Basiliximab

Dosage Forms

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

Solution Reconstituted, Intravenous [preservative free]:

Simulect: 10 mg (1 ea); 20 mg (1 ea)

Pharmacology

Mechanism of Action

Basiliximab is a chimeric (murine/human) immunosuppressant 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

Pharmacokinetics/Pharmacodynamics

Distribution

Mean: V_d: Children 1 to 11 years: 4.8 ± 2.1 L; Adolescents 12 to 16 years: 7.8 ± 5.1 L; Adults: 8.6 ± 4.1 L

Excretion

Clearance:

Children 1 to 11 years: 17 ± 6 mL/hour; in pediatric liver transplant patients, significant basiliximab loss through ascites fluid can increase total body clearance and reduce IL-2R (CD25) saturation duration; dosage adjustments may be necessary (Cintorino 2006; Kovarik 2002; Spada 2006)

Adolescents 12 to 16 years: 31 ±19 mL/hour

Adults: 41 ± 19 mL/hour

Duration of Action

Mean: 36 ± 14 days (determined by IL-2R alpha saturation in patients also on cyclosporine and corticosteroids)

Half-Life Elimination

Children 1 to 11 years: 9.5 ± 4.5 days; Adolescents 12 to 16 years: 9.1 ± 3.9 days; Adults: Mean: 7.2 ± 3.2 days

Use: Labeled Indications

Renal transplant (prophylaxis of acute rejection): Prophylaxis of acute organ rejection in renal transplantation in combination with cyclosporine (modified) and corticosteroids

Guideline recommendations: While basiliximab is FDA-approved for prophylaxis of acute organ rejection in renal transplantation in combination with cyclosporine (modified) and corticosteroids, cyclosporine is no longer recommended as the first line agent of choice. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for care of kidney transplant recipients recommend induction as part of the initial immunosuppressive regimen for all kidney transplants to reduce the risk of acute rejection. KDIGO recommends an interleukin 2 receptor antagonist (eg,basiliximab) as the first line induction agent for acute rejection prophylaxis except in those patients at high immunologic risk. (KDIGO [Kasiske 2009]).

Use: Off Label

Acute graft-versus-host disease, refractory (treatment)c

Data from a small nonrandomized phase II study in patients with steroid refractory acute graft-versus-host-disease (aGVHD) following allogeneic stem cell transplant suggest that basiliximab may be beneficial in the treatment of refractory aGVHD Schmidt-Hieber 2005. Additional data may be necessary to further define the role of basiliximab in this condition.

Heart transplant (prophylaxis of acute rejection)b

Data from a randomized, placebo-controlled, double blind, multicenter study in de novo heart transplant recipients supports the use of basiliximab (in combination with other immunosuppressants [ie, cyclosporine, mycophenolate, and prednisone]) in the prevention cardiac transplant rejection Mehra 2005. Additional trials may be necessary to further define the role of basiliximab in this condition.

Liver transplant (prophylaxis of acute rejection)b

Data from a multicenter, randomized, open-label phase IIIb trial in liver transplant patients supports the use of basiliximab (in combination with tacrolimus) for the prevention of acute rejection Trunecka 2015. Additional data from a multicenter, randomized, placebo-controlled, double blind study in liver transplant recipients supports the use of basiliximab (in combination with other immunosuppressants [ie, cyclosporine and corticosteroids]) in the prevention of liver transplant rejection Neuhaus 2002. A meta analysis evaluating rejection prevention in liver transplant recipients suggests that interleukin 2 receptor antagonist therapy (eg, basiliximab) may be beneficial in reducing episodes of acute rejection, but does not appear to improve overall survival in these patients Zhang 2016. Additional trials may be necessary to further define the role of basiliximab in this condition.

Lung transplant (prophylaxis of acute rejection)c

A retrospective analysis of data obtained from the United Network for Organ Sharing (UNOS) registry supports the use of basiliximab as induction therapy in patients receiving double lung transplants Furuya 2016. Data from other retrospective reviews suggest that basiliximab may be beneficial in prevention of lung transplant rejection Clinckart 2009, Swarup 2011. Additional data may be necessary to further define the role of basiliximab in prevention of lung transplant rejection.

Contraindications

Known hypersensitivity to basiliximab or any component of the formulation

Dosage and Administration

Dosing: Adult

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

Renal transplant (prophylaxis of acute rejection): IV: 20 mg within 2 hours prior to transplant surgery, followed by a second 20 mg dose 4 days after transplantation (in combination with other immunosuppressants). The second dose should be withheld if complications occur (including severe hypersensitivity reactions or graft loss). Timing of basiliximab dosing may vary based on clinical and institutional factors; refer to institutional protocol for specific information.

