Basiliximab

Simulect® (basiliximab) is a chimeric (murine/human) monoclonal antibody (IgG1K), produced by recombinant DNA technology, that functions as an immunosuppressive agent, specifically binding to and blocking the interleukin-2 receptor α-chain (IL-2Rα, also known as CD25 antigen) on the surface of activated T-lymphocytes. Based on the amino acid sequence, the calculated molecular weight of the protein is 144 kilodaltons. It is a glycoprotein obtained from fermentation of an established mouse myeloma cell line genetically engineered to express plasmids containing the human heavy and light chain constant region genes and mouse heavy and light chain variable region genes encoding the RFT5 antibody that binds selectively to the IL-2Rα.

The active ingredient, basiliximab, is water soluble. The drug product, Simulect (basiliximab) , is a sterile lyophilisate which is available in 6 mL colorless glass vials and is available in 10 mg and 20 mg strengths.

Each 10-mg vial contains 10 mg basiliximab, 3.61 mg monobasic potassium phosphate, 0.50 mg disodium hydrogen phosphate (anhydrous), 0.80 mg sodium chloride, 10 mg sucrose, 40 mg mannitol and 20 mg glycine, to be reconstituted in 2.5 mL of Sterile Water for Injection, USP. No preservatives are added.

Each 20-mg vial contains 20 mg basiliximab, 7.21 mg monobasic potassium phosphate, 0.99 mg disodium hydrogen phosphate (anhydrous), 1.61 mg sodium chloride, 20 mg sucrose, 80 mg mannitol and 40 mg glycine, to be reconstituted in 5 mL of Sterile Water for Injection, USP. No preservatives are added.

See Boxed WARNING.

General

Simulect® (basiliximab) should be administered under qualified medical supervision. Patients should be informed of the potential benefits of therapy and the risks associated with administration of immunosuppressive therapy.

While neither the incidence of lymphoproliferative disorders nor opportunistic infections was higher in Simulect (basiliximab) -treated patients than in placebo-treated patients, patients on immunosuppressive therapy are at increased risk for developing these complications and should be monitored accordingly.

Hypersensitivity

Severe acute (onset within 24 hours) hypersensitivity reactions including anaphylaxis have been observed both on initial exposure to Simulect (basiliximab) and/or following re-exposure after several months. These reactions may include hypotension, tachycardia, cardiac failure, dyspnea, wheezing, bronchospasm, pulmonary edema, respiratory failure, urticaria, rash, pruritus, and/or sneezing. Extreme caution should be exercised in all patients previously given Simulect (basiliximab) when being administered a subsequent course of Simulect (basiliximab) . A subgroup of patients may be particularly at risk of developing severe hypersensitivity reactions on re-administration. These are patients in whom concomitant immunosuppression was discontinued prematurely (e.g., due to abandoned transplantation or early loss of the graft) following the initial administration of Simulect (basiliximab) . If a severe hypersensitivity reaction occurs, therapy with Simulect (basiliximab) should be permanently discontinued. Medications for the treatment of severe hypersensitivity reactions including anaphylaxis should be available for immediate use.

Dosage Forms & Strengths

powder for injection

• 10mg
• 20mg

Prophylaxis of Renal Transplant Rejection

20 mg IV within 2 hr prior to transplant surgery, THEN

20 mg IV 4 days after transplant

Withhold second dose if complications (severe hypersensitivity, or graft loss) occur after first dose

Used in regimen containing cyclosporine and corticosteroids

Acute Cardiac Transplant Rejection Prophylaxis (Unlabeled)

20 mg IV on day of transplant surgery, THEN

20 mg IV 4 days after transplant

Withhold second dose if complications (severe hypersensitivity, or graft loss) occur after first dose

Used in regimen containing cyclosporine and corticosteroids

Acute Liver Transplant Rejection Prophylaxis (Unlabeled)

20 mg IV within 6 hr of organ reperfusion, THEN

20 mg IV 4 days after transplant

Withhold second dose if complications (severe hypersensitivity, or graft loss) occur after first dose

Used in regimen containing cyclosporine and corticosteroids

Treatment of Refractory Acute GVHD (Unlabeled)

