Donislecel
FDA Drug Information • Also known as: Lantidra
- Brand Names
- Lantidra
- Route
- INTRAVASCULAR
- Dosage Form
- SOLUTION
- Product Type
- CELLULAR THERAPY
Description
11 DESCRIPTION LANTIDRA consists of a suspension of allogeneic pancreatic islets in buffered transplant medium containing sodium chloride, dextrose, minerals, amino acids, vitamins, and other compounds supplemented with HEPES (2-[4-(2-hydroxyethyl)piperazin-1-yl] ethanesulfonic acid; 10 mM final concentration) and human serum albumin (0.5% final concentration). The active ingredient in LANTIDRA is allogeneic islets of Langerhans derived from a donor pancreas. Islets contain several types of endocrine (hormone-secreting) cells, including β-, α-, pancreatic peptide- (PP-), δ-, and ε-cells. Each single-donor islet batch consists of two infusion bags connected to each other via a sterile connector. One LANTIDRA bag containing up to a maximum of 1 × 10 6 EIN in 400 ml of transplant media, and the second Rinse Bag containing 200 ml transplant media used to rinse the LANTIDRA bag and the infusion line. Ingredients present in transplant media are : CaC1 2 , anhydrous, biotin, MgSO 4 , anhydrous, folic acid, Na acetate, anhydrous, riboflavin, NaH 2 PO 4 H 2 O, cocarboxylase, dextrose, Li3 coenzyme A 2 H 2 O, KCl, cozymase, NaCl, Na 2 flavin adenine dinucleotide, Na gluconate H 2 O, Na triphosphopyridine nucleotide, L-alanine, Na3 uridine 5'-triphosphoric acid H 2 O, L-arginine HCl, ascorbic acid, L-aspartic acid, D-Ca-pantothenate, L-cysteine HCl H 2 O, choline chloride, L-cystine 2 HCl, i-inositol, L-glutamic acid, nicotinic acid, glycine, nicotinamide, L-histidine HCl H 2 O, para-aminobenzoic acid, hydroxy-L-proline, pyridoxine HCl, L-isoleucine, thiamine HCl, L-leucine, glutathione (reduced), L-lysine HCl, thymidine, L-methionine, 2D-adenosine, L-phenylalanine, 2D-cytidine HCl, L-proline, 2D-guanosine, L-serine, 5-methyl-2'- deoxycytidine, L-threonine, cholesterol, L-tryptophan, Tween 80, L-valine, L-alanyl-L-glutamine, L-tyrosine 2 Na 2 H 2 O
What Is Donislecel Used For?
1 INDICATIONS AND USAGE LANTIDRA is an allogeneic pancreatic islet cellular therapy indicated for the treatment of adults with Type 1 diabetes who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education. Use LANTIDRA in conjunction with concomitant immunosuppression. LANTIDRA is an allogeneic pancreatic islet cellular therapy indicated for the treatment of adults with Type 1 diabetes who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education. Use in conjunction with concomitant immunosuppression. ( 1 ) Limitations of Use When considering the risks associated with the infusion procedure and long-term immunosuppression, there is no evidence to show a benefit of administration of LANTIDRA in patients whose diabetes is well-controlled with insulin therapy or patients with hypoglycemic unawareness who are able to prevent current repeated severe hypoglycemic events (neuroglycopenia requiring active intervention from a third party) using intensive diabetes management (including insulin, devices, and education). Repeated intraportal islet infusions are not recommended in patients who have experienced prior portal thrombosis, unless the thrombosis was limited to second- or third-order portal vein branches. There is no evidence to support the safe and effective use of LANTIDRA in patients with liver disease, renal failure, or who have received a renal transplant.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For infusion into the hepatic portal vein only. For infusion into the hepatic portal vein only. Do not irradiate. Do not use leukodepleting filters . Do not use if product time exceeds 48-hours post product release or if temperature is not maintained between 15 and 25° C To be prepared and administered only by medical professionals experienced in islet cell transplantation ( 2.2 ) ( 2.3 ) The recommended minimum dose is 5,000 equivalent islet number (EIN) per kg patient body weight for initial infusion (transplant) and 4,500 EIN/kg for subsequent infusions (same recipient). ( 2.1 ) Administer cells through the hepatic portal vein using a 5 or 6 French angiographic catheter indicated for infusion of LANTIDRA ( 2.3 ). The estimated tissue volume should not exceed 10 cc per transplant infusion. ( 2.1 ) 2.1 Recommended Dose The recommended minimum dose is 5,000 EIN/kg for initial infusion and 4,500 EIN/kg for subsequent infusion in the same recipient. The maximum dose per infusion is dictated by the estimated tissue volume, which should not exceed 10 cc per infusion, and the total EIN present in the infusion bag (up to a maximum of 1 × 10 6 EIN per bag). A second infusion may be performed if the patient does not achieve independence from exogenous insulin within one year of infusion or within one year after losing independence from exogenous insulin after a previous infusion. A third infusion may be performed using the same criteria as for the second infusion. There are no data regarding the effectiveness or safety for patients receiving more than three infusions. Pre-procedural medications Provide pre-procedural induction immunosuppression 30 – 360 minutes prior to LANTIDRA infusion. Include the following, at the discretion of the treating physician who is experienced with management of immunosuppression regimens for islet cell transplantation: Non-depleting monoclonal anti-interleukin-2 (anti-IL-2) receptor antibody 120 minutes prior to islet infusion Note: In patients who are sensitized (hypersensitivity with a past history of anaphylactic reaction) to non-depleting monoclonal anti-interleukin-2 (anti-IL-2) receptor antibody therapies, a polyclonal, T-cell-depleting antibody should be used instead. Calcineurin inhibitor Mammalian target of rapamycin (mTOR) inhibitor Tumor necrosis factor (TNF) blocker. Periprocedural antibiotic prophylaxis is recommended. 2.2 Preparation Keep LANTIDRA in the insulated container at 15°C to 25°C no longer than 48 hours from time of product release (See carton label and certificate of analysis). Dispose of any product not used within 48 hours. Do not irradiate. Select and prepare units under the direction of a medical professional who is experienced in islet infusion (transplantation). Use LANTIDRA as supplied and without further dilution. 