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LANTIDRA DONISLECEL 5000 [arb'U]/400mL Solution, 400 mL
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other drugs used in diabetes class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII P582C98ULC
A nucleoside (a building block similar to those found in DNA) used as an active pharmaceutical ingredient in some antiviral medicines. It works by interfering with virus replication rather than serving a traditional excipient role like binding or coating.
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UNII G9481N71RO
A nucleoside compound derived from natural sources or synthesized in the lab. It may be used as an active pharmaceutical ingredient rather than a typical inactive excipient, though its specific role depends on the formulation.
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UNII B200GV71QM
A nucleoside compound used in pharmaceutical formulations as an active pharmaceutical ingredient or excipient to support drug stability, cellular delivery, or bioavailability enhancement in specialized medicine formulations.
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UNII OF5P57N2ZX
Alanine is a naturally occurring amino acid used in medicines as a buffering agent and pH stabilizer. It helps maintain the proper acidity level in liquid formulations to improve stability and taste.
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UNII U5JDO2770Z
Alanyl glutamine is an amino acid compound used as a nutritional additive and stabilizer in medications. It helps maintain product stability and may serve as a source of amino acids in injectable or oral formulations.
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UNII ZIF514RVZR
A protein derived from human blood plasma. In medicines, it acts as a stabilizer and binder, helping maintain drug potency and form, and may improve how the medication disperses or dissolves in the body.
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UNII TL2TJE8QTX
A white crystalline compound derived from benzoic acid. It serves as a preservative and UV absorber in medications, helping protect the drug from degradation and light damage.
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UNII 5SL0G7R0OK
A simple sugar made from corn or other plants, used in medicines as a filler and sweetener. It helps create the right texture and taste in tablets, powders, and liquid formulations.
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UNII F7LTH1E20Y
Arginine hydrochloride is an amino acid salt used as a buffer and pH adjuster in medicines. It helps maintain the correct acidity level to keep the drug stable and effective.
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UNII PQ6CK8PD0R
Ascorbic acid, also known as vitamin C, is a white crystalline powder. It serves as an antioxidant to prevent degradation of other ingredients and may also function as a preservative in the formulation.
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UNII 30KYC7MIAI
Aspartic acid is an amino acid used in pharmaceutical formulations as a pH buffer and to help stabilize active ingredients. It works to maintain the proper acidity level in the medicine.
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UNII 6SO6U10H04
Biotin is a B-vitamin used as a nutritional supplement in some medications. It may also serve as a colorant or marker in formulations.
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UNII OFM21057LP
A mineral salt form of calcium and chloride. Used as a tonicity agent to balance salt concentration in liquid medicines and as a firming agent in some formulations.
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UNII 568ET80C3D
Calcium pantothenate is a salt form of pantothenic acid, a B-vitamin derivative. It's used as a nutritional supplement or vitamin fortification ingredient in medicines and formulations.
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UNII 97C5T2UQ7J
Cholesterol is a fatty substance found naturally in animal tissues. In medications, it's used as an ingredient in liposomal formulations and lipid-based drug delivery systems to help encapsulate and stabilize active drugs for better absorption.
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UNII 45I14D8O27
Choline chloride is a salt form of choline, a nutrient compound. It functions as a nutritional supplement or processing aid in formulations, sometimes serving as a buffer or stabilizer to maintain product pH and integrity.
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UNII Q57971654Y
Cocarboxylase is a naturally occurring form of thiamine (vitamin B1) used in some medications as an active cofactor. It functions as a coenzyme to support the formulation's intended biochemical role in the body.
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UNII 6GHL9SC2QT
Coenzyme A trilithium dihydrate is a form of coenzyme A, a natural compound that helps cells produce energy. It may be included in medicines as an active metabolic support ingredient or to enhance cellular function in the formulation.
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UNII ZT934N0X4W
A naturally occurring amino acid salt used as a reducing agent and antioxidant in medications. It helps prevent ingredient breakdown and may improve product stability during storage.
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UNII WFN1A47EIG
Cystine dihydrochloride is an amino acid salt used as a buffering agent and pH stabilizer in medications. It helps maintain the correct acidity level and chemical stability of the formulation.
