In general, rituximab is safe and well tolerated. However, the following contraindications should be applied:
- Hypersensitivity to rituximab or its constituents
- Allergy to any murine (mouse) products or other severe allergies or hypersensitivities
- Immunocompromised patients (e.g. neutropenia)
- Acute or chronic infections (including TB, hepatitis C or active severe infections)
- Severe heart failure (NYHA class IV) or severe uncontrolled cardiac disease
- Pregnancy / Breast feeding
- Recent Live vaccination
Serious infections, including fatalities, can occur during therapy with rituximab. Rituximab should not be administered to patients with an active and / or severe infection (eg tuberculosis, sepsis and opportunistic infections) or severely immunocompromised patients (eg in hypogammaglobulinaemia). Caution should be exercised when considering the use of rituximab in patients with a history of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection.
Patients reporting signs and symptoms of infection following rituximab therapy should be promptly evaluated and treated. Before giving a subsequent course of rituximab treatment, patients should be re‐evaluated for any potential risk for infections.
b) Hepatitis B
Very rare cases of hepatitis B reactivation, including reports of fulminant hepatitis, have been reported in subjects receiving rituximab and patients should be screened prior to commencement of therapy. Testing should include Hepatitis B surface antibody, Hepatitis B surface antigen and hepatitis B core antibody. If positive, refer to a hepatologist.
c) Chicken pox
Patients should be advised to avoid coming into close contact with chickenpox. In the event, that they come into contact with chicken pox or develop chicken pox and immune status is unknown then check for Varicella zoster IgG and refer to the ‘Green book’3 for further advice. Significant exposure to varicella zoster (VZ) is defined as face to face contact or more than 15 minutes in the same room during infective period (from 48 hours prior to development of rash up until crusting of rash). If the patient can confirm that they have definitely had chickenpox in the past, then immunoglobulin infusion is not required3.
d) Progressive multifocal leuko‐encephalopathy (PML)
Very rare cases of PML have occurred with rituximab therapy1. Patients must be monitored for any new or worsening neurological symptoms or signs that may be suggestive of PML. If PML is suspected, further dosing must be suspended until PML has been excluded. Patients must be fully informed of this rare complication. Patients may not notice some symptoms (eg cognitive, neurological or psychiatric symptoms), therefore should also be advised to inform their partner or caregivers about their treatment, since they may notice symptoms that the patient is not aware of. If a patient develops PML, rituximab must be permanently discontinued. Any suspected or confirmed cases should be reported to the MHRA using the yellow card reporting scheme.
The vaccination status of patients being considered for treatment with rituximab should be reviewed and local/national guidance for adult vaccination followed. If possible, vaccinations (including influenza and pneumococcal) should be completed at least four weeks prior to the first administration of rituximab or seven months after. If this is not possible, they should still be given but patients may not receive full benefit. Live vaccines are not recommended in patients while B cell depleted and should be avoided.
f) Cardiovascular history
Use of rituximab in severe heart failure (NYHA class IV) or severe uncontrolled cardiac disease is contraindicated. In patients treated with rituximab, the occurrence of pre‐existing ischaemic cardiac conditions becoming symptomatic, such as angina pectoris, has been observed, as well as atrial fibrillation and flutter. Therefore, in patients with a known cardiac history, the risk of cardiovascular complications resulting from infusion reactions should be considered before treatment with rituximab and patients closely monitored during administration.
Since hypotension may occur, anti‐hypertensive medications should be withheld 12 hours prior to the rituximab infusion. The rapid infusion regimen should not be used for patients with clinically significant cardiovascular disease, including arrhythmias.
g) Treatment in patients undergoing surgical procedures
Patients with planned elective procedures should ideally have their procedure completed before treatment with rituximab or timed to allow B-cells to recover. If this is not possible, the risk/benefit should be discussed between the Consultant Nephrologist and Surgeon. In the case of emergency surgical procedures, it is important to monitor the patient closely for any signs of post‐operative infection.