MabThera - Physicians Area of MabThera for Rheumatoid Arthritis

Dosage and Administration: A course of MabThera consists of two infusions: the recommended dosage is 1000 mg by IV infusion followed by a second 1000 mg IV infusion 2 weeks later. Administer prepared MabThera solution as IV infusion through a dedicated line, with full resuscitation facilities immediately available and under the supervision of an experienced physician. Premedication with antipyretic, antihistamine and 100 mg methylprednisolone IV should be given before each infusion. Monitor closely for onset of cytokine release syndrome. Severe reactions e.g. severe dyspnoea, bronchospasm or hypoxia require immediate interruption of infusion. First Infusion: Recommended initial infusion rate is 50 mg/hr; after the first 30 minutes, escalation in 50 mg/hr increments every 30 minutes to a maximum of 400 mg/hr. Second Infusion: Initial rate of 100 mg/hr, increase by 100 mg/hr increments at 30-minute intervals to a maximum of 400 mg/hr.

Dose A djustments: No dose adjustment is required in elderly patients.

Contraindications: Hypersensitivity to any component of this product or to murine proteins; active, severe infections; severe heart failure (NYHA Class IV) or severe, uncontrolled cardiac disease.

Precautions: Infusion Reactions: MabThera is associated with infusion reactions, including anaphylactic and other hypersensitivity reactions. Premedication with IV glucocorticoid significantly reduced the incidence and severity of these events. Medicinal products for the treatment of hypersensitivity reactions e.g. adrenaline, antihistamines and glucocorticoids should be available for immediate use. Presence of human antichimeric antibody (HACA) may be associated with worsening infusion/allergic reactions after the second infusion of subsequent courses. Patients with a known cardiac history should be considered carefully, and monitored closely during administration. Hypotension may occur during MabThera infusion therefore consider withholding anti-hypertensive medications 12 hours prior to infusion. Infections: Do not give to patients with an active and/or severe infection, or severely immunocompromised patients. Exercise caution in patients with a history of recurring/chronic infections, or other underlying conditions which may predispose to serious infection. Treated patients reporting signs and symptoms of infection should be evaluated promptly, treated appropriately and re-evaluated for potential risk before any subsequent course of MabThera. Immunisation : Vaccination should be completed at least 4 weeks prior to administration of MabThera. Live vaccines are not recommended in patients while B cell depleted. Concomitant/sequential Use of O ther DMARDs: Concomitant use with anti-rheumatic therapies other than methotrexate not recommended. Observe patients closely for signs of infection if biologic agents and/or DMARDs are used sequentially. Malignancy: On the basis of limited experience in RA patients, a possible risk for the development of solid tumours cannot be excluded.

Drug Interactions: There are limited data on possible drug interactions with MabThera. Co-administration with methotrexate had no effect on the pharmacokinetics of MabThera. Patients receiving subsequent therapy with other DMARDs 4-6 months following MabThera, generally while peripherally B cell depleted, experienced clinically relevant infections at a rate of 7.8 per 100 patient-years.

Pregnancy and Lactation: No adequate data from use in pregnant women. MabThera should not be given to a pregnant woman unless potential benefit outweighs potential risk. Women of childbearing potential should use effective contraceptive methods during, and 12 months following, treatment. Women should not breastfeed during, and for 12 months following, treatment with MabThera.

Undesirable Effects: Common Adverse Reactions: Symptoms suggesting acute infusion reaction (hypertension, nausea, rash, pyrexia, pruritis, urticaria, rhinitis, throat irritation, hot flush, hypotension, chills) observed in 15% of patients following first exposure to MabThera. Incidence generally lower following subsequent treatment courses. Infection (UTI, URTI, LRTI) rate approximately 0.9 per patient-year. Cardiac events observed in 11% of patients. Other: Asthenia, dyspepsia, upper abdominal pain, hypercholesterolaemia, arthralgia/musculoskeletal pain, muscle spasms, osteoarthritis, parasthesia, migraine. Medically Significant Events: Incidence of clinically significant infection, some of which were fatal, was 0.05 per patient-year. Serious cardiac events reported equally in 2% of MabThera- and placebo-treated patients. Other: Generalised oedema, bronchospasm, wheezing, laryngeal oedema, angioneurotic oedema, generalised pruritis, anaphylaxis, anaphylactoid reaction. Prescriber should consult the SPC in relation to other side effects.

Legal Category: POM

Presentations: 100 mg of rituximab in 10 ml (10 mg/ml) pack of two vials, 500 mg of rituximab in 50 ml (10 mg/ml) pack of one vial.

Marketing Authorisation Numbers: EU/1/98/067/001 (100 mg), EU/1/98/067/002 (500 mg).

Marketing Authorisation Holder: Roche Registration Limited, 6 Falcon Way, Welwyn Garden City, Herts AL7 1TW. MABTHERA is a registered trade mark.

Date of Preparation: June 2006.