Donislecel

Donislecel 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 donislecel in conjunction with concomitant immunosuppression.

• Donislecel is available under the following different brand names: Lantidra.

Common side effects of Donislecel include:

• nausea
• fatigue
• anemia
• diarrhea
• abdominal pain

Serious side effects of Donislecel include:

• not available

Rare side effects of Donislecel include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Cellular suspension of allogeneic pancreatic islets

• Provided as two infusion bags connected via a sterile connector
• One bag: Contains islet cells up to a maximum of 1 × 106 equivalent islet number (EIN) in 400 mL of transplant media
• Second bag (rinse bag): Contains transplant media used to rinse the islet cell bag and infusion line

Type 1 diabetes

Adult dosage

• Minimum dose: 5000 EIN/kg for initial portal vein infusion and 4500 EIN/kg for subsequent infusion in the same recipient
• Maximum dose per infusion is determined by estimated tissue volume, which should not exceed 10 mL/infusion, and total EIN present in the infusion bag (up to a maximum of 1 × 106 EIN/bag)
• Second infusion may be given if the patient does not achieve independence from exogenous insulin within 1 year of infusion or 1 year after losing independence from exogenous insulin after a previous infusion
• May perform the third infusion using the same criteria as for the second infusion
• There are no data regarding the effectiveness or safety of more than 3 infusions

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Donislecel has no noted severe interactions with any other drugs.
• Donislecel has no noted serious interactions with any other drugs.
• Donislecel has no noted moderate interactions with any other drugs.
• Donislecel has no noted minor interactions with any other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Patients who have concomitant diseases or conditions (including pregnancy) that contraindicate the procedure for infusion or immunosuppression

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Donislecel?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Donislecel?”

Cautions

• Risks from concomitant immunosuppression
• Concomitant use of immunosuppression is required to maintain islet cell viability
• Immunosuppression increases the risk for serious and potentially fatal adverse reactions
• Immunosuppressants increase the risk for
• 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 for infection, patients should receive recommended immunizations before treatment
• After treatment
  • Administer Pneumocystis jirovecii pneumonia and cytomegalovirus prophylaxis following the infusion of donislecel
  • 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 life-threatening infection or cancer develops and treatment requires discontinuation of immunosuppression
  • If a patient has been dependent on exogenous insulin for 2 years after their last infusion, then immunosuppression should be discontinued; however, continuation of immunosuppression can be considered if the patient has achieved target HbA1c without recurrent severe hypoglycemia in the presence of clinically relevant C-peptide, which provides a potential ongoing benefit that outweighs the risk for severe and potentially life-threatening effects of immunosuppression
  • If a patient becomes pregnant
• Procedural complications
  • Liver laceration, hemorrhage, and intra-abdominal bleeding have occurred with portal administration
  • Manage hemostasis in catheter track using standard practices following infusion of donislecel to reduce the risk for bleeding
  • Monitor for bleeding clinically and with laboratory assessments
• Blood transfusions have been required
  • Elevated portal blood pressure has occurred during and following intraportal islet infusion
  • 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 more than 10 minutes
  • Portal vein branch thrombosis may occur following infusion
  • Repeated intraportal islet infusions are not recommended in patients who have experienced prior portal thrombosis unless thrombosis was limited to second- or third-order portal vein branches
• Increased risk for islet graft rejection
  • Patients with a positive T- and B-cell cross-match between recipient serum and donor lymphocytes may immediately reject the islet cells
  • T- and B-cell cross-match assay is binary
  • T- and B-cell both need to be negative
  • Transmission of donor-derived infections
  • Risk for communicable disease transmission from donor to recipient
  • Monitor for signs of active infection following infusion, and treat appropriately if infection is suspected
• Panel-reactive antibodies (PRA)
  • Product administration may elevate PRA and negatively impact candidacy for renal transplant
  • Consider benefits vs risks in case of a patient who may require a future renal transplant

Pregnancy and Lactation

• Contraindicated
  • Owing to the risk for fetal malformations associated with required concomitant medications, including immunosuppressants, women of reproductive potential should have a confirmed negative pregnancy test before administration
  • Counsel women of reproductive potential to contact their transplant team immediately if they become pregnant
• Contraception
  • Inform women of childbearing potential of potential risks that immunosuppressants pose during pregnancy
  • Instruct women to use effective contraception before 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
  • Males, review concomitant medications and determine if there is potential to produce abnormal sperm
• Lactation
  • The risk of exposing children to donislecel components during breastfeeding has not been assessed
  • However, some required concomitant medications, including immunosuppressants, may be excreted in milk in at least trace amounts; because of this, a decision should be made about whether to discontinue breastfeeding in patients who will receive a donislecel infusion