Drugs Details

Drugs Info of Simulect
Drugs Details
  • Drugs Type  : FDA
  • Date : 27th Dec 2014 04:27 am
  • Brand Name : Simulect
  • Generic Name : basiliximab (Pronunciation: bass il IX im ab)
Descriptions

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.

What are the possible side effects of basiliximab (Simulect)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing, difficult breathing and/or sneezing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • pain or burning when you urinate;
  • easy bruising or bleeding, unusual weakness;
  • tremors, shaking;
  • fever, chills, body aches, flu symptoms, vomiting, diarrhea;
  • trouble breathing;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble...

Read All Potential Side Effects and See Pictures of Simulect »

What are the precautions when taking basiliximab (Simulect)?

Before using basiliximab, tell your doctor or pharmacist if you are allergic to it; or to mouse proteins; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain infection (cytomegalovirus).

Previous treatment with basiliximab may increase your risk of a serious allergic reaction (see Side Effects section). Before using this medication, tell your doctor or pharmacist if you have received basiliximab in the past. If you must stop using this drug due to an allergic reaction, do not use the drug again. Consult your doctor or pharmacist for more...

Read All Potential Precautions of Simulect »

This monograph has been modified to include the generic and brand name in many instances.

Indications

Simulect® (basiliximab) is indicated for the prophylaxis of acute organ rejection in patients receiving renal transplantation when used as part of an immunosuppressive regimen that includes cyclosporine, USP (MODIFIED) and corticosteroids.

The efficacy of Simulect (basiliximab) for the prophylaxis of acute rejection in recipients of other solid organ allografts has not been demonstrated

Dosage Administration

Simulect® (basiliximab) is used as part of an immunosuppressive regimen that includes cyclosporine, USP (MODIFIED) and corticosteroids. Simulect (basiliximab) is for central or peripheral intravenous administration only. Reconstituted Simulect (basiliximab) should be given either as a bolus injection or diluted to a volume of 25 mL (10-mg vial) or 50 mL (20-mg vial) with normal saline or dextrose 5% and administered as an intravenous infusion over 20 to 30 minutes. Bolus administration may be associated with nausea, vomiting and local reactions, including pain.

Simulect (basiliximab) should only be administered once it has been determined that the patient will receive the graft and concomitant immunosuppression. Patients previously administered

Simulect (basiliximab) should only be re-exposed to a subsequent course of therapy with extreme caution due to the potential risk of hypersensitivity (see WARNINGS).

Parenteral drug products should be inspected visually for particulate matter and discoloration before administration. After reconstitution, Simulect (basiliximab) should be a clear-to-opalescent, colorless solution. If particulate matter is present or the solution is colored, do not use.

Care must be taken to assure sterility of the prepared solution because the drug product does not contain any antimicrobial preservatives or bacteriostatic agents.

It is recommended that after reconstitution, the solution should be used immediately. If not used immediately, it can be stored at 2ºC to 8ºC for 24 hours or at room temperature for 4 hours. Discard the reconstituted solution if not used within 24 hours.

No incompatibility between Simulect (basiliximab) and polyvinyl chloride bags or infusion sets has been observed. No data are available on the compatibility of Simulect (basiliximab) with other intravenous substances. Other drug substances should not be added or infused simultaneously through the same intravenous line.

Adults

In adult patients, the recommended regimen is two doses of 20 mg each. The first 20-mg dose should be given within 2 hours prior to transplantation surgery. The recommended second 20-mg dose should be given 4 days after transplantation. The second dose should be withheld if complications such as severe hypersensitivity reactions to Simulect (basiliximab) or graft loss occur.

Pediatric

In pediatric patients weighing less than 35 kg, the recommended regimen is two doses of 10 mg each. In pediatric patients weighing 35 kg or more, the recommended 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. The second dose should be withheld if complications such as severe hypersensitivity reactions to Simulect (basiliximab) or graft loss occur.

Reconstitution of 10 mg Simulect® (basiliximab) Vial

To prepare the reconstituted solution, add 2.5 mL of Sterile Water for Injection, USP, using aseptic technique, to the vial containing the Simulect (basiliximab) powder. Shake the vial gently to dissolve the powder.

The reconstituted solution is isotonic and may be given either as a bolus injection or diluted to a volume of 25 mL with normal saline or dextrose 5% for infusion. When mixing the solution, gently invert the bag in order to avoid foaming; DO NOT SHAKE.