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UNII X8FX60E66D
A nucleoside compound that serves as an active pharmaceutical ingredient or therapeutic agent in certain medications, rather than a traditional inactive filler or binder.
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UNII VC2W18DGKR
Thymidine is a nucleoside compound, a building block of DNA. In medicines, it may serve as a nutrient supplement or processing agent, though it is not commonly used as a standard tablet filler or binder.
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UNII 67U7UHJ04C
Flavin adenine dinucleotide disodium is a B-vitamin compound used as a color additive and nutritional fortification ingredient in medicines. It gives products a yellow or orange hue and adds riboflavin (vitamin B2) content.
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UNII 935E97BOY8
Folic acid is a synthetic form of a B vitamin. In medicines, it's added as a nutritional supplement or to help prevent vitamin deficiency, especially in prenatal formulas.
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UNII 3KX376GY7L
Glutamic acid is an amino acid used in pharmaceuticals as a buffer and pH regulator. It helps maintain the medicine's chemical stability and proper acidity level.
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UNII GAN16C9B8O
Glutathione is a naturally occurring antioxidant compound made from three amino acids. In medications, it may serve as an antioxidant to protect the drug's active ingredients from breaking down or degrading over time.
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UNII TE7660XO1C
Glycine is an amino acid used in medicines as a buffer to help stabilize pH and improve taste. It may also serve as a filler or binder to give the product proper form and consistency.
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UNII X573657P6P
Histidine monohydrochloride monohydrate is an amino acid salt used as a buffer in medicines. It helps maintain the proper acidity level of liquid formulations to keep the drug stable and effective.
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UNII RWW266YE9I
A buffering agent derived from piperazine chemistry. It helps maintain stable pH levels in liquid medicines, particularly in injectable or ophthalmic formulations, preventing degradation of active ingredients.
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UNII RMB44WO89X
Hydroxyproline is an amino acid derived from collagen. In medications, it serves as a structural component or filler that may help provide stability and texture to the formulation.
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UNII 4L6452S749
Inositol is a naturally occurring sugar-like compound. It acts as an osmotic agent and sweetener in medications, helping draw water into the formulation and improve taste.
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UNII 04Y7590D77
A naturally occurring amino acid used as a buffering agent and pH stabilizer in medications. It helps maintain the chemical balance of the formulation to protect drug stability.
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UNII GMW67QNF9C
Leucine is an amino acid derived from natural sources. It acts as a glidant and flow agent in powders and tablets, helping the medicine move smoothly during manufacturing and packaging.
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UNII JNJ23Q2COM
Lysine hydrochloride is an amino acid salt used in medicines as a buffer and pH stabilizer. It helps maintain the acidity level of the product to keep the active ingredient stable and effective.
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UNII ML30MJ2U7I
A mineral salt form of magnesium and sulfate. It serves as a filler to add bulk to the tablet or capsule and may help the medicine dissolve or disintegrate properly in the body.
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UNII AE28F7PNPL
Methionine is an amino acid used as a nutrient supplement and pH buffer in medicines. It helps stabilize the formulation and supports the product's overall composition.
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UNII 0U46U6E8UK
Nicotinamide adenine dinucleotide is a coenzyme naturally found in cells that helps transfer energy during metabolism. In medicines, it may serve as an active supplement ingredient rather than a traditional inactive filler or binder.
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UNII NR2O7P57YA
A coenzyme form of niacin (vitamin B3) that supports cellular energy production. In medicines, it serves as an active nutritional supplement ingredient to help maintain normal metabolic function.
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UNII 2679MF687A
Niacin is a B vitamin used in medications as a nutritional supplement and pH buffer. It helps stabilize the product and may support formulation integrity during manufacturing and storage.
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UNII 25X51I8RD4
Niacinamide is a form of vitamin B3, a water-soluble nutrient. In medicines, it may be added as a nutritional supplement or to support skin health, though its primary role here is as an active ingredient rather than a traditional inactive filler.
