Zynyz
(Retifanlimab-Dlwr)Dosage & Administration
The recommended dosage of ZYNYZ is 500 mg as an intravenous infusion over 30 minutes every 4 weeks. (
Indication | Recommended Dosage of ZYNYZ | Duration of Treatment |
Combination TherapyRefer to the Prescribing Information for the agents administered in combination with ZYNYZ for recommended dosing information, as appropriate. | ||
Adult patients with inoperable locally recurrent or metastatic SCAC in combination with carboplatin and paclitaxel | 500 mg every 4 weeks | Until disease progression, unacceptable toxicity, or up to 12 months |
Monotherapy | ||
Adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy | 500 mg every 4 weeks | Until disease progression, unacceptable toxicity, or up to 24 months |
Adult patients with metastatic or recurrent locally advanced MCC | 500 mg every 4 weeks | Until disease progression, unacceptable toxicity, or up to 24 months |
See full prescribing information for dosage modifications for adverse reactions (
Reactions
No dose reduction of ZYNYZ is recommended. In general, withhold ZYNYZ for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue ZYNYZ 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 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.
Dosage modifications for ZYNYZ for adverse reactions that require management different from these general guidelines are summarized in Table 2.
| AST = aspartate aminotransferase; ALT = alanine aminotransferase; DRESS = drug rash with eosinophilia and systemic symptoms; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal. | ||
Adverse Reaction | SeverityToxicity graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5. | ZYNYZ Dosage Modifications |
Immune-Mediated Adverse Reactions [see Warnings and Precautions ] | ||
| Pneumonitis | Grade 2 | WithholdResume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. |
| Grade 3 or 4 | Permanently discontinue | |
| Colitis | Grade 2 or 3 | Withhold |
| Grade 4 | Permanently discontinue | |
Hepatitis with no tumor involvement of the liver | AST or ALT greater than 3 but no more than 8 times ULN OR Total bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold |
AST or ALT increases to more than 8 times ULN OR Total bilirubin greater than 3 times ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverIf AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue ZYNYZ based on recommendations for hepatitis with no liver involvement. | Baseline AST or ALT is more than 1 and up to 3 times ULN and increases 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 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 | |
EndocrinopathiesDepending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved. | Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with renal dysfunction | Grade 2 or 3 increased blood creatinine | Withhold |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative dermatologic conditions | Grade 3 or suspected SJS, TEN, or DRESS | Withhold |
| Grade 4 or confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis | Grade 2, 3, or 4 | Permanently discontinue |
| Neurological toxicities | Grade 2 | Withhold |
| Grade 3 or 4 | Permanently discontinue | |
Other Adverse Reactions | ||
| Infusion-related reactions [see Warnings and Precautions ] | Grade 1 or 2 | Interrupt or slow the rate of infusion |
Grade 3 or 4 | Permanently discontinue | |
Visually inspect the vial for particulate matter and discoloration prior to administration. ZYNYZ is a clear to slightly opalescent, colorless to pale yellow solution and is free of particles. Discard the vial if the solution is cloudy, discolored, or contains particulate matter.
Do not shake the vial.
Protect the diluted ZYNYZ solution from light during storage.
Store diluted ZYNYZ solution:
OR
Do not freeze or shake diluted solution.
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Zynyz Prescribing Information
Indications and Usage (
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Dosage and Administration (The recommended dosages of ZYNYZ are provided in Table 1. Administer ZYNYZ as an intravenous infusion after dilution, over 30 minutes, as recommended [see Dosage and Administration ] .