Reconstitution of 20 mg Simulect® (basiliximab) Vial

To prepare the reconstituted solution, add 5 mL of Sterile Water for Injection, USP, using aseptic technique, to the vial containing the Simulect (basiliximab) powder. Shake the vial gently to dissolve the powder.

The reconstituted solution is isotonic and may be given either as a bolus injection or diluted to a volume of 50 mL with normal saline or dextrose 5% for infusion. When mixing the solution, gently invert the bag in order to avoid foaming; DO NOT SHAKE.

How Supplied

Simulect® (basiliximab) is supplied in a single-use glass vial. Each carton contains one of the following

1 Simulect (basiliximab) 10 mg vial...............................................NDC 0078-0393-61
1 Simulect (basiliximab) 20 mg vial...............................................NDC 0078-0331-84

Store lyophilized Simulect (basiliximab) under refrigerated conditions (2ºC to 8ºC; 36ºF to 46ºF).

Do not use beyond the expiration date stamped on the vial.

Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936. 11/14/2003. FDA Rev date: 11/14/2003

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

The incidence of adverse events for Simulect® (basiliximab) was determined in four randomized, double-blind, placebo-controlled clinical trials for the prevention of renal allograft rejection. Two of the studies (Study 1 and Study 2), used a dual maintenance immunosuppressive regimen comprised of cyclosporine, USP (MODIFIED) and corticosteroids, whereas the other two studies (Study 3 and Study 4) used a triple-immunosuppressive regimen comprised of cyclosporine, USP (MODIFIED), corticosteroids, and either azathioprine or mycophenolate mofetil.

Simulect (basiliximab) did not appear to add to the background of adverse events seen in organ transplantation patients as a consequence of their underlying disease and the concurrent administration of immunosuppressants and other medications. Adverse events were reported by 96% of the patients in the placebo-treated group and 96% of the patients in the Simulect (basiliximab) -treated group. In the four placebo-controlled studies, the pattern of adverse events in 590 patients treated with the recommended dose of Simulect (basiliximab) was similar to that in 594 patients treated with placebo. Simulect (basiliximab) did not increase the incidence of serious adverse events observed compared with placebo.

The most frequently reported adverse events were gastrointestinal disorders, reported in 69% of Simulect (basiliximab) -treated patients and 67% of placebo-treated patients.

The incidence and types of adverse events were similar in Simulect (basiliximab) -treated and placebo-treated patients. The following adverse events occurred in ≥ 10% of Simulect (basiliximab) -treated patients: Gastrointestinal System: constipation, nausea, abdominal pain, vomiting, diarrhea, dyspepsia; Body as a Whole-General: pain, peripheral edema, fever, viral infection; Metabolic and Nutritional: hyperkalemia, hypokalemia, hyperglycemia, hypercholesterolemia, hypophosphatemia, hyperuricemia; Urinary System: urinary tract infection;Respiratory System: dyspnea, upper respiratory tract infection; Skin and Appendages: surgical wound complications, acne;Cardiovascular Disorders-General: hypertension; Central and Peripheral Nervous System: headache, tremor; Psychiatric: insomnia; Red Blood Cell: anemia.

