Allogenic Thymocyte-Depleted Thymus Tissue-Agdc
FDA Drug Information • Also known as: Rethymic
- Brand Names
- Rethymic
- Route
- INTRAMUSCULAR
- Dosage Form
- IMPLANT
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION RETHYMIC consists of yellow to brown slices of allogeneic processed thymus tissue for administration by surgical implantation. Three to 11 drug product containers, with a total of 10 to 42 RETHYMIC slices, are provided for each patient. Each drug product container provides up to 4 RETHYMIC slices of variable size. The total dose, based on the number of slices administered to the patient, is 5,000 to 22,000 mm 2 of RETHYMIC/m 2 recipient BSA. Thymus tissue is obtained from donors less than or equal to 9 months of age undergoing cardiac surgery. This thymus tissue is aseptically processed and cultured for 12 to 21 days to produce RETHYMIC slices. Each product lot is manufactured from a single unrelated donor and one product lot treats a single patient. The manufacturing process preserves the thymic epithelial cells and tissue structure and depletes most of the donor thymocytes from the tissue. These RETHYMIC slices are then surgically implanted into patients with congenital athymia. The product manufacture uses reagents derived from animal materials. The surgical sponge used during culturing is porcine-derived. Fetal bovine serum is a component in the culture medium used to culture the thymus slices and RETHYMIC is formulated in media that is supplemented with fetal bovine serum. Therefore, bovine- and porcine-derived proteins will be present in RETHYMIC. These animal-derived reagents are tested for animal viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma before use.
What Is Allogenic Thymocyte-Depleted Thymus Tissue-Agdc Used For?
1 INDICATIONS AND USAGE RETHYMIC ® is indicated for immune reconstitution in pediatric patients with congenital athymia. RETHYMIC is indicated for immune reconstitution in pediatric patients with congenital athymia. ( 1 ) Limitations of Use : RETHYMIC is not indicated for the treatment of patients with severe combined immunodeficiency (SCID). Limitations of Use RETHYMIC is not indicated for the treatment of patients with severe combined immunodeficiency (SCID).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION RETHYMIC is administered by a surgical procedure. The recommended dose range is 5,000 to 22,000 mm 2 of RETHYMIC/m 2 recipient body surface area (BSA). (2) Immunosuppressive therapy is recommended for patients receiving RETHYMIC based on disease phenotype and PHA levels. ( 14 ) 2.1 Dosage RETHYMIC is administered by a surgical procedure. The dosage is determined by the total surface area of the RETHYMIC slices and recipient body surface area (BSA). A RETHYMIC slice is defined as the contents on a single filter membrane; the RETHYMIC slices are variable in size and shape. The recommended dose range is 5,000 to 22,000 mm 2 of RETHYMIC surface area/m 2 recipient BSA. The manufacturer calculates the dose in advance for the specific patient; the amount of product provided is adjusted at the manufacturing facility to ensure the maximum dose for the patient cannot be exceeded. Up to 42 cultured RETHYMIC slices will be provided for each patient. At the time of surgery, the manufacturing personnel communicate to the surgical team the portion of the product that represents the minimum dose. Patients with evidence of maternal engraftment or an elevated response to phytohemagglutinin (PHA) should receive RETHYMIC with immunosuppressive medications (Table 2). 2.2 Administration Instructions Surgical implantation of RETHYMIC should be done by a qualified surgical team in a single surgical session at a qualified hospital. RETHYMIC should be implanted in the quadriceps muscle in accordance with the instructions provided below. Implantation of RETHYMIC into the quadriceps requires a healthy bed of muscle tissue. Preparation for the Implantation Procedure: Operating room culture dishes (sterile 100 mm tissue culture dishes) and saline for injection are supplied by the operating room; a sufficient supply of operating room culture dishes and saline must be provided by the hospital for use in the implantation procedure. The product is delivered to the operating room by manufacturing personnel. The recommended dose is determined based on the patient's BSA. The manufacturer calculates the dose in advance for the specific patient. Manufacturing personnel and the operating room staff confirm that the lot delivered is for the intended recipient. Manufacturing personnel communicate to the surgical team the minimum number of RETHYMIC slices to be implanted to achieve the minimum dose. The product expiration date and time for the entire lot is labeled on each polystyrene dish (drug product dish). Always handle RETHYMIC slices aseptically. Do not use if there is evidence of contamination. Outside the sterile field, manufacturing personnel unpack RETHYMIC from the shipping box. One drug product dish at a time is removed from the drug product box and shipping box. Manufacturing personnel inspect the drug product box and each drug product dish for signs of contamination, damage, spills, or leakage. If damage to the drug product dishes, leaks,...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reactions (incidence in at least 10% of patients) reported following administration of RETHYMIC were hypertension (high blood pressure), cytokine release syndrome, rash, hypomagnesemia (low magnesium), renal impairment / failure (decrease of kidney function), thrombocytopenia (low platelets), and graft versus host disease. The most common (>10%) adverse events related to RETHYMIC included: hypertension (high blood pressure, 19%), cytokine release syndrome (18%), rash (15%), hypomagnesemia (low magnesium, 16%), renal impairment / failure (decrease of kidney function, 12%), thrombocytopenia (low platelets, 12%), and graft versus host disease, (10%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sumitomo Pharma America at 833-369-9868 or FDA at 1-800-FDA-1088 or https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in this section are derived from 10 prospective, single-center, open-label studies, and include 105 patients who were treated with RETHYMIC in these studies and who had at least one year of follow-up. Table 1 lists the adverse reactions occurring in 105 patients who were treated with RETHYMIC in these studies. Table 1: Adverse Reactions Occurring in at least 5% of Patients Treated with RETHYMIC During Clinical Studies System Organ Class Preferred Term RETHYMIC (N=105) n (%) Number of Patients with Adverse Reactions Reactions which occurred in the 2 years after treatment. 