Drugs List

Therapeutic Indications

Uses

Metachromatic leukodystrophy

Treatment of metachromatic leukodystrophy (MLD) in children with late infantile or early juvenile forms, without clinical manifestations of the disease and in children with the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline.

Dosage

Pre-medication
Pre-medicate with 0.25mg/kg (maximum dose 10mg) intravenous chlorpheniramine or an equivalent 15 to 30 minutes before the atidarsagene automcel before the infusion.

The dose of atidarsagene autotemcel is based on the patient's weight at the time of infusion. The minimum recommended dose is 3 x 10 to the power of 6 CD34+ cells/kg.

The maximum volume of atidarsagene autotemcel to be administered should be less that 20% of the patient's estimated plasma volume. Only one bag should be infused per hour.

Administration

Atidarsagene autotemcel should be prepared according to the manufacturer's instructions and using appropriate precautions. It should then be administered by intravenous infusion centrally.

Atidarsagene autotemcel is strictly for autologous use only.

Contraindications

History of haematopoietic stem cell gene therapy
Within 6 weeks of live vaccines

Precautions and Warnings

Children aged 7 to 18 years
Restricted sodium intake
Hepatic impairment
Renal impairment

Avoid live vaccines 6 weeks before, during and until immune recovery
Sodium content of formulation may be significant
Adhere to standard protective measures to avoid infection
Consider use of anti-infective prophylaxis during neutropenic phase
Correct acid-base disorders prior to treatment
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Premedicate with intravenous antihistamines
Treatment to be initiated and supervised by a specialist
Contains dimethyl sulfoxide (DMSO)
For autologous use only
Record name and batch number of administered product
Monitor thyroid function prior to and periodically during treatment
Screen all patients for HIV, HTLV, HBV, HCV and mycoplasma
Monitor for cytopenia for at least 6 weeks after infusion
Monitor for signs and symptoms of infection after treatment
Monitor for signs and symptoms of metabolic acidosis
Monitor for signs and symptoms of thrombosis
Monitor for signs of leukaemia or lymphoma
Monitor full blood count regularly
Monitor patient before, throughout infusion & for at least 3 hrs afterwards
Monitor patient for catheter-related adverse events
Monitor patient for signs of serious infection
Antibodies to ingredient may develop
May lead to false positive HIV test result in non-infected individuals
Advise patient to avoid donating blood, organs, tissues or cells
Remind patient of importance of carrying Alert Card with them at all times

Gloves and glasses should be worn to avoid the transmission of infectious blood-borne diseases.

As atidarsagene autotemcel is strictly for autologous use only, it must be verified before infusion that the patient's identity matches the identifiers on the infusion bag label and lot information sheet.

Patients should avoid anti-retroviral products from at least one month prior to mobilisation and/or bone marrow harvest until at least 7 days after atidarsagene autotemcel infusion. If anti-retrovirals are required following exposure to HIV/HTLV then initiation of atidarsagene autotemcel should be delayed until an HIV/HTLV western blot ad viral load assay have been performed at 6 months post-exposure.

If cytopenia persists beyond 6 to 7 weeks despite granulocyte mobilising medicines, then the non-transduced back up stem cells should be infused. If cytopenia then still persists, alternative treatments should be sought.

Monitor for anti-ARSA antibodies prior to treatment, between 1 and 2 months after gene therapy and then at 6 months, 1 year, 3 years, 5 years, 7 years, 9 years 12 years and 15 years post treatment. Additional monitoring is recommended in the case of disease onset or significant disease progression.

Immunoglobulin G should be maintained above 5g/l to prevent potential late infections occurring later than 100 days post therapy, associated with severe hypogammaglobinaemia.

If by day 60 after the infusion neutrophil engraftment failure exists, then the non-transduced back-up stem cells should be infused according to local standards.

Mobilisation and conditioning medicines may cause dizziness and fatigue.

Pregnancy and Lactation

Pregnancy

Not indicated in patients of child bearing age, relevant data is not available.

Lactation

Not indicated in patients of child bearing age, relevant data is not available.

Side Effects

Alanine aminotransferase increased
Anaemia
Antibody formation
Ascites
Aspartate aminotransferase increased
Back pain
Bone pain
Cytomegalovirus infection
Diarrhoea
Epistaxis
Fluid overload
Gastro-intestinal haemorrhage
Headache
Hepatomegaly
Increase of liver transaminases
Insomnia
Metabolic acidosis
Nausea
Neutropenia
Oliguria
Oropharyngeal pain
Ovarian failure
Pneumonia
Positive Aspergillus test
Pyrexia
Skin exfoliation
Staphylococcal infection
Stomatitis
Thrombocytopenia
Urinary tract infections
Veno-occlusive disease
Viral infection
Vomiting

Presentation

Infusions of atidarsagene autotemcel.

