Because clinical trials are conducted under widely varying conditions, adverse
reaction rates observed in the clinical trials of a drug cannot be directly
compared to rates in the clinical trials of another drug and may not reflect
the rates observed in practice. The adverse reaction information from clinical
trials does, however, provide a basis for identifying the adverse events that
appear to be related to drug use and for approximating rates.
The incidence of adverse events for Simulect® (basiliximab) was determined
in four randomized, double-blind, placebo-controlled clinical trials for the
prevention of renal allograft rejection. Two of the studies (Study 1 and Study
2), used a dual maintenance immunosuppressive regimen comprised of cyclosporine,
USP (MODIFIED) and corticosteroids, whereas the other two studies (Study 3 and
Study 4) used a triple-immunosuppressive regimen comprised of cyclosporine,
USP (MODIFIED), corticosteroids, and either azathioprine or mycophenolate mofetil.
Simulect (basiliximab) did not appear to add to the background of adverse events seen in
organ transplantation patients as a consequence of their underlying disease
and the concurrent administration of immunosuppressants and other medications.
Adverse events were reported by 96% of the patients in the placebo-treated group
and 96% of the patients in the Simulect (basiliximab) -treated group. In the four placebo-controlled
studies, the pattern of adverse events in 590 patients treated with the recommended
dose of Simulect (basiliximab) was similar to that in 594 patients treated with placebo. Simulect (basiliximab)
did not increase the incidence of serious adverse events observed compared with
The most frequently reported adverse events were gastrointestinal disorders,
reported in 69% of Simulect (basiliximab) -treated patients and 67% of placebo-treated patients.
The incidence and types of adverse events were similar in Simulect (basiliximab) -treated
and placebo-treated patients. The following adverse events occurred in ≥ 10%
of Simulect (basiliximab) -treated patients: Gastrointestinal System: constipation,
nausea, abdominal pain, vomiting, diarrhea, dyspepsia; Body as a Whole-General:
pain, peripheral edema, fever, viral infection; Metabolic and Nutritional:
hyperkalemia, hypokalemia, hyperglycemia, hypercholesterolemia, hypophosphatemia,
hyperuricemia; Urinary System: urinary tract infection;Respiratory
System: dyspnea, upper respiratory tract infection; Skin and Appendages:
surgical wound complications, acne;Cardiovascular Disorders-General:
hypertension; Central and Peripheral Nervous System: headache,
tremor; Psychiatric: insomnia; Red Blood Cell: anemia.
The following adverse events, not mentioned above, were reported with an incidence
of ≥ 3% and < 10% in pooled analysis of patients treated with Simulect (basiliximab) in
the four controlled clinical trials, or in an analysis of the two dual-therapy
trials: Body as a Whole-General: accidental trauma, asthenia,
chest pain, increased drug level, infection, face edema, fatigue, dependent
edema, generalized edema, leg edema, malaise, rigors, sepsis; Cardiovascular:
abnormal heart sounds, aggravated hypertension, angina pectoris, cardiac failure,
chest pain, hypotension; Endocrine: increased glucocorticoids;
Gastrointestinal:enlarged abdomen, esophagitis, flatulence,
gastrointestinal disorder, gastroenteritis, GI hemorrhage, gum hyperplasia,
melena, moniliasis, ulcerative stomatitis; Heart Rate and Rhythm: arrhythmia,
atrial fibrillation, tachycardia; Metabolic and Nutritional: acidosis,
dehydration, diabetes mellitus, fluid overload, hypercalcemia, hyperlipemia,
hypertriglyceridemia, hypocalcemia, hypoglycemia, hypomagnesemia, hypoproteinemia,
weight increase; Musculoskeletal: arthralgia, arthropathy, back
pain, bone fracture, cramps, hernia, myalgia, leg pain; Nervous System:
dizziness, neuropathy, paraesthesia, hypoesthesia; Platelet and
Bleeding: hematoma, hemorrhage, purpura, thrombocytopenia, thrombosis;
Psychiatric:agitation, anxiety, depression; Red Blood
Cell: polycythemia; Reproductive Disorders, Male: genital
edema, impotence; Respiratory: bronchitis, bronchospasm, abnormal
chest sounds, coughing, pharyngitis, pneumonia, pulmonary disorder, pulmonary
edema, rhinitis, sinusitis; Skin and Appendages: cyst, herpes
simplex, herpes zoster, hypertrichosis, pruritus, rash, skin disorder, skin
ulceration; Urinary: albuminuria, bladder disorder, dysuria, frequent
micturition, hematuria, increased non-protein nitrogen, oliguria, abnormal renal
function, renal tubular necrosis, surgery, ureteral disorder, urinary retention;
Vascular Disorders:vascular disorder; Vision Disorders:
cataract, conjunctivitis, abnormal vision; White Blood Cell: leucopenia.
Among these events, leucopenia and hypertriglyceridemia occurred more frequently
in the two triple-therapy studies using azathioprine and mycophenolate mofetil
than in the dual-therapy studies.
The incidence of malignancies in the controlled clinical trials of renal transplant was not significantly different between groups at 1 year (9/590 Simulect (basiliximab) -treated patients vs. 12/594 placebo-treated patients) or among patients with 5-year follow-up from Studies 1 and 2 (21/295 Simulect (basiliximab) -treated patients vs. 21/291 placebo-treated patients). The incidence of lymphoproliferative disease was not significantly different between groups, and less than 1% in the Simulect (basiliximab) -treated patients.
The overall incidence of cytomegalovirus infection was similar in Simulect (basiliximab) - and placebo-treated patients (15% vs. 17%) receiving a dual- or triple-immunosuppression regimen. However, in patients receiving a triple-immunosuppression regimen, the incidence of serious cytomegalovirus infection was higher in Simulect (basiliximab) -treated patients compared to placebo-treated patients (11% vs. 5%). The rates of infections, serious infections, and infectious organisms were similar in the Simulect (basiliximab) - and placebo-treatment groups among dual- and triple-therapy treated patients.
Severe acute hypersensitivity reactions including anaphylaxis characterized by hypotension, tachycardia, cardiac failure, dyspnea, wheezing, bronchospasm, pulmonary edema, respiratory failure, urticaria, rash, pruritus, and/or sneezing, as well as capillary leak syndrome and cytokine release syndrome, have been reported during post-marketing experience with Simulect (basiliximab) .