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    Interleukin-2 (IL-2) Inhibitors

    BOXED WARNING

    Immunosuppression, requires a specialized care setting, requires an experienced clinician

    Basiliximab therapy requires an experienced clinician in immunosuppressive therapy and management of organ transplantation patients. The health care provider responsible for basiliximab administration should have complete information requisite for the follow-up of the patient. Basiliximab administration also requires a specialized care setting, facilities that are equipped and staffed with adequate laboratory and supportive medical resources. While neither the incidence of lymphoproliferative disorders nor opportunistic infections was higher in basiliximab-treated patients than in placebo-treated patients, patients on immunosuppression therapy are at increased risk for developing these complications and should be monitored accordingly.

    DEA CLASS

    Rx

    DESCRIPTION

    Immunosuppressant; chimeric (murine/human) monoclonal antibody (IgG); binds to and blocks the interleukin-2 receptor alpha chain (CD25); has not been associated with an increased risk of lymphoma or other malignancies.

    COMMON BRAND NAMES

    Simulect

    HOW SUPPLIED

    Simulect Intravenous Inj Pwd F/Sol: 10mg, 20mg

    DOSAGE & INDICATIONS

    For acute kidney transplant rejection prophylaxis when used as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids.
    NOTE: Basiliximab should only be administered once it has been determined that the patient will receive the graft and concomitant immunosuppression.
    NOTE: Do not give the second basiliximab dose on day 4 after transplantation if graft loss or a severe hypersensitivity reaction occurs after the initial dose.
    NOTE: Patients previously administered basiliximab should only be re-exposed to a subsequent course of therapy with extreme caution. The potential risks of another treatment course, specifically those associated with immunosuppression and/or the occurrence of anaphylaxis/anaphylactoid reactions, are not known.
    Intravenous dosage
    Adults, Adolescents, and Children >= 35 kg

    20 mg IV within 2 hours prior to transplantation surgery, followed by 20 mg IV 4 days after transplantation. Guidelines recommend induction therapy with an interleukin-2 receptor antagonist such as basiliximab as part of the initial immunosuppressive regimen for patients at low or moderate immunologic risk.

    Children and Adolescents < 35 kg

    10 mg IV within 2 hours prior to transplantation surgery, followed by 10 mg IV 4 days after transplantation. Guidelines recommend induction therapy with an interleukin-2 receptor antagonist such as basiliximab as part of the initial immunosuppressive regimen for patients at low or moderate immunologic risk.

    For acute liver transplant rejection prophylaxis† when used as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids.
    Intravenous dosage
    Adults

    20 mg IV on the day of transplant (day 0) and a second 20 mg dose on day 4 post-transplant. In clinical trials, the first basiliximab dose was primarily administered at the time of liver reperfusion; however, in 3 studies it was given once hemostasis had been achieved or immediately post-transplant, within 6 hours of reperfusion, or 8 hours of reperfusion. [30987][31402][63924][63925][63926][63927][63928][63929] In these studies, basiliximab was given in combination with a calcineurin inhibitor (tacrolimus or cyclosporine) with or without a steroid (methylprednisolone or hydrocortisone); mycophenolate mofetil was also given in one study.[30987][31402][63924][63925][63926][63928][63929]

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    20 mg IV as a single dose.

    Elderly

    20 mg IV as a single dose.

    Adolescents

    >= 35 kg: 20 mg IV as a single dose.
    < 35 kg: 10 mg IV as a single dose.

    Children

    >= 35 kg: 20 mg IV as a single dose.
    < 35 kg: 10 mg IV as a single dose.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Anaphylactic reactions following the administration of basiliximab have been reported. Medications for the treatment of severe hypersensitivity reactions should be available for immediate use during administration of the drug.
    Withhold the second dose of a treatment course if a severe hypersensitivity reaction or graft loss occurs.
    Patients previously treated with basiliximab should receive any subsequent courses with extreme caution.

    Injectable Administration

    Basiliximab is administered by intravenous bolus or infusion via central or peripheral venous access.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Reconstitution:
    Reconstitute 10 mg vials with 2.5 mL and 20 mg vials with 5 mL of Sterile Water for Injection for a final concentration of 4 mg/mL. Shake vial gently to dissolve the powder.
    After reconstitution, the solution should be clear to opalescent. If particulate matter is present or the solution is colored, do not use.
    The solution should be used immediately after preparation. If not used immediately, it can be stored at 2—8 degrees C for 24 hours or at room temperature for 4 hours.
     
