Version May 2024
Infusion reactions may be fatal. Monitor patients during infusion and discontinue for severe reactions. Use is contraindicated in patients with known allergy to dimethyl sulfoxide, Dextran 40, gentamicin, human serum albumin, or bovine material.
Graft-vs-host disease (GvHD) may be fatal. Administration of immunosuppressive therapy may decrease the risk of GvHD.
Engraftment syndrome may be fatal. Treat engraftment syndrome promptly with corticosteroids.
Graft failure may be fatal. Monitor patients for laboratory evidence of hematopoietic recovery.
Note: Confirm patient identity prior to thaw or administration. Ensure patient identity matches the patient-specific identifiers on the omidubicel metal cassettes, the cultured fraction and noncultured fraction bags, and the infusion solution dilution bags. Do not use if the information on the patient-specific labels do not match the intended patient. Confirm the omidubicel Release for Infusion certificate is available prior to initiating conditioning regimen. Administer appropriate conditioning regimen prior to infusing omidubicel. Ensure patient is adequately hydrated. Premedications are recommended.
Prophylaxis and supportive medications: Administer prophylactic and supportive therapies for prevention and treatment of transplant complications (eg, infection prophylaxis, graft-versus-host disease prophylaxis). Confirm emergency medications are available prior to infusion and during recovery period.
Allogeneic hematopoietic cell transplantation, umbilical cord blood: Note: A single dose consists of a cultured fraction and a noncultured fraction (which are provided in separate cryopreserved bags).
Premedications: Premedicate with acetaminophen, diphenhydramine, and hydrocortisone ~30 to 60 minutes prior to omidubicel infusion. Avoid prophylactic use of methylprednisolone in conjunction with omidubicel.
Children ≥12 years and Adolescents:
Cultured fraction (CF): IV: A minimum of 8 × 108 total viable cells of which a minimum of 8.7% are CD34-positive (CD34+) cells and a minimum of 9.2 × 107 CD34+ cells.
Non-cultured fraction (NF): IV: A minimum of 4 × 108 total viable cells with a minimum of 2.4 × 107 CD3-positive (CD3+) cells; infusion of the NF should begin within 1 hour after completion of CF.
Dosage adjustment for toxicity:
Engraftment syndrome: Manage with corticosteroids (to improve symptoms) as soon as engraftment syndrome is recognized.
Fluid load (intolerable): Reduce infusion rate if fluid load is not tolerated.
Hypersensitivity: Pause infusion and manage appropriately with supportive care.
Infusion reaction (moderate to severe): Pause infusion and manage appropriately with supportive care. Discontinue for severe infusion reaction.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Omidubicel: Drug information")
Note: Confirm patient identity matches the patient-specific identifiers on the omidubicel metal cassettes, the cultured fraction and noncultured fraction bags, and the infusion solution dilution bags. Do not use if the information on the patient-specific labels do not match the intended patient. Confirm the omidubicel Released for Infusion (RFI) certificate is available prior to initiating conditioning regimen. Administer an appropriate transplant-conditioning regimen prior to infusing omidubicel. Ensure patient is adequately hydrated. Premedications are recommended.
Prophylaxis and supportive medications: Administer prophylactic and supportive therapies for prevention and treatment of transplant complications (eg, infection prophylaxis, graft-versus-host disease prophylaxis). Confirm emergency medications are available prior to infusion and during recovery period.
Allogeneic hematopoietic cell transplantation, umbilical cord blood: Note: A single dose consists of a cultured fraction and a noncultured fraction (which are provided in separate cryopreserved bags).
Cultured fraction: IV: A minimum of 8 × 108 viable cells of which a minimum of 8.7% are CD34-positive (CD34+) cells and a minimum of 9.2 × 107 CD34+ cells.
Noncultured fraction: IV: A minimum of 4 × 108 viable cells with a minimum of 2.4 × 107 CD3+ cells; infusion of the NF should begin within 1 hour after completion of CF.
Premedications: Premedicate ~30 to 60 minutes prior to omidubicel with an antihistamine, a corticosteroid, and an antipyretic as follows:
Antihistamine: Diphenhydramine 50 mg IV (or 0.5 mg/kg up to a maximum of 50 mg) or dexchlorpheniramine 10 mg IV.
Corticosteroid: Hydrocortisone 50 mg IV (0.5 mg/kg up to a maximum of 50 mg). Avoid the use of methylprednisolone in conjunction with omidubicel.
Antipyretic: Acetaminophen 650 mg orally (or 10 mg/kg up to a maximum of 650 mg).
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and adolescents.
