Professional Information
Basiliximab (Systemic)
VA CLASSIFICATION
Primary: IM403
Commonly used brand name(s): Simulect.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Immunosuppressant—
monoclonal antibody—
Indications
General considerations
The efficacy of basiliximab was demonstrated in two placebo-controlled, multicenter trials in which basiliximab was administered in conjunction with cyclosporine and corticosteroids {01}. The primary endpoint in the trials was the incidence of death, loss of the graft, or acute rejection within the first 6 months following transplantation {01}. The incidence of the primary endpoint was lower in the basiliximab-treated group than it was in the placebo-treated group in both the U.S. study and the European and Canadian study ( P = 0.002 and 0.003, respectively) {01}.
Note: The finding of significance in this combined primary endpoint is attributed to the significant difference observed in the incidence of acute rejection in the basiliximab-treated group. The incidences of death and loss of graft were not significantly different between the control group and the basiliximab-treated group (see below).
A secondary endpoint in the trials was the incidence of death, loss of the graft, or acute rejection within the first 12 months following transplantation {01}. The incidence of this secondary endpoint was lower in the basiliximab-treated group than it was in the placebo-treated group in both studies ( P = 0.001 and 0.007, respectively) {01}. The finding of significance in this combined endpoint is attributed to the significant difference in acute rejection between the placebo-treated group and the basiliximab-treated group.
Additional secondary endpoints in the trials were the incidences of biopsy-confirmed rejection at 6 and at 12 months. There was significantly less biopsy-confirmed rejection at 6 months and at 12 months in the basiliximab-treated group than in the placebo-treated group in both studies {01}.
The trials also compared patient survival at 1 year following transplantation. Patient survival was not significantly different between the placebo-treated groups and the basiliximab-treated groups ( P = 0.56 and 0.29, respectively) {01}. There was no significant difference in the percentage of patients with a functioning graft at 12 months between the placebo-treated groups and the basiliximab-treated groups ( P = 0.5 and 0.7, respectively) {01}.
The incidences of lymphoproliferative disorders and opportunistic infections were not increased in the basiliximab-treated patients in the trials {01}. However, only 363 patients were treated with basiliximab in these trials, and the follow-up period was short. Additional experience with basiliximab is needed to evaluate its potential for causing lymphoproliferative disorders and opportunistic infections {01}.
The long-term ability of the immune system to respond to antigens first encountered while being treated with basiliximab is not known {01}.
Accepted
Transplant rejection, kidney (prophylaxis)—Basiliximab is indicated, in combination with cyclosporine and corticosteroids, for the prevention of acute rejection of transplanted kidneys {01}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Source—
Composite of human and murine antibody sequences obtained through recombinant DNA technology {01}.
Molecular weight—
Approximately 144,000 daltons
Solubility
Soluble in water.
Mechanism of action/Effect:
Basiliximab is an interleukin-2 (IL-2) receptor antagonist that binds to the alpha subunit of the IL-2 receptor complex and inhibits IL-2 binding {01}. By inhibiting IL-2 binding, IL-2–mediated activation of lymphocytes is prevented, and the response of the immune system to antigens is impaired {01}.
Distribution:
Volume of distribution (Vol D):
Adults: 8.6 ± 4.1 liters (L) {01}.
Children: 5.2 ± 2.8 L {01}.
Adolescents: 10.1 ± 7.6 L {01}.
Half-life:
Elimination:
Adults: 7.2 ± 3.2 days.
Children: 11.5 ± 6.3 days.
Adolescents: 7.2 ± 3.6 days.
Duration of action:
The mean duration of complete binding to the alpha subunit of the IL-2 receptor complex is 36 ± 14 days.
Therapeutic serum concentration
Complete binding to the alpha subunit of the IL-2 receptor complex occurs when the serum concentration of basiliximab exceeds 0.2 microgram per milliliter (mcg/mL) {01}.
Precautions to Consider
Carcinogenicity
Studies have not been done to evaluate the carcinogenic potential of basiliximab. In the preapproval trials of basiliximab, there was not an increased incidence of lymphoproliferative disorders in the basiliximab-treated patients during the short follow-up period {01}. Long-term follow-up studies are not available in these patients. However, it is known that patients receiving immunosuppressive therapy are at increased risk for developing malignancies.