20 mg IV on day of organ reperfusion, THEN

20 mg IV 4 days after transplant

May repeat for recurrent acute GVHD

Dosage Forms & Strengths

powder for injection

• 10mg
• 20mg

Prophylaxis of Renal Transplant Rejection

<35 kg: 10 mg IV within 2 hr prior to transplant surgery, THEN 10 mg IV 4 days after transplant

>35 kg: Administer as in adults; 20 mg IV within 2 hr prior to transplant surgery, THEN, 20 mg IV 4 days after transplant

Used in regimen containing cyclosporine and corticosteroids

Basiliximab is part of the drug class:

• Interleukin inhibitors

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• how you respond to this medication

In adult patients, the recommended Simulect (basiliximab) regimen is two doses of 20 mg each. The first dose should be given within 2 hours prior to transplantation surgery. The recommended second dose should be given 4 days after transplantation.

Basiliximab is injected into a vein through an IV. You will receive this injection just before your transplant and again 4 days afterward. Basiliximab must be given slowly, and the IV infusion can take up to 30 minutes to complete.

Basiliximab can lower blood cells that help your body fight infections and help your blood clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Visit your doctor regularly.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Contraindications

• Known hypersensitivity to basiliximab or any ingredient in the formulation.1

Warnings/Precautions

Warnings

(See Boxed Warning.)

Monitor patients for lymphoproliferative disorders and/or opportunistic infections; risk is increased with immunosuppressive therapy.1

Neither complication occurred more often with basiliximab than with placebo in clinical trials.1

Sensitivity Reactions

Severe, acute (onset within 24 hours) hypersensitivity reactions, including anaphylaxis, have occurred after initial basiliximab exposure and subsequent reexposure.1

Drugs to treat severe hypersensitivity reactions, including anaphylaxis, should be immediately available.1

In patients who have previously received the drug, a subsequent course of therapy with basiliximab should be given with extreme caution; risks of subsequent administration not known.1

If hypersensitivity reaction occurs, immediately and permanently discontinue basiliximab and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).1

Patients who have a severe hypersensitivity reaction to basiliximab should not receive the drug again.1

Not known whether the immune response to vaccines, infection, and other antigens is impaired during therapy or will remain impaired following therapy.1

An anti-idiotype antibody response has been detected in renal-transplant patients treated with basiliximab.1 5 No deleterious clinical effect and no evidence of faster basiliximab clearance or shorter duration of basiliximab saturation of IL-2Rα detected in the presence of anti-idiotype antibody.1 Clinical data suggest that subsequent use of muromonab-CD3 or other murine anti-lymphocytic antibody preparations is not precluded.1

Specific Populations

Category B.1

Manufacturer recommends use of effective contraception before, during, and for 4 months following basiliximab use in women of childbearing potential.1

Not known whether basiliximab is distributed into milk.1 Discontinue nursing or the drug.1

Use in children 1–16 years of age for prevention of renal allograft rejection is supported by limited data from a pediatric safety and pharmacokinetic study.1 7

Limited data in patients ≥65 years of age suggest an adverse effect profile similar to that in younger adults; use immunosuppressive drugs with caution in such patients.1 7

Common Adverse Effects

Constipation, nausea, diarrhea, abdominal pain, vomiting, dyspepsia, hyperkalemia, hypokalemia, hyperglycemia, hyperuricemia, hypophosphatemia, hypercholesterolemia, headache, tremor, urinary tract infection, pain, peripheral edema, fever, viral infection, hypertension, dyspnea, upper respiratory tract infection, surgical wound complications, acne, insomnia, anemia.1 2 3

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Not able to sleep.
• Pimples (acne).
• Hard stools (constipation).
• Loose stools (diarrhea).
• Upset stomach or throwing up.
• Belly pain or heartburn.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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

Distribution

Mean: Vd: 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

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

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)

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)

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)

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.

Known hypersensitivity to basiliximab or any component of the formulation

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.

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.

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

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. 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

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

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

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. 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

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. Avoid combination

Data not available

The second dose (in pediatric or adult patients) should be withheld if complications such as severe hypersensitivity reactions to basiliximab or graft loss occur.