Version May 2024
Note: For use under the direction of a medical professional who is experienced in islet cell infusion (transplantation). Appropriate candidate selection and testing is required prior to administration, along with concomitant immunosuppression and infection prophylaxis; refer to prescribing information and institutional protocols for further information. Not all patients who receive donislecel are able to achieve and maintain independence from exogenous insulin; continue insulin treatment and glycemic monitoring following administration.
Diabetes mellitus, type 1, treatment (adjunctive agent):
Initial dose: Minimum effective dose: Infusion (via hepatic portal vein): 5,000 equivalent islet number per kg (EIN/kg) as a single infusion; maximum: 1 × 106 EIN (ie, contents of 1 infusion bag) and 10 mL per infusion.
Subsequent doses: Note: A second dose may be administered if independence from exogenous insulin is not achieved within 1 year of initial infusion or within 1 year after losing independence from exogenous insulin after a previous infusion. A third infusion may be administered using the same dose and criteria as the second dose if needed; there are no data for administration of >3 infusions.
Minimum effective dose: Infusion (via hepatic portal vein): 4,500 EIN/kg as a single infusion; maximum: 1 × 106 EIN (ie, contents of 1 infusion bag) and 10 mL per infusion.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Elevated portal BP: Pause infusion if portal pressure rises >22 mm Hg and do not resume until it falls below 18 mm Hg; terminate infusion if portal pressure remains >22 mm Hg for longer than 10 minutes.
Refer to adult dosing; clinical studies did not include a sufficient number of patients ≥65 years of age.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Adverse reactions reported in adults on concomitant immunosuppression.
Frequency not defined:
Cardiovascular: Chest pain, hypertension, ischemic heart disease, occlusive arterial disease, palpitations, peripheral edema, syncope
Dermatologic: Acne vulgaris, alopecia, basal cell carcinoma of skin, cellulitis, dermatitis, erythema of skin, exfoliation of skin, nail disease (including onychomycosis, paronychia), night sweats, pruritic rash, pruritus, pyoderma (hidradenitis), rosacea, skin lesion, skin rash, xeroderma
Endocrine & metabolic: Decreased libido, decreased serum bicarbonate, dehydration, heavy menstrual bleeding, hyperchloremia, hypercholesterolemia (including increased LDL cholesterol), hyperkalemia, hypertriglyceridemia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, increased thirst, irregular menses, thyroid nodule, weight gain, weight loss
Gastrointestinal: Abdominal pain, Barrett esophagus, change in appetite (including anorexia and bulimia nervosa), cholelithiasis, colitis, constipation, diarrhea, dysgeusia, dyspepsia, gastroenteritis (including viral gastroenteritis), gastroesophageal reflux disease, mouth pain, nausea, oral candidiasis, oral herpes simplex infection, oral mucosa ulcer, stomatitis, vomiting, xerostomia
Genitourinary: Bladder dysfunction (overactive), erectile dysfunction, hematuria, hemoglobinuria, nocturia, pollakiuria, proteinuria, reduced urine flow, urinary incontinence, vaginal hemorrhage
Hematologic & oncologic: Anemia, bruise, hematoma (hepatic), leukopenia, lymphadenopathy, lymphoproliferative disorder, malignant neoplasm (including malignant neoplasm of breast, malignant neoplasm of skin, malignant neoplasm of thyroid), neutropenia, squamous cell carcinoma, thrombocytopenia
Hepatic: Hyperbilirubinemia, increased serum transaminases (including increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase), liver steatosis
Immunologic: Antibody development (panel reactive antibodies)
Infection: Infection (including cytomegalovirus disease, Epstein-Barr infection, eye infection, fungal infection, herpes zoster infection, local infection, serious infection, upper respiratory tract infection, urinary tract infection, vaginal infection [including bacterial vaginosis, vulvovaginal candidiasis], viral upper respiratory tract infection)
Nervous system: Abnormal gait, agitation, anxiety, asthenia, chills, cognitive dysfunction, depressed mood, depression, disruption of body temperature regulation, disturbance in attention, dizziness, fatigue, headache, hypoesthesia, insomnia, migraine, myasthenia, nervousness, pain, paresthesia, peripheral neuropathy, sensation of cold, sleep disorder (poor quality of sleep), tremor (including head titubation), vertigo, voice disorder
Neuromuscular & skeletal: Arthralgia, arthritis, back pain, dyskinesia, joint stiffness, joint swelling, limb pain, muscle rigidity, muscle spasm, musculoskeletal pain, myalgia, neck pain, osteoarthritis, osteomyelitis, osteopenia, osteoporosis
Ophthalmic: Blurred vision, cataract, conjunctival hemorrhage, eye pain, eye pruritus, periorbital edema
Otic: Deafness, otalgia, tinnitus
Renal: Decreased estimated GFR (eGFR), hydronephrosis, increased serum creatinine
Respiratory: Cough, dyspnea, epistaxis, flu-like symptoms, nasopharyngitis, oropharyngeal pain, paranasal sinus disease (including nasal congestion, sinusitis), pleural effusion, pneumonia, rhinitis, rhinorrhea, sinus headache, wheezing
Miscellaneous: Fever
Concomitant diseases or conditions, including pregnancy, that contraindicate the procedure for donislecel infusion or immunosuppression.