The following adverse events, not mentioned above, were reported with an incidence of ≥ 3% and < 10% in pooled analysis of patients treated with Simulect (basiliximab) in the four controlled clinical trials, or in an analysis of the two dual-therapy trials: Body as a Whole-General: accidental trauma, asthenia, chest pain, increased drug level, infection, face edema, fatigue, dependent edema, generalized edema, leg edema, malaise, rigors, sepsis; Cardiovascular: abnormal heart sounds, aggravated hypertension, angina pectoris, cardiac failure, chest pain, hypotension; Endocrine: increased glucocorticoids; Gastrointestinal:enlarged abdomen, esophagitis, flatulence, gastrointestinal disorder, gastroenteritis, GI hemorrhage, gum hyperplasia, melena, moniliasis, ulcerative stomatitis; Heart Rate and Rhythm: arrhythmia, atrial fibrillation, tachycardia; Metabolic and Nutritional: acidosis, dehydration, diabetes mellitus, fluid overload, hypercalcemia, hyperlipemia, hypertriglyceridemia, hypocalcemia, hypoglycemia, hypomagnesemia, hypoproteinemia, weight increase; Musculoskeletal: arthralgia, arthropathy, back pain, bone fracture, cramps, hernia, myalgia, leg pain; Nervous System: dizziness, neuropathy, paraesthesia, hypoesthesia; Platelet and Bleeding: hematoma, hemorrhage, purpura, thrombocytopenia, thrombosis; Psychiatric:agitation, anxiety, depression; Red Blood Cell: polycythemia; Reproductive Disorders, Male: genital edema, impotence; Respiratory: bronchitis, bronchospasm, abnormal chest sounds, coughing, pharyngitis, pneumonia, pulmonary disorder, pulmonary edema, rhinitis, sinusitis; Skin and Appendages: cyst, herpes simplex, herpes zoster, hypertrichosis, pruritus, rash, skin disorder, skin ulceration; Urinary: albuminuria, bladder disorder, dysuria, frequent micturition, hematuria, increased non-protein nitrogen, oliguria, abnormal renal function, renal tubular necrosis, surgery, ureteral disorder, urinary retention; Vascular Disorders:vascular disorder; Vision Disorders: cataract, conjunctivitis, abnormal vision; White Blood Cell: leucopenia. Among these events, leucopenia and hypertriglyceridemia occurred more frequently in the two triple-therapy studies using azathioprine and mycophenolate mofetil than in the dual-therapy studies.

Malignancies

The incidence of malignancies in the controlled clinical trials of renal transplant was not significantly different between groups at 1 year (9/590 Simulect (basiliximab) -treated patients vs. 12/594 placebo-treated patients) or among patients with 5-year follow-up from Studies 1 and 2 (21/295 Simulect (basiliximab) -treated patients vs. 21/291 placebo-treated patients). The incidence of lymphoproliferative disease was not significantly different between groups, and less than 1% in the Simulect (basiliximab) -treated patients.

Infections

The overall incidence of cytomegalovirus infection was similar in Simulect (basiliximab) - and placebo-treated patients (15% vs. 17%) receiving a dual- or triple-immunosuppression regimen. However, in patients receiving a triple-immunosuppression regimen, the incidence of serious cytomegalovirus infection was higher in Simulect (basiliximab) -treated patients compared to placebo-treated patients (11% vs. 5%). The rates of infections, serious infections, and infectious organisms were similar in the Simulect (basiliximab) - and placebo-treatment groups among dual- and triple-therapy treated patients.

Post-Marketing Experience

Severe acute hypersensitivity reactions including anaphylaxis characterized by hypotension, tachycardia, cardiac failure, dyspnea, wheezing, bronchospasm, pulmonary edema, respiratory failure, urticaria, rash, pruritus, and/or sneezing, as well as capillary leak syndrome and cytokine release syndrome, have been reported during post-marketing experience with Simulect (basiliximab) .

Read the Simulect (basiliximab) Side Effects Center for a complete guide to possible side effects

Interactions

No dose adjustment is necessary when Simulect (basiliximab) is added to triple-immunosuppression regimens including cyclosporine, corticosteroids, and either azathioprine or mycophenolate mofetil. Three clinical trials have investigated Simulect (basiliximab) use in combination with triple-therapy regimens. Pharmacokinetics were assessed in two of these trials. Total body clearance of Simulect (basiliximab) was reduced by an average 22% and 51% when azathioprine and mycophenolate mofetil, respectively, were added to a regimen consisting of cyclosporine, USP (MODIFIED) and corticosteroids. Nonetheless, the range of individual Simulect (basiliximab) clearance values in the presence of azathioprine (12-57 mL/h) or mycophenolate mofetil (7-54 mL/h) did not extend outside the range observed with dual therapy (10-78 mL/h). The following medications have been administered in clinical trials with Simulect (basiliximab) with no increase in adverse reactions: ATG/ALG, azathioprine, corticosteroids, cyclosporine, mycophenolate mofetil, and muromonab-CD3.

Read the Simulect Drug Interactions Center for a complete guide to possible interactions

Learn More »

This monograph has been modified to include the generic and brand name in many instances.

Warnings

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.

Precautions

General

It is not known whether Simulect® (basiliximab) use will have a long-term effect on the ability of the immune system to respond to antigens first encountered during Simulect (basiliximab) -induced immunosuppression.

