Other considerations and special circumstances when prescribing rituximab
| Circumstance | Known risks | Recommended management |
| Pregnancy | The safety of B-cell-depleting biologic therapies is not fully known. In 153 exposed pregnancies, rates of miscarriage and congenital malformation were similar to expected rates in the general population.82 Placental transfer of immunoglobulins (including rituximab) occurs from the second trimester onwards. Exposure during organogenesis is therefore likely to be very limited. Exposure in later pregnancy has resulted in neonatal B-cell depletion, which recovered in 3–6 months.82 | Effective contraception (in both sexes) is advised by manufacturers during and for 12 months after treatment.6 56 Avoid in pregnancy unless potential benefit to the mother outweighs risk of B-cell depletion in the fetus6 56 (see the text section ‘risks and adverse events’ for further discussion). Live vaccines should not be given to exposed babies for the first 6 months of life. We counsel women before starting rituximab and perform a pregnancy test before each infusion. |
| Breast feeding | There are no studies formally assessing safety of rituximab during lactation.As a large molecule, it is unlikely to transfer to breast milk in any significant amounts. The exception to this is the first 3 days post partum when gaps between breast alveolar cells are larger and transfer of immunoglobulins is possible. Rituximab has poor gastrointestinal absorption and is likely be destroyed in the baby’s gut.92 | Despite apparent low risks there is still insufficient evidence to guarantee safety. Manufacturers advise that women avoid breast feeding during and for 12 months after treatment.6 56
We counsel mothers and support their decision if they choose to breast feed. |
| Existing cardiac disease | Severe cardiac disease is a contraindication to rituximab when used for rheumatoid arthritis or ANCA-associated vasculitis (but not lymphoma) due to a higher risk of myocardial infarction, arrhythmia or decompensating severe heart failure. | Consider alternative treatment options in patients with severe uncontrolled cardiac disease. |
| Previous hepatitis B virus (HBV) infection | Risk of HBV reactivation after rituximab is well described and includes fatal cases of fulminant hepatitis.93 Reactivation can occur in both HBVsAg-positive and HBVsAg-negative HBVcAb-positive patients (‘reverse seroconversion’).93 | Do not give rituximab to patients with active HBV hepatitis. Test HBVsAg, HBVcAb and liver function tests in all patients prior to starting rituximab.93 Refer those with positive serology to a specialist for prophylactic antiviral therapy, which must be continued for the duration of therapy. Monitor these patients with serial HBV DNA titres, liver function tests and HBVsAg (if HBVsAg negative at baseline).94 |
| Previous hepatitis C virus (HCV) infection | Information is conflicting but reactivation of HCV seems to be much less common than HBV.Increases in HCV RNA load and hepatic flares are reported, but many cases are confounded by additional immunosuppressive/hepatotoxic medications.95 96 | We recommend screening for HCV antibody prior to starting treatment. Positivity is not a contraindication to rituximab but we suggest such patients should be jointly managed with hepatology and monitored for HCV activity (HCV RNA titres and liver function tests). |
| Previous/latent tuberculosis (TB) | Risk of TB reactivation after rituximab appears negligible,97 though coadministration with glucocorticoids may contribute additional risk. | Do not give rituximab in cases of active TB. Although routine TB screening may be unnecessary,98 we screen for latent TB with QuantiFERON-TB Gold or tuberculin skin testing in high-risk patients (eg, from endemic regions). |
| Vaccinations | There is a theoretical risk that live vaccines (eg, yellow fever, varicella-zoster) may cause infection.Other standard inactivated vaccines are safe but they may be less effective after receiving rituximab.99 100 | Where possible give all routine vaccinations at least 4 weeks prior to initiating rituximab (and at least 8 weeks prior for live vaccines).56 98Do not give live vaccines to patients treated with rituximab. We recommend annual influenza vaccine and five-yearly pneumococcal vaccine throughout treatment. |
Italicisedpoints reflect personal practice rather than established recommendations.
ANCA, antineutrophil cytoplasmic antibody; HBVcAb, hepatitis B virus core antibody; HBVsAg, hepatitis B virus surface antigen.