Drugs List

Therapeutic Indications

Uses

Desensitisation treatment for highly sensitised kidney transplant patients

Treatment for desensitisation of highly sensitised adult kidney transplant patients with a positive crossmatch against an available donor.

Dosage

0.25 mg/kg administered as a single dose preferably within 24 hours of transplantation.

A second dose can be administered within 24 hours after the first dose.

A confirmation of crossmatch conversion from positive to negative is required before transplantation.

Administration

Imlifidase is for intravenous use only.

The fully diluted infusion should be administered over a period of 15 minutes.

It is recommended that the intravenous line is flushed with infusion fluid to ensure administration of the complete dose.

Contraindications

Children under 18 years
Uncontrolled systemic infection
Breastfeeding
Pregnancy
Thrombotic thrombocytopenic purpura (TTP)

Precautions and Warnings

Concomitant medication consider washout period, see prescribing information
Patients over 65 years
Moderate hepatic impairment

Disease reactivation may occur in patients with latent TB
Respiratory tract pathogen prophylaxis required for 4 weeks post therapy
Concomitant medication consider washout period: See prescribing information
Consider premedication with antihistamine and/or corticosteroid
Ensure access to facilities to perform biopsy in case AMR is suspected
Treatment to be prescribed under the supervision of a specialist
Monitor human leukocyte antigen (HLA) antibodies
Monitor serum or plasma creatinine
Interrupt therapy/reduce infusion rate if infusion-related reactions occur
May reduce vaccinations effectiveness for up to 4 weeks following treatment
Discontinue if serious allergic or anaphylactic reaction occurs
Hospital use only

Considerations should be given to a temporary reduction of IgG by imlifidase. Patients not transplanted after imlifidase treatment will still require prophylactic oral antibiotics for respiratory tract infections for 4 weeks.

Patients should receive standard of care induction T-cell depleting therapy with or without memory B-cell depleting therapies, however this may increase the risk of reactivation of live-attenuated vaccines and latent tuberculosis.

Patients with high levels of donor-specific antibodies (DSA) before transplantation are more likely to experience early antibody-mediated rejection (AMR) that requires intervention. In clinical studies, 30% of patients developed AMR and were successfully managed with standard treatment. However, it is crucial that the clinician is experienced in managing sensitised patients and that resources to diagnose and treat acute AMRs are in place.

Influence of anti-imlifidase antibodies (ADA) on efficacy and safety of a second imlifidase dose within 24 hours of the first is negligible as production of ADA has not yet started.

Crossmatch conversion confirmation
When using complement-dependent cytotoxicity crossmatch (CDCXM) the following needs to be considered to avoid false positive results:

IgM has to be inactivated to be able to specifically assess the cytotoxic capacity of IgG.

If unavoidable, the use of an anti-human globulin (AHG) step requires confirmation that the AHG is directed against the Fc-part and not the Fab-part of IgG.

There is very limited experience in patients with a confirmed positive T-cell complement-dependent cytotoxicity (CDC) crossmatch test.

Pregnancy and Lactation

Pregnancy

Imlifidase is contraindicated during pregnancy.

The manufacturer advises that imlifidase should be avoided during pregnancy as a precautionary measure.

Animal studies did not indicate any harmful effects to embryonic and foetal development.

Lactation

Imlifidase is contraindicated during breastfeeding.

The manufacturer advises that it is unknown whether imlifidase is excreted in human milk and a risk to the child cannot be excluded.

Side Effects

Abdominal infection
Adenovirus infection
Alanine aminotransferase increased
Anaemia
Aspartate aminotransferase increased
Bacterial infection
Catheter related infection
Dyspnoea
Feeling hot
Flushing
Headache
Hypertension
Hypotension
Infections
Influenza
Infusion related reaction
Infusion site pain
Myalgia
Parvovirus B19 infection
Pneumonia
Post operative wound infection
Postural dizziness
Rash
Sepsis
Sinus tachycardia
Solid organ graft rejection
Upper respiratory tract infection
Urinary tract infections
Viral infection
Visual disturbances
Wound infection

Presentation

Infusion of imlifidase.

These products have been produced by recombinant technology using E.coli.

