Myelosuppressive doses of radiation with Haematopoietic Sub-syndrome of Acute Radiation Syndrome (H-ARS)

Active Ingredient: Sargramostim

Indication for Sargramostim

Population group: only infants (40 days - 1 year old) , children (1 year - 12 years old) , adolescents (12 years - 18 years old) , adults (18 years old or older)
Therapeutic intent: Curative procedure

Sargramostim is indicated for treatment of patients of all ages acutely exposed to myelosuppressive doses of radiation with Haematopoietic Sub-syndrome of Acute Radiation Syndrome (H-ARS).

Sargramostim should be used in accordance with official radiological/nuclear emergency recommendations.

For this indication, competent medicine agencies globally authorize below treatments:

7, 10 or 12 ug/kg once daily based on body weight

For:

Dosage regimens

Regimen A, in case that patient weight is > 40 kg

Subcutaneous, 7 micrograms sargramostim per kilogram of body weight, once daily.

Regimen B, in case that patient weight is ≥ 15 kg and patient weight is < 40 kg

Subcutaneous, 10 micrograms sargramostim per kilogram of body weight, once daily.

Regimen C, in case that patient weight is < 15 kg

Subcutaneous, 12 micrograms sargramostim per kilogram of body weight, once daily.

Detailed description

Sargramostim should be administered once daily as a subcutaneous injection and dosing is based on body weight as follows:

  • 7 micrograms/kg in children and adolescents weighing greater than 40 kg
  • 10 micrograms/kg in children and adolescents weighing 15 kg to 40 kg
  • 12 micrograms/kg in neonates, infants or children weighing less than 15 kg

See Treatment Response for guidance regarding sargramostim duration of treatment.

Dose modification

For grade 3 or 4 adverse reactions, sargramostim dose should be reduced to 50%, or interrupted until the adverse reaction abates and then resumed at 50% of the dose. Other measures to manage the adverse reaction should be instituted and continued as necessary. If a grade 3 or 4 adverse reaction persists or recurs following dose adjustment/resumption, sargramostim should be permanently discontinued.

For grade 1 or 2 adverse reactions, sargramostim should be continued with close patient monitoring and management of the adverse reaction.

Treatment response

A baseline CBC with differential and then serial CBCs should be obtained approximately every third day (when possible) until the absolute neutrophil count (ANC) remains greater than 1 000/mm³ for 3 consecutive CBCs. After the first achievement of ANC greater than 1 000/mm³, then serial CBCs should be collected daily (when possible) to avoid unnecessary treatment and minimise any risk of leucocytosis. The start or continuation of administration of sargramostim should not be delayed if a CBC is not available.

Administration of sargramostim should continue until the ANC remains greater than 1 000/mm³ for 3 consecutive CBCs or exceeds 10 000/mm³ after a radiation-induced nadir. If CBCs are not available or in absence of treatment response, sargramostim may be discontinued after 23 consecutive days of dosing.

Dosage considerations

Sargramostim should be administered subcutaneously in the abdomen, thigh, or upper arm.

7 ug/kg once daily

For:

Dosage regimens

Subcutaneous, 7 micrograms sargramostim per kilogram of body weight, once daily.

Detailed description

Sargramostim should be administered once daily as a subcutaneous injection and the dose is 7 micrograms/kg.

See Treatment Response for guidance regarding sargramostim duration of treatment.

Dose modification

For grade 3 or 4 adverse reactions, sargramostim dose should be reduced to 50%, or interrupted until the adverse reaction abates and then resumed at 50% of the dose. Other measures to manage the adverse reaction should be instituted and continued as necessary. If a grade 3 or 4 adverse reaction persists or recurs following dose adjustment/resumption, sargramostim should be permanently discontinued.

For grade 1 or 2 adverse reactions, sargramostim should be continued with close patient monitoring and management of the adverse reaction.

Treatment response

A baseline CBC with differential and then serial CBCs should be obtained approximately every third day (when possible) until the absolute neutrophil count (ANC) remains greater than 1 000/mm³ for 3 consecutive CBCs. After the first achievement of ANC greater than 1 000/mm³, then serial CBCs should be collected daily (when possible) to avoid unnecessary treatment and minimise any risk of leucocytosis. The start or continuation of administration of sargramostim should not be delayed if a CBC is not available.

Administration of sargramostim should continue until the ANC remains greater than 1 000/mm³ for 3 consecutive CBCs or exceeds 10 000/mm³ after a radiation-induced nadir. If CBCs are not available or in absence of treatment response, sargramostim may be discontinued after 23 consecutive days of dosing.

Dosage considerations

Sargramostim should be administered subcutaneously in the abdomen, thigh, or upper arm.

Active ingredient

Sargramostim

Sargramostim is a recombinant human GM-CSF. The binding to GM-CSF receptors expressed on the surface of target cells (haematopoietic progenitors and mature immune cells), initiates an intracellular signalling cascade which induces the cellular responses (i.e., division, maturation, activation). GM-CSF is a multilineage factor and, in addition to dose-dependent effects on the myelomonocytic lineage, it can promote the proliferation and maturation of megakaryocytic and erythroid progenitors.

Read more about Sargramostim

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