Dosing and administration for ZYNYZ1
IV dosing every 4 weeks may align with routine office visits1
No dose reduction of ZYNYZ for adverse reactions is recommended1
- 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 below
Dosage modifications for adverse reactions1
Recommended dosage modifications for adverse reactions1
|ZYNYZ DOSAGE MODIFICATIONS
|IMMUNE-MEDIATED ADVERSE REACTIONS
|Grade 3 or 4
|Grade 2 or 3
|Hepatitis with no tumor involvement of the liver
|AST or ALT greater than 3 but no more than 8 times ULN
Total bilirubin increases to more than 1.5 and up to 3 times ULN
|AST or ALT increases to more than 8 times ULN
Total bilirubin greater than 3 times ULN
|Hepatitis with tumor involvement of the liverc
|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
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
|AST or ALT increases to more than 10 times ULN
Total bilirubin increases to more than 3 times ULN
|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
|Grade 4 increased blood creatinine
|Exfoliative dermatologic conditions
|Grade 3 or suspected SJS, TEN, or DRESS
|Grade 4 or confirmed SJS, TEN, or DRESS
|Grade 2, 3, or 4
|Grade 3 or 4
|OTHER ADVERSE REACTIONS
|Grade 1 or 2
|Interrupt or slow the rate of infusion
|Grade 3 or 4
Please see Warnings and Precautions in the Full Prescribing Information.
a Toxicity graded per NCI CTCAE v5.
b Resume 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.
c If 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.
d Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved.
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.
ZYNYZ storage, preparation, and administration
Supplied in a carton containing one single-dose vial of 500 mg/20 mL (25 mg/mL) (NDC 50881-006-03)1
- ZYNYZ injection is a clear to slightly opalescent, colorless to pale yellow solution
- Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake
Withdraw 20 mL (500 mg) of ZYNYZ from one vial and discard vial with any unused portion1
Dilute ZYNYZ with either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final concentration between 1.4 mg/mL to 10 mg/mL. Use polyvinylchloride (PVC) and di-2-ethylhexyl phthalate (DEHP), polyolefin copolymer, polyolefin with polyamide, or ethylene vinyl acetate infusion bags1
Mix diluted solution by gentle inversion. Do not shake1
Visually inspect the infusion bag for particulate matter and discoloration prior to administration. Discard if the solution is discolored or contains particulate matter1
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.
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 IV infusion over 30 minutes1
- Use a polyethylene 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 filter1
- Do not administer ZYNYZ using a polyurethane infusion set1
- Do not co-administer other drugs through the same infusion line1
- Do not administer ZYNYZ as an intravenous push or bolus injection1
Reference: 1. ZYNYZ Prescribing Information. Wilmington, DE: Incyte Corporation.