Immunogenicity

Of renal transplantation patients treated with Simulect (basiliximab) and tested for anti-idiotype antibodies, 4/339 developed an anti-idiotype antibody response, with no deleterious clinical effect upon the patient. In none of these cases was there evidence that the presence of anti-idiotype antibody accelerated Simulect (basiliximab) clearance or decreased the period of receptor saturation. In Study 2, the incidence of human anti-murine antibody (HAMA) in renal transplantation patients treated with Simulect (basiliximab) was 2/138 in patients not exposed to muromonab-CD3 and 4/34 in patients who subsequently received muromonab-CD3. The available clinical data on the use of muromonab-CD3 in patients previously treated with Simulect (basiliximab) suggest that subsequent use of muromonab-CD3 or other murine anti-lymphocytic antibody preparations is not precluded.

These data reflect the percentage of patients whose test results were considered positive for antibodies to Simulect (basiliximab) in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Simulect (basiliximab) with the incidence of antibodies to other products may be misleading.

Carcinogenesis/Mutagenesis/Impairment of Fertility

No mutagenic potential of Simulect (basiliximab) was observed in the in vitro assays with Salmonella (Ames) and V79 Chinese hamster cells. No long-term or fertility studies in laboratory animals have been performed to evaluate the potential of Simulect (basiliximab) to produce carcinogenicity or fertility impairment, respectively.

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. No maternal toxicity, embryotoxicity, or teratogenicity was observed in cynomolgus monkeys 100 days post coitum following dosing with basiliximab during the organogenesis period; blood levels in pregnant monkeys were 13-fold higher than those seen in human patients. Immunotoxicology studies have not been performed in the offspring. Because IgG molecules are known to cross the placental barrier, because the IL-2 receptor may play an important role in development of the immune system, and because animal reproduction studies are not always predictive of human response, Simulect (basiliximab) should only be used in pregnant women when the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should use effective contraception before beginning Simulect (basiliximab) therapy, during therapy, and for 4 months after completion of Simulect (basiliximab) therapy.

Nursing Mothers

It is not known whether Simulect (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, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

No randomized, placebo-controlled studies have been completed in pediatric patients. In a safety and pharmacokinetic study, 41 pediatric patients (1-11 years of age [n=27], 12-16 years of age [n=14], median age 8.1 years) were treated with Simulect (basiliximab) via intravenous bolus injection in addition to standard immunosuppressive agents including cyclosporine, USP (MODIFIED), corticosteroids, azathioprine, and mycophenolate mofetil. The acute rejection rate at 6 months was comparable to that in adults in the triple-therapy trials. The most frequently reported adverse events were hypertension, hypertrichosis, and rhinitis (49% each), urinary tract infections (46%), and fever (39%). Overall, the adverse event profile was consistent with general clinical experience in the pediatric renal transplantation population and with the profile in the controlled adult renal transplantation studies. The available pharmacokinetic data in children and adolescents are described in CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.

It is not known whether the immune response to vaccines, infection, and other antigenic stimuli administered or encountered during Simulect (basiliximab) therapy is impaired or whether such response will remain impaired after Simulect (basiliximab) therapy.

Geriatric Use

Controlled clinical studies of Simulect (basiliximab) have included a small number of patients 65 years and older (Simulect (basiliximab) 28; placebo 32). From the available data comparing Simulect (basiliximab) and placebo-treated patients, the adverse event profile in patients ≥ 65 years of age is not different from patients < 65 years of age and no age-related dosing adjustment is required. Caution must be used in giving immunosuppressive drugs to elderly patients.

This monograph has been modified to include the generic and brand name in many instances.

OverDose

A maximum tolerated dose of Simulect® (basiliximab) has not been determined in patients. During the course of clinical studies, Simulect (basiliximab) has been administered to adult renal transplantation patients in single doses of up to 60 mg, or in divided doses over 3-5 days of up to 120 mg, without any associated serious adverse events. There has been one spontaneous report of a pediatric renal transplantation patient who received a single 20-mg dose (2.3 mg/kg) without adverse events.

ContrainDications

Simulect® (basiliximab) is contraindicated in patients with known hypersensitivity to basiliximab or any other component of the formulation. See composition of Simulect under DESCRIPTION.