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Warnings and Precautions (Reactions ZYNYZ is a monoclonal antibody that belongs to a class of drugs that binds to either the programmed death receptor-1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response with the potential for breaking of peripheral tolerance and induction of immune-mediated adverse reactions. Important immune‑mediated adverse reactions listed under Warnings and Precautions may not be inclusive of all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies. 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 patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function 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. Withhold or permanently discontinue ZYNYZ depending on severity [see Dosage and Administration ] . In general, if ZYNYZ requires interruption or discontinuation, administer systemic corticosteroid therapy (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 reactions are not controlled with corticosteroids.Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis ZYNYZ 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 3% (13/440) of patients receiving ZYNYZ, including 1 (0.2%) patient with fatal pneumonitis, Grade 3 (0.9%), and Grade 2 (1.4%). Pneumonitis led to permanent discontinuation of ZYNYZ in 1 patient and withholding of ZYNYZ in 0.9% of patients. Systemic corticosteroids were required in 77% (10/13) of patients with pneumonitis. Pneumonitis resolved in 10 of the 13 patients. Of the 4 patients in whom ZYNYZ was withheld for pneumonitis, 3 reinitiated ZYNYZ after symptom improvement; of these, 1 had recurrence of pneumonitis. Immune-Mediated Colitis ZYNYZ can cause immune-mediated colitis. Cytomegalovirus infection/reactivation have 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. ZYNYZ as a Single Agent : Immune-mediated colitis occurred in 1.6% (7/440) of patients receiving ZYNYZ, including Grade 4 (0.2%), Grade 3 (0.2%), and Grade 2 (0.7%). Colitis led to permanent discontinuation of ZYNYZ in 1 patient and withholding of ZYNYZ in 0.9% of patients. Systemic corticosteroids were required in 71% (5/7) of patients. Colitis resolved in 4 of the 7 patients. Of the 4 patients in whom ZYNYZ was withheld for colitis, 1 reinitiated ZYNYZ after symptom improvement; this patient did not have recurrence of colitis.ZYNYZ in Combination with Carboplatin and Paclitaxel: Immune-mediated colitis occurred in 10% (16/154) of patients receiving ZYNYZ in combination with carboplatin and paclitaxel, including Grade 4 (0.6%), Grade 3 (2.6%), and Grade 2 (3.2%). Colitis led to permanent discontinuation of ZYNYZ in 2 patients and withholding of ZYNYZ in 2 patients. Systemic corticosteroids were required in 94% (15/16) of patients. Colitis resolved in 15 of the 16 patients. Of the 2 patients in whom ZYNYZ was withheld for colitis, both reinitiated ZYNYZ after symptom improvement; neither patient had a recurrence of colitis.Immune-Mediated Hepatitis ZYNYZ can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 3% (13/440) of patients receiving ZYNYZ, including Grade 4 (0.2%), Grade 3 (2.3%), and Grade 2 (0.5%). Hepatitis led to permanent discontinuation of ZYNYZ in 1.4% of patients and withholding of ZYNYZ in 0.9% of patients. Systemic corticosteroids were required in 85% (11/13) of patients. Hepatitis resolved in 6 of the 13 patients. Of the 4 patients in whom ZYNYZ was withheld for hepatitis, 2 reinitiated ZYNYZ after symptom improvement; of these, 1 had recurrence of hepatitis. Immune-Mediated Endocrinopathies Adrenal Insufficiency ZYNYZ 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. Withhold or permanently discontinue ZYNYZ depending on severity [see Dosage and Administration ( 2.2 )] .ZYNYZ as a Single Agent: Adrenal insufficiency occurred in 0.7% (3/440) of patients receiving ZYNYZ, including Grade 3 (0.5%) and Grade 2 (0.2%). Adrenal insufficiency did not lead to permanent discontinuation of ZYNYZ. ZYNYZ was withheld for 1 patient with adrenal insufficiency. All patients required systemic corticosteroids. Adrenal insufficiency resolved in 1 of the 3 patients.ZYNYZ in Combination with Carboplatin and Paclitaxel: Hypophysitis ZYNYZ 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. Withhold or permanently discontinue ZYNYZ depending on severity [see Dosage and Administration ( 2.2 )] .Hypophysitis occurred in 0.5% (2/440, both Grade 2) of patients receiving ZYNYZ. No patients discontinued or withheld ZYNYZ due to hypophysitis. All patients required systemic steroids. Hypophysitis resolved in 1 of the 2 patients. Thyroid Disorders ZYNYZ 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. Withhold or permanently discontinue ZYNYZ depending on severity [see Dosage and Administration ( 2.2 )] .Thyroiditis occurred in 0.7% (3/440, all Grade 1) of patients receiving ZYNYZ. No patients discontinued or withheld ZYNYZ due to thyroiditis. Thyroiditis resolved in 1 of the 3 patients. Hypothyroidism Hypothyroidism occurred in 10% (42/440) of patients receiving ZYNYZ, including Grade 2 (4.8%). No patients discontinued ZYNYZ due to hypothyroidism. Hypothyroidism led to withholding of ZYNYZ in 0.5% of patients. Systemic corticosteroids were required for 1 patient and 79% (33/42) of patients received endocrine therapy. Hyperthyroidism Hyperthyroidism occurred in 6% (24/440) of patients receiving ZYNYZ, including Grade 2 (2.5%). No patients discontinued ZYNYZ due to hyperthyroidism. Hyperthyroidism led to withholding of ZYNYZ in 1 patient. Systemic corticosteroids were required for 13% (3/24) of patients and 46% (11/24) of patients received endocrine therapy. 