MABTHERA INFUSION

Dosage

Children: Refer to BNF for Children for precise dosing information.

Adults: Refer to specific drug guidelines and BNF for precise dosing information.

Mechanism of action

The mechanism of action for any drug is directly related to its concentration in the system. Generally, a drug's effects depend on its interaction with specific receptors, enzymes, or cellular components, where the concentration determines the extent of these interactions. For example, higher concentrations may lead to greater receptor binding, resulting in enhanced pharmacological effects. Conversely, very high concentrations may lead to adverse effects or toxicity.

Pharmacodynamics

Pharmacodynamics studies how a drug affects the body, focusing on the relationship between drug concentration and effect. The concentration-response relationship can follow various patterns, such as linear, sigmoid, or threshold effects. Key factors include the affinity of the drug for its target, the mechanism of receptor activation, and the downstream effects initiated by the drug-receptor interaction. Concentration also influences the therapeutic window, which is the range of drug concentrations within which the drug is effective without being toxic.

Pharmacokinetics

Pharmacokinetics involves the study of the absorption, distribution, metabolism, and excretion (ADME) of drugs. Concentration plays a crucial role in these processes. For instance, after administration, the drug concentration in the bloodstream influences its distribution to tissues. Metabolism may alter the drug concentration, affecting its efficacy and safety. Excretion mechanisms are also concentration-dependent, with renal clearance often influenced by the drug's concentration in plasma. Understanding these dynamics is essential for optimizing dosing regimens.

Pregnancy

There is limited data on the safety of concentration during pregnancy. Consult healthcare professionals before use.

Breast-feeding

Caution is advised when using concentration while breastfeeding. Consult healthcare professionals for guidance.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Non-Hodgkin's lymphoma (specialist use only)
• Chronic lymphocytic leukaemia (specialist use only)
• Rheumatoid arthritis (specialist use only)
• Granulomatosis with polyangiitis and microscopic polyangiitis (specialist use only)

Dosage

Children: Refer to BNF for Children for specific paediatric dosing information related to indicated conditions

Adults: By intravenous infusion: 1 g, then 1 g after 2 weeks. Consult product literature for information on retreatment.

Mechanism of action

Rituximab binds specifically to the CD20 antigen on B cells, leading to their destruction through various mechanisms including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and induction of apoptosis. This results in a reduction of B cell populations, which is beneficial in conditions where B cells are pathologically active, such as in certain malignancies and autoimmune diseases.

Pharmacodynamics

The pharmacodynamics of rituximab involve the modulation of B cell activity and reduction in B cell counts. The drug's action leads to decreased levels of immunoglobulins and altered immune responses, which can be advantageous in treating autoimmune conditions. However, this immunosuppressive effect also increases the risk of infections, particularly during treatment and for some time after cessation, due to the depletion of B lymphocytes.

Pharmacokinetics

Rituximab exhibits a monoclonal antibody pharmacokinetic profile, characterized by a long half-life, which allows for less frequent dosing schedules. The drug is primarily eliminated through the reticuloendothelial system. After intravenous administration, peak serum concentrations are reached approximately 3 to 6 hours post-infusion. The clearance of rituximab can be influenced by factors such as the presence of anti-drug antibodies, body weight, and the presence of disease.

Contra-indications

• Severe infection
• Progressive multifocal leucoencephalopathy
• Severe heart failure
• Uncontrolled heart disease
• Active hepatitis B infection

Adverse effects

• Angioedema
• Anxiety
• Decreased appetite
• Arrhythmias
• Bone marrow disorders
• Bursitis
• Cancer pain
• Cardiac disorders
• Chest pain
• Chills
• Dizziness
• Fatigue
• Fever
• Headaches
• Hypertension
• Hypotension
• Insomnia
• Nausea
• Oedema
• Skin reactions
• Throat irritation
• Tinnitus
• Tumour lysis syndrome
• Vision changes

Interactions

• Filgotinib (increases risk of immunosuppression)

Precautions

• Monitor for cognitive, neurological, or psychiatric signs
• Effective contraception required during and for 12 months post-treatment
• Pre-medication recommended to minimise adverse reactions
• Patients with positive hepatitis B serology should be monitored closely

Pregnancy

Avoid unless potential benefit to mother outweighs risk of B-lymphocyte depletion in fetus.

Breast-feeding

Avoid breastfeeding during and for 12 months after treatment.

Storage

Store in a refrigerator at 2 to 8 degrees Celsius. Protect from light.

Formulations

• Solution for infusion 100 mg/10 ml
• Concentrate for solution for infusion 500 mg/50 ml