    Intravenous injection:
    Further dilution is not necessary. Administer as a bolus injection. Discard any unused drug; the solution does not contain preservatives.
    Bolus administration may be associated with nausea, vomiting, and local reactions including pain.
     
    Dilution:
    Dilute 10 mg in 25 mL or 20 mg in 50 mL of 0.9% Sodium Chloride or 5% Dextrose injection. Discard any unused drug; the solution does not contain preservatives.
    When mixing the solution, gently invert the bag. In order to avoid foaming; do not shake.
     
    Intravenous infusion:
    Infuse IV over 20—30 minutes. Do not mix basiliximab with other medicines or administer other medications through the same intravenous line.

    STORAGE

    Simulect:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Refrigerate (between 36 and 46 degrees F)
    - Store reconstituted product in refrigerator (36 to 46 degrees F) and administer within 24 hours

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Basiliximab is contraindicated in patients with known hypersensitivity to basiliximab or to any other component of the formulation.

    Human anti-murine antibody (HAMA)

    Human anti-murine antibody (HAMA) has been reported in patients who have received basiliximab with or without previous exposure to muromonab CD3. The available clinical data on the use of muromonab-CD3 in patients previously treated with basiliximab suggest that subsequent use of muromonab-CD3 or other murine anti-lymphocytic antibody preparations is not precluded.

    Immunosuppression, requires a specialized care setting, requires an experienced clinician

    Basiliximab therapy requires an experienced clinician in immunosuppressive therapy and management of organ transplantation patients. The health care provider responsible for basiliximab administration should have complete information requisite for the follow-up of the patient. Basiliximab administration also requires a specialized care setting, facilities that are equipped and staffed with adequate laboratory and supportive medical resources. While neither the incidence of lymphoproliferative disorders nor opportunistic infections was higher in basiliximab-treated patients than in placebo-treated patients, patients on immunosuppression therapy are at increased risk for developing these complications and should be monitored accordingly.

    Vaccination

    It is not known whether the immune response to vaccination administered during basiliximab therapy is impaired or whether such response will remain impaired after basiliximab therapy.

    Pregnancy

    Use basiliximab during pregnancy only when the potential benefit justifies the potential risk to the fetus. The IL-2 receptor may play an important role in the development of the immune system, and IgG molecules are known to cross the placental barrier. There are no adequate and well-controlled studies of basiliximab in pregnant women. In a study involving cynomolgus monkeys, basiliximab administration during organogenesis was not associated with maternal toxicity, embryotoxicity, or teratogenicity. Blood concentrations in pregnant monkeys were 13-fold higher than those seen in human patients.

    Breast-feeding

    It is not known whether basiliximab is excreted in human milk. Because many drugs, including human antibodies are excreted in human milk, and because of the potential for adverse reactions, discontinue breast-feeding or discontinue basiliximab, taking into account the importance of the drug to the mother.

    Contraception requirements, reproductive risk

    Basiliximab may be associated with reproductive risk. The IL-2 receptor may play an important role in the development of the immune system, and IgG molecules are known to cross the placental barrier. Discuss contraception requirements with females of reproductive potential. Advise females of childbearing potential to use effective contraception before initiating therapy, during treatment, and for 4 months after completion of basiliximab therapy.

    ADVERSE REACTIONS

    Severe

    GI bleeding / Delayed / 3.0-10.0
    thrombosis / Delayed / 3.0-10.0
    heart failure / Delayed / 3.0-10.0
    atrial fibrillation / Early / 3.0-10.0
    bronchospasm / Rapid / 3.0-10.0
    pulmonary edema / Early / 3.0-10.0
    bone fractures / Delayed / 3.0-10.0
    oliguria / Early / 3.0-10.0
    renal tubular necrosis / Delayed / 3.0-10.0
    visual impairment / Early / 3.0-10.0
    post-transplant lymphoproliferative disorder (PTLD) / Delayed / 0-1.0
    hyperkalemia / Delayed / 10.0
    anaphylactoid reactions / Rapid / Incidence not known
    cardiac arrest / Early / Incidence not known
    respiratory arrest / Rapid / Incidence not known

