Version July 2025
Exposure to zanidatamab during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.
Dosage guidance:
Safety: Actively manage modifiable cardiac risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) before initiating treatment (Ref). Premedicate with acetaminophen, an antihistamine (eg, diphenhydramine), and a corticosteroid (eg, hydrocortisone) 30 to 60 minutes prior to each dose to reduce the risk of infusion-related reactions (IRRs). Ensure medications and emergency equipment to treat IRRs are available for immediate use.
Biliary tract cancer, unresectable or metastatic, HER2 positive (previously treated): Note: Select patients for therapy based on HER2 positivity (IHC 3+) in tumor specimens.
IV: 20 mg/kg once every 2 weeks; continue until disease progression or unacceptable toxicity (Ref).
Missed dose: If a planned zanidatamab dose is delayed or missed, administer the dose as soon as possible; do not wait until the next planned dose. Then adjust the administration schedule to maintain the 2-week interval between doses.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function prior to treatment initiation:
Note: Kidney function estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method.
eGFR ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in zanidatamab pharmacokinetics in patients with CrCl 30 to 89 mL/minute.
eGFR 15 to <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effect of severe kidney impairment on zanidatamab pharmacokinetics is unknown).
End-stage kidney disease (eGFR <15 mL/minute) with or without dialysis: There are no dosage adjustments provided in the manufacturer's labeling (effect of end-stage kidney disease on zanidatamab pharmacokinetics is unknown).
Liver impairment prior to treatment initiation:
Mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in zanidatamab pharmacokinetics in patients with mild hepatic impairment.
Moderate (total bilirubin >1.5 to 3 times ULN and any AST) or severe (total bilirubin >3 times ULN and any AST) hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (effect of moderate or severe hepatic impairment on zanidatamab pharmacokinetics is unknown).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status. If dose reduction for toxicity is recommended in the prescribing information, the dose should be increased back to the initial or previously tolerated dose only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
|
Dose level |
Zanidatamab dose |
|---|---|
|
a Permanently discontinue if unable to tolerate 15 mg/kg once every 2 weeks. | |
|
Usual (initial dose) |
20 mg/kg once every 2 weeks |
|
First dose reduction |
15 mg/kg once every 2 weeksa |
|
Adverse reaction |
Severity |
Zanidatamab dosage modification |
|---|---|---|
|
a LVEF = left ventricular ejection fraction. | ||
|
b Excluding left ventricular dysfunction, infusion-related reactions, diarrhea, pneumonitis, and grade 4 electrolyte imbalance/lab abnormalities. | ||
|
Cardiovascular toxicity: Left ventricular dysfunction |
Absolute decrease of ≥16% in LVEFa from pretreatment baseline or LVEF ≤50% and absolute decrease of ≥10% below pretreatment baseline |
Withhold zanidatamab for at least 4 weeks. Repeat LVEF assessment within 4 weeks. Resume zanidatamab within 4 to 8 weeks if LVEF returns to normal and the absolute decrease is ≤15% from baseline. Permanently discontinue zanidatamab if LVEF has not recovered to within 15% from pretreatment baseline. |
|
Confirmed symptomatic heart failure |
Permanently discontinue zanidatamab. | |
|
Electrolyte imbalances or laboratory abnormalities |
Life-threatening (grade 4) |
Withhold zanidatamab. Initiate appropriate medical therapy and monitor as clinically indicated. Resume zanidatamab at the same dose level for grade 4 electrolyte imbalances or laboratory abnormalities that are corrected within 3 days of onset and symptoms have improved to ≤ grade 1. |
|
Recurrent life-threatening (grade 4) |
Permanently discontinue zanidatamab. | |
|
GI toxicity: Diarrhea |
Any |
Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Administer antidiarrheal treatment as clinically indicated. |
|
Mild or moderate (grade 1 or 2) |
No zanidatamab dose modification is required. Initiate appropriate medical therapy and monitor as clinically indicated. | |
|
Severe (grade 3) |
Withhold zanidatamab until severity improves to ≤ grade 1. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Administer subsequent zanidatamab doses at the same dose level or consider a dose reduction to 15 mg/kg. | |
|
Recurrent severe (grade 3) |
Withhold zanidatamab and ensure medical management has been optimized. Resume zanidatamab at a reduced dose of 15 mg/kg after severity improves to ≤ grade 1. Permanently discontinue zanidatamab for recurrent grade 3 symptoms lasting >3 days despite optimized medical management. | |
|
Life-threatening (grade 4) |
Permanently discontinue zanidatamab. | |
|