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

General

Mechanism of Action: Basiliximab functions as an IL-2 receptor antagonist by binding with high affinity (Ka = 1 x 1010 M-1) to the alpha chain of the high affinity IL-2 receptor complex and inhibiting IL-2 binding. Basiliximab is specifically targeted against IL-2Rα, which is selectively expressed on the surface of activated T-lymphocytes. This specific high affinity binding of Simulect® (basiliximab) to IL-2Rα competitively inhibits IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection. While in the circulation, Simulect (basiliximab) impairs the 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 Simulect is cleared is unknown (see PRECAUTIONS).

Pharmacokinetics

Adults: Single-dose and multiple-dose pharmacokinetic studies have been conducted in patients undergoing first kidney transplantation. Cumulative doses ranged from 15 mg up to 150 mg. Peak mean ± SD serum concentration following intravenous infusion of 20 mg over 30 minutes is 7.1 ± 5.1 mg/L. There is a dose-proportional increase in Cmax and AUC up to the highest tested single dose of 60 mg. The volume of distribution at steady state is 8.6 ± 4.1 L. The extent and degree of distribution to various body compartments have not been fully studied. The terminal half-life is 7.2 ± 3.2 days. Total body clearance is 41 ± 19 mL/h. No clinically relevant influence of body weight or gender on distribution volume or clearance has been observed in adult patients. Elimination half-life was not influenced by age (20-69 years), gender or race (see DOSAGE AND ADMINISTRATION).

Pediatric: The pharmacokinetics of Simulect (basiliximab) have been assessed in 39 pediatric patients undergoing renal transplantation. In infants and children (1-11 years of age, n=25), the distribution volume and clearance were reduced by about 50% compared to adult renal transplantation patients. The volume of distribution at steady state was 4.8 ± 2.1 L, half-life was 9.5 ± 4.5 days and clearance was 17 ± 6 mL/h. Disposition parameters were not influenced to a clinically relevant extent by age (1-11 years of age), body weight (9-37 kg) or body surface area (0.44-1.20 m2) in this age group. In adolescents (12-16 years of age, n=14), disposition was similar to that in adult renal transplantation patients. The volume of distribution at steady state was 7.8 ± 5.1 L, half-life was 9.1 ± 3.9 days and clearance was 31 ± 19 mL/h (see DOSAGE AND ADMINISTRATION).

Pharmacodynamics

Complete and consistent binding to IL-2Rα in adults is maintained as long as serum Simulect (basiliximab) levels exceed 0.2 µg/mL. As concentrations fall below this threshold, the IL-2Rα sites are no longer fully bound and the number of T-cells expressing unbound IL-2Rα returns to pretherapy values within 1-2 weeks. The relationship between serum concentration and receptor saturation was assessed in 13 pediatric patients and was similar to that characterized in adult renal transplantation patients. In vitro studies using human tissues indicate that Simulect (basiliximab) binds only to lymphocytes.

The duration of clinically relevant IL-2 receptor blockade after the recommended course of Simulect is not known. When basiliximab was added to a regimen of cyclosporine, USP (MODIFIED) and corticosteroids in adult patients, the duration of IL-2Rα saturation was 36 ± 14 days (mean ± SD), similar to that observed in pediatric patients (36 ± 14 days) (see DOSAGE AND ADMINISTRATION). When basiliximab was added to a triple therapy regimen consisting of cyclosporine, USP (MODIFIED), corticosteroids, and azathioprine in adults, the duration was 50 ± 20 days and when added to cyclosporine, USP (MODIFIED), corticosteroids, and mycophenolate mofetil in adults, the duration was 59 ± 17 days (see PRECAUTIONS: DRUG INTERACTIONS). No significant changes to circulating lymphocyte numbers or cell phenotypes were observed by flow cytometry.

Clinical Studies

The safety and efficacy of Simulect® (basiliximab) for the prophylaxis of acute organ rejection in adults following cadaveric- or living-donor renal transplantation were assessed in four randomized, double-blind, placebo-controlled clinical studies (1,184 patients). Of these four, two studies (Study 1 [EU/CAN] and Study 2 [US Study]) compared two 20-mg doses of Simulect (basiliximab) with placebo, each administered intravenously as an infusion, as part of a standard immunosuppressive regimen comprised of cyclosporine, USP (MODIFIED) and corticosteroids. The other two controlled studies compared two 20-mg doses of Simulect (basiliximab) with placebo, each administered intravenously as a bolus injection, as part of a standard triple-immunosuppressive regimen comprised of cyclosporine, USP (MODIFIED), corticosteroids and either azathioprine or mycophenolate mofetil (Study 3 and Study 4, respectively). The first dose of Simulect (basiliximab) or placebo was administered within 2 hours prior to transplantation surgery (Day 0) and the second dose administered on Day 4 post-transplantation. The regimen of Simulect (basiliximab) was chosen to provide 30-45 days of IL-2Rα saturation.