80 (76) Hypertension (high blood pressure) 20 (19) Cytokine release syndrome All events (19/19) of cytokine release syndrome occurred in association with ATG-R treatment. 19 (18) Hypomagnesemia (low magnesium) 17 (16) Rash Rash includes rash, granuloma skin, rash papular, urticaria. 16 (15) Renal impairment / failure Renal impairment / failure includes renal failure and acute kidney injury, proteinuria and blood creatinine increased. (decrease of kidney function) 13 (12) Thrombocytopenia Thrombocytopenia includes thrombocytopenia and Immune thrombocytopenic purpura. (low platelets) 13 (12) Graft versus host disease GVHD includes GVHD, GVHD-gut, GVHD-skin, Omenn syndrome. 11 (10) Hemolytic anemia Hemolytic anemia includes autoimmune hemolytic anemia, Coombs-positive hemolytic anemia, hemolysis, hemolytic anemia. (low red bloods cells) 9 (9) Neutropenia (low white blood cells) 9 (9) Respiratory distress Respiratory distress includes respiratory distress, hypoxia, respiratory failure. (difficulty breathing) 8 (8) Proteinuria (protein in urine) 7 (7) Pyrexia (fever) 6 (6) Acidosis Acidosis includes acidosis, renal tubular acidosis and blood bicarbonate decreased. 6 (6) Diarrhea Diarrhea includes diarrhea and hemorrhagic diarrhea. 5 (5) Seizure Seizures include infantile spasms, seizures and febrile convulsion. 5 (5) Of the 105 patients, 29 patients died after receiving RETHYMIC, including 23 deaths in the first year (<365 days) after treatment with RETHYMIC. Causes of death in the first year included 13 deaths due to infection or complications due to infection, 5 deaths due to respiratory failure / hypoxia, 3 deaths due to hemorrhage-related events, and 2 deaths due to cardiorespiratory arrest. Of the 6 patients who died more than 1 year after treatment with RETHYMIC, the deaths were considered unrelated to study treatment: 2 died due to respiratory failure and 1 died due to each of the following: cardiopulmonary arrest, intracranial hemorrhage, infection, and unknown cause. Severe combined immunodeficiency (SCID) Patients Two patients with SCID were treated in the RETHYMIC clinical program. One patient died two years after receiving RETHYMIC, and...
Drug Interactions
7 DRUG INTERACTIONS No drug interaction studies have been conducted with RETHYMIC. If possible, prolonged use of immunosuppressive therapies, including high-dose corticosteroids, should be avoided.
Contraindications
4 CONTRAINDICATIONS None. None.
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no clinical data with RETHYMIC in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with RETHYMIC. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Overdosage
10 OVERDOSAGE The maximum recommended dose is 22,000 mm 2 of RETHYMIC/m 2 recipient body surface area (BSA). Standard clinical care is recommended for patients receiving a dose > 22,000 mm 2 of RETHYMIC/m 2 recipient BSA. The product, as provided, has been adjusted at the manufacturing facility to not exceed the maximum dose based on the patient body surface area. During clinical development one patient received a dose higher (23,755 mm 2 /m 2 ) than the maximum recommended dose. This patient developed enteritis. A biopsy showed T cell, B cell, and neutrophil infiltration of the gut which resolved after treatment with immunosuppression, 5 months after treatment with RETHYMIC. The enteritis may have been related to the high dose of RETHYMIC.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied RETHYMIC, NDC 72359-001-01, contains a single-dose unit, supplied ready for use as slices of processed thymus tissue, in sterile, polystyrene dishes (drug product dishes). Each drug product dish contains up to 4 RETHYMIC slices, adhered to circular filter membranes on top of surgical sponges in 5 mL of medium containing fetal bovine serum. Up to 42 RETHYMIC slices are supplied in a single-dose unit according to the dosage calculated in advance by the manufacturer for the specific patient. The dosage is determined by the total surface area of the RETHYMIC slices and recipient body surface area (BSA). The recommended dose range is 5,000 to 22,000 mm 2 of RETHYMIC surface area/m 2 recipient BSA. At the time of surgery, the manufacturing personnel communicate to the surgical team the portion of the product that represents the minimum dose. All drug product dishes are supplied in a polycarbonate container in an insulated shipping box. Storage and Handling Use RETHYMIC prior to the time and date of expiration printed on the polycarbonate container. Store RETHYMIC at room temperature in the polycarbonate container in the insulated shipping box until ready for use. Do not refrigerate, freeze, agitate, or sterilize RETHYMIC. In the operating room, manufacturing personnel inspect the drug product containers as they are removed from the shipping box. If damage to the drug product dishes, leaks, spillage or evidence of contamination is noted, manufacturing personnel will notify the surgical team that the lot cannot be implanted. Match the patient's identity with the patient identifiers on the patient label on the polycarbonate container. Do not remove the drug product containers from the polycarbonate container if the information on the patient label does not match the intended patient. Manufacturing personnel record which RETHYMIC slices are used during the surgery. If any RETHYMIC slices are not administered to the patient,...
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.