Basiliximab

U.S. BRAND NAMES — Simulect®

PHARMACOLOGIC CATEGORY
Monoclonal Antibody

DOSING: ADULTS — Note: Patients previously administered basiliximab should only be re-exposed to a subsequent course of therapy with extreme caution.

Renal transplantation: I.V.: 20 mg within 2 hours prior to transplant surgery, followed by a second 20 mg dose 4 days after transplantation. The second dose should be withheld if complications occur (including severe hypersensitivity reactions or graft loss).

DOSING: PEDIATRIC — Note: Patients previously administered basiliximab should only be re-exposed to a subsequent course of therapy with extreme caution.

(For additional information see "Basiliximab: Pediatric drug information")

Renal transplantation: I.V.:
Children <35 kg: 10 mg within 2 hours prior to transplant surgery, followed by a second 10 mg dose 4 days after transplantation; the second dose should be withheld if complications occur (including severe hypersensitivity reactions or graft loss)
Children ≥ 35 kg: Refer to adult dosing

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — No specific dosing adjustment is recommended.

DOSING: HEPATIC IMPAIRMENT — No specific dosing adjustment is recommended.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [preservative free]:
Simulect®: 10 mg, 20 mg

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Simulect®: 10 mg, 20 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — For intravenous administration only. Infuse as a bolus or I.V. infusion over 20-30 minutes. (Bolus dosing is associated with nausea, vomiting, and local pain at the injection site.)

USE — Prophylaxis of acute organ rejection in renal transplantation

ADVERSE REACTIONS SIGNIFICANT — Administration of basiliximab did not appear to increase the incidence or severity of adverse effects in clinical trials. Adverse events were reported in 96% of both the placebo and basiliximab groups.

>10%:
Cardiovascular: Hypertension, peripheral edema
Central nervous system: Fever, headache, insomnia, pain
Dermatologic: Acne, wound complications
Endocrine & metabolic: Hypercholesterolemia, hyperglycemia, hyper-/hypokalemia, hyperuricemia, hypophosphatemia
Gastrointestinal: Abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting
Genitourinary: Urinary tract infection
Hematologic: Anemia
Neuromuscular & skeletal: Tremor
Respiratory: Dyspnea, infection (upper respiratory)
Miscellaneous: Viral infection

3% to 10%:
Cardiovascular: Abnormal heart sounds, angina pectoris, arrhythmia, atrial fibrillation, cardiac failure, chest pain, generalized edema, hypotension, tachycardia
Central nervous system: Agitation, anxiety, depression, dizziness, fatigue, hypoesthesia, malaise, neuropathy, rigors
Dermatologic: Cyst, hypertrichosis, pruritus, rash, skin disorder, skin ulceration
Endocrine & metabolic: Acidosis, dehydration, diabetes mellitus, fluid overload, hyper-/hypocalcemia, hyperlipidemia, hypertriglyceridemia, hypoglycemia, hypomagnesemia, hyponatremia
Gastrointestinal: Abdomen enlarged, esophagitis, flatulence, gastroenteritis, GI hemorrhage, gingival hyperplasia, melena, moniliasis, stomatitis (including ulcerative), weight gain
Genitourinary: Albuminuria, bladder disorder, dysuria, genital edema, hematuria, impotence, oliguria, renal function abnormal, renal tubular necrosis, ureteral disorder, urinary frequency, urinary retention
Hematologic: Hematoma, hemorrhage, leukopenia, polycythemia, purpura, thrombocytopenia, thrombosis
Neuromuscular & skeletal: Arthralgia, arthropathy, back pain, cramps, fracture, hernia, leg pain, myalgia, paresthesia, weakness
Ocular: Abnormal vision, cataract, conjunctivitis
Respiratory: Bronchitis, bronchospasm, cough, pharyngitis, pneumonia, pulmonary edema, sinusitis, rhinitis
Miscellaneous: Accidental trauma, facial edema, glucocorticoids increased, herpes infection, sepsis

Postmarketing and/or case reports: Capillary leak syndrome, cytokine release syndrome; severe hypersensitivity reactions, including anaphylaxis, have been reported (symptoms may include hypotension, tachycardia, cardiac failure, dyspnea, bronchospasm, pulmonary edema, urticaria, rash, pruritus, sneezing, and respiratory failure)

CONTRAINDICATIONS — Hypersensitivity to basiliximab, murine proteins, or any component of the formulation

WARNINGS / PRECAUTIONS
Boxed warnings: Experienced physician: See "Other warnings/precautions" below.

Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Severe hypersensitivity reactions, occurring within 24 hours, have been reported. Reactions, including anaphylaxis, have occurred both with the initial exposure and/or following re-exposure after several months; use caution during re-exposure to a subsequent course of therapy in a patient who has previously received basiliximab. Discontinue the drug permanently if a reaction occurs. Medications for the treatment of hypersensitivity reactions should be available for immediate use. Human antimurine antibodies (HAMA): Treatment may result in the development of HAMA; however, limited evidence suggesting the use of muromonab-CD3 or other murine products is not precluded. Lymphoproliferative disorders: The incidence of lymphoproliferative disorders may be increased by immunosuppressive therapy. Opportunistic infections: The incidence opportunistic infections may be increased by immunosuppressive therapy.

Other warnings/precautions: Appropriate use: To be used as a component of immunosuppressive regimen which includes cyclosporine and corticosteroids. Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of a physician experienced in immunosuppression therapy.

DRUG INTERACTIONS
Abciximab: May enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Risk C: Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy

Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Echinacea may diminish the therapeutic effect of basiliximab. Avoid hypoglycemic herbs, including alfalfa, bilberry, bitter melon, burdock, celery, damiana, fenugreek, garcinia, garlic, ginger, ginseng, gymnema, marshmallow, and stinging nettle (may enhance the hypoglycemic effect of basiliximab).

PREGNANCY RISK FACTOR — B (show table) (manufacturer)

PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. IL-2 receptors play an important role in the development of the immune system. Use in pregnant women only when benefit exceeds potential risk to the fetus. Women of childbearing potential should use effective contraceptive measures before beginning treatment and for 4 months after completion of therapy with this agent.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — It is not known whether basiliximab is excreted in human milk. Because many immunoglobulins are secreted in milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

MONITORING PARAMETERS — Signs and symptoms of acute rejection

CANADIAN BRAND NAMES — Simulect®

INTERNATIONAL BRAND NAMES — Simulect (AR, AT, AU, BE, BG, BR, CH, CL, CN, CO, CZ, DE, DK, EC, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, KP, MX, MY, NL, NO, PE, PH, PK, PL, PT, PY, RU, SE, SG, TH, TR, TW, UY, VE)

MECHANISM OF ACTION — Chimeric (murine/human) monoclonal antibody which blocks the alpha-chain of the interleukin-2 (IL-2) receptor complex; this receptor is expressed on activated T lymphocytes and is a critical pathway for activating cell-mediated allograft rejection

PHARMACODYNAMICS / KINETICS
Duration: Mean: 36 days (determined by IL-2R alpha saturation)

Distribution: Mean: Vd: Children 1-11 years: 4.8 +/- 2.1 L; Adolescents 12-16 years: 7.8 +/- 5.1 L; Adults: 8.6 +/- 4.1 L

Half-life elimination: Children 1-11 years: 9.5 days; Adolescents 12-16 years: 9.1 days; Adults: Mean: 7.2 days

Excretion: Clearance: Children 1-11 years: 17 mL/hour; Adolescents 12-16 years: 31 mL/hour; Adults: Mean: 41 mL/hour