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Imreplys is a brand name for Sargramostim. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Imreplys 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). Imreplys should be used in accordance with official radiological/nuclear emergency recommendations.
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with Imreplys should be started as soon as possible in any adult, adolescent, child, or infant who has been acutely exposed to myelosuppressive doses (greater than 2 gray [Gy]) of radiation with suspected H-ARS based on clinical signs and symptoms or confirmed H-ARS based on laboratory tests.
If possible, a baseline complete blood count (CBC) with differential should be obtained. , level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical features and laboratory findings such as lymphocyte depletion kinetics.
Treatment should not be withheld if H-ARS is suspected or diagnosed even if the absorbed radiation dose is estimated as lower than 2 Gy. Imreplys should not be delayed if a CBC is not readily available or absorbed radiation dose cannot be estimated.
Posology Imreplys should be administered once daily as a subcutaneous injection and dosing is based on body weight as follows: 3 • 7 micrograms/kg in children and adolescents weighing greater than 40 kg and in adults • 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 Imreplys duration of treatment.
8), Imreplys 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, Imreplys should be permanently discontinued.
8), sargramostim should be continued with close patient monitoring and management of the adverse reaction. Special populations Elderly No dose adjustment is required in elderly individuals ≥ 65 years of age. 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.
4). The start or continuation of administration of Imreplys should not be delayed if a CBC is not available. Administration of Imreplys 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.
6 The safety of sargramostim was evaluated using all available sources, including clinical studies in adults and children across various indications, healthy human volunteer studies, solicited and unsolicited reports, and literature-reported events.
Summary of the safety profile The most serious adverse drug reactions (ADR) that occurred during sargramostim treatment were: • Serious hypersensitivity reactions including anaphylaxis • Haemodynamic oedema, effusions and fluid overload • Supraventricular arrhythmias The most common ADRs observed in haematological cancer patients treated with intravenously administered sargramostim are: fever (without infection; up to 95%), diarrhoea (up to 88%), vomiting (up to 84%), skin reactions (up to 77%), rash (up to 70%), asthenia (up to 69%), metabolic laboratory abnormalities (up to 58%), malaise (up to 58%), high glucose (up to 49%), abdominal pain (up to 38%), weight loss (up to 37%), low albumin (up to 36%), pruritis (up to 23%), GI haemorrhage (up to 27%), chills (up to 25%), pharyngitis (up to 23%), bone pain (up to 21%), chest pain (up to 15%), hypomagnesaemia (up to 15%), haematemesis (up to 13%), arthralgia (joint pain; up to 11%), anxiety (up to 11%), eye haemorrhage (up to 11%).
In some subjects, the underlying diseases may have contributed to the occurrence of those ADRs. Tabulated list of adverse reactions The tabulated ADRs table is based on 5 clinical studies in 182 patients with haematological cancers where WBC are affected similarly to what occurs during acute exposure to myelosuppressive doses of radiation.
In these studies, sargramostim was administered intravenously. The adverse reactions are listed by MedDRA system organ class and categories of frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000) and not known (cannot be estimated from the available data).
Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 4 General recommendations Imreplys may be used in conjunction with other supportive care to treat H-ARS.
Given that the mechanism of radiation toxicity begins at the time of exposure, treatment with Imreplys should start as soon as possible after radiation exposure. However, efficacy studies for sargramostim when administered earlier than 24 hours after exposure to myelosuppressive doses of radiation, have not been conducted in a large animal model of total body irradiation-induced H-ARS.
Hypersensitivity and anaphylaxis Hypersensitivity reactions, including anaphylactic reactions, have been reported with sargramostim. Sargramostim treatment should be discontinued in those who have experienced anaphylaxis after a prior dose of sargramostim.
Haemodynamic oedema, effusions and fluid overload Oedema, capillary leak syndrome, and pleural and/or pericardial effusion have been reported in patients after sargramostim administration in haematological conditions. In patients with pre-existing pleural and pericardial effusions, administration of sargramostim may aggravate fluid retention.
Fluid retention associated with or worsened by sargramostim has been reversible after interruption or dose reduction of sargramostim with or without diuretic therapy. Imreplys should be used with caution in patients with pre-existing fluid retention, pulmonary infiltrates, or congestive heart failure.
Body weight and hydration status should be carefully monitored during sargramostim administration. Supraventricular arrhythmias Supraventricular arrhythmia has been reported in uncontrolled studies during sargramostim administration in haematological conditions, particularly in patients with a previous history of cardiac arrhythmia.