>10%:
Cardiovascular: Hypertension (25%)
Endocrine & metabolic: Decreased serum magnesium (94%), hypermagnesemia (15%)
Gastrointestinal: Dysphagia (12%), gastrointestinal toxicity (19%), stomatitis (31%)
Hematologic & oncologic: Hemorrhage (12%; including gastrointestinal hemorrhage, hemorrhagic cystitis, pulmonary hemorrhage, and subarachnoid hemorrhage)
Hepatic: Increased serum alanine aminotransferase (56%), increased serum alkaline phosphatase (42%), increased serum aspartate aminotransferase (56%), increased serum bilirubin (42%)
Hypersensitivity: Infusion-related reaction (47% to 56%)
Immunologic: Graft-versus-host disease (acute and chronic: 35% to 58%)
Infection: Infection (including bacterial infection [65%], fungal infection [21%], serious infection, viral infection [75%])
Nervous system: Pain (33%)
Renal: Increased serum creatinine (50%), renal insufficiency (12%; including acute kidney injury and renal failure syndrome)
Respiratory: Respiratory failure (12%; including acute respiratory distress syndrome)
1% to 10%:
Nervous system: Fatigue (4%)
Respiratory: Dyspnea (8%)
Miscellaneous: Fever (2%)
Frequency not defined:
Hematologic & oncologic: Lymphoproliferative disorder (post-transplant [PTLD])
Immunologic: Graft complications (engraftment syndrome)
Known hypersensitivity to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin, bovine products, or any component of the formulation.
Concerns related to adverse effects:
• Engraftment syndrome: Because omidubicel is derived from umbilical cord blood, engraftment syndrome may occur. Signs/symptoms of engraftment syndrome include unexplained fever, rash, hypoxemia, weight gain, and/or pulmonary infiltrates in the peri-engraftment period. If untreated, engraftment syndrome may progress to multiorgan failure and death.
• Graft failure: Primary graft failure occurred in a small percentage of patients in omidubicel clinical studies. Primary graft failure (which may be fatal), is defined as failure to achieve an ANC >500/mm3 by day 42 after transplant. The primary cause of graft failure is immunologic rejection.
• Graft-versus-host disease: Acute and chronic graft-versus-host disease (GVHD), including life-threatening and fatal cases, has occurred following omidubicel. Grades 2 to 4 acute GVHD was reported in over half of patients, with grade 3 or 4 acute GVHD occurring in less than one-fifth of patients. Chronic GVHD occurred in over one-third of patients. Manifestations of acute GVHD included maculopapular rash, GI symptoms, and elevated bilirubin.
• Hypersensitivity: Allergic reactions may occur with omidubicel, including bronchospasm, wheezing, angioedema, pruritus, and hives. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO), residual gentamicin, Dextran 40, human serum albumin, and/or bovine material in omidubicel. If the cord blood donor was exposed to antibiotics in utero, omidubicel may contain residual antibiotics; patients with a history of allergic reactions to antibiotics should be monitored for allergic reactions following omidubicel infusions.
• Infection: Omidubicel is derived from umbilical cord blood and therefore has a risk of transmitting infectious diseases caused by known or unknown agents. Donors are screened for increased infection risk (infection with HIV, human T-cell lymphotropic virus [HTLV], hepatitis B virus [HBV], hepatitis C virus [HCV], T. pallidum, West Nile virus [WNV], transmissible spongiform encephalopathy agents, vaccinia, and Zika virus [for umbilical cord blood collected since March 2016]). Donors are also screened for clinical evidence of sepsis as well as communicable disease risks associated with xenotransplantation. Maternal blood samples are tested for HIV types 1 and 2, HTLV types I and II, HBV, HCV, T. pallidum, and WNV. Omidubicel is tested for sterility; however, the reliability of the sterility test results may be affected if the cord blood donor was exposed to antibiotics in utero. Omidubicel is also tested for endotoxin and mycoplasma; however, these measures do not eliminate risk of transmitting these or other transmissible infectious diseases. Testing of maternal and infant donor blood is also performed for evidence of donor infection due to cytomegalovirus. Test results are located on the container label and/or in accompanying records. Product is manufactured with bovine-derived reagents. Although animal-derived reagents are tested for animal viruses, bacteria, fungi, and mycoplasma prior to use, these measures may not eliminate the risk of transmission of these or other infectious diseases/agents. If final sterility results are not available at the time of use, any positive results will be communicated to the physician. Any transmitted infection occurrence should be reported to the omidubicel manufacturer.
• Infusion-related reactions: Infusion reactions have occurred with omidubicel; symptoms have included hypertension, mucosal inflammation, dysphagia, dyspnea, vomiting, and GI toxicity. Premedication (with antipyretics, antihistamines, and corticosteroids) may reduce the incidence/intensity of infusion reactions. Nearly half of patients experienced an infusion reaction (any severity); grade 3 to 4 infusion reactions were reported in some patients. The onset of infusion reactions may be within minutes of the start of omidubicel infusion, although symptoms may continue to intensify and may not peak for several hours after the infusion is completed.
