Retifanlimab
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From MedlinePlus, U.S. National Library of Medicine
Specialty pharmacy: therapy management checklist, storage and cold chain, dosing calendar, Medicare Part D coverage.
Programmed Death Receptor-1 Blocking Antibody
Dosing in kidney impairment
4 CONTRAINDICATIONS None. None. 5 WARNINGS AND PRECAUTIONS Immune-Mediated Adverse Reactions Immune-mediated adverse reactions, which may be severe or fatal, 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 nephritis with renal dysfunction, and immune‑mediated dermatologic adverse reactions, and solid organ transplant rejection.
Systemic corticosteroids were required in 81% (13/16) of patients. Hepatitis resolved in 9 of the 16 patients. Of the 5 patients in whom ZYNYZ was withheld for hepatitis, 3 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] . ZYNYZ as a Single Agent: Adrenal insufficiency occurred in 0.9% (4/452) of patients receiving ZYNYZ, including Grade 3 (0.4%) and Grade 2 (0.4%).
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 4 patients. ZYNYZ in Combination with Carboplatin and Paclitaxel: Adrenal insufficiency occurred in 5.8% (9/154) of patients receiving ZYNYZ in combination with carboplatin and paclitaxel, including Grade 3 and Grade 2 (1.9% each).
Adrenal insufficiency led to permanent discontinuation of ZYNYZ in 1 patient and withholding of ZYNYZ in 3 patients. All patients required systemic corticosteroids. Adrenal insufficiency resolved in 4 of the 9 patients. 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.
The patient received insulin. Immune-Mediated Nephritis with Renal Dysfunction ZYNYZ can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 2% (9/452) of patients receiving ZYNYZ, including Grade 4 (0.4%), Grade 3 (1.1%), and Grade 2 (0.4%). Nephritis led to permanent discontinuation of ZYNYZ in 1.1% of patients and withholding of ZYNYZ in 0.7% of patients.
| 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 (5.1)] | ||
| Pneumonitis | Grade 2 | WithholdResume in patients with complete or partial resolution (Grade 0-1) 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 ULNOR Total bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold |
| AST or ALT increases to more than 8 times ULNOR 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 ULNOR 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 ULNOR 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 (5.2)] | Grade 1 or 2 | Interrupt or slow the rate of infusion |
| Grade 3 or 4 | Permanently discontinue | |
Preparation and administration
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Preparation and Administration 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.
Preparation Withdraw the appropriate volume from a vial of ZYNYZ: 20 mL for the 500 mg dose 15 mL for the 375 mg dose Discard the vial with any unused portion. Each vial is for one-time use in only one patient. 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.
Storage of diluted ZYNYZ solution 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. Administration 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.
| 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 (5.1)] | ||
| Pneumonitis | Grade 2 | WithholdResume in patients with complete or partial resolution (Grade 0-1) 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 ULNOR Total bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold |
| AST or ALT increases to more than 8 times ULNOR 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 ULNOR 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 ULNOR 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 (5.2)] | Grade 1 or 2 | Interrupt or slow the rate of infusion |
| Grade 3 or 4 | Permanently discontinue | |
Drug interactions
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- Retifanlimab
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for retifanlimab. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on its mechanism of action, ZYNYZ can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on the use of ZYNYZ in pregnant women. 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 ( see Data ). Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, retifanlimab-dlwr has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with ZYNYZ to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus.
In murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering ZYNYZ during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1/PD-L1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to retifanlimab-dlwr may increase the risk of developing immune-mediated disorders or altering the normal immune response.
Breastfeeding (LactMed)
No information is available on the clinical use of retifanlimab during breastfeeding. Because retifanlimab is a large protein molecule with a molecular weight of 148,000 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal. Waiting for at least 2 weeks postpartum to resume therapy may minimize transfer to the infant. The manufacturer recommends avoiding breastfeeding during therapy and for 4 months after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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