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UNLOXCYT is a brand name for Cosibelimab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1. INDICATIONS AND USAGE UNLOXCYT is indicated for the treatment of adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation. UNLOXCYT is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the…
Verbatim from this product's FDA label. Tap a section to expand.
2. DOSAGE AND ADMINISTRATION The recommended dosage of UNLOXCYT is 1,200 mg as an intravenous infusion over 60 minutes every 3 weeks. 1. Recommended Dosage The recommended dosage of UNLOXCYT is 1,200 mg administered as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.
2. Dose Modifications for Adverse Reactions No dose reductions of UNLOXCYT are recommended. In general, withhold UNLOXCYT for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue UNLOXCYT for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to a prednisone equivalent of 10 mg or less per day within 12 weeks of initiating steroids.
Dosage modifications for UNLOXCYT for adverse reactions that require management different from these general guidelines are summarized in Table 1.
Table 1:
Recommended Dose Modifications for Adverse Reactions Adverse Reaction Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 5. UNLOXCYT Dosage Modifications ALT = alanine aminotransferase; AST = aspartate aminotransferase; DRESS: drug rash with eosinophilia and systemic symptoms; SJS: Stevens-Johnson Syndrome; TEN: toxic epidermal necrolysis; ULN: upper limit of normal.
1) ] Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce corticosteroid to a prednisone equivalent of 10 mg/day or less within 12 weeks of initiating steroids.
5 and up to 3 times ULN Withhold AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue UNLOXCYT based on recommendations for hepatitis with no tumor involvement of the liver.
Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN Withhold AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Endocrinopathies Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement.
6. 3) ] The most common adverse reactions (≥10%) were fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection. 1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc.
gov/medwatch. 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to UNLOXCYT as a single agent in 223 patients in two open-label, single-arm, multicohort studies, including 141 patients with advanced CSCC and 82 patients with other solid tumors and hematologic malignancies.
UNLOXCYT was administered intravenously at doses of 800 mg every 2 weeks (n=174), 1,200 mg every 3 weeks (n=35), or other doses (n=14). Among the 223 patients, 54% were exposed for ≥24 weeks and 17% were exposed for ≥72 weeks. The safety of UNLOXCYT was evaluated in Study CK-301-101 in 141 patients with metastatic or locally advanced disease CSCC [see Clinical Studies (14) ] .
Patients received UNLOXCYT 800 mg every 2 weeks (n=115) or 1,200 mg every 3 weeks (n=26) as an intravenous infusion until disease progression or unacceptable toxicity. 7 years). Serious adverse reactions occurred in 31% of advanced patients with CSCC who received UNLOXCYT.
1%). Permanent discontinuation of UNLOXCYT due to an adverse reaction occurred in 8% of patients. Adverse reactions resulting in permanent discontinuation of UNLOXCYT were COVID-19, COVID-19 pneumonia, sepsis, ulcerative keratitis, tumor thrombosis, axillary pain, paresthesia, cholestasis, hepatic cytolysis, wound hemorrhage, neck pain, pemphigoid, and eye pain (1 patient each).
5. 1 ) Immune-mediated adverse reactions can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection.
Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue UNLOXCYT based on the severity of reaction. 2 ) Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue based on severity of reaction.
2 ) Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody.
3 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. 1. Severe and Fatal Immune-Mediated Adverse Reactions UNLOXCYT is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.
Important immune-mediated adverse reactions listed in WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue.
Immune-mediated adverse reactions can occur at any time after starting a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, they can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies.
4. CONTRAINDICATIONS None. None. ( 4 )
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Resume once acute symptoms have resolved. 3. Preparation and Administration Visually inspect the vial for particulate matter and discoloration. UNLOXCYT is clear to opalescent, colorless to yellow or slightly brown. Discard the vial if visible particles are observed.
Do not shake the vial. 9% Sodium Chloride Injection. UNLOXCYT is compatible with an infusion bag made of polyolefin or polyvinyl chloride. Mix diluted solution by gentle inversion. Do not shake . Discard any unused portion left in the vial.
Storage of Infusion Solution:
The prepared infusion solution may be stored either: At room temperature up to 25°C (77°F) for no more than 24 hours from the time of preparation until the end of infusion. Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from time of preparation until end of infusion.
If refrigerated, allow the diluted solution to come to room temperature prior to administration. Discard after 24 hours. Do not freeze.
Administration:
Visually inspect the infusion bag for particulate matter and discoloration prior to administration. Discard if the solution is discolored or contains particulate matter. 22-micron filter. Do not administer UNLOXCYT as an intravenous push or bolus injection.
Do not co-administer other drugs through the same infusion line.
Dosage interruptions due to an adverse reaction occurred in 36% of patients who received UNLOXCYT. The adverse reaction that required dosage interruption in ≥ 2% of patients who received UNLOXCYT was COVID-19 (2%). The most common (≥ 10%) adverse reactions were fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.