Concerns related to adverse effects:
• Procedural complications: Liver laceration, hemorrhage, and intra-abdominal bleeding have occurred with portal administration of donislecel; manage hemostasis in the catheter track using standard practices following infusion to reduce bleeding risk. Elevation in portal BP has also occurred during and following intraportal donislecel infusion. Portal vein branch thrombosis may occur following infusion; repeat 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.
• Transmission of donor derived infection: Infection following infusion may occur; treatment may be required.
Concurrent drug therapy issues:
• Immunosuppression: Concomitant immunosuppression is required as part of transplant procedure, which requires monitoring for and/or prophylaxis against various complications (eg, anemia, infection, malignancy). Refer to the specific immunosuppressant monographs for additional information.
Other warnings/precautions:
• 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.
• Panel reactive antibodies: Donislecel administration may elevate panel reactive antibodies and negatively impact candidacy for kidney transplant. Consider risk vs benefit of administering donislecel to a patient who may require a kidney transplant in the future.
Lantidra: FDA approved June 2023; anticipated availability is currently unknown.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Lantidra: Donislecel-jujn (1 ea) [contains albumin human, phenylalanine, polysorbate 80]
No
Hepatic portal vein infusion: For infusion into the hepatic portal vein only. For administration by experienced interventional radiologists and surgeons in an interventional radiology suite or operating room under aseptic conditions. Administer as soon as possible after product release. Refer to prescribing information and institutional protocols for further information.
Diabetes mellitus, type 1, treatment: Treatment of type 1 diabetes mellitus, in conjunction with concomitant immunosuppression, in adults who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education.
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 donislecel 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 donislecel in patients with liver disease, renal failure, or who have received a renal transplant.
Donislecel may be confused with docetaxel, donepezil.
Lantidra may be confused with lanreotide.
None known.
There are no known significant interactions.
Evaluate pregnancy status prior to use. A negative pregnancy test is required prior to treatment initiation in patients who could become pregnant.
Due to the long-term requirement of immunosuppression, patients who could become pregnant should use effective contraception prior to treatment initiation and until the patient is no longer of reproductive potential. If a patient has a partner who may become pregnant, the partner should follow the same recommendations for pregnancy testing and contraception.
The required use of concomitant immunosuppressants may impair fertility. Refer to the specific immunosuppressant monographs for additional information.
Animal reproduction studies have not been conducted.
The effects of the procedure on pregnancy are unknown. Concomitant immunosuppressants are required and may be associated with risks to the fetus. Therefore, use of donislecel is contraindicated during pregnancy; discontinue immunosuppression if pregnancy occurs. Also refer to the specific immunosuppressant monographs for additional information.
It is not known if donislecel is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant that may occur with use of the required concomitant medications, the manufacturer recommends breastfeeding be discontinued prior to initiating therapy.
Monitor glucose levels frequently during the infusion and for 4 to 8 hours afterward; refer to prescribing information and institutional protocols for details. After the first 4 to 8 hours following infusion, continue to monitor blood glucose (laboratory, capillary blood glucose, or continuous glucose monitor) according to inpatient standard of care.
Abdominal ultrasound and Doppler examination of the liver after catheter removal to detect portal vein thrombosis and intra-abdominal bleeding; repeat these examinations at least on days 1 and 7 post infusion procedure; also monitor for clinical signs of bleeding and portal vein branch thrombosis.
Following treatment, monitor for fever and other signs of infection; clinical signs/symptoms of malignancy (including skin cancer); blood glucose levels; bleeding, including periodic hemoglobin/hematocrit.
The active ingredient in donislecel is allogeneic islets of Langerhans derived from a single donor pancreas. 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 alpha- and beta-cell secretions; pancreatic peptide inhibits pancreatic exocrine secretion; and ghrelin inhibits insulin secretion. The primary mechanism of action of donislecel is believed to be secretion of insulin by infused (transplanted) beta-cells.
The pharmacodynamic effects of donislecel are a result of hormones, especially insulin, that are secreted by the infused (transplanted) islets in response to fluctuations in blood glucose levels.
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