Mutagenicity
Basiliximab was not mutagenic in the Ames test or the V79 chromosomal aberration assay {01}.
Pregnancy/Reproduction
Fertility—
Adequate and well-controlled studies have not been done {01}.
Pregnancy—
Basiliximab crosses the placenta {01}. Adequate and well-controlled studies have not been done in humans {01}. The manufacturer recommends that women of childbearing potential use effective contraception before beginning therapy with basiliximab and continuing for 2 months after completion of therapy with basiliximab {01}.
FDA Pregnancy Category B {01}.
Breast-feeding
It is not known whether basiliximab is distributed into breast milk {01}. The manufacturer recommends that patients receiving basiliximab discontinue breast-feeding {01}.
Pediatrics
Appropriate studies on the relationship of age to the effects of basiliximab have not been performed in pediatric patients {01}. Preliminary data from the use of basiliximab in 12 pediatric patients 2 to 15 years of age suggest that pediatric patients receiving basiliximab experience similar incidences of graft rejection and adverse effects as those experienced by adult patients {01}.
Geriatrics
Geriatric patients were included in preapproval clinical trials of basiliximab in kidney transplantation. The adverse effect profile in geriatric patients was similar to that in younger adults {01}.
Dental
The immunosuppressive effects of basiliximab may result in an increased incidence of certain microbial infections and delayed healing. Dental work, whenever possible, should be completed prior to initiation of therapy and undertaken with caution during therapy. Patients should be instructed in proper oral hygiene.
Drug interactions and/or related problems
Note: In clinical trials, basiliximab was administered to patients receiving other immunosuppressants (antilymphocyte globulin, antithymocyte globulin, azathioprine, corticosteroids, cyclosporine, muromonab-CD3, and mycophenolate mofetil). No drug interactions have been evaluated or reported with basiliximab {01}.
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With physiology/laboratory test values
Calcium, serum and
Glucose, blood
Potassium, serum (concentrations may be decreased or increased {01})
Cholesterol, serum (values may be increased {01})
Blood urea nitrogen (BUN) and
Serum creatinine and
Uric acid, serum (concentrations may be increased {01})
Hematocrit value and
Hemoglobin concentration (may be decreased or increased {01})
Magnesium and
Phosphate, serum (concentrations may be decreased {01})
Platelets, blood (counts may be decreased {01})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Except under special circumstances, this medication should not be used when the following medical problem exists:
» Allergy to basiliximab, history of
Note: Anaphylactoid reactions have not been reported following administration of basiliximab {01}. However, anaphylactoid reactions are possible following administration of proteins.
Risk-benefit should be considered when the following medical problems exist
Infection (immunosuppression may exacerbate infection)
Malignancy, current or history of (immunosuppression is associated with an increased incidence of some malignancies)
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Blood pressure and
Heart rate and
Respiratory rate (routine monitoring of vital signs is recommended while basiliximab is administered and for a short period of time following the infusion to monitor for anaphylactoid reaction {01})
Wound infection (basiliximab may cause an increased risk of wound infection {01})
Note: Although the incidences of malignancies and systemic infection were not increased in the basiliximab-treated group in preapproval clinical trials, patients receiving basiliximab should be monitored routinely for malignancy and systemic infection {01}.
Side/Adverse Effects
Note: The product labeling for basiliximab contains an extensive list of adverse effects observed in patients during clinical trials {01}. Because all the patients were receiving other immunosuppressant drugs, some of the adverse effects may have resulted from the use of the other immunosuppressant drugs {01}. Basiliximab did not seem to add additional side effects to those which would have been expected in transplant patients receiving standard immunosuppressant drug regimens. The incidence of adverse effects, including serious adverse effects, was similar between the basiliximab-treated group and the placebo-treated group {01}. The side effect profile of basiliximab may become better known as additional experience is gained with its use.