2.3 Administration Failure to follow these directions may result in damage and decreased viability of the islets. Do not administer with leukodepleting...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Ninety percent (90%) of subjects had at least one serious adverse reaction. The major causes were attributed to: Infusion procedure liver laceration/hematoma, hemorrhage, and intra-abdominal bleeding (13%) elevation of portal pressure (7%) Immunosuppression Infection (87%) Malignancy (37%) Ninety percent (90%) of subjects had at least one serious adverse reaction. ( 6.1 ) The major causes are attributed to: Infusion procedure liver laceration/hematoma, hemorrhage, and intra-abdominal bleeding (13%) elevation of portal pressure (7%) Immunosuppression Infection (87%) Malignancy (37%) To report SUSPECTED ADVERSE REACTIONS, contact CellTrans at 1-800-500-1617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 of LANTIDRA in subjects with type 1 diabetes and hypoglycemic unawareness was demonstrated in two clinical trials (Study 1, Study 2) involving a total of 30 subjects who received between one and three doses of LANTIDRA. Duration between first and second transplant was one month to 2.8 years and between second and third dose from 3 months to 7.8 years (See Figure 1 ). Because of the variable duration of follow-up, number of infusions, and interval between infusions, adverse reactions were reported for the total duration for which each subject was followed. [Clinical Studies (14)] Subjects were followed for 0.3 to 14.5 years (mean 3 ± 3.7 years) after the first infusion. Serious reactions were reported in 27 (90%) of subjects. There were two (7%) deaths; one death from multi-organ failure with sepsis (1.6 years after the first infusion), and one from progressive confusion, global atrophy and micro-ischemic disease (9.7 years after the first infusion). Both subjects were using immunosuppression at the time of the event. Additionally, 8 (27%) subjects experienced at least one life-threatening adverse reaction and 26 (87%) subjects experienced at least one severe reaction before their last follow-up. Immunosuppression-Related Adverse Reactions Risks of common community-acquired infections and opportunistic infections increases with immunosuppression. In total, 211 infections were reported for 26 subjects; one was life-threatening, 22 reactions severe, and 115 events moderate in severity. Additionally, one subject died of multi-organ failure from sepsis in the second year after infusion. Discontinuation of immunosuppression resulted in loss of islet cell function and if achieved insulin independence. This was described for 8 (27%) subjects. Malignancy risk is known to increase with immunosuppression. In total, 16 adverse reactions of malignancy were reported in 11 subjects; three malignancies were life-threatening. The malignancies included 12 skin cancers, and one post-transplant lymphoproliferative disease, one breast cancer, and one thyroid cancer. Anemia was reported in 24 (80%) of subjects. Of the 90 adverse reactions reported, one reaction was life-threatening (Hgb <6.5gm/dL), 9 reactions were severe (<8-6.5 gm/dL), and 27 reactions were moderate in severity (<10-8 gm/dL). Anemia was attributed to bleeding because of procedural complications as well as immunosuppression. Transfusion was required for severe and life-threatening reactions. Overall, five transfusions were administered to five subjects. Three transfusions were for procedural related complications and two were non-procedure related. Alterations in red blood cell turnover and transfusion can alter the accuracy of HbA1c measurements. Therefore, in addition to monitoring for the development of anemia as a result of immunosuppression or a result of a procedural complications, healthcare providers should consider the occurrence of anemia in the...
Contraindications
4 CONTRAINDICATIONS Do not administer LANTIDRA to patients who have concomitant diseases or conditions, including pregnancy, that contraindicate the procedure for LANTIDRA infusion or immunosuppression. LANTIDRA is contraindicated in patients for whom immunosuppression is contraindicated. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Pregnancy risk has not been assessed for LANTIDRA. No animal reproductive and development toxicity studies have been conducted with LANTIDRA. However, there is a risk of fetal malformations associated with certain immunosuppression medications that may be used following LANTIDRA administration. Additionally, the risks to the patient and fetus from the procedure for LANTIDRA infusion in pregnant women has not been assessed. 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING LANTIDRA (NDC 73539-001-01) is supplied as purified allogeneic islets of Langerhans suspended in buffered transplant medium containing sodium chloride, dextrose, minerals, amino acids, vitamins, and other compounds supplemented with HEPES (2-[4-(2-hydroxyethyl)piperazin-1-yl] ethanesulfonic acid; 10 mM final concentration) and human serum albumin (0.5% final concentration)). [Description (11)] . LANTIDRA is contained in one 1000 mL infusion bag filled with a supplied volume of 400 mL, containing not more than 10 cc of estimated packed islet tissue and not more than 1 × 10 6 EIN. The 1000 mL infusion bag is aseptically connected to a smaller 750 mL Rinse Bag (NDC 73539-002-01) containing 200 mL of supplied volume of transplant media for use in rinsing the 1000 mL bag containing LANTIDRA and infusion line following infusion to assure complete transfer of islets to the patient. Additional product information, including islet number, is included on the Final Islet Product Certificate of Analysis and the container label. Store in the insulated container at 15°C to 25°C for up to 48 hours from time of product release. Dispose used bags and infusion lines as biohazard material.
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.