• Malignancies of donor origin: Two patients who received omidubicel developed posttransplant lymphoproliferative disorder (PTLD) in the second year following transplant. PTLD manifests as a lymphoma-like condition that favors nonnodal sites and is usually fatal if untreated. PTLD is thought to be due to donor lymphoid cells transformed by Epstein-Barr virus (EBV). One case of donor-cell derived myelodysplastic syndrome (MDS) was observed with omidubicel during the fourth year after transplant; the natural history was presumed to be like that of de novo MDS. If a secondary malignancy occurs, contact the omidubicel manufacturer.
• Rare genetic disease transmission: Because omidubicel is derived from umbilical cord blood, it may transmit rare genetic diseases involving the hematopoietic system. Cord blood donors have been screened to exclude donors with sickle cell anemia and anemias due to abnormal hemoglobins C, D, and E. The ability to exclude rare genetic diseases is severely limited due to the age of the donor at the time cord blood collection takes place.
Dosage form specific issues:
• Excipients: Omidubicel contains excipients (dimethyl sulfoxide [DMSO], residual gentamicin, Dextran 40, human serum albumin, and/or bovine material), which are associated with hypersensitivity reactions; some excipients are associated with severe reactions, including anaphylaxis.
• Universal precautions: Omidubicel contains human umbilical cord blood cells; follow universal precautions and facility biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Omisirge: Omidubicel-onlv (1 ea) [contains albumin human, beef extract (bovine), dextran 40]
No
Note: Confirm patient identity matches patient identifier on cultured fraction (CF) and a noncultured fraction (NF) bags prior to infusion. Should only be administered at a facility with experience in hematologic malignancies and hematopoietic cell transplantation. Follow universal precautions for handling and disposal.
Parenteral: IV: For IV use only. A single dose consists of a CF and a NF, which are provided in separate bags and administered as separate infusions. A central line is recommended for omidubicel infusion. Do not use a leukodepleting filter. Prime the infusion set with NS prior to spiking the CF and NF bags. Infuse the CF bag first; infuse by gravity infusion at a rate not to exceed a maximum of 10 mL/kg/hour. Infusion time should not exceed 2 hours from end of dilution to completion of CF infusion. If an infusion reaction occurs during the CF infusion, manage infusion reaction prior to thawing NF bag. After entire contents of the CF bag is infused, flush tubing with NS (at the same infusion rate) to ensure the patient receives as many cells as possible. Infusion of the NF bag should begin within 1 hour after completion of the CF infusion; infuse by gravity infusion at a rate not to exceed a maximum of 10 mL/kg/hour. NF infusion time should not exceed 1 hour from end of dilution to completion of NF infusion. After entire contents of the NF bags are infused, flush tubing with NS (at the same infusion rate) to ensure the patient receives as many cells as possible. Entire contents of both the CF and NF bags should be infused. Contact the manufacturer if deviations from the dosing schedule occur.
Monitor for signs and symptoms of hypersensitivity or other infusion-related reactions during and after infusion. Pause infusion and manage appropriately for hypersensitivity or moderate to severe infusion reaction. Reduce infusion rate if fluid load is not tolerated.
Note: Verify patient identity upon receipt of product, prior to thaw, and prior to infusion. Thaw immediately prior to infusion. Do not use if the information on the patient-specific labels does not match the intended patient. Do not open metal cassettes until time of thaw. Should only be administered at a facility with experience in hematologic malignancies and hematopoietic cell transplantation. Follow universal precautions for handling and disposal.
IV: For IV use only. A single dose consists of a cultured fraction (CF) and a noncultured fraction (NF), which are provided in separate bags. A central line is recommended for omidubicel infusion. Do not use a leukodepleting filter. Prime the infusion set with NS prior to spiking the CF and NF bags. Infuse the CF bag first; infuse by gravity infusion at a rate not to exceed a maximum of 10 mL/kg/hour. Infusion time should not exceed 2 hours from end of dilution to completion of CF infusion. If an infusion reaction occurs during the CF infusion, manage infusion reaction prior to thawing NF. After entire contents of the CF bag is infused, flush tubing with NS (at the same infusion rate) to ensure the patient receives as many cells as possible. Infusion of the NF bag should begin within 1 hour after completion of the CF infusion; infuse by gravity infusion at a rate not to exceed a maximum of 10 mL/kg/hour. NF infusion time should not exceed 1 hour from end of dilution to completion of NF infusion. After entire contents of the NF bag are infused, flush tubing with NS (at the same infusion rate) to ensure the patient receives as many cells as possible. Entire contents of both the CF and NF bags should be infused. Contact the manufacturer if deviations from the dosing schedule occur.