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent
Abdominal pain
asthenia (loss of energy or weakness)
back pain
candidiasis (white patches in the mouth or throat or on the tongue)
cough
dizziness
dyspnea (shortness of breath)
dysuria (painful urination)
edema (swelling of ankles, body, face, feet, or lower legs)
fever
hypertension —asymptomatic
infection (fever or chills)
pharyngitis (sore throat)
tremor (trembling or shaking of hands or feet)
vomiting
Incidence less frequent
Abnormal vision
agitation
anxiety
arrhythmia (dizziness)—may be asymptomatic
chest pain
depression
fatigue
gastrointestinal bleeding (blood in the stool)—usually asymptomatic
gingival hyperplasia (bleeding, tender, or enlarged gums)
hematoma (bruising)
hypoesthesia (“stocking and gloves” sensation of the hands or feet)
hypotension (dizziness)
neuropathy (numbness or pain in the legs)
paresthesia (tingling)
pruritus (itching)
pulmonary edema (coughing; shortness of breath)
skin rash
stomatitis (sores in the mouth)
urinary retention (difficulty in urinating)
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
Acne
constipation
diarrhea
dyspepsia (heartburn)
headache
insomnia (trouble in sleeping)
nausea
weight gain
Incidence less frequent
Arthralgia (joint pain)
hypertrichosis (excessive hair growth)
myalgia (muscle pain)
Overdose
There is no clinical experience with overdose of basiliximab, and a maximum tolerated dose has not been established. Some patients have received doses of up to 60 mg without any adverse effects {01}.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Basiliximab (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Allergy to basiliximab
Carcinogenicity—
Use of basiliximab may be associated with an increased risk of malignancy
Pregnancy—Basiliximab crosses the placenta
Breast-feeding—Use is not recommended
Dental—Dental work should be completed prior to initiation of therapy whenever possible
Proper use of this medication
Advisability of women of childbearing age using effective contraception before, during, and for 2 months after receiving basiliximab
» Proper dosing
Precautions while receiving this medication
» Importance of close monitoring by a physician
Side/adverse effects
Signs of potential side effects, especially abdominal pain, asthenia, back pain, candidiasis, cough, dizziness, dyspnea, dysuria, edema, fever, hypertension, infection, pharyngitis, tremor, vomiting, abnormal vision, agitation, anxiety, arrhythmia, chest pain, depression, fatigue, gastrointestinal bleeding, gingival hyperplasia, hematoma, hypoesthesia, hypotension, neuropathy, paresthesia, pruritus, pulmonary edema, skin rash, stomatitis, and urinary retention
General Dosing Information
Basiliximab should be used only by physicians experienced in the management of organ transplant patients {01}. Medications for the treatment of severe hypersensitivity reactions should be immediately available when basiliximab is administered {01}.
Shaking of the vial of prepared solution of basiliximab may cause foaming and should be avoided {01}.
Parenteral Dosage Forms
BASILIXIMAB FOR INJECTION
Usual adult dose
Transplant rejection, kidney (prophylaxis)
Intravenous infusion over twenty to thirty minutes, 20 mg within two hours prior to transplantation surgery {01}. The dose should be repeated four days after transplantation.
Usual pediatric dose
Transplant rejection, kidney (prophylaxis)
Intravenous infusion over twenty to thirty minutes, 12 mg per square meter of body surface area within two hours prior to transplantation surgery. The dose should be repeated four days after transplantation.
Usual pediatric prescribing limits
20 mg for each infusion.
Usual geriatric dose
See Usual adult dose .
Strength(s) usually available
U.S.—
20 mg (Rx) [Simulect (lyophilized powder) (potassium phosphate monobasic 7.21 mg) (disodium hydrogen phosphate [anhydrous] 0.99 mg) (sodium chloride 1.61 mg) (sucrose 20 mg) (mannitol 80 mg) (glycine 40 mg)]
Packaging and storage:
Store between 2 and 8 ºC (36 and 46 ºF).
Preparation of dosage form:
Reconstitute vial with 5 mL of Sterile Water for Injection USP. The reconstituted solution should be diluted to a volume of 50 mL with 0.9% sodium chloride injection or 5% dextrose injection {01}.
Stability:
Basiliximab does not contain preservatives. Prepared solutions of basiliximab should be used within 4 hours. If refrigerated at 4 ºC (39 ºF), solutions should be used within 24 hours. The prepared solution should be inspected for particulate matter and clarity before administration to the patient, and should be discarded if particulate matter is present {01}.
Incompatibilities:
There are no data on the compatibility or incompatibility of other drugs or solutions with basiliximab. Until more data are available, other drugs should not be infused simultaneously through the same intravenous line {01}.
Developed: 07/09/1998
References
- Basiliximab package insert (Novartis—US), New 05/12/98, Rec 06/11/98.
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