Infusion-related reactions |
Mild (grade 1) |
Reduce zanidatamab infusion rate by 50%. For subsequent zanidatamab infusions increase the infusion rate gradually, as tolerated, to the rate prior to the adverse reaction. |
|
Moderate (grade 2) |
Stop zanidatamab infusion immediately. Manage as clinically appropriate. Once symptoms resolve, resume zanidatamab infusion at 50% of the previous infusion rate. For subsequent zanidatamab infusions increase the infusion rate gradually, as tolerated, to the rate prior to the adverse reaction. | |
|
Severe (grade 3) |
Stop zanidatamab infusion immediately. Promptly manage as clinically appropriate; do not restart infusion during the same cycle even if signs/symptoms completely resolve. Subsequent zanidatamab infusions should be administered at 50% of the previous infusion rate. | |
|
Recurrent severe (grade 3) |
Stop zanidatamab infusion immediately. Promptly manage as clinically appropriate. Permanently discontinue zanidatamab. | |
|
Life-threatening (grade 4) |
Stop zanidatamab infusion immediately and permanently discontinue. Promptly manage as clinically appropriate. | |
|
Pulmonary toxicity: Pneumonitis |
Confirmed ≥ grade 2 |
Permanently discontinue zanidatamab. |
|
Other adverse reactionsb |
Mild or moderate (grade 1 or 2) |
No zanidatamab dose modification is required. Initiate appropriate medical therapy and monitor as clinically indicated. |
|
Severe (grade 3) |
Withhold zanidatamab until severity improves to ≤ grade 1. Initiate appropriate medical therapy and monitor as clinically indicated. Administer subsequent zanidatamab doses at the same dose level. | |
|
Recurrent severe (grade 3) |
Withhold zanidatamab until severity improves to ≤ grade 1. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Consider a dose reduction to 15 mg/kg. | |
|
Life-threatening (grade 4) |
Permanently discontinue zanidatamab. Initiate appropriate medical therapy and monitor as clinically indicated. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Dermatologic: Skin rash (19%; including acneiform eruption, maculopapular rash, palmar-plantar erythrodysesthesia, pustular rash)
Endocrine & metabolic: Decreased serum albumin (53%), decreased serum potassium (34%), decreased serum sodium (35%), increased lactate dehydrogenase (55%)
Gastrointestinal: Abdominal pain (29%), decreased appetite (16%), diarrhea (50%; grades 3/4: 10%; including enteritis), nausea (18%; grades 3/4: 1%), vomiting (15%; grades 3/4: 1%)
Hematologic & oncologic: Decreased hemoglobin (88%; grades 3/4: 14%), lymphocytopenia (44%; grades 3/4: 8%)
Hepatic: Increased serum alanine aminotransferase (46%), increased serum alkaline phosphatase (41%), increased serum aspartate aminotransferase (47%)
Hypersensitivity: Infusion-related reaction (35%)
Nervous system: Fatigue (24%; including asthenia)
1% to 10%:
Gastrointestinal: Gastric outlet obstruction (4%)
Infection: Sepsis (8%)
Respiratory: Pneumonia (5%)
Frequency not defined:
Cardiovascular: Reduced ejection fraction (including decreased left ventricular ejection fraction)
Endocrine & metabolic: Weight loss
Gastrointestinal: Cholangitis
Renal: Increased serum creatinine
Respiratory: Pneumonitis
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Cardiotoxicity: Zanidatamab may cause left ventricular ejection fraction (LVEF) decreases. LVEF declined by >10% and decreased to <50% in a small percentage of patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation occurred rarely. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7 months). LVD resolved in a majority of patients. The safety of zanidatamab has not been established in patients with a baseline ejection fraction of <50%.
• Diarrhea: Zanidatamab may cause severe diarrhea. In clinical studies, diarrhea was reported in nearly half of zanidatamab-treated patients, including grades 2 and 3 events.
• Infusion-related reactions: Zanidatamab may cause infusion-related reactions (IRRs). IRRs were reported in nearly one-third of zanidatamab-treated patients. One-fourth of IRRs were grade 2; grade 3 events and IRRs leading to permanent discontinuation were rare. IRRs occurred on the first day of dosing in over one-fourth of patients; most IRRs resolved within 1 day.
Other warnings/precautions:
• Appropriate use: Select patients for the treatment of unresectable or metastatic biliary tract cancer based on HER2 positivity (IHC 3+) in tumor specimens. Information on approved tests for HER2 protein expression in biliary tract cancers may be found at http://www.fda.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Ziihera: Zanidatamab-hrii 300 mg (1 ea)
No
Solution (reconstituted) (Ziihera Intravenous)
300 mg (per each): $4,266.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Zanidatamab is available through specialty pharmacy distributors. Information is available from the manufacturer at https://www.ziiherahcp.com/sites/default/pdfs/product-flashcard.pdf.