Acute graft-versus-host disease (aGVHD), refractory (treatment) (off-label use): IV: 20 mg on days 1 and 4; may repeat for recurrent acute GVHD (Schmidt-Hieber 2005). Additional data may be necessary to further define the role of basiliximab in this condition.

Heart transplant (prophylaxis of acute rejection) (off-label use): IV: 20 mg on the day of transplant, followed by a second 20 mg dose on day 4 post-transplantation (in combination with other immunosuppressants) (Mehra 2005). The first dose is usually administered immediately prior to transplant or within the first hours postoperatively.

Liver transplant (prophylaxis of acute rejection) (off-label use): IV: 20 mg on the day of transplant (day 0), followed by a second 20 mg dose on day 4 post-transplantation (in combination with other immunosuppressants) (Neuhaus 2002; Trunecka 2015). In clinical trials, the first dose was administered during the procedure once hemostasis was achieved or immediately post-transplant, or within 6 hours of organ reperfusion.

Lung transplant (prophylaxis of acute rejection) (off-label use): IV: 20 mg prior to transplantation, followed by a second 20 mg dose 4 days after transplantation (in combination with other immunosuppressants) (Clinckart 2009; Swarup 2011). Additional trials may be necessary to further define the role of basiliximab in this condition.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Patients previously administered basiliximab should only be re-exposed to a subsequent course of therapy with extreme caution due to increased risk of hypersensitivity reactions. Hold second or subsequent dose(s) if severe hypersensitivity reactions or graft failure occurs.

Heart transplantation: Limited data available (Ford 2005; Grundy 2009): Infants, Children, and Adolescents: IV:

Patient weight <35 kg:

Initial dose: 10 mg administered immediately before cardiopulmonary bypass started is recommended or may administer within 6 hours of organ perfusion; reported timing of doses is variable; however, superior outcomes have been reported with pretransplant basiliximab administration (Grundy 2009)

Second dose: 10 mg administered 4 days after transplantation

Patient weight ≥35 kg:

Initial dose: 20 mg administered immediately before cardiopulmonary bypass started is recommended or may administer within 6 hours of organ perfusion; reported timing of doses is variable; however, superior outcomes have been reported with pretransplant basiliximab administration (Grundy 2009)

Second dose: 20 mg administered 4 days after transplantation

Liver transplantation: Limited data available: Infants, Children, and Adolescents: IV (Cintorino 2006; Kovarik 2002; Spada 2006):

Patient weight <35 kg:

Initial dose: 10 mg administered within 6 hours of organ perfusion

Second dose: 10 mg administered 4 days after transplantation

Third dose: 10 mg has been repeated on postoperative days 8 to 10 if ascites fluid loss exceeds 70 mL/kg or >5 L

Patient weight ≥35 kg:

Initial dose: 20 mg administered within 6 hours of organ perfusion

Second dose: 20 mg administered 4 days after transplantation

Third dose: 20 mg has been repeated on postoperative days 8 to 10 if ascites fluid loss exceeds 70 mL/kg or if total ascites volume ≥5 L

Renal transplantation: Children and Adolescents: IV:

Patient weight <35 kg:

Initial dose: 10 mg administered within 2 hours prior to renal transplant surgery

Second dose: 10 mg administered 4 days after transplantation

Patient weight ≥35 kg:

Initial dose: 20 mg administered within 2 hours prior to renal transplant surgery

Second dose: 20 mg administered 4 days after transplantation

Reconstitution

Reconstitute with preservative-free sterile water for injection (reconstitute 10 mg vial with 2.5 mL, 20 mg vial with 5 mL). Shake gently to dissolve. May further dilute reconstituted solution with 25 mL (10 mg) or 50 mL (20 mg) 0.9% sodium chloride or dextrose 5% in water. When mixing the solution, gently invert the bag to avoid foaming. Do not shake solutions diluted for infusion.

For the treatment of acute GVHD (off-label use), the dose was diluted in 250 mL NS (Schmidt-Hieber 2005).

Administration

IV: For intravenous administration only. Infuse as a bolus or IV infusion over 20 to 30 minutes (bolus dosing is associated with nausea, vomiting, and local pain at the injection site); may be administered through either a peripheral or central line. For the treatment of acute GVHD (off-label use), the dose was administered over 30 minutes (Schmidt-Hieber 2005).

Storage

Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F). Should be used immediately after reconstitution; however, if not used immediately, reconstituted solution may be stored at 2°C to 8°C for up to 24 hours or at room temperature for up to 4 hours. Discard the reconstituted solution if not used within 24 hours.

