Simulect

Generic Name: Basiliximab
Class: Immunosuppressive Agents
VA Class: IM600
CAS Number: 179045-86-4

Warning(s)

  • Should be prescribed only by clinicians experienced in immunosuppressive therapy and the management of organ transplant patients.1

  • The clinician responsible for the administration of basiliximab should have complete information necessary for follow-up of the patient.1

  • Should only be administered by medical personnel trained in administration of the drug and who have adequate laboratory and supportive medical resources.1

Introduction

Immunosuppressive agent; recombinant DNA-derived chimeric (human-murine) monoclonal antibody.1 2 3 4 5

Uses for Simulect

Renal Allotransplantation

Prevention of renal allograft rejection.1 2 3 5

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Manufacturer recommends use in conjunction with cyclosporine and corticosteroids.1

Efficacy in preventing acute rejection of a second renal allograft or other solid organ transplants (e.g., liver transplantation) has not been demonstrated.1

Simulect Dosage and Administration

Administration

IV Administration

Administer only by direct IV (“bolus”) injection or IV infusion via a central or peripheral line.1 7

Direct IV injection may be associated with nausea, vomiting, and local reactions, including pain.1 7

Administer in conjunction with cyclosporine and corticosteroid therapy.1

Administer only when it has been determined that the patient will receive the graft and concomitant immunosuppressive therapy.1

Reconstitution

10 mg vial: add 2.5 mL of sterile water for injection.a Reconstituted solution is isotonic; may administer by direct IV injection or dilute for IV infusion.a

20 mg vial: add 5 mL of sterile water for injection.1 Reconstituted solution is isotonic; may administer by direct IV injection or dilute for IV infusion.1

Shake vial gently to dissolve.1

Dilution

10 mg vial: for IV infusion, dilute reconstituted solution to 25 mL with 0.9% sodium chloride or 5% dextrose injection.a

20 mg vial: for IV infusion, dilute reconstituted solution to 50 mL with 0.9% sodium chloride or 5% dextrose injection.1

Gently invert the IV bag to mix the solution without foaming; do not shake.1

Rate of Administration

For IV infusion, administer over 20–30 minutes.1

Dosage

Pediatric Patients

Renal Allotransplantation
Prevention of Allograft Rejection in Children 1–16 Years of Age
IV

Weight < 35 kg: 2 doses, 10 mg each, by direct IV injection or IV infusions.1 7

Weight ≥ 35 kg: 2 doses, 20 mg each.1 7

Administer first dose within 2 hours prior to transplantation, second dose 4 days after transplantation.1 2 3 5

Withhold second dose if complications (e.g., severe hypersensitivity reactions, graft loss) occur after the first dose.1

Adults

Renal Allotransplantation
Prevention of Allograft Rejection
IV

2 doses, 20 mg each, by direct IV injection or IV infusion.

Administer first dose within 2 hours prior to transplantation, second dose 4 days after transplantation.1 2 3 5

Withhold second dose if complications (e.g., severe hypersensitivity reactions, graft loss) occur after the first dose.1

Prescribing Limits

Pediatric Patients

Renal Allograft
IV

Not determined; at least one pediatric renal transplant patient received single 20-mg dose (2.3 mg/kg) without adverse events.1

Adults

Renal Allograft
IV

Not determined; single doses up to 60 mg or divided doses over 3-5 days of up to 120 mg given without serious adverse effects.1

Special Populations

Geriatric Patients

Dosage adjustment is not required for geriatric patients; in general, use immunosupressive agents with caution.1

Cautions for Simulect

Contraindications

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

Warnings/Precautions

Warnings

(See Boxed Warning.)

