Zanidatamab Dosage

Medically reviewed by Drugs.com. Last updated on Jan 13, 2025.

Usual Adult Dose for Cholangiocarcinoma of biliary tract

20 mg/kg IV every 2 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Approved under accelerated approval based on overall response rate and duration of response; continued approval may depend on verification and description of clinical benefit in confirmatory trials.
• Patients should be selected based on HER2-positive (immunohistochemistry [IHC] 3+) tumor specimens, as detected by a US FDA-approved test.
• Duration of infusion:
• First and second: 120 to 150 minutes
• Third and fourth: 90 minutes (if previous infusions were well-tolerated)
• Subsequent: 60 minutes (if previous infusions were well-tolerated)

Use: For the treatment of patients with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, as detected by a US FDA-approved test

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Some adverse reactions require a dose reduction to 15 mg/kg (as described below). Permanently discontinue this drug in patients who cannot tolerate 15 mg/kg.

Dosage Modifications for Adverse Reactions:
Left ventricular dysfunction (LVD):

• Absolute decrease of at least 16% points in left ventricular ejection fraction (LVEF) from pretreatment baseline or LVEF up to 50% and absolute decrease of at least 10% points below pretreatment baseline:
• Withhold this drug for at least 4 weeks; repeat LVEF assessment within 4 weeks.
• Resume this drug within 4 to 8 weeks if LVEF returns to normal limits and the absolute decrease is no more than 15% points from baseline.
• Permanently discontinue this drug if LVEF has not recovered to within 15% points from pretreatment baseline.
• Confirmed symptomatic CHF: Permanently discontinue this drug.

Infusion-related reactions (IRR):

• Mild (grade 1):
• Reduce infusion rate by 50%.
• For subsequent infusions, increase infusion rate gradually to the rate prior to the adverse reaction, as tolerated.
• Moderate (grade 2):
• Stop infusion immediately.
• Treat with appropriate therapy.
• Resume infusion at 50% of previous infusion rate once symptoms resolve.
• For subsequent infusions, increase infusion rate gradually to the rate prior to the adverse reaction, as tolerated.
• Severe (grade 3):
• Stop infusion immediately.
• Promptly treat with appropriate therapy; do not restart infusion during the same cycle even if signs/symptoms completely resolve.
• Administer subsequent infusions at 50% of previous infusion rate.
• Permanently discontinue this drug for recurrent grade 3 reaction.
• Life-threatening (grade 4):
• Stop infusion immediately and permanently discontinue this drug.
• Promptly treat with appropriate therapy.

Diarrhea:

• Mild/moderate (grade 1 or 2):
• No dose modification is required.
• Start appropriate medical therapy and monitor as clinically indicated.
• Severe (grade 3):
• Withhold this drug until severity improves to grade 1 or lower.
• Start or intensify appropriate medical therapy and monitor as clinically indicated.
• Administer subsequent therapy at the same dose level or consider dose reduction to 15 mg/kg.
• For recurrent grade 3 symptoms, withhold this drug and ensure medical management has been optimized; resume therapy at a reduced dose of 15 mg/kg after severity improves to grade 1 or lower. Permanently discontinue this drug for recurrent grade 3 symptoms that last more than 3 days despite optimized medical management.
• Life-threatening (grade 4): Permanently discontinue this drug.

Pneumonitis:

• Confirmed grade 2 or higher: Permanently discontinue this drug.

Other adverse reactions (excluding LVD, IRR, diarrhea, and pneumonitis):

• Mild/moderate (grade 1 or 2):
• No dose modification is required.
• Start appropriate medical therapy and monitor as clinically indicated.
• Severe (grade 3):
• Withhold this drug until severity improves to grade 1 or lower.
• Start appropriate medical therapy and monitor as clinically indicated.
• Administer subsequent therapy at the same dose; consider dose reduction to 15 mg/kg if grade 3 symptoms recur.
• Life-threatening (grade 4):
• Permanently discontinue this drug, except as described below.
• Start appropriate medical therapy and monitor as clinically indicated.
• This drug may be resumed at the same dose level for grade 4 electrolyte imbalances or laboratory abnormalities that are corrected within 3 days of onset; do not resume until symptoms improve to grade 1 or lower.
• Permanently discontinue this drug for recurrent grade 4 electrolyte imbalances or laboratory abnormalities.

Precautions

US BOXED WARNING:

• EMBRYOFETAL TOXICITY: Exposure to this drug during pregnancy can cause embryofetal harm. Patients should be apprised of the risk and need for effective contraception.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Premedicate all patients 30 to 60 minutes before each dose of this drug to reduce the risk of infusion-related reactions.
• Administer acetaminophen, an antihistamine (e.g., diphenhydramine), and a corticosteroid (e.g., hydrocortisone).
• Administer as an IV infusion with a 0.2 or 0.22 micron filter; do not administer as an IV push or bolus.
• Administer via IV infusion.
• Do not coadminister this and other IV drugs through the same IV line.
• If a planned dose is delayed or missed, administer the dose as soon as possible; do not wait until the next planned dose. Adjust the administration schedule to maintain a frequency of every 2 weeks.

Storage requirements:

• Lyophilized powder: Store in refrigerator at 2C to 8C (36F to 46F) in original carton until time of reconstitution; do not freeze.
• After reconstitution: Dilute solution immediately or store up to 4 hours, either at room temperature (18C to 24C [64F to 75F]) or in refrigerator (2C to 8C [36F to 46F]).
• After dilution: Use infusion solution immediately or store at room temperature (18C to 24C [64F to 75F]) up to 12 hours or in refrigerator (2C to 8C [36F to 46F]) up to 24 hours.
• Time limits include the beginning of reconstitution through the duration of infusion.
• If specified times are exceeded, discontinue the current infusion bag and prepare a new bag containing the remaining dosage to be infused.

Reconstitution/preparation techniques:

• Reconstitute and dilute before administration.
• The manufacturer product information should be consulted.

IV compatibility:

• Compatible: Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, and the following materials:
• IV bags: Polyvinyl chloride (PVC), polyolefin (PO), ethyl vinyl acetate (EVA), polypropylene (PP) and ethylene-propylene copolymer
• Infusion sets: PVC/bis(2-ethylhexyl) phthalate (PVC/DEHP), polyurethane (PUR), polyethylene-lined (PE-lined) acrylonitrile butadiene styrene (ABS)
• Inline filters: Polyethersulfone solution filter (PES), polyvinylidene fluoride air filter (PVDF)
• Closed system transfer devices: ABS, acrylic c-polymer, polycarbonate (PC), polyisoprene (PI), polyester, polypropylene (PP) polytetrafluoroethylene (PTFE), silicone and stainless steel (SS)

General:

• For information on US FDA-approved tests for HER2 protein expression in biliary tract cancers: www.fda.gov/CompanionDiagnostics

Monitoring:

• Cardiovascular: LVEF (before starting and regularly during therapy)
• General: For signs/symptoms of IRR (during and as clinically indicated after infusion)
• Pregnancy: For oligohydramnios in patients exposed to this drug during pregnancy or within 4 months before conception

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Patients of childbearing potential: Contact your health care provider with a known/suspected pregnancy; use effective contraception during therapy and for 4 months after the last dose.
• Contact a health care provider immediately for signs/symptoms of cardiac dysfunction.
• Inform a health care provider immediately for symptoms of an infusion-related reaction.
• Contact your health care provider for sustained diarrhea that does not respond to supportive care.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer