Consumer medicine information

Simulect

Basiliximab

BRAND INFORMATION

Brand name

Simulect

Active ingredient

Basiliximab

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Simulect.

What is in this leaflet

This leaflet answers some common questions about Simulect.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up-to-date information on the medicine. You can also download the most up-to-date leaflet from www.novartis.com.au. Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you having Simulect against the benefits they expect it will give you.

If you have any concerns about having this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What Simulect is used for

Simulect is used for people who have had a kidney transplant, to prevent the body from rejecting the new organ.

Two doses of Simulect injection will be given to you around the time of the transplant operation, while you are still in hospital. You will also be given other medicines to help protect your new kidney and you will need to continue taking some of these medicines every day after you leave hospital.

Simulect belongs to a group of medicines called immuno-suppressants. These medicines help to control your body's immune system.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

Before you have Simulect

When you must not have it

Do not have Simulect if you have ever had an allergic reaction to basiliximab, the active ingredient in Simulect, or to any of the other ingredients of Simulect listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, fast heart beat, dizziness or light headedness, shortness of breath, wheezing or troubled breathing.

Do not have Simulect if you are pregnant. You must use adequate contraception to prevent pregnancy and continue its use for an additional four months after the last dose of Simulect. There is no experience with Simulect in pregnancy. As with other immunosuppressant medicines, this medicine could affect your developing baby.

Before you are given it

Tell your doctor if you are breast-feeding. You must stop breast-feeding while you are having Simulect and for 4 months after you have had the last dose. It is not known if basiliximab, the active ingredient in Simulect, passes into breast milk and could affect your baby.

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop. It is possible that some medicines and Simulect could interfere with each other.

Tell your doctor if you have any health problems or medical conditions other than your kidney problems.

If you have not told your doctor about any of these things, tell him/her before you have Simulect.

How Simulect is given

Simulect can either be injected directly into a vein using a syringe or it can be given slowly as an intravenous infusion (drip) over 20 to 30 minutes.

How much is given

You will usually have two doses of Simulect. The first dose is given just before your transplant operation starts, and the second dose is given four days after the operation. If you have experienced a severe allergic reaction to Simulect or if you had complications after your surgery such as graft loss, the second dose of Simulect should not be given to you.

For an adult or a child weighing 35 kg or more, each dose of Simulect is 20 mg. For a child weighing less than 35 kg, each dose of Simulect is 10 mg.

If you are given too much (Overdose)

If you think that you may have been given too much Simulect, immediately tell your doctor or nurse.

No cases of overdose with this medicine have been reported. If an overdose occurs, it should not cause immediate side effects but it may increase the time that the activity of your immune system is reduced. Your doctor will watch for any effects and treat them if necessary.

While you are having Simulect

Things you must do

If you find out that you are pregnant while you are having Simulect or in the four months following the last dose, tell your doctor immediately. Your doctor can discuss with you the risks this medicine may have for your developing baby.

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert while you are taking Simulect until you know how it affects you. This medicine may cause dizziness or tiredness in some people. If you have any of these symptoms, do not drive or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given Simulect, or for 8 weeks afterward, even if you do not think it is connected with the medicine.

Sudden severe allergic reactions have been reported in patients treated with Simulect.

Tell your doctor or nurse immediately if you notice any of the following signs of a possible allergic reaction to Simulect:

  • rash, itching or hives on the skin
  • swelling of the face, lips, tongue or other parts of the body
  • fast heart beat
  • dizziness or light headedness
  • shortness of breath, sneezing, wheezing or troubled breathing
  • severe decrease in urine output
  • fever and flu-like symptoms

Allergic reactions are rare but have serious side effects that may require urgent medical attention. Your doctor or nurse will have medicines to treat this type of reaction near at hand.

Generally, patients who have had a kidney transplant take several medicines as well as Simulect. You may get some side effects from your medicines or feel unwell after your transplant.

Tell your doctor if you notice any of the following symptoms and they worry you:

  • pain
  • fever
  • shaking
  • swelling of hands, ankles or feet due to fluid retention
  • headache
  • difficulty sleeping
  • change in bowel habits (constipation or diarrhoea)
  • pain in the abdomen
  • nausea (feeling sick) or vomiting
  • difficulty or pain on urinating, which may be signs of a urinary infection
  • runny or blocked nose, sore throat or cough, which may be signs of an infection of the respiratory system
  • weight increase
  • increase in blood creatinine (which may cause dehydration, fatigue, shortness of breath and confusion)
  • low phosphate levels in the blood (this will be measured by your doctor)

The above list includes side effects that were commonly reported during clinical trials of Simulect.