Lymphoproliferative Disorders and Opportunistic Infections

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

Immune Response

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

Immunogenicity

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

Pregnancy

Category B.1

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

Lactation

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

Pediatric Use

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

Geriatric Use

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

Interactions for Simulect

Specific Drugs

Drug

Interaction

Comments

Immunosuppressive triple-agent regimen (azathioprine or mycophenolate mofetil with cyclosporine and corticosteroids)

Clearance of basiliximab reduced by 22% with azathioprine or by 51% with mycophenolate mofetil triple regimen; however, clearance consistent with dual regimens1

Basiliximab dosage adjustment unnecessary1

Antilymphocyte globulin

No increase in adverse effects1

Antithymocyte globulin

No increase in adverse effects1

Azathioprine

No increase in adverse effects1

Corticosteroids

No increase in adverse effects1

Cyclosporine

No increase in adverse effects1

Mycophenolate mofetil

No increase in adverse effects1

Muromonab-CD3

No increase in adverse effects1

Simulect Pharmacokinetics

Absorption

Duration

Duration of clinically important IL-2 receptor blockade by basiliximab is unknown.a

Duration of basiliximab IL-2 Rα saturation when added to double regimen (cyclosporine and corticosteroids) averages 36 days in children and adults.a

Duration of basiliximab IL-2 Rα saturation varies with regimen; when added to triple regimens (cyclosporine and corticosteroids plus azathioprine or mycophenolate mofetil), duration averages 50 days with azathioprine regimen and 59 days with mycophenolate mofetil regimen.a

Distribution

Extent

Generally, immune globulin molecules cross the placenta; not known whether basiliximab crosses placenta or is distributed into milk.a

Elimination

Half-life

Adults: average 7.2 days.a

Children 1–11 years of age: average 9.5 days.a

Children 12–16 years of age: average 9.1 days.a

Special Populations

In adults (20–69 years of age), half-life not affected by age.a

Stability

Storage

Parenteral

Powder for Injection

2–8°C.1

Reconstituted Solution

Use immediately or within 4 hours of preparation if stored at 15–30°C.1 7

Alternatively, may be stored at 2–8°C for up to 24 hours after preparation.1 7

Discard unused solutions within 24 hours.1

Diluted Solution

Manufacturer makes no storage recommendation.a

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

5% Dextrose Injection

0.9% Sodium Chloride Injection

Incompatibility not observed with polyvinyl chloride bags or infusion sets.1

Drug Compatibility

Unknown whether basiliximab is compatible with other IV drugs.1

Do not mix with other drugs or infuse simultaneously with other drugs in the same IV line.1

Actions

  • A recombinant DNA-derived chimeric (human-murine) monoclonal antibody immunosuppressive agent.1 2 3 4 5

  • Competitively inhibits IL-2-mediated lymphocyte activation, integral to the cell-mediated immune response involved in allograft rejection.1 2

  • Binds with high affinity to IL-2Rα and inhibits binding of IL-2 to antigenically stimulated T lymphocytes.1 2

Advice to Patients

  • Importance of understanding potential benefits of basiliximab and risks of immunosuppressive therapy.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Basiliximab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

10 mg

Simulect

Novartis

20 mg

Simulect

Novartis

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Novartis Pharmaceuticals Corporation. Simulect (basiliximab) for injection prescribing information. East Hanover, NJ; 2000 Jun.

2. Nashan B, Moore R, Amlot P et al. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. Lancet. 1997; 350:1193-8. [IDIS 394766] [PubMed 9652559]

3. Kahan BD, Rajagopalan PR, Hall M. Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. Transplantation. 1999; 67:276-84. [IDIS 422843] [PubMed 10075594]

4. Kovarik JM, Kahan BD, Rajagopalan PR et al. Population pharmacokinetics and exposure-response relationships for basiliximab in kidney transplantation. Transplantation. 1999; 68:1288-94. [IDIS 439006] [PubMed 10573065]

5. Onrust SV, Wiseman LR. Basiliximab. Drugs. 1999; 57:207-13. [PubMed 10188761]

6. Ponticelli C, Yussim A, Cambi V et al. Basiliximab significantly reduces acute rejection in renal transplant patients given triple therapy with azathioprine. Transplant Proc. 2001; 33:1009-10. [IDIS 461658] [PubMed 11267167]

7. Novartis Pharmaceuticals Corporation: Personal communication.

a. Novartis. Simulect (basiliximab) prescribing information. East Hanover, NJ; 2003 Jan.

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