Basiliximab

No data are available on either the effects of live and inactive vaccination or the transmission of infection by live vaccines in patients receiving basiliximab. Nevertheless, live vaccines are not recommended for immunosuppressed patients. The use of live attenuated vaccines should therefore be avoided in patients treated with basiliximab. Inactivated vaccines may be administered to immunosuppressed patients; however, response to the vaccine may depend on the degree of the immunosuppression, therefore vaccination during treatment with basiliximab may be less effective.

Three clinical trials have investigated basiliximab use in combination with a triple therapy regimen which included either azathioprine or mycophenolate mofetil. The total body clearance of basiliximab was reduced by an average 22% when azathioprine was added to a regimen consisting of ciclosporin for microemulsion and corticosteroids. The total body clearance of basiliximab was reduced by an average 51% when mycophenolate mofetil was added to a regimen consisting of ciclosporin for microemulsion and corticosteroids. The use of basiliximab in a triple therapy regimen including azathioprine or mycophenolate mofetil did not increase adverse events or infections in the basiliximab group as compared to placebo.

Severe acute (less than 24 hours) hypersensitivity reactions have been observed both on initial exposure to basiliximab and on re-exposure to a subsequent course of therapy. These included anaphylactoid-type reactions such as rash, urticaria, pruritus, sneezing, wheezing, hypotension, tachycardia, dyspnoea, bronchospasm, pulmonary oedema, cardiac failure, respiratory failure and capillary leak syndrome. If a severe hypersensitivity reaction occurs, therapy with basiliximab must be permanently discontinued and no further dose be administered.

Caution should be exercised when patients previously given basiliximab are re-exposed to a subsequent course of therapy with this medicinal product. There is accumulating evidence that a subgroup of patients is at an increased risk of developing hypersensitivity reactions. These are patients in whom, following the initial administration of basiliximab, the concomitant immunosuppression was discontinued prematurely due, for example, to abandoned transplantation or early loss of the graft. Acute hypersensitivity reactions were observed on re-administration of basiliximab for a subsequent transplantation in some of these patients.

Transplant patients receiving immunosuppressive regimens involving combinations with or without basiliximab are at increased risk of developing lymphoproliferative disorders (LPDs) (such as lymphoma) and opportunistic infections (such as cytomegalovirus [CMV], BK virus). In clinical trials, the incidence of opportunistic infections was similar in patients using immunosuppressive regimens with or without basiliximab. In a pooled analysis of two five-year extension studies, no differences were found in the incidence of malignancies and LPDs between immunosuppressive regimens with or without combination of basiliximab.

Simulect is contraindicated in pregnancy. Basiliximab has potentially hazardous immunosuppressive effects with respect to the course of gestation. Women of childbearing potential must use effective contraception during and up to 16 weeks after treatment.

Simulect is contraindicated in lactation. Basiliximab has potentially hazardous immunosuppressive effects with respect to the course of the suckling neonate exposed to basiliximab in breast milk.

There is no animal or human data available concerning excretion of basiliximab into breast milk. However, based on the IgG₁ nature of basiliximab, excretion into milk should be expected. Breast-feeding must therefore be avoided.

No studies on the effects on the ability to drive and use machines have been performed.

Basiliximab has been tested in four randomised, double-blind, placebo-controlled studies in renal transplant recipients as an induction agent in combination with the following immunosuppressive regimens: ciclosporin for microemulsion and corticosteroids in two studies (346 and 380 patients), ciclosporin for microemulsion, azathioprine and corticosteroids in one study (340 patients), and ciclosporin for microemulsion, mycophenolate mofetil and corticosteroids in another study (123 patients). Safety data in paediatric patients have been obtained from one open-label pharmacokinetic and pharmacodynamic study in renal transplant recipients (41 patients).

Incidence of adverse events: In the above four placebo-controlled trials, the pattern of adverse events in 590 patients treated with the recommended dose of basiliximab was comparable to that observed in 595 patients treated with placebo. The overall incidence of treatment-related adverse events among all patients in the individual studies was not significantly different between the basiliximab (7.1%-40%) and the placebo (7.6%-39%) treatment groups.

Adult patients

The most commonly reported (>20%) events following dual or triple therapy in both treatment groups (basiliximab vs. placebo) were constipation, urinary tract infection, pain, nausea, peripheral oedema, hypertension, anaemia, headache, hyperkalaemia, hypercholesterolaemia, postoperative wound complication, weight increase, increase in blood creatinine, hypophosphataemia, diarrhoea and upper respiratory tract infection.

Paediatric patients

The most commonly reported (>20%) events following dual therapy in both (<35 kg vs. ≥35 kg weight) cohorts were urinary tract infection, hypertrichosis, rhinitis, pyrexia, hypertension, upper respiratory tract infection, viral infection, sepsis and constipation.

Incidence of malignant neoplasms: The overall incidence of malignancies among all patients in the individual studies was similar between the basiliximab and the comparator treatment groups. Overall, lymphoma/lymphoproliferative disease occurred in 0.1% (1/701) of patients in the basiliximab group compared with 0.3% (2/595) of patients receiving placebo, both in combination with dual and triple immunosuppressive therapy. Other malignancies were reported among 1.0% (7/701) of patients in the basiliximab group compared with 1.2% (7/595) of placebo patients. In a pooled analysis of two five-year extension studies, the incidence of LPDs and cancer was found to be equal with basiliximab 7% (21/295) and placebo 7% (21/291).

Incidence of infectious episodes: The overall incidence and profile of viral, bacterial and fungal infections among patients treated with basiliximab or placebo in combination with dual and triple immunosuppressive therapy was comparable between the groups. The overall incidence of infections was 75.9% in the basiliximab group and 75.6% in the placebo group and the incidence of serious infections was 26.1% and 24.8%, respectively. The incidence of CMV infections was similar in both groups (14.6% vs. 17.3%), following either dual or triple therapy regimen.

The incidence and causes of deaths following dual or triple therapy were similar in basiliximab (2.9%) and placebo groups (2.6%), with the most common cause of deaths in both treatment groups being infections (basiliximab = 1.3%, placebo = 1.4%). In a pooled analysis of two five-year extension studies the incidence and cause of death remained similar in both treatment groups, (basiliximab 15%, placebo 11%), the primary cause of death being cardiac-related disorders such as cardiac failure and myocardial infarction (basiliximab 5%, placebo 4%).

Listing of adverse reactions from post-marketing spontaneous reports

The following adverse reactions have been identified based on post-marketing spontaneous reports and are organised by system organ class. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

Immune system disorders: Hypersensitivity/anaphylactoid reactions such as rash, urticaria, pruritus, sneezing, wheezing, bronchospasm, dyspnoea, pulmonary oedema, cardiac failure, hypotension, tachycardia, respiratory failure, capillary leak syndrome. Cytokine release syndrome.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.