IV: Administer as an IV infusion with a 0.2- or 0.22-micron filter. Do not infuse as an IV push or bolus. Do not administer other IV medications through the same infusion line. Premedicate with acetaminophen, an antihistamine, and a corticosteroid 30 to 60 minutes prior to dose to reduce the risk of infusion-related reactions.
|
Infusion dose number(s) |
Zanidatamab infusion duration |
|---|---|
|
Doses 1 and 2 |
Infuse over 120 to 150 minutes |
|
Doses 3 and 4 |
Infuse over 90 minutes (if previous doses were well tolerated) |
|
Doses 5 and beyond |
Infuse over 60 minutes (if previous doses were well tolerated) |
Medications and emergency equipment to treat infusion-related reactions (IRRs) should be available for immediate use if needed. Monitor for signs/symptoms of IRRs during administration and as clinically indicated after completion of infusion. If an IRR occurs, slow or stop the infusion and administer appropriate medical management; if appropriate to resume infusion, monitor until complete resolution of signs/symptoms prior to restarting. Permanently discontinue for recurrent severe or life-threatening IRRs.
Compatibility has been demonstrated with IV administration materials or IV sets made of polyvinyl chloride/bis (2-ethylhexyl) phthalate, polyurethane, polyethylene-lined acrylonitrile-butadiene-styrene (ABS); with polyethersulfone solution inline filters and polyvinylidene fluoride air inline filters; and with closed system transfer devices made of ABS, acrylic c-polymer, polycarbonate, polyisoprene, polyester, polypropylene, polytetrafluoroethylene, silicone, and stainless steel.
Biliary tract cancer, unresectable or metastatic, HER2 positive : Treatment of previously treated, unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ [as detected by an approved test]) biliary tract cancer in adults.
Zanidatamab may be confused with zanubrutinib, zolbetuximab.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Verify pregnancy status prior to initiating treatment in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last zanidatamab dose.
Animal reproduction studies have not been conducted.
Based on the mechanism of action, in utero exposure to zanidatamab may cause fetal harm. Exposure to similar agents has resulted in oligohydramnios, oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
Advise patients of the potential risk to a fetus if exposure to zanidatamab occurs during pregnancy or within 4 months prior to conception. Monitor exposed pregnancies for oligohydramnios and perform fetal testing as appropriate for GA.
It is not known if zanidatamab is present in breast milk.
Zanidatamab is a humanized IgG-like antibody; human IgG is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Consider the half-life of zanidatamab (~21 days) and washout period of 4 months.
HER2 positivity (IHC 3+) in tumor specimens. Monitor electrolytes as clinically indicated. Verify pregnancy status prior to initiating treatment (in patients who could become pregnant). Assess left ventricular ejection fraction prior to zanidatamab initiation and at regular intervals during treatment. If diarrhea occurs, perform diagnostic testing as clinically indicated to exclude other causes. Monitor for signs/symptoms of infusion-related reactions during administration and as clinically indicated after completion of infusion; monitor patients until complete resolution of signs/symptoms prior to resuming. Monitor for signs/symptoms of cardiotoxicity and pneumonitis.
Additional cardiovascular monitoring (guideline recommendations): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (Ref). Obtain a baseline echocardiography (transthoracic preferred) and repeat every 3 months during treatment (may reduce to every 4 to 6 months if normal and asymptomatic), assess more frequently if clinically indicated and obtain echocardiography within 12 months after completion; in high- and very high-risk patients, assess troponin and natriuretic peptide at baseline and consider assessing every 2 to 3 cycles, and at 3 and 12 months after completion of therapy; in low- and moderate-risk patients, consider troponin and natriuretic peptide at baseline (post-anthracycline), every 3 months and 12 months after completion of therapy (Ref).
The American Society of Clinical Oncology HBV screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Zanidatamab is a humanized, IgG-like, bispecific antibody directed at HER2 that binds to 2 extracellular sites on HER2, the HER2 dimerization and the extracellular juxtamembrane domains, leading to receptor-antibody cluster formation, receptor internalization, and HER2 downregulation (Ref). Zanidatamab induces complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis, resulting in inhibition of tumor growth and cell death.
Onset: Median time to first response: 1.8 months (range: 1.6 to 5.5 months) (Ref).
Distribution: Vd: 7.5 L.
Metabolism: Zanidatamab is expected to be metabolized via catabolic pathways into small peptides.
Half-life elimination: ~21 days.
Excretion: Clearance: 0.012 L/hour.