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UNII 47E5O17Y3R
Phenylalanine is an amino acid used as a sweetener and flavor enhancer in medicines and supplements. It helps make products taste better while keeping them shelf-stable.
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UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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UNII 660YQ98I10
Potassium chloride is a mineral salt used in medicines as a buffer and to help maintain the proper pH balance and stability of the formulation during storage and use.
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UNII 9DLQ4CIU6V
Proline is an amino acid used in pharmaceutical formulations as a bulking agent and stabilizer. It helps maintain product stability and can improve the texture or consistency of medicines, particularly in powders and freeze-dried products.
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UNII 68Y4CF58BV
Pyridoxine hydrochloride is a form of vitamin B6, added to medicines as a nutritional supplement or to meet dietary requirements. It supports the body's metabolism and nerve function.
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UNII TLM2976OFR
Riboflavin is a B vitamin used as a colorant and nutritional additive in medications. It gives products a yellow color and may provide supplemental vitamin B2 value.
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UNII 452VLY9402
Serine is an amino acid, a building block of proteins. In medications, it functions as a buffering agent and stabilizer to help maintain the product's pH balance and protect active ingredients during storage.
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UNII NVG71ZZ7P0
A salt derived from acetic acid, sodium acetate anhydrous is used in medicines as a buffer to help maintain stable pH levels and sometimes as a preservative or bulking agent in solid formulations.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII R6Q3791S76
Sodium gluconate is a salt derived from gluconic acid, a naturally occurring compound. In medicines, it functions as a buffering agent to help maintain stable pH and as a chelating agent that can bind minerals in formulations.
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UNII 593YOG76RN
A salt made from sodium and phosphate that helps regulate acidity and maintain proper pH balance in the medicine. It also acts as a buffer to keep the product stable.
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UNII M572600E5P
Thiamine hydrochloride is a form of vitamin B1, a water-soluble nutrient. It's added to some medicines as a nutritional supplement or active ingredient component, though when listed as an excipient it typically serves as a stabilizer or minor additive in the formulation.
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UNII 2ZD004190S
Threonine is an amino acid, a naturally occurring protein building block. It functions as a buffering agent and pH stabilizer in medicines to maintain proper acidity levels and product stability.
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UNII 05161190OB
A nucleotide compound derived from uridine that serves as an active pharmaceutical ingredient in some specialized medications. It functions to support cellular energy metabolism and nucleic acid synthesis in the body.
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UNII 8DUH1N11BX
Tryptophan is an amino acid, a building block of proteins. In medications, it may be used as a nutrient supplement or component in formulations designed to support specific therapeutic effects.
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UNII 5RFD27DQ22
Tyrosine disodium dihydrate is a salt form of the amino acid tyrosine. It is used as a buffer and pH regulator to help keep the medicine at the proper acidity level for stability and effectiveness.
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UNII HG18B9YRS7
Valine is an amino acid, one of the building blocks of proteins. In medicines, it acts as a filler and bulking agent to give the product proper volume and texture.
57 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Lantidra 5000 [arb'U]/400mLthis 73539-0001-01 | CellTrans | 400 ml | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Jun 28, 2035 |
Is there a biosimilar for LANTIDRA INFUSION BAG?
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 73539-0001-01 You're viewing this | 400 mL in 1 BAG (73539-001-01) | 2023-06-28 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full FDA label FDA SPL
🎯 Indications and Usage ▾
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 )
2.1Recommended 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.
2.2Preparation 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.
2.3Administration Failure to follow these directions may result in damage and decreased viability of the islets. Do not administer with leukodepleting filters. To optimize viability, administer LANTIDRA as soon as possible after product release.
LANTIDRA should be administered only by interventional radiologists and surgeons with experience in islet cell transplantation under aseptic conditions in an interventional radiology or operating suite. Perform all steps aseptically. Use a 5 or 6 French angiographic catheter indicated for the delivery of drugs or other therapeutic fluids for infusion of LANTIDRA.
Catheter length: 65 cm or less. Internal diameter: 0.97mm (0.038 inches) or greater. Use only sheaths and introducers in combination with a catheter with the specified dimensions listed above to deliver LANTIDRA.