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If CBCs are not available or in absence of treatment response, Imreplys may be discontinued after 23 consecutive days of dosing. Method of administration Imreplys should be administered subcutaneously in the abdomen, thigh, or upper arm.
Imreplys may be self-administered or administered by a caregiver. Imreplys must be reconstituted in 1 mL of water for injections. Instructions for the preparation and administration of the reconstituted Imreplys powder are given in the package leaflet, section 3, "How to use Imreplys".
Table 1:
Adverse reactions reported in adults and children with haematological cancers treated with intravenous sargramostim in controlled clinical studies System Organ Class (MedDRA) Very common Common Uncommon Rare Very rare Nervous system disorders Anxiety Eye disorders Eye haemorrhage Vascular disorders Vasodilation Respiratory, thoracic and mediastinal disorders Pharyngitis Gastrointestinal disorders Abdominal pain Diarrhoea Gastrointestinal haemorrhage Haematemesis Vomiting Skin and subcutaneous tissue disorders Pruritis Rash Skin reactions Bone pain 7 Paediatric population A total of 332 paediatric subjects were treated with intravenous sargramostim in 15 clinical studies in haematological conditions, premature neonates and Crohn’s disease of which 5 were controlled, 190 patients were 0-1 month of age, 6 patients were > 1 month to < 2 years of age, 1 patient was < 1 year of age (not otherwise specified), 86 patients were 2 to < 12 years of age, and 49 patients were 12 to < 18 years of age.
The overall safety profile was similar to that seen in adults. Adverse drug reactions reported with subcutaneous administration of sargramostim Additional ADRs have been observed in clinical studies in healthy adult volunteers and children with Crohn’s disease, where the majority of patients were administered sargramostim via the subcutaneous route.
From these studies, in addition to Table 1, ADRs include injection site reactions (up to 91%), headache (up to 50%) back pain, (up to 47%), nausea (up to 23%), abdominal cramps (up to 17%), dyspnoea (up to 12%), and general body pain (up to 13%).
Solicited, unsolicited, and literature-reported events in patients treated with sargramostim (across various routes of administration) The most common ADRs were pyrexia, injection site reaction, dyspnoea, nausea, chest pain, vomiting, diarrhoea, chills, rash, hypotension, abdominal pain, febrile neutropenia, sepsis, pneumonia, dizziness, and syncope.
Serious hypersensitivity reactions including anaphylaxis, haemodynamic oedema, effusions and fluid overload and supraventricular arrhythmias have been reported with the use of sargramostim in various health conditions. No overall differences in safety profile are observed between reports from adult and paediatric populations.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation 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 via the national reporting system listed in Appendix V.
System Organ Class (MedDRA) Very common Common Uncommon Rare Very rare Musculoskeletal and connective tissue disorders Arthralgia General disorders and administration site conditions Asthenia Chest pain Chills Fever (no infection) Malaise Weight loss Investigations High glucose Low albumin Hypomagnesaemia Metabolic function test abnormalities NOS 8
These arrhythmias have been reversible after discontinuation of treatment. Imreplys should be used with caution in patients with pre-existing cardiac disease. A physician or other health care professional should be consulted if any new or worsening arrhythmia is observed.
Potential effect on malignant cells Sargramostim is a growth factor that stimulates normal myeloid precursors. However, the possibility that sargramostim can act as a growth factor for any tumour type, particularly myeloid malignancies, cannot be excluded.
Patients with pre-existing, or a history of, cancer should be treated with Imreplys as soon as possible following radiation exposure due to the life-threatening nature of the exposure and consult an oncologist as soon as practical.
Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Treatment with sargramostim in persons who have not been exposed to myelosuppressive doses of radiation may induce neutralising anti-drug antibodies which may be related to duration of exposure to sargramostim.
Risk of leucocytosis 5 White blood cell (WBC) counts of ≥ 50 000/mm3 were observed in patients receiving sargramostim for haematological conditions. Following discontinuation of sargramostim treatment, leucocytosis has resolved within 3 to 7 days.
If WBC counts exceed ≥ 50 000/mm3 in any patient, Imreplys should be discontinued immediately. Limitations of effectiveness The effectiveness of sargramostim may be limited in immunocompromised patients and those with underlying conditions affecting bone marrow function.
Patients with pre-existing bone marrow suppression, such as those with haematologic malignancies, autoimmune disorders, or those undergoing chemotherapy/radiation therapy, may exhibit a suboptimal response to sargramostim due to reduced progenitor cell reserves or impaired haematopoiesis.
1, nonclinical efficacy). High-dose radiation exposure can cause irreversible bone marrow failure, limiting the potential benefit of Imreplys in promoting haematopoietic recovery.