    Moderate

    antibody formation / Delayed / 1.2-11.8
    melena / Delayed / 3.0-10.0
    stomatitis / Delayed / 3.0-10.0
    gingival hyperplasia / Delayed / 3.0-10.0
    esophagitis / Delayed / 3.0-10.0
    skin ulcer / Delayed / 3.0-10.0
    depression / Delayed / 3.0-10.0
    hematoma / Early / 3.0-10.0
    leukopenia / Delayed / 3.0-10.0
    bleeding / Early / 3.0-10.0
    thrombocytopenia / Delayed / 3.0-10.0
    polycythemia / Delayed / 3.0-10.0
    diabetes mellitus / Delayed / 3.0-10.0
    hypomagnesemia / Delayed / 3.0-10.0
    fluid retention / Delayed / 3.0-10.0
    hypoglycemia / Early / 3.0-10.0
    hyperlipidemia / Delayed / 3.0-10.0
    dehydration / Delayed / 3.0-10.0
    hypocalcemia / Delayed / 3.0-10.0
    hypertriglyceridemia / Delayed / 3.0-10.0
    metabolic acidosis / Delayed / 3.0-10.0
    hypercalcemia / Delayed / 3.0-10.0
    angina / Early / 3.0-10.0
    hypotension / Rapid / 3.0-10.0
    sinus tachycardia / Rapid / 3.0-10.0
    chest pain (unspecified) / Early / 3.0-10.0
    peripheral neuropathy / Delayed / 3.0-10.0
    edema / Delayed / 3.0-10.0
    impotence (erectile dysfunction) / Delayed / 3.0-10.0
    dysuria / Early / 3.0-10.0
    urinary retention / Early / 3.0-10.0
    proteinuria / Delayed / 3.0-10.0
    hematuria / Delayed / 3.0-10.0
    conjunctivitis / Delayed / 3.0-10.0
    cataracts / Delayed / 3.0-10.0
    constipation / Delayed / 10.0
    anemia / Delayed / 10.0
    hypercholesterolemia / Delayed / 10.0
    hyperuricemia / Delayed / 10.0
    hypokalemia / Delayed / 10.0
    hypophosphatemia / Delayed / 10.0
    hyperglycemia / Delayed / 10.0
    hypertension / Early / 10.0
    dyspnea / Early / 10.0
    peripheral edema / Delayed / 10.0
    wheezing / Rapid / Incidence not known