Pre-Infusion Patient Preparation 1. Confirm the identity of the patient for the specified unit of LANTIDRA. 2.
Confirm that the patient has received appropriate premedication [See Pre-procedural medication (2.1) ] . 3. Confirm that appropriate medications and blood products are available to manage any potential emergencies,…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS LANTIDRA is a cellular suspension of allogeneic pancreatic islets (islets of Langerhans) in buffered transplant media 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). Each infusion uses one lot of LANTIDRA which consists of islets manufactured from the pancreas of a single deceased donor.
Each dose of LANTIDRA is provided as two (2) infusion bags connected to each other via sterile connector. One bag contains LANTIDRA up to a maximum of 1 × 10 6 EIN in 400 ml of transplant media and the second bag (Rinse Bag) contains transplant media used to rinse the LANTIDRA bag and the infusion line. The dosage strength is represented by the total EIN in a single preparation and varies between product batches.
Dosage strength information for an individual batch is provided on the container label and in accompanying documentation (Final Islet Product Certificate of Analysis). The dosage form is a cellular suspension. Dosage strength depends on the total number of islets packaged for infusion, which is reported on the container label and associated documents.
( 3 )
⛔ 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 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Risks from Concomitant Immunosuppression: Increased risk of severe infections including opportunistic infections, malignancy, and severe anemia. Monitor closely. Administer PCP and CMV prophylaxis.
( 5.1 ) Procedural Complications: Liver laceration and hemorrhage have occurred. Monitor for bleeding, portal hypertension, and portal vein thrombosis during and immediately following infusion. ( 5.2 ) Increased Risk of Graft Rejection : Patients with a positive T- and B-cell crossmatch between recipient serum and donor lymphocytes may be at increased risk for graft rejection.
( 5.3 ) Transmission of Donor-Derived Infections : Monitor for signs of infection following infusion and treat accordingly. ( 5.4 ) Panel Reactive Antibodies (PRA) : Product administration may elevate PRA and negatively impact candidacy for renal transplant. ( 5.5 )
5.1Risks from Concomitant Immunosuppression Concomitant use of immunosuppression is required to maintain islet cell viability. The use of immunosuppression in patients receiving LANTIDRA increases the risk of serious and potentially fatal adverse reactions. [Adverse Reactions (6.1)] Patients receiving immunosuppressants are at increased risk of: Bacterial, viral, fungal, and parasitic infections, including opportunistic infections. Lymphomas and other malignancies, particularly of the skin.
Severe anemia, sometimes requiring transfusion. Before Treatment Vaccination: To mitigate the risk of infection, patients should receive recommended immunizations prior to treatment. After Treatment Administer PCP and CMV prophylaxis following administration of LANTIDRA.
Avoid live vaccination while receiving immunosuppression. Monitor for fever and other signs of infection; initiate appropriate treatment early. Clinically monitor for malignancy, including skin cancer.
Monitor hemoglobin/hematocrit and give blood products as indicated. Considerations for discontinuation of immunosuppression If a patient develops a life-threatening infection or cancer and treatment requires discontinuation of immunosuppression. If a patient has been dependent on exogenous insulin for two years after their last infusion, then immunosuppression should be discontinued.
However, the treatment team may consider continuation of immunosuppression if they determine that the patient has achieved target HbA1c without recurrent severe hypoglycemia in the presence of clinically relevant C-peptide, that provides a potential ongoing benefit that outweighs the risks of severe and potentially life-threatening effects of immunosuppression. If a patient becomes pregnant.
5.2Procedural Complications Liver laceration, hemorrhage and intra-abdominal bleeding have occurred with portal administration of LANTIDRA. Manage hemostasis in the catheter track using standard practices following infusion of LANTIDRA to reduce the risk of bleeding. Monitor for bleeding clinically and with laboratory assessments.
Blood transfusions have been required. Elevation in portal blood pressure has occurred during and following intraportal islet infusion [Adverse Reactions (6.1)] . Monitor portal pressure; pause infusion if portal pressure rises above 22 mmHg and do not resume until it falls below 18 mmHg.
