Pediatric Formulary

Metachromatic leukodystrophy
Intravenous 1 month up to 18 years At least 3 x 10⁶ CD34⁺ cells/kg once, doses up to 30 x 10⁶ CD34⁺ cells/kg have been administered in clinical studies Directions for administration: The maximum volume to be administered should be less than 20% of the estimated plasma volume. Prior to infusion, myeloablative conditioning (with preferably busulfan) is necessary to promote efficient engraftment of the genetically modified autologous CD34+ cells. in children with late infantile or early juvenile forms, without clinical manifestations of the disease, or 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.

Metachromatic leukodystrophy

Intravenous
- 1 month up to 18 years
  - At least 3 x 10⁶ CD34⁺ cells/kg once, doses up to 30 x 10⁶ CD34⁺ cells/kg have been administered in clinical studies
  - Directions for administration:
    The maximum volume to be administered should be less than 20% of the estimated plasma volume.
    
    Prior to infusion, myeloablative conditioning (with preferably busulfan) is necessary to promote efficient engraftment of the genetically modified autologous CD34+ cells.
  - in children with late infantile or early juvenile forms, without clinical manifestations of the disease, or 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.

Renal impaiment in children > 3 months

No information available on dose adjustment in renal impairment.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

In more than 10% of patients: anti-ARSA antibodies (no effects on clinical efficacy or safety have been observed).

In addition, prolonged cytopenia, metabolic acidosis, increases in thyroid levels (TSH, FT3 and FT4), hypersensitivity reactions, infusion-related reactions, and infections and thrombosis may occur as a complication of the central venous catheter.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications in children

Hypersensitivity.

Do not administer if previous treatment with gene therapy with haematopoietic stem cells has taken place.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Atidarsagen autotem cell is intended for autologous use only and should not be administered to other patients under any circumstances.

Treatment should take place before the disease enters the rapidly progressive phase. Complete neurological examination, assessment of motor functions and neurocognitive assessment should take place before treatment.

Patients should be closely monitored for possible infections and catheter-related events (such as thrombosis).

Because of possible anaphylactic reactions following parenteral administration of one of the excipients (dimethyl sulfoxide), patients who have not been previously exposed to it should be closely observed. Vital signs (blood pressure, heart rate, and oxygen saturation) and the occurrence of symptoms should be monitored before the infusion begins, approximately every ten minutes during the infusion, and every hour for 3 hours after the infusion.

When more than one bag is required, only one bag should be administered by infusion per hour.

In case of failed engraftment, non-transduced reserve stem cells should be administered via infusion according to local standards.

Patients should be monitored for signs and symptoms of cytopenia for at least 6 weeks after infusion. Red blood cells should be monitored until, in medical judgment, engraftment of these cells and recovery are achieved. The administration of supportive transfusion of red blood cells and platelets should be done according to medical judgment and institutional practice. If clinical signs suggestive of anemia occur, blood cell count determination and other appropriate tests should be considered immediately. If cytopenia persists for more than six to seven weeks despite the use of granulocyte-mobilizing drugs, nontransduced reserve stem cells should be administered by infusion. If cytopenia persists despite infusion with nontransduced reserve stem cells, other treatments should be considered.

The platelet count should be monitored until, in medical judgment, engraftment of these cells and recovery are achieved. The administration of supportive transfusion of platelets should be done according to medical judgment and institutional practice.

Prior to treatment with Libmeldy, the presence of renal tubular acidosis should be evaluated, in addition to the risks of the conditioning drug and the risks of the gene therapy procedure, which may contribute to the development of metabolic acidosis. Acid-base balance should be monitored during conditioning and until the patient is no longer experiencing metabolic stress. The treating physician should consider sodium bicarbonate substitution in addition to other necessary treatments and should attempt to ameliorate any co-occurring side effects that may contribute to metabolic acidosis.

Although sterility and mycoplasma testing is performed upon release, there is a small risk of transmission of infectious agents. Health care professionals, should therefore monitor patients for signs and symptoms of infection after treatment and treat appropriately if necessary.

Patients should be examined for thyroid function and structure before treatment. Thyroid function and structure should also be monitored shortly after treatment and thereafter as needed.

If leukemia or lymphoma is detected in a patient, blood samples should be collected for analysis of the integration site.

Monitoring for anti-ARSA antibodies (AAA) is recommended prior to treatment, between 1 and 2 months after gene therapy and then 6 months, 1 year, 3 years, 5 years, 7 years, 9 years, 12 years and 15 years after treatment. Additional AAA monitoring is recommended upon the occurrence of disease or significant disease progression.

All patients should be tested for HIV-1/2, HTLV-1/2, HBV, HCV and mycoplasma prior to mobilization or bone marrow collection to ensure acceptance of the cellular source material for preparation.

Patients should not take antiretroviral drugs from at least one month prior to mobilization and/or bone marrow collection until at least 7 days after the infusion. If a patient requires antiretroviral drugs after exposure to HIV/HTLV, initiation of treatment with Libmeldy should be delayed until 6 months after exposure a western blot test and viral load test for HIV/HTLV have been performed.

Patients on treatment should not donate blood, organs, tissues and cells for transplantation in the future.

Immunoglobulin G should be maintained above 5 g/l to avoid potential late infections (later than 100 days after treatment) associated with severe hypogammaglobinemia due to apheresis/bone marrow decline and conditioning.

All blood products required in the first 3 months after infusion should be irradiated.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Reference

Orchard Therapeutics (Netherlands) B.V., SmPC Libmeldy (EU/1/20/1493/001) 28-06-2021, www.ema.europa.eu

Atidarsagen autotemcel

Atidarsagen autotemcel

Atidarsagen autotemcel

Pharmacokinetics in children

dose recommendation of formulary compared to licensed use (on-label versus off-label)

Available formulations

Dosages

Renal impaiment in children > 3 months

Side effects in children

Contra-indications in children

Warnings & precautions in children

Interactions

Reference

Changes

Therapeutic Drug Monitoring

Overdose