Drug Interactions

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

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

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

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. Consider therapy modification

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

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

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

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

Frequency not defined. 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: Headache, insomnia, pain

Dermatologic: Acne vulgaris

Endocrine & metabolic: Hypercholesterolemia, hyperglycemia, hyperkalemia, hyperuricemia, hypokalemia, hypophosphatemia

Gastrointestinal: Abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting

Genitourinary: Urinary tract infection

Hematologic & oncologic: Anemia

Infection: Viral infection

Neuromuscular & skeletal: Tremor

Respiratory: Dyspnea, upper respiratory infection

Miscellaneous: Fever, postoperative wound complication

3% to 10%:

Cardiovascular: Abnormal heart sounds, angina pectoris, atrial fibrillation, cardiac arrhythmia, cardiac failure, chest pain, hypotension, tachycardia, thrombosis

Central nervous system: Agitation, anxiety, depression, dizziness, fatigue, hypoesthesia, malaise, rigors

Dermatologic: Dermal ulcer, dermatological disease, hypertrichosis, pruritus, skin rash

Endocrine & metabolic: Acidosis, albuminuria, anasarca, dehydration, diabetes mellitus, hypercalcemia, hyperlipidemia, hypertriglyceridemia, hypervolemia, hypocalcemia, hypoglycemia, hypomagnesemia, hyponatremia, increased nonprotein nitrogen, increased serum glucocorticoids, weight gain

Gastrointestinal: Enlargement of abdomen, esophagitis, flatulence, gastroenteritis, gastrointestinal hemorrhage, GI moniliasis, gingival hyperplasia, hernia, melena, stomatitis (including ulcerative)

Genitourinary: Bladder dysfunction, dysuria, genital edema (male), hematuria, impotence, oliguria, ureteral disease, urinary frequency, urinary retention

Hematologic & oncologic: Hematoma, hemorrhage, hypoproteinemia, leukopenia, polycythemia, purpura, thrombocytopenia

Infection: Cytomegalovirus disease, herpes virus infection (simplex and zoster), infection, sepsis

Neuromuscular & skeletal: Arthralgia, arthropathy, back pain, bone fracture, leg pain, muscle cramps, myalgia, neuropathy, paresthesia, weakness

Ophthalmic: Cataract, conjunctivitis, visual disturbance

Renal: Renal insufficiency, renal tubular necrosis

Respiratory: Bronchitis, bronchospasm, cough, pharyngitis, pneumonia, pulmonary edema, rhinitis, sinusitis

Miscellaneous: Accidental injury, cyst

<1%, postmarketing, and/or case reports: Anaphylaxis, capillary leak syndrome, cytokine release syndrome, diabetes (new onset), hypersensitivity reaction (includes bronchospasm, cardiac failure, dyspnea, hypotension, pruritus, pulmonary edema, respiratory failure, skin rash, sneezing, tachycardia, urticaria), impaired glucose tolerance, increase in fasting plasma glucose, lymphoproliferative disorder

Warnings/Precautions

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. Patients in whom concomitant immunosuppression was prematurely discontinued due to abandoned transplantation or early graft loss are at increased risk for developing a severe hypersensitivity reaction upon re-exposure. Discontinue permanently if a severe reaction occurs. Medications for the treatment of hypersensitivity reactions should be available for immediate use.
• Diabetes: In renal transplant patients receiving basiliximab plus prednisone, cyclosporine, and mycophenolate, new-onset diabetes, glucose intolerance, and impaired fasting glucose were observed at rates significantly higher than observed in patients receiving prednisone, cyclosporine, and mycophenolate without basiliximab (Aasebo 2010).
• 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 of opportunistic infections may be increased by immunosuppressive therapy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: To be used as a component of an immunosuppressive regimen which includes cyclosporine and corticosteroids.
• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of a physician experienced in immunosuppression therapy and organ transplant management.

Monitoring Parameters

Monitor for signs and symptoms of acute rejection; hypersensitivity, infection

Pregnancy

Pregnancy Considerations

Basiliximab is a monoclonal IgG antibody which targets IL-2 receptors. IgG is known to cross the placenta; IL-2 receptors play an important role in the development of the immune system.

Women of childbearing potential should use effective contraceptive measures before beginning treatment, during, and for 4 months after completion of basiliximab treatment.

The Transplant Pregnancy Registry International (TPR) is a registry that follows pregnancies that occur in maternal transplant recipients or those fathered by male transplant recipients. The TPR encourages reporting of pregnancies following solid organ transplant by contacting them at 1-877-955-6877 or https://www.transplantpregnancyregistry.org.

Patient Education

What is this drug used for?

• It is used after a kidney transplant to keep the body from rejecting the kidney.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Trouble sleeping
• Acne
• Constipation
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Heartburn
• Common cold symptoms

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
• Severe dizziness
• Passing out
• Chest pain
• Fast heartbeat
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Sneezing
• Severe headache
• Tremors
• Severe loss of strength and energy
• Vision changes
• Wound site pain, swelling, or drainage
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.