729 patients were enrolled in the two studies using a dual maintenance immunosuppressive regimen comprised of cyclosporine, USP (MODIFIED) and corticosteroids, of which 363 patients were treated with Simulect (basiliximab) and 358 patients were placebo-treated. Study 1 was conducted at 21 sites in Europe and Canada (EU/CAN Study); Study 2 was conducted at 21 sites in the USA (US Study). Patients 18-75 years of age undergoing first cadaveric- (Study 1 and Study 2) or living-donor (Study 2 only) renal transplantation, with ≥ 1 HLA mismatch, were enrolled.1,2

The primary efficacy endpoint in both studies was the incidence of death, graft loss or an episode of acute rejection during the first 6 months post-transplantation. Secondary efficacy endpoints included the primary efficacy variable measured during the first 12 months post-transplantation, the incidence of biopsy-confirmed acute rejection during the first 6 and 12 months post-transplantation, and patient survival and graft survival, each measured at 12 months post-transplantation. Table 1 summarizes the results of these studies. Figure 1 displays the Kaplan-Meier estimates of the percentage of patients by treatment group experiencing the primary efficacy endpoint during the first 12 months post-transplantation for Study 2. Patients in both studies receiving Simulect (basiliximab) experienced a significantly lower incidence of biopsy-confirmed rejection episodes at both 6 and 12 months post-transplantation. There was no difference in the rate of delayed graft function, patient survival, or graft survival between Simulect (basiliximab) -treated patients and placebo-treated patients in either study.

There was no evidence that the clinical benefit of Simulect (basiliximab) was limited to specific subpopulations based on age, gender, race, donor type (cadaveric or living donor allograft) or history of diabetes mellitus.

Table 1. Efficacy Parameters (Percentage of Patients)

Dual-therapy Regimen (cyclosporine*and corticosteroids)
Study 1 Study 2
Placebo
(N=185)
Simulect®
(N=190)
p-value Placebo
(N=173)
Simulect®
(N=173)
p-value
Primary endpoint
Death, graft loss or acute rejection episode (0-6months)
57% 42% 0.003 55% 38% 0.002
Secondary endpoints
Death, graft loss or acute rejection episode (0-12months)
60% 46% 0.007 58% 41% 0.001
Biopsy-confirmed rejection episode (0-6months)
44% 30% 0.007 46% 33% 0.015
Biopsy-confirmed rejection episode (0-12months)
46% 32% 0.005 49% 35% 0.009
Patient survival (12 months)
97% 95% 0.29 96% 97% 0.56
Patients with functioning graft (12 months)
87% 88% 0.70 93% 95% 0.50
* USP (MODIFIED)

Figure 1: Kaplan Meier Estimate of the Percentage of Subjects with Death, Graft Loss or First Rejection Episode (Dual Therapy) Month: 0-12

Kaplan Meier Estimate of the Percentage of Subjects with Death, Graft Loss or First Rejection Episode - Illustration

Two double-blind, randomized, placebo-controlled studies (Study 3 and Study 4) assessed the safety and efficacy of Simulect (basiliximab) for the prophylaxis of acute renal transplant rejection in adults when used in combination with a triple immunosuppressive regimen. In Study 3, 340 patients were concomitantly treated with cyclosporine, USP (MODIFIED), corticosteroids and azathioprine (AZA), of which 168 patients were treated with Simulect (basiliximab) and 172 patients were treated with placebo. In Study 4, 123 patients were concomitantly treated with cyclosporine, USP (MODIFIED), corticosteroids and mycophenolate mofetil (MMF), of which 59 patients were treated with Simulect (basiliximab) and 64 patients were treated with placebo. Patients 18-70 years of age undergoing first or second cadaveric or living donor (related or unrelated) renal transplantation were enrolled in both studies. The results of Study 3 are shown in Table 2.

These results are consistent with the findings from Study 1 and Study 2.