Table 2 and Table 3 summarize adverse reactions and laboratory abnormalities, respectively in CK-301-101. 7 Urinary tract infection 10 0 Table 3: Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥ 1% of Patients with Metastatic or Locally Advanced CSCC Receiving UNLOXCYT in Study CK-301-101 Laboratory Abnormality UNLOXCYT (N = 141) All Grades % The denominator used to calculate the rate varied from 122-140 based on the number of patients with a baseline value and at least one post-treatment value.
Grade 3 or 4 % Toxicity graded per NCI CTCAE v5 Hematology Hemoglobin decreased 45 4 Lymphocytes decreased 41 6 Platelets decreased 14 1 Leukocytes decreased 10 1 Chemistry Sodium decreased 38 5 Alkaline phosphatase increased 26 1 Alanine transferase increased 25 4 Lipase increased 25 3 Aspartate transaminase increased 24 3 Potassium increased 23 3 Calcium increased 14 2
Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1–blocking antibodies.
Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment.
In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. 2) ] .
In general, if UNLOXCYT requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.
Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids. , endocrinopathies, dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis UNLOXCYT can cause immune-mediated pneumonitis.
In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 1% (3/223, Grade 2) of patients receiving UNLOXCYT.
4% (1/223) of patients. All 3 patients required systemic corticosteroids and pneumonitis did not resolve. One patient in whom UNLOXCYT was withheld for pneumonitis, had UNLOXCYT reinitiated after symptom improvement and had recurrence of pneumonitis.
Immune-Mediated Colitis UNLOXCYT can cause immune-mediated colitis, which may present with diarrhea, abdominal pain, and lower gastrointestinal (GI) bleeding. Cytomegalovirus infection/reactivation has occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies.
In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. 4% (1/223, Grade 1) of patients receiving UNLOXCYT. Systemic corticosteroids were required in the patient experiencing colitis.
The event of colitis did not resolve, and UNLOXCYT was not reinitiated. Immune-Mediated Hepatitis UNLOXCYT can cause immune-mediated hepatitis, defined as requiring the use of systemic corticosteroids and the absence of a clear alternate etiology.
Immune-Mediated Endocrinopathies Adrenal Insufficiency UNLOXCYT can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated.
2) ] . 4% (1/223) of patients. UNLOXCYT was withheld for adrenal insufficiency in one of these patients and was reinitiated after symptom improvement. Systemic corticosteroids were required in both patients with adrenal insufficiency.
Hypophysitis UNLOXCYT can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated.
3) ]. Thyroid Disorders UNLOXCYT can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated.
2) ] .
Hypothyroidism :
Hypothyroidism occurred in 10% (22/223) of patients receiving UNLOXCYT, including Grade 2 in 5% (10/223) of patients. Hypothyroidism resolved in 7 of the 22 patients. 4% (1/223) of patients. Hyperthyroidism resolved in 10 of the 12 patients.
Type 1 Diabetes Mellitus , which can present with diabetic ketoacidosis UNLOXCYT can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes.
Initiate treatment with insulin as clinically indicated. 2) ] . Immune-Mediated Nephritis with Renal Dysfunction UNLOXCYT can cause immune-mediated nephritis, defined as the required use of systemic corticosteroids or other immunosuppressants and the absence of a clear alternate etiology.
Immune-Mediated Dermatologic Adverse Reactions UNLOXCYT can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies.
Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. 2) ] . 9% (2/223) of patients and Grade 2 in 4% (9/223) of patients. 9% (2/223) of patients. Systemic corticosteroids were required in 33% (5/15) of patients with dermatologic adverse reactions.
Dermatologic adverse reactions resolved in 7 of the 15 patients. Of the 2 patients in whom UNLOXCYT was withheld for dermatologic adverse reactions, 1 patient reinitiated UNLOXCYT after symptom improvement and had recurrence of the dermatologic adverse reaction, which resolved after UNLOXCYT was withheld a second time.
1) ] or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.
Cardiac/Vascular :
Myocarditis, pericarditis, vasculitis.
Nervous System :
Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy.
Ocular :
Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Gastrointestinal :
Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis.
Musculoskeletal and Connective Tissue :
Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica.
Endocrine :
Hypoparathyroidism.
Other (Hematologic/Immune) :
Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
2. Infusion-Related Reactions UNLOXCYT can cause severe or life-threatening infusion-related reactions. 8% (13/223) of patients receiving UNLOXCYT. Monitor patients for signs and symptoms of infusion-related reactions. 2) ]. Consider premedication with an antipyretic and/or an antihistamine for patients who have had previous systemic reactions to infusions of therapeutic proteins.
3. Complications of Allogeneic HSCT Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody.
Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).
These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT.
4. Embryo-Fetal Toxicity Based on its mechanism of action, UNLOXCYT can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death.
Advise pregnant women of the potential risk to a fetus. 3) ].