Terminate infusion if portal pressure remains above 22 mmHg for longer than 10 minutes. [Dosage and Administration (2.3)] Portal vein branch thrombosis may occur following infusion of LANTIDRA. 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. [Limitations of Use (2.1)]
5.3Increased Risk of Islet Graft Rejection Patients with a positive T- and B-cell crossmatch between recipient serum and donor lymphocytes may immediately reject the islet cells. The T- and B-cell crossmatch assay is binary. T- and B-cell both need to be negative.
5.4 Transmission of Donor-Derived Infections There is a risk of comm…
🤒 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.
6.1Clinical 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 inter…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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.
8.2Lactation Risk Summary The risk of exposing a child to LANTIDRA components during breastfeeding has not been assessed. However, some required concomitant medications, including immunosuppressants, may be excreted in milk at least in trace amounts. Because of this, a decision should be made about whether to discontinue breastfeeding in patients who will receive a LANTIDRA infusion.
8.3Females and Males of Reproductive Potential Pregnancy Testing Due to the risk of fetal malformations associated with required concomitant medications, including immunosuppressants, females of reproductive potential should have a confirmed negative pregnancy test prior to LANTIDRA infusion. Female patients of reproductive potential should be counselled to contact their transplant team immediately if they become pregnant. Contraception Because long-term immunosuppression is required following LANTIDRA administration, women of childbearing potential should be informed of the potential risks that these medications pose during pregnancy and should be told to use effective contraception prior to initiation of immunosuppression and thereafter for as long as they retain reproductive potential.
Infertility Male and female fertility may be compromised by certain medications used for maintenance immunosuppression following LANTIDRA administration. For male patients, review the concomitant medications and determine if there is a potential for production of abnormal sperm.
8.4Pediatric Use The safety and effectiveness of LANTIDRA have not been established in pediatric patients with type 1 diabetes.
8.5Geriatric Use The safety and effectiveness of LANTIDRA have not been established in geriatric patients with type 1 diabetes and hypoglycemic unawareness. Clinical studies of LANTIDRA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
🤰 Pregnancy ▾
8.1Pregnancy 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.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of LANTIDRA have not been established in pediatric patients with type 1 diabetes.
🧓 Geriatric Use ▾
8.5Geriatric Use The safety and effectiveness of LANTIDRA have not been established in geriatric patients with type 1 diabetes and hypoglycemic unawareness. Clinical studies of LANTIDRA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Pancreatic islets regulate blood glucose levels through secretion of multiple hormones in response to increases and decreases in blood glucose. Endocrine cells within pancreatic islets release insulin, glucagon, somatostatin, pancreatic peptide, and ghrelin. Insulin stimulates glucose uptake by peripheral tissues; glucagon mobilizes glucose from the liver into circulation; somatostatin inhibits both α- and β-cell secretions; pancreatic peptide inhibits pancreatic exocrine secretion; and ghrelin inhibits insulin secretion.
The primary mechanism of action of LANTIDRA is believed to be secretion of insulin by infused (transplanted) β- cells.
12.2Pharmacodynamics The pharmacodynamic effects of LANTIDRA are a result of hormones, especially insulin, that are secreted by the infused (transplanted) islets in response to fluctuations in blood glucose levels. Basal and stimulated blood glucose were determined at baseline and at 1 year following a subject's last transplant during Study 1 and Study 2 using a mixed meal tolerance test (MMTT). Combined results from these studies are summarized in Table 2. [Clinical Studies (14)] The pharmacodynamic profile of the allogeneic islet cells is most clearly demonstrated in subjects who are free from the requirement of exogenous insulin.