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. Withhold ZYNYZ depending on severity [see Dosage and Administration ( 2.2 )] .Type 1 diabetes mellitus occurred in 0.2% (1/440) of patients receiving ZYNYZ, including Grade 3 (0.2%) adverse reactions. Type 1 diabetes mellitus led to withholding of ZYNYZ in 1 patient. This event led to ZYNYZ being withheld and did not lead to permanent discontinuation of ZYNYZ. The patient received insulin. Immune-Mediated Nephritis with Renal Dysfunction ZYNYZ can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 1.6% (7/440) of patients receiving ZYNYZ, including Grade 4 (0.5%), Grade 3 (0.7%), and Grade 2 (0.5%). Nephritis led to permanent discontinuation of ZYNYZ in 0.9% of patients and withholding of ZYNYZ in 1 patient. Systemic corticosteroids were required in 57% (4/7) of patients. Nephritis resolved in 3 of the 7 patients. The 1 patient in whom ZYNYZ was withheld for immune-mediated nephritis had ZYNYZ reinitiated after symptom improvement and did not have recurrence of immune-mediated nephritis. Immune-Mediated Dermatologic Adverse Reactions ZYNYZ can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue ZYNYZ depending on severity [see Dosage and Administration ( 2.2 )] .Immune-mediated skin reactions occurred in 8% (36/440) of patients receiving ZYNYZ, including Grade 3 (1.1%) and Grade 2 (7%). Immune-mediated dermatologic adverse reactions led to permanent discontinuation of ZYNYZ in 1 patient and withholding of ZYNYZ in 2.3% of patients. Systemic corticosteroids were required in 25% (9/36) of patients. Immune-mediated dermatologic adverse reactions resolved in 75% (27/36) of patients. Of the 10 patients in whom ZYNYZ was withheld for immune-mediated dermatologic adverse reactions, 7 reinitiated ZYNYZ after symptom improvement; of these, 1 had recurrence of immune-mediated dermatologic adverse reactions. Other Immune-Mediated Adverse Reactions The following clinically significant immune-mediated adverse reactions occurred at an incidence of < 1% in 440 patients who received ZYNYZ [see Adverse Reactions ( 6.1 )] or were reported with the use of other PD-1/PD-L1–blocking antibodies, including severe or fatal cases.Cardiac/vascular: myocarditis, pericarditis, vasculitisGastrointestinal: pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitisMusculoskeletal: myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis, polymyalgia rheumaticaNeurological: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathyOcular: uveitis, iritis, and 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.Endocrine: hypoparathyroidismOther (Hematologic/Immune): | 5/2025 | ||||||||||||||||||
ZYNYZ is a programmed death receptor-1 (PD-1)–blocking antibody indicated:
- in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). ()
1.1 Squamous Cell Carcinoma of the Anal Canal- ZYNYZ, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC).
- ZYNYZ, as a single agent, is indicated for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum‑based chemotherapy.
- as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. ()
1.1 Squamous Cell Carcinoma of the Anal Canal- ZYNYZ, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC).
- ZYNYZ, as a single agent, is indicated for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum‑based chemotherapy.
- for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). ()
1.2 Merkel Cell CarcinomaZYNYZ is indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials
[see Clinical Studies ].
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. (
ZYNYZ is indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials
The efficacy of ZYNYZ was evaluated in study POD1UM-201 (NCT03599713), an open-label, multiregional, single-arm study in 65 patients with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease. Patients with active autoimmune disease or a medical condition that required immunosuppression were ineligible. Patients who were HIV-positive, with an undetectable viral load, a CD4+ count ≥ 300 cells/microliter and receiving antiretroviral therapy were eligible.
Patients received ZYNYZ 500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months. Tumor response assessments were performed every 8 weeks for the first year of therapy and 12 weeks thereafter.
The major efficacy outcomes were ORR and DOR as assessed by an IRC according to RECIST v1.1.
The median age of enrolled patients was 71 years (range: 44-90); 37% were ≥ 75 years; 65% of patients were male; 78% of patients were White, 20% were race unknown or not reported, 2% were Asian; 74% had an ECOG PS of 0 and 26% had an ECOG PS of 1; 98% were HIV-negative. Seventy-two percent of patients had prior surgery and 38% of patients had prior radiotherapy. Eighty-eight percent of patients had metastatic disease at baseline. Tumor samples were evaluated for Merkel cell polyomavirus (MCPyV): 71% were positive, 23% negative, 2% equivocal, and 5% missing.
Efficacy results are summarized in Table 11.