Drugs List

Therapeutic Indications

Uses

Desensitisation treatment for highly sensitised kidney transplant patients

Treatment for desensitisation of highly sensitised adult kidney transplant patients with a positive crossmatch against an available donor.

Dosage

0.25 mg/kg administered as a single dose preferably within 24 hours of transplantation.

A second dose can be administered within 24 hours after the first dose.

A confirmation of crossmatch conversion from positive to negative is required before transplantation.

Administration

Imlifidase is for intravenous use only.

The fully diluted infusion should be administered over a period of 15 minutes.

It is recommended that the intravenous line is flushed with infusion fluid to ensure administration of the complete dose.

Contraindications

Children under 18 years
Uncontrolled systemic infection
Breastfeeding
Pregnancy
Thrombotic thrombocytopenic purpura (TTP)

Precautions and Warnings

Concomitant medication consider washout period, see prescribing information
Patients over 65 years
Moderate hepatic impairment

Disease reactivation may occur in patients with latent TB
Respiratory tract pathogen prophylaxis required for 4 weeks post therapy
Concomitant medication consider washout period: See prescribing information
Consider premedication with antihistamine and/or corticosteroid
Ensure access to facilities to perform biopsy in case AMR is suspected
Treatment to be prescribed under the supervision of a specialist
Monitor human leukocyte antigen (HLA) antibodies
Monitor serum or plasma creatinine
Interrupt therapy/reduce infusion rate if infusion-related reactions occur
May reduce vaccinations effectiveness for up to 4 weeks following treatment
Discontinue if serious allergic or anaphylactic reaction occurs
Hospital use only

Considerations should be given to a temporary reduction of IgG by imlifidase. Patients not transplanted after imlifidase treatment will still require prophylactic oral antibiotics for respiratory tract infections for 4 weeks.

Patients should receive standard of care induction T-cell depleting therapy with or without memory B-cell depleting therapies, however this may increase the risk of reactivation of live-attenuated vaccines and latent tuberculosis.

Patients with high levels of donor-specific antibodies (DSA) before transplantation are more likely to experience early antibody-mediated rejection (AMR) that requires intervention. In clinical studies, 30% of patients developed AMR and were successfully managed with standard treatment. However, it is crucial that the clinician is experienced in managing sensitised patients and that resources to diagnose and treat acute AMRs are in place.

Influence of anti-imlifidase antibodies (ADA) on efficacy and safety of a second imlifidase dose within 24 hours of the first is negligible as production of ADA has not yet started.

Crossmatch conversion confirmation
When using complement-dependent cytotoxicity crossmatch (CDCXM) the following needs to be considered to avoid false positive results:

IgM has to be inactivated to be able to specifically assess the cytotoxic capacity of IgG.

If unavoidable, the use of an anti-human globulin (AHG) step requires confirmation that the AHG is directed against the Fc-part and not the Fab-part of IgG.

There is very limited experience in patients with a confirmed positive T-cell complement-dependent cytotoxicity (CDC) crossmatch test.

Pregnancy and Lactation

Pregnancy

Imlifidase is contraindicated during pregnancy.

The manufacturer advises that imlifidase should be avoided during pregnancy as a precautionary measure.

Animal studies did not indicate any harmful effects to embryonic and foetal development.

Lactation

Imlifidase is contraindicated during breastfeeding.

The manufacturer advises that it is unknown whether imlifidase is excreted in human milk and a risk to the child cannot be excluded.

Side Effects

Abdominal infection
Adenovirus infection
Alanine aminotransferase increased
Anaemia
Aspartate aminotransferase increased
Bacterial infection
Catheter related infection
Dyspnoea
Feeling hot
Flushing
Headache
Hypertension
Hypotension
Infections
Influenza
Infusion related reaction
Infusion site pain
Myalgia
Parvovirus B19 infection
Pneumonia
Post operative wound infection
Postural dizziness
Rash
Sepsis
Sinus tachycardia
Solid organ graft rejection
Upper respiratory tract infection
Urinary tract infections
Viral infection
Visual disturbances
Wound infection

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: February 2021

Reference Sources

Summary of product characteristics: Idefirix 11mg powder for concentrate for solution for infusion. Hansa Biopharma AB. Revised August 2020.