TABLE 2: Effect of donislecel on Levels of Blood Glucose (mg/dl) at Baseline and 1 Year After Final Infusion (Study 1 and Study 2) for Subjects Insulin-Independent at the time of Mixed Meal Tolerance Test (MMT). Subjects Insulin Independent at time of 1-year MMT N Mean (mg/dl) Std Dev (mg/dl) Min (mg/dl) Max (mg/dl) Baseline Glucose Basal 19 178 76 78 348 Baseline Glucose 90-min 19 357 91 122 559 1-year Glucose Basal 19 106 17 81 144 1-year Glucose 90-min 19 142 40 65 202
🧬 Mechanism of Action ▾
12.1Mechanism of Action Pancreatic islets regulate blood glucose levels through secretion of multiple hormones in response to increases and decreases in blood glucose. Endocrine cells within pancreatic islets release insulin, glucagon, somatostatin, pancreatic peptide, and ghrelin. Insulin stimulates glucose uptake by peripheral tissues; glucagon mobilizes glucose from the liver into circulation; somatostatin inhibits both α- and β-cell secretions; pancreatic peptide inhibits pancreatic exocrine secretion; and ghrelin inhibits insulin secretion.
The primary mechanism of action of LANTIDRA is believed to be secretion of insulin by infused (transplanted) β- cells.
📦 How Supplied / Storage and Handling ▾
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.
📦 Storage and Handling ▾
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.
📋 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
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Prior to prescribing LANTIDRA discuss the following: Procedural risks Portal vein delivery liver laceration and hematoma with severe, potentially life-threatening bleeding, which may require prolonged hospitalization and blood transfusions liver injury from portal vein thrombosis and possible portal hypertension Acute infusion reaction symptoms may include fever, chills, fatigue, breathing problems, dizziness, nausea, vomiting, headache, or muscle aches a minimum 24-hour stay in the hospital after the procedure will be required for monitoring Immunosuppression requirements and risks Treatment with immunosuppression Is required long-term If stopped would lead to loss of islet cell function and insulin production Can interfere with response to immunizations and that they should avoid live vaccines Increased risk of infection Infections can be severe and life-threatening Infections may require withdraw of immunosuppression Development of lymphoma and other malignancies Skin malignancies are most common Lymphoma and some malignancies may require discontinuation of immunosuppression Can interfere with usual response to immunizations Patients should receive all appropriate immunizations prior to treatment.
Requirements for ongoing diabetes management and risks Not all patients who receive LANTIDRA are able to achieve independence from exogenous insulin (stop insulin injections). Not all patients who achieve independence from exogenous insulin can maintain this independence. Continued blood glucose monitoring is required after the procedure.
Advise patient to follow all instructions regarding glucose monitoring from their endocrinologist and transplant physician. Failure to perform continued monitoring can increase the risk of hypoglycemia and hyperglycemia. Continued insulin treatment is required after the procedure.
Advise patient to follow all instructions regarding insulin dosing from their endocrinologist and transplant physician. Failure to continue or restart insulin when required puts patients at risk for severe and potentially life-threatening hyperglycemia, including diabetic ketoacidosis (DKA). Patients should seek emergency medical care for severe hypoglycemic episodes and DKA.
Considerations for pregnancy, lactation, and infertility Pregnancy Inform female patients who are of childbearing potential that immunosuppressive drugs required to maintain islet cell survival can cause serious harm, including malformations in the fetus. Advise female patients that if they are able to become pregnant, then they should use effective birth control. Advise female patients to notify their endocrinologist and transplant physician if they become pregnant.
Inform male patients receiving LANTIDRA who have female partners who are able to become pregnant that they should use effective birth control before and during treatment. If applicable, advise male patients whose partner becomes pregnant, to inform her that she should seek medical advice from her healthcare provider. Lactation If the immunosuppressive drugs have the potential to affect the ability of the patient to breast feed, inform the patient that breast feeding would be discontinued prior to starting the pre-procedural medications needed for administration of LANTIDRA.
Fertility Inform patients that treatment with immunosuppression drugs may impair fertility and the ability to achieve pregnancy in the future. Considerations for future transplants Inform patients that administration of LANTIDRA has been associated with the development of panel reactive antibodies (PRA). PRA can adversely affect the ability to achieve a donor match for those patients who require kidney transplant.
After infusion of LANTIDRA, discuss the following: In preparation for discharge after the procedure and at appropriate follow up appointments, repeat the information for immunosuppression,…