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may happen in some people. Some side effects such as changes in your blood chemistry (e.g. iron, cholesterol or potassium levels) or in your blood pressure may only be detected when you have tests during your stay in hospital.

Product description

What it looks like

Simulect is a sterile powder supplied in a glass vial. An ampoule containing 5 mL of sterile water, which is used to dissolve the powder before injection, is also provided in the pack.

Ingredients

Each vial of Simulect contains 20mg of the active ingredient, basiliximab. It also contains:

  • potassium phosphate monobasic
  • sodium phosphate dibasic anhydrous
  • sodium chloride
  • sucrose
  • mannitol
  • glycine

Sponsor

Simulect is supplied in Australia by:

NOVARTIS Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone: 1 800 671 203

®= Registered Trademark

This leaflet was prepared in July 2020

Australian Registration Number.

Simulect AUST R 66740

(sml221020c.doc) based on PI (sml221020i.doc)

Published by MIMS December 2020

BRAND INFORMATION

Brand name

Simulect

Active ingredient

Basiliximab

Schedule

S4

 

1 Name of Medicine

Basiliximab (rmc).

2 Qualitative and Quantitative Composition

Each vial of Simulect contains 20 mg basiliximab as a sterile freeze-dried powder for reconstitution with water for injections.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection with diluent.

4 Clinical Particulars

4.1 Therapeutic Indications

Simulect is indicated for the prophylaxis of acute organ rejection in renal transplantation.

4.2 Dose and Method of Administration

Adult dose.

The adult dose of Simulect is 40 mg, given as two 20 mg doses, by intravenous injection. The first 20 mg dose is given within 2 hours prior to transplantation surgery. Simulect must not be administered unless it is absolutely certain that the patient will receive the graft and concomitant immunosuppression. The second 20 mg dose is given 4 days after transplantation. The second dose should be withheld if severe hypersensitivity reactions to Simulect or postoperative complications such as graft loss occur (see Section 4.4 Special Warnings and Precautions for Use).

Paediatric dose.

In paediatric patients weighing less than 35 kg, the recommended total dose of Simulect is 20 mg, given in two doses of 10 mg each. In paediatric patients weighing 35 kg or more, the recommended dose is the adult dose, i.e. a total dose of 40 mg, given in two doses of 20 mg each. The first dose is given within 2 hours prior to transplantation surgery. Simulect must not be administered unless it is absolutely certain that the patient will receive the graft and concomitant immunosuppression. The second dose is given 4 days after transplantation. The second dose should be withheld if severe hypersensitivity reactions to Simulect or postoperative complications such as graft loss occur (see Section 4.4 Special Warnings and Precautions for Use).

Instructions for use.

Simulect is reconstituted and administered either as an intravenous infusion over 20 to 30 minutes or as a bolus injection. Since no data are available on the compatibility of Simulect with other intravenous substances, Simulect should always be given through a separate infusion line.

Simulect 20 mg.

To prepare the injection solution, add 5 mL water for injections from the accompanying ampoule aseptically to the vial containing the Simulect powder. Shake the vial gently to dissolve the powder. Use the reconstituted solution as soon as possible and discard any residue. However, if needed, the reconstituted solution can be stored at 2 to 8°C for 24 hours. Discard the reconstituted solution if not used within 24 hours.
The reconstituted solution is isotonic and may be given as a bolus injection or diluted to a volume of 50 mL or greater with normal saline or dextrose 5% for infusion.

4.3 Contraindications

Simulect is contraindicated in patients with known hypersensitivity to basiliximab or any other component of the formulation (see Section 6.1 List of Excipients).

4.4 Special Warnings and Precautions for Use

Basiliximab should be prescribed only by physicians who are experienced in immunosuppressive therapy following organ transplantation.

Hypersensitivity reactions.

Patients receiving Simulect should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. Medications for treatment of hypersensitivity should be available for immediate use (e.g. adrenaline). Severe acute (less than 24 hours) hypersensitivity reactions have been observed, both on initial exposure to Simulect and on re-exposure to a subsequent course of therapy. These included anaphylactoid type reactions such as rash, urticaria, pruritus, sneezing, wheezing, hypotension, tachycardia, dyspnoea, bronchospasm, pulmonary oedema, cardiac failure, respiratory failure and capillary leak syndrome. If severe hypersensitivity occurs, therapy with Simulect should be permanently discontinued and no further dose should be administered. Caution should be exercised when patients previously given Simulect are re-exposed to a subsequent course of therapy with this medicine.
There is accumulating evidence that a subgroup of patients is at increased risk of developing hypersensitivity reactions. These are patients in whom, following the initial administration of Simulect, the concomitant immunosuppression was discontinued prematurely due, for example, to abandoned transplantation or early loss of the graft. Acute hypersensitivity reactions were observed on readministration of Simulect for a subsequent transplantation in some of these patients.

Malignancy and lymphoproliferative disorders.

Transplant patients receiving immunosuppressive regimens involving combinations with or without Simulect are at an increased risk of developing cancer and lymphoproliferative disorders (such as lymphoma). In a pooled analysis of two five year extension studies, no differences were found in the incidence of malignancies and LPDs between immunosuppressive regimens with or without Simulect (see Section 4.8 Adverse Effects (Undesirable Effects)).

Opportunistic infections.

Transplant patients receiving immunosuppressive regimens involving combinations with or without Simulect are at an increased risk of developing opportunistic infections (such as cytomegalovirus, CMV) and should be appropriately monitored. In clinical trials, the incidence of opportunistic infections was similar in patients using immunosuppressive regimens with or without Simulect.

Vaccination.

No data are available on either the effect of live and inactive vaccination or the transmission of infection by live vaccines in patients receiving Simulect. Nevertheless, live vaccines are not recommended for immunosuppressed patients. Inactivated vaccines may be administered to immunosuppressed patients; however, response to the vaccine may depend on the degree of the immunosuppression.

Heart transplant.

The efficacy and safety of Simulect for the prophylaxis of acute rejection in recipients of solid organ allographs other than renal have not been demonstrated. In several small clinical trials in heart transplant recipients, serious cardiac adverse events such as cardiac arrest (2.2%), atrial flutter (1.9%) and palpitations (1.4%) have been reported more frequently with Simulect than with other induction agents.

Use in the elderly.

There are limited data available on the use of basiliximab in the elderly, but there is no evidence that elderly patients require a different dosage or experience side effects different from those in younger adult patients.

Paediatric use.

See Section 5.1 Pharmacodynamic Properties, Clinical trials; Section 4.8 Adverse Effects (Undesirable Effects); Section 4.2 Dose and Method of Administration.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Because basiliximab is an immunoglobulin, no metabolic interactions are to be expected with basiliximab.

Concomitant medications routinely administered in organ transplant.

In addition to Neoral, corticosteroids, azathioprine and mycophenolate mofetil, other concomitant medications routinely administered in organ transplantation have been administered in clinical trials without any incremental adverse reactions. These concomitant medications include systemic antiviral, antibacterial and antimycotic medications, analgesics, antihypertensive medications such as beta-blocking agents or calcium channel blockers, and diuretics.
Three clinical trials have investigated Simulect use in combination with a triple therapy regimen which included either azathioprine (study CHI INT 10) or mycophenolate mofetil (studies CHI INT 11 and CHI US 01). The total body clearance of basiliximab was reduced by an average of 22% when azathioprine was added to a regimen consisting of Neoral and corticosteroids. The total body clearance of basiliximab was reduced by an average of 51% when mycophenolate mofetil was added to a regimen consisting of Neoral and corticosteroids. The use of Simulect in a triple therapy regimen including azathioprine or mycophenolate mofetil did not increase adverse events or infections in the basiliximab group as compared to placebo (see Section 4.8 Adverse Effects (Undesirable Effects)).

Human antimurine antibody (HAMA).

Human antimurine antibody (HAMA) responses were reported in a clinical trial of 172 patients treated with Simulect. The incidence was 2/138 in patients not exposed to muromonab-CD3 and 4/34 in patients who received muromonab-CD3 concomitantly (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No fertility studies have been conducted.
(Category D)
Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for an additional four months after the last dose of basiliximab. Basiliximab has potentially hazardous pharmacological effects based on its immunosuppressive action. There is no adequate information for use in pregnant women.
No maternal toxicity, embryotoxicity or teratogenicity was observed in cynomolgous monkeys 100 days post-coitum following dosing with basiliximab during the organogenesis period. Serum basiliximab AUC values were about 6 to 13-fold higher than those seen in women at the maximum recommended dose.
 It is not known whether basiliximab is excreted in human milk. Since basiliximab is an immunoglobulin G (IgG1κ) antibody, it may be excreted in human milk. Because of its immunosuppressive action, basiliximab has potentially hazardous pharmacological effects with respect to the neonate exposed to basiliximab in breast milk. Women receiving basiliximab should not breastfeed for four months following the last dose.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. Basiliximab is not expected to affect the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

Simulect has been tested in four randomised, double blind, placebo controlled studies in renal transplant recipients. In two studies patients were concomitantly treated with Neoral and corticosteroids (studies B201 and B352). In one study patients were concomitantly treated with Neoral, azathioprine and corticosteroids (study CHI INT 10) and in one study patients were concomitantly treated with Neoral, mycophenolate mofetil and corticosteroids (study CHI INT 11). Simulect has also been compared to a polyclonal anti-T-lymphocyte immunoglobulin preparation (ATG/ALG) in one active controlled study in renal transplant recipients (study CHI US 01). In that study, all patients were concomitantly treated with Neoral, mycophenolate mofetil and corticosteroids.

Incidence of adverse effects.

Basiliximab does not appear to add to the notable background of adverse events seen in organ transplant patients as a consequence of their underlying disease and the concurrent administration of immunosuppressants and other medications. In the four placebo controlled trials the pattern of adverse events in 590 patients treated with the recommended dose of basiliximab was indistinguishable from that in 595 patients treated with placebo. Basiliximab did not increase the incidence of serious adverse events observed when compared to placebo. The overall incidence of treatment related adverse events among all patients in the individual studies was not significantly different between the basiliximab (7.1%-40%) and the placebo (7.6%-39%) treatment groups. In the active controlled study, fewer basiliximab (11.4%, n = 70) than ATG/ALG (41.5%, n = 65) patients experienced treatment related adverse events.

Adult experience.

The most commonly reported events (≥ 20%) in the four placebo controlled studies are shown in Tables 1 and 2. The pattern of adverse events was similar in patients receiving the recommended dose in uncontrolled trials.
Weight increase, increase blood creatinine, hypophosphataemia were also commonly reported (> 20%) following dual or triple therapy in both treatment groups (Simulect vs placebo or ATG/ALG).

Experience in paediatric patients.

Safety data in paediatric patients have been obtained from one open label pharmacokinetic and pharmacodynamic study in 41 renal transplant recipients (study CHIB 152-E-00). The most commonly reported (> 20%) events following dual therapy in both (< 35 kg vs. ≥ 35 kg weight) cohorts combined were hypertrichosis, rhinitis, pyrexia, hypertension, urinary tract infection, fever, upper respiratory tract infection, sepsis, constipation, viral infection, bronchitis, pharyngitis, diarrhoea and gum hyperplasia.

Antibody response.

Of 339 renal transplant patients treated with basiliximab and tested for anti-idiotype antibodies, four (1.2%) developed an anti-idiotype antibody response. Of 172 patients receiving basiliximab in a clinical trial, six (3.5%) developed a human antimouse antibody (HAMA) response. However, the use of basiliximab does not preclude subsequent treatment with murine antilymphocytic antibody preparations (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Malignancy and lymphoproliferative disorders.

The overall incidence of malignancies among all patients in the individual studies was similar between the basiliximab and the comparator treatment groups. Overall, lymphoma/ lymphoproliferative disease occurred in 0.1% (1/701) of patients in the basiliximab group compared with 0.3% (2/595) of placebo and 0% of ATG/ALG patients.
Other malignancies were reported among 1.0% (7/701) of patients in the basiliximab group compared with 1.2% (7/595) of placebo and 4.6% (3/65) of ATG/ALG patients.
In uncontrolled, phase I-II studies, post-transplantation lymphoproliferative disorder occurred in approximately 4% (4/94) of patients who received basiliximab. Three of the four patients received a higher dose of basiliximab than that recommended and all four patients received a regimen with three or four other immunosuppressants combined with basiliximab. No increase in lymphoproliferative disorders was observed in clinical trials of patients receiving triple therapy regimens which included Neoral and either azathioprine (study CHI INT 10) or mycophenolate mofetil (studies CHI INT 11 and CHI US 01).
The incidences of malignancy and lymphoproliferative disorder were similar in the 12 month to 5 year extension phases of trials B201 and B352 and comparable in the two treatment groups: malignancy 7% and lymphoproliferative disorder < 1%.

Incidence of infectious episodes.

