: Rituximab may cause immunologic disturbances that affect fertility; reversible B-cell depletion observed.

• Primary Class: Monoclonal Antibody (mAb)
• Subclass: Anti-CD20 Chimeric Monoclonal Antibody
• Generation: First-generation CD20 monoclonal antibody

• Known hypersensitivity to Rituximab or murine proteins
• Severe active infections
• Active severe infections such as tuberculosis or hepatitis B reactivation
• Severe uncontrolled cardiac disease (infusion risk)
• Known progressive multifocal leukoencephalopathy (PML)

• Infusion-Related Reactions: Life-threatening reactions including anaphylaxis may occur; premedication and monitoring essential.
• Hepatitis B Reactivation: Screen for HBV prior to initiation. Reactivation can be fatal.
• Progressive Multifocal Leukoencephalopathy (PML): Rare but fatal CNS infection; monitor for neurological changes.
• Tumor Lysis Syndrome (TLS): Especially in high tumor burden NHL.
• Severe Mucocutaneous Reactions: Includes Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.
• Myelosuppression: Monitor CBC during therapy.
• Immunosuppression/Infections: Increases risk of serious bacterial, fungal, and viral infections.
• Cardiac Events: Use caution in patients with pre-existing cardiovascular disease.

Common:

• Infusion reactions: fever, chills, hypotension
• Fatigue
• Nausea, vomiting
• Rash, pruritus
• Headache
• Muscle aches

Hematologic:

• Neutropenia
• Anemia
• Thrombocytopenia

Infectious:

• Upper respiratory tract infections
• Urinary tract infections
• Reactivation of hepatitis B

Serious/Rare:

• Progressive multifocal leukoencephalopathy (PML)
• Cytokine release syndrome
• Severe mucocutaneous reactions
• Tumor lysis syndrome
• Cardiac arrhythmias

• Immunosuppressive agents (e.g., methotrexate, corticosteroids): May increase risk of infection and bone marrow suppression.
• Live vaccines: Contraindicated; avoid during and for several months after therapy.
• Antihypertensives: Hypotension may be worsened during infusion; consider withholding prior to infusion.
• No known interactions via CYP450 pathway (not metabolized hepatically via cytochrome enzymes)

• FDA Update: Approved for expanded use in pemphigus vulgaris and pediatric GPA/MPA.
• EMA/NICE: Recommend Rituximab as first-line biologic for relapsing GPA/MPA.
• WHO Essential Medicines List: Included for cancer and autoimmune indications.
• Ongoing studies evaluating biosimilars and subcutaneous administration forms.

• Storage Temperature: 2°C to 8°C (refrigerated); do not freeze.
• Protect from light
• Do not shake
• Diluted infusion solution: Stable for up to 24 hours refrigerated or 12 hours at room temperature (must be used within this time)
• Reconstitution not required (comes as ready-to-dilute concentrate)