    Mild

    flatulence / Early / 3.0-10.0
    pruritus / Rapid / 3.0-10.0
    rash / Early / 3.0-10.0
    hypertrichosis / Delayed / 3.0-10.0
    anxiety / Delayed / 3.0-10.0
    agitation / Early / 3.0-10.0
    purpura / Delayed / 3.0-10.0
    weight gain / Delayed / 3.0-10.0
    rhinitis / Early / 3.0-10.0
    cough / Delayed / 3.0-10.0
    pharyngitis / Delayed / 3.0-10.0
    sinusitis / Delayed / 3.0-10.0
    paresthesias / Delayed / 3.0-10.0
    hypoesthesia / Delayed / 3.0-10.0
    dizziness / Early / 3.0-10.0
    chills / Rapid / 3.0-10.0
    myalgia / Early / 3.0-10.0
    muscle cramps / Delayed / 3.0-10.0
    back pain / Delayed / 3.0-10.0
    arthropathy / Delayed / 3.0-10.0
    arthralgia / Delayed / 3.0-10.0
    malaise / Early / 3.0-10.0
    asthenia / Delayed / 3.0-10.0
    fatigue / Early / 3.0-10.0
    increased urinary frequency / Early / 3.0-10.0
    abdominal pain / Early / 10.0
    vomiting / Early / 10.0
    dyspepsia / Early / 10.0
    nausea / Early / 10.0
    diarrhea / Early / 10.0
    acne vulgaris / Delayed / 10.0
    insomnia / Early / 10.0
    infection / Delayed / 3.0
    headache / Early / 10.0
    tremor / Early / 10.0
    fever / Early / 10.0
    injection site reaction / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Abatacept: (Moderate) Concomitant use of immunosuppressives may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
    Alefacept: (Contraindicated) Patients receiving other immunosuppressives should not receive concurrent therapy with alefacept; there is the possibility of excessive immunosuppression and subsequent risks of infection and other serious side effects. In clinical efficacy trials, concurrent treatment of alefacept with these types of agents did not occur. The duration of the period following treatment with alefacept that is appropriate before starting other immunosuppressive therapy has not been evaluated.
    Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Azathioprine: (Minor) Because azathioprine is an immunosuppressant with myelosuppressive actions, additive affects may be seen with other immunosuppressives.
    Canakinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as basilixumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
    Certolizumab pegol: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
    Cladribine: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
    Corticosteroids: (Minor) Because systemically administered corticosteroids have immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives.
    Cyclosporine: (Minor) Because basiliximab is an immunosuppressant, additive effects may be seen with other immunosuppressives.
    Daclizumab: (Minor) Because daclizumab is an immunosuppressant, additive effects may be seen with other immunosuppressives. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections, malignancies including lymphoma and leukemia, myelodysplastic syndromes, and lymphoproliferative disorders. The risk is related to the intensity and duration of immunosuppression rather than the specific agents.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and basiliximab together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Echinacea: (Major) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to drugs that alter immune system activity like antineoplastic drugs. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
    Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with basiliximab may cause the plasma concentrations of elbasvir and grazoprevir to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Basiliximab is a mild CYP3A inhibitor. Both elbasvir and grazoprevir are metabolized by CYP3A. If these drugs are used together, closely monitor for signs of hepatotoxicity.
    Fludarabine: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
    Golimumab: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
    Interferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Interferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Interferon Alfa-2b; Ribavirin: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Interferon Alfacon-1: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Interferon Alfa-n3: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Live Vaccines: (Contraindicated) Do not administer live vaccines to basiliximab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving basiliximab. At least 2 weeks before initiation of basiliximab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Basiliximab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
    Mercaptopurine, 6-MP: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
    Methotrexate: (Minor) Because basiliximab is an immunosuppressant, additive effects may be seen with other immunosuppressives such as methotrexate.
    Mycophenolate: (Minor) Because mycophenolate mofetil is an immunosuppressant, additive effects may be seen with other immunosuppressives. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections, malignancies including lymphoma and leukemia, myelodysplastic syndromes, and lymphoproliferative disorders. The risk is related to the intensity and duration of immunosuppression rather than the specific agents.
    Nanoparticle Albumin-Bound Sirolimus: (Minor) Because sirolimus is an immunosuppressant, additive affects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk of infection or other side effects.
    Natalizumab: (Major) The concomitant use of natalizumab and immunosuppressives, such as basiliximab, may further increase the risk of serious infections over the risk observed with use of natalizumab alone. The safety and efficacy of natalizumab in combination with basiliximab has not been evaluated. Patients receiving chronic immunosuppressant therapy should not ordinarily be treated with natalizumab.
    Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Peginterferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Penicillamine: (Major) Agents such as immunosuppressives have adverse reactions similar to those of penicillamine. Concomitant use of penicillamine with these agents is contraindicated because of the increased risk of developing severe hematologic and renal toxicity.
    Pentostatin: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
    Purine analogs: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
    Rilonacept: (Moderate) Patients receiving immunosuppressives along with rilonacept may be at a greater risk of developing an infection.
    Ropeginterferon alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Saquinavir: (Moderate) Both saquinavir boosted with ritonavir and basiliximab are inhibitors of CYP3A4; an isoenzyme responsible for the metabolism of saquinavir. The use of saquinavir/ritonavir with basiliximab may result in large increases in saquinavir plasma concentrations, which could cause adverse events such as life threatening cardiac arrhythmias (e.g., torsades de pointes [TdP]).
    Sipuleucel-T: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
    Sirolimus: (Minor) Because sirolimus is an immunosuppressant, additive affects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk of infection or other side effects.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with basiliximab. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a substrate of CYP3A4. Basiliximab may cause a down-regulation of 3A4 activity by increasing IL-2 binding to IL-2 receptors on hepatic and intestinal cells.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with basiliximab. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a substrate of CYP3A4. Basiliximab may cause a down-regulation of 3A4 activity by increasing IL-2 binding to IL-2 receptors on hepatic and intestinal cells.
    Tacrolimus: (Major) Basiliximab acts as an IL-2 receptor antagonist. Binding of basiliximab to the IL-2 receptors on activated T cells may allow circulating IL-2 to bind to IL-2 receptors on hepatic and intestinal cells, which may cause a down-regulation of CYP3A4 enzyme activity. Reduced CYP3A4 activity may increase concentrations of CYP3A4 substrates such as tacrolimus. In a retrospective evaluation, the tacrolimus dose needed to achieve a trough concentration of 15 to 20 ng/ml was lower among basiliximab recipients as compared with antithymocyte globulin recipients. Over the 60 days after transplantation, tacrolimus dose requirements were 0.16 mg/kg/day for basiliximab recipients and 0.24 mg/kg/day for antithymocyte globulin recipients. All patients initially received oral tacrolimus 0.075 to 0.15 mg/kg with the dose titrated to achieve the desired trough concentration. On day 3 after transplantation, tacrolimus trough concentrations were higher than 20 ng/ml in 6 of 12 adults who also got basiliximab 20 mg on the day of transplantation and 4 days later; three patients with an elevated trough concentration had acute tubular necrosis and underwent hemodialysis. In contrast, 2 of 8 patients who got antithymocyte globulin daily for the first 7 days had a tacrolimus trough concentration higher than 20 ng/ml - no significant adverse effects were noted. The half-life of basiliximab is 7.2 days, so the tacrolimus dose may need upward adjustment as the effects of basiliximab on IL-2 dissipate. For example, one month after transplantation, 6 of the 12 basiliximab recipients had tacrolimus trough concentrations below the targeted range of 15 to 20 ng/ml.
    Thioguanine, 6-TG: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
    Tocilizumab: (Major) Avoid using tocilizumab with immunosuppressive biological agents such as basilixumab because of the possibility of increased immunosuppression and increased risk of infection. The concurrent use of tocilizumab with other biological agents has not been studied. Most patients taking tocilizumab who developed serious infections were taking concomitant immunosuppressives.