Monitor for signs/symptoms of hypersensitivity or other infusion-related reactions during and after infusion. Pause infusion and manage appropriately for hypersensitivity or moderate to severe infusion reaction. Reduce infusion rate if fluid load is not tolerated.
Refer to manufacturer’s labeling and instructions for additional details.
Omidubicel is shipped in 2 shipping containers, a liquid nitrogen dry vapor (at ≤−150℃) container that contains 2 metal cassettes (one for the cultured fraction [CF] cryopreserved bag and one for the noncultured fraction [NF] cryopreserved bag) and a second refrigerated (at 2ºC to 8ºC [36ºF to 46ºF]) container with the infusion solutions for the CF and NF (including tubing and spike adapters for each infusion solution).
Liquid nitrogen container: Do not open the metal cassettes until time of thaw (opening cassettes may inflate overwraps and prevent cassette closure). Upon arrival, confirm that the batch number and patient-specific identifiers on both shipping container labels match the intended patient and the information on the documents from the manufacturer. Verify that the patient-specific identifiers on the labels on the outside of the CF and NF metal cassettes and on the CF and NF cryopreserved bags visible through the cassette window match the intended patient (do not open cassettes). Confirm receipt of the Release for Shipping Certificate. Confirm patient-specific identifiers on the Release for Infusion (RFI) certificate and Certificates of Analysis (COAs) match the patient’s identity. Ensure that omidubicel was received in appropriate conditions and confirm that the temperature of the liquid nitrogen dry vapor shipper upon receipt was ≤−150ºC and the temperature of the refrigerated shipping container was 2ºC to 8ºC (36ºF to 46ºF). Verify that the products are within the expiration date by checking the label located on the front of the metal cassettes and through the cassette windows (do not open cassettes to locate expiration date). If either of the shippers have expired upon arrival, or if unable to confirm the patient identity with the patient-specific identifiers on any of the labels, contact the manufacturer. Transfer the metal cassettes containing the CF and NF cryopreserved bags and the chimerism testing sample(s) to onsite vapor phase of liquid nitrogen storage at ≤−150ºC.
Refrigerated container: Ensure that both infusion solution bags are intact and within the expiration date. Ensure that infusion solutions were received in appropriate conditions and confirm that the temperature of the shipping container was 2ºC to 8ºC (36ºF to 46ºF). Verify that the patient-specific identifiers on the infusion solution bag labels match the intended patient. Transfer both infusion solution bags to refrigerated storage at 2ºC to 8ºC (36ºF to 46ºF).
To reduce the time to neutrophil recovery and the incidence of infection following myeloablative conditioning in patients with hematologic malignancies who are planned for umbilical cord blood transplantation (FDA approved in ages ≥12 years and adults).
Omidubicel may be confused with donislecel.
None known.
There are no known significant interactions.
Evaluate pregnancy status. Pregnancy testing is recommended prior to starting the conditioning regimen in sexually active patients who could become pregnant. Review each medication used in the conditioning regimen for potential contraception requirements.
Animal reproduction studies have not been conducted.
Monitor for signs and symptoms of hypersensitivity or other infusion-related reactions during and after infusion. Monitor for laboratory evidence of hematopoietic recovery; consider serial monitoring of blood for Epstein-Barr virus in patients with persistent cytopenias. Pregnancy testing is recommended prior to starting the conditioning regimen (in sexually active patients who could become pregnant). Monitor fluid load status. Monitor for signs and symptoms of engraftment syndrome (unexplained fever, rash, hypoxemia, weight gain, and/or pulmonary infiltrates in the peri-engraftment period), graft failure, graft-versus-host disease (acute and chronic), infection, and other post-transplant complications. Monitor for development of rare genetic diseases. Monitor life-long for development of secondary malignancies.
Omidubicel is a nicotinamide-modified, patient-specific, allogeneic hematopoietic cell product derived from umbilical cord blood (Horwitz 2021). Omidubicel consists of 2 fractions, an ex-vivo expanded CD133+ fraction (containing hematopoietic cells) produced via a nicotinamide (NAM) modification process, and a nonexpanded CD133- fraction (containing primarily mature myeloid and lymphoid cells). The NAM modification process produces an expansion of enriched hematopoietic cells with preserved primitive function, increased bone marrow homing, and engraftment capacity (Anand 2017; Horwitz 2021). The ex-vivo NAM-expanded product has the ability to overcome signaling pathways typically activated by removing hematopoietic cells from their natural environment, leading to rapid neutrophil engraftment and multilineage immune reconstitution.
Onset: Omidubicel transplantation resulted in rapid/broad immune reconstitution of dendritic cells, monocytes, natural killer cells, CD4+ T cells, and CD8+ T cells beginning 1 week after transplant, B cells 28 days after transplant, and all lineages throughout the 1-year follow-up period.
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