Drugs List

Therapeutic Indications

Uses

Metachromatic leukodystrophy

Treatment of metachromatic leukodystrophy (MLD) in children with late infantile or early juvenile forms, without clinical manifestations of the disease and in children with the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline.

Dosage

Pre-medication
Pre-medicate with 0.25mg/kg (maximum dose 10mg) intravenous chlorpheniramine or an equivalent 15 to 30 minutes before the atidarsagene automcel before the infusion.

The dose of atidarsagene autotemcel is based on the patient's weight at the time of infusion. The minimum recommended dose is 3 x 10 to the power of 6 CD34+ cells/kg.

The maximum volume of atidarsagene autotemcel to be administered should be less that 20% of the patient's estimated plasma volume. Only one bag should be infused per hour.

Administration

Atidarsagene autotemcel should be prepared according to the manufacturer's instructions and using appropriate precautions. It should then be administered by intravenous infusion centrally.

Atidarsagene autotemcel is strictly for autologous use only.

Contraindications

History of haematopoietic stem cell gene therapy
Within 6 weeks of live vaccines

Precautions and Warnings

Children aged 7 to 18 years
Restricted sodium intake
Hepatic impairment
Renal impairment

Avoid live vaccines 6 weeks before, during and until immune recovery
Sodium content of formulation may be significant
Adhere to standard protective measures to avoid infection
Consider use of anti-infective prophylaxis during neutropenic phase
Correct acid-base disorders prior to treatment
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Premedicate with intravenous antihistamines
Treatment to be initiated and supervised by a specialist
Contains dimethyl sulfoxide (DMSO)
For autologous use only
Record name and batch number of administered product
Monitor thyroid function prior to and periodically during treatment
Screen all patients for HIV, HTLV, HBV, HCV and mycoplasma
Monitor for cytopenia for at least 6 weeks after infusion
Monitor for signs and symptoms of infection after treatment
Monitor for signs and symptoms of metabolic acidosis
Monitor for signs and symptoms of thrombosis
Monitor for signs of leukaemia or lymphoma
Monitor full blood count regularly
Monitor patient before, throughout infusion & for at least 3 hrs afterwards
Monitor patient for catheter-related adverse events
Monitor patient for signs of serious infection
Antibodies to ingredient may develop
May lead to false positive HIV test result in non-infected individuals
Advise patient to avoid donating blood, organs, tissues or cells
Remind patient of importance of carrying Alert Card with them at all times

Gloves and glasses should be worn to avoid the transmission of infectious blood-borne diseases.

As atidarsagene autotemcel is strictly for autologous use only, it must be verified before infusion that the patient's identity matches the identifiers on the infusion bag label and lot information sheet.

Patients should avoid anti-retroviral products from at least one month prior to mobilisation and/or bone marrow harvest until at least 7 days after atidarsagene autotemcel infusion. If anti-retrovirals are required following exposure to HIV/HTLV then initiation of atidarsagene autotemcel should be delayed until an HIV/HTLV western blot ad viral load assay have been performed at 6 months post-exposure.

If cytopenia persists beyond 6 to 7 weeks despite granulocyte mobilising medicines, then the non-transduced back up stem cells should be infused. If cytopenia then still persists, alternative treatments should be sought.

Monitor for anti-ARSA antibodies prior to treatment, between 1 and 2 months after gene therapy and then at 6 months, 1 year, 3 years, 5 years, 7 years, 9 years 12 years and 15 years post treatment. Additional monitoring is recommended in the case of disease onset or significant disease progression.

Immunoglobulin G should be maintained above 5g/l to prevent potential late infections occurring later than 100 days post therapy, associated with severe hypogammaglobinaemia.

If by day 60 after the infusion neutrophil engraftment failure exists, then the non-transduced back-up stem cells should be infused according to local standards.

Mobilisation and conditioning medicines may cause dizziness and fatigue.

Pregnancy and Lactation

Pregnancy

Not indicated in patients of child bearing age, relevant data is not available.

Lactation

Not indicated in patients of child bearing age, relevant data is not available.

Side Effects

Alanine aminotransferase increased
Anaemia
Antibody formation
Ascites
Aspartate aminotransferase increased
Back pain
Bone pain
Cytomegalovirus infection
Diarrhoea
Epistaxis
Fluid overload
Gastro-intestinal haemorrhage
Headache
Hepatomegaly
Increase of liver transaminases
Insomnia
Metabolic acidosis
Nausea
Neutropenia
Oliguria
Oropharyngeal pain
Ovarian failure
Pneumonia
Positive Aspergillus test
Pyrexia
Skin exfoliation
Staphylococcal infection
Stomatitis
Thrombocytopenia
Urinary tract infections
Veno-occlusive disease
Viral infection
Vomiting

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: March 2022

Reference Sources

Summary of Product Characteristics: Libmeldy dispersion for infusion. Orchard Therapeutics (Europe) Limited. Revised April 2021.