| CI = confidence interval; DOR = duration of response; + denotes ongoing response. | ||
Endpoint | ZYNYZ (N = 65) | |
Objective Response Rate (95% CI) | 52% (40, 65) | |
| Complete responses, n (%) | 12 (18) | |
| Partial responses, n (%) | 22 (34) | |
Duration of Response | N = 34 | |
| Range, months | 1.1 to 24.9+ | |
| Patients with DOR ≥ 6 months, n (%) | 26 (76) | |
| Patients with DOR ≥ 12 months, n (%) | 21 (62) | |
The recommended dosage of ZYNYZ is 500 mg as an intravenous infusion over 30 minutes every 4 weeks. (
Indication | Recommended Dosage of ZYNYZ | Duration of Treatment |
Combination TherapyRefer to the Prescribing Information for the agents administered in combination with ZYNYZ for recommended dosing information, as appropriate. | ||
Adult patients with inoperable locally recurrent or metastatic SCAC in combination with carboplatin and paclitaxel | 500 mg every 4 weeks | Until disease progression, unacceptable toxicity, or up to 12 months |
Monotherapy | ||
Adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy | 500 mg every 4 weeks | Until disease progression, unacceptable toxicity, or up to 24 months |
Adult patients with metastatic or recurrent locally advanced MCC | 500 mg every 4 weeks | Until disease progression, unacceptable toxicity, or up to 24 months |
See full prescribing information for dosage modifications for adverse reactions (
Reactions
No dose reduction of ZYNYZ is recommended. In general, withhold ZYNYZ for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue ZYNYZ 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 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.
Dosage modifications for ZYNYZ for adverse reactions that require management different from these general guidelines are summarized in Table 2.
| AST = aspartate aminotransferase; ALT = alanine aminotransferase; DRESS = drug rash with eosinophilia and systemic symptoms; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal. | ||
Adverse Reaction | SeverityToxicity graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5. | ZYNYZ Dosage Modifications |
Immune-Mediated Adverse Reactions [see Warnings and Precautions ] | ||
| Pneumonitis | Grade 2 | WithholdResume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. |
| Grade 3 or 4 | Permanently discontinue | |
| Colitis | Grade 2 or 3 | Withhold |
| Grade 4 | Permanently discontinue | |
Hepatitis with no tumor involvement of the liver | AST or ALT greater than 3 but no more than 8 times ULN OR Total bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold |
AST or ALT increases to more than 8 times ULN OR Total bilirubin greater than 3 times ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverIf AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue ZYNYZ based on recommendations for hepatitis with no liver involvement. | Baseline AST or ALT is more than 1 and up to 3 times ULN and increases 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 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 | |
EndocrinopathiesDepending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved. | Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with renal dysfunction | Grade 2 or 3 increased blood creatinine | Withhold |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative dermatologic conditions | Grade 3 or suspected SJS, TEN, or DRESS | Withhold |
| Grade 4 or confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis | Grade 2, 3, or 4 | Permanently discontinue |
| Neurological toxicities | Grade 2 | Withhold |
| Grade 3 or 4 | Permanently discontinue | |
Other Adverse Reactions | ||
| Infusion-related reactions [see Warnings and Precautions ] | Grade 1 or 2 | Interrupt or slow the rate of infusion |
Grade 3 or 4 | Permanently discontinue | |
Visually inspect the vial for particulate matter and discoloration prior to administration. ZYNYZ is a clear to slightly opalescent, colorless to pale yellow solution and is free of particles. Discard the vial if the solution is cloudy, discolored, or contains particulate matter.
Do not shake the vial.
- Withdraw 20 mL (500 mg) of ZYNYZ from one vial and discard vial with any unused portion.
- Dilute ZYNYZ with either 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a final concentration between 1.4 mg/mL and 10 mg/mL. Use polyvinylchloride (PVC) and di-2-ethylhexyl phthalate (DEHP), polyolefin copolymer, polyolefin with polyamide, or ethylene vinyl acetate infusion bags.
- Mix diluted solution by gentle inversion. Do not shake.
- Visually inspect the infusion bag for particulate matter and discoloration prior to administration. Discard if the solution is discolored or contains particulate matter.
Protect the diluted ZYNYZ solution from light during storage.
Store diluted ZYNYZ solution:
- At room temperature [up to 25°C (77°F)] for no more than 8 hours from the time of preparation to the end of the infusion.
OR
- Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from the time of preparation to the end of the infusion. If refrigerated, allow the diluted solution to come to room temperature prior to administration. The diluted solution must be administered within 4 hours (including infusion time) once it is removed from the refrigerator.
Do not freeze or shake diluted solution.
- Administer diluted ZYNYZ solution by intravenous infusion over 30 minutes through a polyethylene, polyurethane, or PVC with DEHP intravenous line containing a sterile, non‑pyrogenic, low-protein binding polyethersulfone, polyvinylidene fluoride, or cellulose acetate 0.2 micron to 5 micron in-line or add-on filter or 15 micron mesh in-line or add-on filter. Do NOT administer ZYNYZ as an intravenous push or bolus injection.
- Do not co‑administer other drugs through the same infusion line.
Injection: 500 mg/20 mL (25 mg/mL), clear to slightly opalescent, colorless to pale yellow solution in a single-dose vial.
Lactation: Advise not to breastfeed. (
There is no information regarding the presence of retifanlimab-dlwr in human milk, or its effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to ZYNYZ are unknown. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose of ZYNYZ.
None.