    PREGNANCY AND LACTATION

    Pregnancy

    Use basiliximab during pregnancy only when the potential benefit justifies the potential risk to the fetus. The IL-2 receptor may play an important role in the development of the immune system, and IgG molecules are known to cross the placental barrier. There are no adequate and well-controlled studies of basiliximab in pregnant women. In a study involving cynomolgus monkeys, basiliximab administration during organogenesis was not associated with maternal toxicity, embryotoxicity, or teratogenicity. Blood concentrations in pregnant monkeys were 13-fold higher than those seen in human patients.

    It is not known whether basiliximab is excreted in human milk. Because many drugs, including human antibodies are excreted in human milk, and because of the potential for adverse reactions, discontinue breast-feeding or discontinue basiliximab, taking into account the importance of the drug to the mother.

    MECHANISM OF ACTION

    Basiliximab binds to and blocks the interleukin-2 receptor alpha-chain receptor (IL-2Ralpha), also known as CD25 antigen or Tac subunit. The IL-2Ralpha is only expressed on the surface of activated T-cells and is important in the clonal expansion of activated T-cells. The specific, high-affinity binding of basiliximab to IL-2Ralpha competitively inhibits IL-2 mediated activation of T-lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection. In vitro studies using human tissues indicate that basiliximab binds only to lymphocytes. Because basiliximab has a long half-life, the IL-2Ralpha blocking effects persist for 4—6 weeks after two infusions. The effect of basiliximab differs from cyclosporine in that cyclosporine inhibits interleukin-2 release while basiliximab acts as an IL-2 receptor antagonist. Basiliximab does not appear to significantly change circulating lymphocyte numbers or cell phenotypes. While in the systemic circulation, basiliximab impairs the normal response of the immune system to antigenic challenges. Whether the ability to respond to repeated or ongoing challenges with those antigens returns to normal after basiliximab is cleared is unknown.

    PHARMACOKINETICS

    Basiliximab is administered intravenously. The extent and degree of distribution to various body compartments have not been fully evaluated. The elimination half-life of basiliximab is roughly 7.2 days.
     
    Complete binding of basiliximab to the interleukin-2 receptor alpha-chain (IL-2Ralpha) in adults is maintained as long as serum concentrations exceed 0.2 mcg/mL. Below 0.2 mcg/mL, the IL-2Ralpha sites are no longer fully bound, and the number of T-cells expressing unbound IL-2Ralpha returns to pretreatment values within 1—2 weeks. At the recommended dosage regimen, the mean duration of basiliximab saturation of IL-2Ralpha was 36 days in both adults and children. The duration of clinically-significant IL-2 receptor blockade, however, is unknown.

    Intravenous Route

    The mean peak basiliximab serum concentration following 20 mg IV over 30 minutes is 7.1 mcg/ml. Dose-proportional increases in Cmax and AUC occur up to the highest tested single dose of 60 mg.