Table 2. Efficacy Parameters (Percentage of Patients)

Study 3: Triple-therapy Regimen (cyclosporine*, corticosteroids, andazathioprine)
  Placebo
(N=172)
Simulect®
(N=168)
p-value
Primary endpoint
  Acute rejection episode (0-6 months) 35% 21% 0.005
Secondary endpoints
  Death, graft loss or acute rejection episode (0-6 months) 40% 26% 0.008
  Biopsy-confirmed rejection episode (0-6 months) 29% 18% 0.023
  Patient survival (12 months) 97% 98% 1.000
  Patients with functioning graft (12 months) 88% 90% 0.599
*USP (MODIFIED)

In Study 4, the percentage of patients experiencing biopsy-proven acute rejection by 6 months was 15% (9 of 59 patients) in the Simulect (basiliximab) group and 27% (17 of 64 patients) in the placebo group. Although numerically lower, the difference in acute rejection was not significant.

In a multicenter, randomized, double-blind, placebo-controlled trial of Simulect (basiliximab) for the prevention of allograft rejection in liver transplant recipients (n=381) receiving concomitant cyclosporine, USP (MODIFIED) and steroids, the incidence of the combined endpoint of death, graft loss, or first biopsy-confirmed rejection episode at either 6 or 12 months was similar between patients randomized to receive Simulect (basiliximab) and those randomized to receive placebo.

The efficacy of Simulect (basiliximab) for the prophylaxis of acute rejection in recipients of a second renal allograft has not been demonstrated.

Long Term Follow-up

Five-year patient survival and graft survival data were provided by 71% and 58% of the original subjects of Study 1 and Study 2, respectively. Subjects in both studies continued to receive a dual-therapy regimen with cyclosporine, USP (MODIFIED) and corticosteroid. No difference was observed between groups in the 5-year graft survival in either Study 1 (91% Simulect (basiliximab) group, 92% placebo group) or Study 2 (85% Simulect (basiliximab) group, 86% placebo group). In Study 1, patient survival was lower in the Simulect (basiliximab) -treated patients compared to the placebo-treated patients (142/163 [87%] vs. 156/164 [95%], respectively). The cause of this difference in survival is unknown. The data do not indicate an increase in malignancy- or infection-related mortality. In Study 2, patient survival in the placebo group (90%) was the same compared to Simulect (basiliximab) group (90%).

REFERENCES

1. Kahan, B.D., Rajagopalan P.R. and Hall M., Transplantation, 67, 276-284 (1999).

2. Nashan, B., Moore R., Amlot P., Schmidt A.-G., Abeywickrama K. and Soulillou J.-P., Lancet 350, 1193-1198 (1997).

This monograph has been modified to include the generic and brand name in many instances.

Patient Information

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

BASILIXIMAB - INJECTION

 

(BA-si-LIX-i-mab)

 

COMMON BRAND NAME(S): Simulect

 

USES: Basiliximab is used to prevent organ rejection in people who have received a kidney transplant. It is usually taken along with other medications (e.g., cyclosporine, corticosteroids) to allow your new organ to function normally. Basiliximab is an immunosuppressant drug known as a monoclonal antibody. It works by slowing down your body's defense system (immune system) to prevent your body from rejecting the new kidney after surgery (acute rejection).

 

HOW TO USE: This medication is given by injection into a vein by a health care professional. It is usually given in 2 doses. The first dose is given within 2 hours before the transplant surgery, and the second dose is given 4 days after surgery.

Dosage is based on your age, weight, medical condition, and response to treatment.

This medication is used with other medications (e.g., cyclosporine, corticosteroids) to prevent rejection of transplanted organs. Take all medications exactly as prescribed by your doctor. If you have any questions, ask your doctor or pharmacist.

Consumer Overview Side Effect

SIDE EFFECTS: Nausea, stomach pain, diarrhea, constipation, or pain/redness at the injection site may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

The use of medications that affect the immune system may lead to increased risk of infection or certain types of cancer. Tell your doctor right away if you have any serious side effects, including: fever, weakness, swollen glands, night sweats, unusual lumps, persistent cough/sore throat, sores around the mouth/genitals, pain with urination, vision changes, unexplained weight loss.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, unusually fast heartbeat, sneezing, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Simulect (basiliximab) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before using basiliximab, tell your doctor or pharmacist if you are allergic to it; or to mouse proteins; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain infection (cytomegalovirus).