The overall incidence and profile of infectious episodes among dual and triple therapy patients was similar between the basiliximab and the placebo treatment groups (basiliximab = 75.9%, placebo or ATG/ALG = 75.6%). The incidence of serious infections was 26.1% in the basiliximab group and 24.8% in the comparator group. The overall incidence of CMV infections was similar in both groups (14.6% vs. 17.3%) following either a dual or triple therapy regimen. In patients receiving dual therapy, there was no difference between the Simulect and placebo groups in the incidence of serious CMV. However, in patients receiving a triple immunosuppression regimen, the incidence of serious CMV infection was numerically higher in Simulect treated patients compared to placebo treated patients (11% vs 5%).

Deaths.

The incidence and causes of death following dual or triple therapy were similar in basiliximab (2.9%) and placebo or ATG/ALG groups (2.6%), with the most common cause of death in both treatment groups being infection (basiliximab = 1.3%, placebo or ATG/ALG = 1.4%). In a pooled analysis of two five year extension studies (B201 and B352) the incidence and cause of death remained similar in both treatment groups (basiliximab 15%, placebo 11%), the primary cause of death being cardiac related disorders, such as cardiac failure and myocardial infarction (basiliximab 5%, placebo 4%).

Postmarketing experience.

The following adverse effects have been identified based on postmarketing spontaneous reports and are organized by system organ classes. Because these reactions are reported voluntary from a population of uncertain size, it is not always possible to reliably estimate their frequency.
Cases of hypersensitivity/ anaphylactoid type reactions such as rash, urticaria, pruritus, sneezing, wheezing, bronchospasm, dyspnoea, pulmonary oedema, cardiac failure, hypotension, tachycardia, respiratory failure, capillary leak syndrome, as well as individual cases of suspected cytokine release syndrome have been reported during postmarketing experience with Simulect.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Basiliximab has been administered to humans in clinical studies in single doses of up to 60 mg and multiple doses of up to 150 mg over 24 days with no untoward acute effects.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Basiliximab is a murine/ human chimeric monoclonal antibody (IgG1κ) that is directed against the interleukin-2 receptor α-chain (CD25 antigen), which is expressed on the surface of T-lymphocytes in response to antigenic challenge. Basiliximab specifically binds to the CD25 antigen on activated T-lymphocytes expressing the high affinity interleukin-2 receptor and thereby prevents binding of interleukin-2, the signal for T-cell proliferation. Complete and consistent blocking of the interleukin-2 receptor is maintained as long as serum basiliximab levels exceed 0.2 microgram/mL. As concentrations fall below this level, expression of the CD25 antigen returns to pretherapy values within 1-2 weeks. Basiliximab does not cause myelosuppression.

Clinical trials.

Simulect in combination with Neoral and corticosteroids.

The safety and efficacy of basiliximab in combination with Neoral and steroids for the prevention of organ rejection following renal transplantations were assessed in two randomised, double blind, multicentre trials (studies B201 and B352). These studies compared placebo with basiliximab 40 mg, administered as two 20 mg IV doses, the first dose given within 2 hours prior to transplantation surgery (day 0) and the second dose given on day 4 post-transplantation. The dose of basiliximab was chosen to provide 30-45 days suppression of the α-chain of the interleukin-2 receptor (IL-2Rα). Chronic dual immunosuppressive therapy consisted of Neoral and steroids, administered starting on day 0. Patients 18-75 years of age undergoing first cadaveric or living donor renal transplantation with ≥ 1 HLA mismatch were enrolled. A total of 729 patients were enrolled in the 2 studies, of which 363 basiliximab treated patients and 359 placebo treated patients received transplants.
The primary study endpoint in both studies was the incidence of death, graft loss or an episode of acute rejection in the first 6 months post-transplantation. The percentage of patients experiencing an episode of biopsy confirmed acute rejection, and the percentage of patients experiencing acute rejection treated with antibody therapy were also compared.
Basiliximab, in combination with Neoral and steroids, produced statistically significant reductions in the incidence of acute rejection, biopsy confirmed acute rejection, and acute rejection treated with antibody therapy during the first 6 months and 12 months post-transplantation. Table 3 summarises the results of the two studies.
Both studies had a voluntary open label extension phase. Approximately 85% of subjects entered the extension of trial B201 and 75% of trial B352. The number and demographic characteristics of subjects entering the extension were similar in the two treatment groups. Deaths and graft losses 5 years post-transplant were similar for basiliximab and placebo in the 2 trials except in one instance, deaths in trial B201, which favoured the placebo group (8% vs basiliximab 17%, p = 0.007) and may have been a chance finding.
Data from the extension studies also showed that patients who experienced an acute rejection episode during the first year after transplantation experienced more graft losses and deaths over the five year follow-up period than patients who had no rejection. These events were not influenced by Simulect.