Previous treatment with basiliximab may increase your risk of a serious allergic reaction (see Side Effects section). Before using this medication, tell your doctor or pharmacist if you have received basiliximab in the past. If you must stop using this drug due to an allergic reaction, do not use the drug again. Consult your doctor or pharmacist for more details.

Before having surgery, tell your doctor or dentist that you are using this medication.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose.

Wash your hands well to prevent the spread of infections.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. Women who may become pregnant should use effective birth control before beginning treatment with this drug, during use, and for 4 months after finishing treatment. Consult your doctor or pharmacist for more information.

It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Laboratory and/or medical tests (e.g., kidney function) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor immediately to establish a new dosing schedule.

 

STORAGE: Not applicable. This medication is given in a clinic and will not be stored at home.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised March 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Simulect

Generic Name: basiliximab (Pronunciation: bass il IX im ab)

  • What is basiliximab (Simulect)?
  • What are the possible side effects of basiliximab (Simulect)?
  • What is the most important information I should know about basiliximab (Simulect)?
  • What should I discuss with my health care provider before receiving basiliximab (Simulect)?
  • How is basiliximab given (Simulect)?
  • What happens if I miss a dose (Simulect)?
  • What happens if I overdose (Simulect)?
  • What should I avoid while receiving basiliximab (Simulect)?
  • What other drugs will affect basiliximab (Simulect)?
  • Where can I get more information?

What is basiliximab (Simulect)?

Basiliximab lowers your body's immune system. The immune system helps your body fight infections. The immune system can also fight or "reject" a transplanted organ such as a liver or kidney. This is because the immune system treats the new organ as an invader.

Basiliximab is used with other medications to prevent organ rejection after a kidney transplant.

Basiliximab may also be used for purposes not listed in this medication guide.

What are the possible side effects of basiliximab (Simulect)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing, difficult breathing and/or sneezing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • pain or burning when you urinate;
  • easy bruising or bleeding, unusual weakness;
  • tremors, shaking;
  • fever, chills, body aches, flu symptoms, vomiting, diarrhea;
  • trouble breathing;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling); or
  • low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling).

Less serious side effects may include:

  • cold symptoms such as stuffy nose, sore throat;
  • acne;
  • sleep problems (insomnia);
  • nausea, constipation, stomach pain;
  • headache; or
  • swelling in your hands, ankles, or feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Simulect (basiliximab) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about basiliximab (Simulect)?

You should not use basiliximab if you are allergic to it.

Before you receive this medicine, tell your doctor if you have cancer, diabetes, high cholesterol, or high or low levels of potassium in your blood.

Basiliximab can lower blood cells that help your body fight infections and help your blood clot. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Tell your doctor at once if you develop signs of infection.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Avoid receiving a vaccine shortly after you have been treated with basiliximab, unless your doctor has told you to.

There may be other drugs that can interact with basiliximab. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Side Effects Centers
  • Simulect

Patient Detailed How Take

What should I discuss with my health care provider before receiving basiliximab (Simulect)?

You should not use basiliximab if you are allergic to it.

To make sure you can safely receive basiliximab, tell your doctor if you have any of these other conditions:

  • cancer;
  • diabetes;
  • high cholesterol; or
  • an electrolyte imbalance (such as high or low levels of potassium in your blood);

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether basiliximab passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using basiliximab.

How is basiliximab given (Simulect)?

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.

Side Effects Centers
  • Simulect

Patient Detailed Avoid Taking

What happens if I miss a dose (Simulect)?

Because you will receive basiliximab in a clinical setting, you are not likely to miss a dose.

What happens if I overdose (Simulect)?

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

What should I avoid while receiving basiliximab (Simulect)?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Avoid receiving a vaccine shortly after you have been treated with basiliximab, unless your doctor has told you to.

What other drugs will affect basiliximab (Simulect)?

Tell your doctor about all other medicines you use, especially:

  • chemotherapy or radiation;
  • steroid medicine;
  • sirolimus (Rapamune), tacrolimus (Prograf);
  • muromonab-CD3 (Orthoclone);
  • mycophenolate mofetil (CellCept); or
  • azathioprine (Azasan, Imuran), leflunomide (Arava), etanercept (Enbrel).

This list is not complete and other drugs may interact with basiliximab. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about basiliximab.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 2.01. Revision date: 2/14/2012.

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