Simulect in triple immunosuppressive regimens.

Two double blind, randomised, placebo controlled studies assessed the safety and efficacy of Simulect for prophylaxis of acute renal transplant rejection in adults when used in combination with a triple immunosuppressive regimen. In study CHI INT 10, Simulect significantly reduced the incidence of acute rejection episodes within 6 months after transplantation, when used concomitantly with Neoral, corticosteroids and azathioprine (21% vs 35%, p = 0.005, Fisher's exact test). In study CHI INT 11, Simulect or placebo was used concomitantly with Neoral, corticosteroids and mycophenolate mofetil. Use of Simulect resulted in a numerically lower incidence of acute rejection episodes in the first six months (15% vs 27%) although the difference was not statistically significant.

Simulect in paediatric de novo renal transplant recipients.

Simulect was used concomitantly with Neoral and steroids in an uncontrolled trial in paediatric de novo renal transplant recipients (study CHIB 152-E-00). Acute rejection occurred in 14.6% of patients by 6 months post-transplantation, and in 24.3% by 12 months. Overall the adverse event profile was consistent with general clinical experience in the paediatric renal transplantation population and with the profile in the controlled adult transplantation studies.

5.2 Pharmacokinetic Properties

Single and multiple dose pharmacokinetic studies have been conducted in patients undergoing renal transplantation. Cumulative doses ranged from 15 mg up to 150 mg.

Absorption.

The mean peak serum concentration of basiliximab following an intravenous infusion of 20 mg over 30 minutes is 7.1 ± 5.1 mg/L. There is a proportional increase in Cmax and AUC with dose, up to the highest tested single dose of 60 mg.

Distribution.

The mean steady-state volume of distribution is 8.6 ± 4.1 L. The extent and degree of distribution to various body compartments have not been fully studied. In vitro studies using human tissues indicate that basiliximab binds only to lymphocytes and macrophages/ monocytes.

Excretion.

Serum concentrations decline in a biphasic manner with a terminal half-life of 7.2 ± 3.2 days. Total body clearance is 41 ± 19 mL/hr. No clinically relevant influence of bodyweight 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.

Pharmacokinetic characteristics in other patient groups.

Paediatric.

The pharmacokinetics of basiliximab were assessed in 39 paediatric de novo renal transplantation patients. In infants and children (age 1-11 years, n = 25), the steady-state distribution volume was 4.8 ± 2.1 L, half-life was 9.5 ± 4.5 days and clearance was 17 ± 6 mL/h. Distribution volume and clearance are reduced by about 50% compared to adult renal transplantation patients. Disposition parameters were not influenced to a clinically relevant extent by age (1-11 years), bodyweight (9-37 kg) or body surface area (0.44-1.20 m2) in this age group. In adolescents (age 12-16 years, n = 14), the steady-state distribution volume was 7.8 ± 5.1 L, half-life was 9.1 ± 3.9 days and clearance was 31 ± 19 mL/h. Disposition in adolescents was similar to that in adult renal transplantation patients. The relationship between serum concentration and receptor saturation was assessed in 13 patients and was similar to that characterised in adult renal transplantation patients.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxic potential was observed in two in vitro studies for gene mutation (an Ames test) and chromosomal damage (cytogenetics assay in V79 Chinese hamster cells).

Carcinogenicity.

No carcinogenicity studies were done.

6 Pharmaceutical Particulars

6.1 List of Excipients

Inactive ingredients: potassium phosphate monobasic, sodium phosphate dibasic anhydrous, sodium chloride, sucrose, mannitol, glycine and water for injections (once reconstituted).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2 to 8°C. Refrigerate, do not freeze.

6.5 Nature and Contents of Container

Glass vials containing 20 mg sterile freeze-dried basiliximab; packs of 1 vial and 1 ampoule of 5 mL of water for injections (WFI).

Note.

Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Simulect (basiliximab) is a monoclonal antibody that functions as an immunosuppressive agent.

Chemical name.

Chimeric murine /human monoclonal antibody (IgG1K).

CAS number.

179045-86-4.
Physical Description: White lyophilisate.
Solubility: Water soluble.
pH value of reconstituted solution: 6.5.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes