Ziihera (zanidatamab-hrii) is an innovative bispecific HER2-targeted antibody drug that provides a new treatment option for patients with HER2-positive biliary tract cancer. Its standard usage methods, dosage adjustment strategies, and precautions for special populations constitute key components of precision therapy.

How to Use Ziihera (Zanidatamab-hrii)

Pre-Administration Preparation

All patients must receive premedication 30 to 60 minutes before each dose to reduce the risk of infusion-related reactions.

The recommended premedication regimen includes: acetaminophen, an antihistamine (e.g., diphenhydramine), and a corticosteroid (e.g., hydrocortisone).

Standard Dosage Regimen

The recommended dosage of Ziihera is 20 mg/kg, administered via intravenous infusion once every two weeks until disease progression or unacceptable toxicity occurs.

If a scheduled dose is delayed or missed, administer it as soon as possible, then adjust the dosing schedule to maintain the two-week treatment cycle interval.

Infusion Duration Schedule

Infusion duration follows a progressive reduction pattern based on the patient’s tolerance to previous infusions.

The first and second doses: Infusion duration of 120-150 minutes.

If well-tolerated, the third and fourth doses can be shortened to 90 minutes.

Subsequent doses can be further shortened to 60 minutes.

Dosage Adjustments for Ziihera (Zanidatamab-hrii)

Principles for Managing Adverse Reactions

When patients experience specific adverse reactions, the recommended reduced dosage of Ziihera is 15 mg/kg.

Patients who cannot tolerate the 15 mg/kg dosage should permanently discontinue the drug.

Left Ventricular Dysfunction

If the left ventricular ejection fraction (LVEF) decreases by ≥16 percentage points absolutely from the pre-treatment baseline, or if LVEF ≤50% with an absolute decrease of ≥10 percentage points from baseline, discontinue administration for at least 4 weeks and repeat LVEF assessment within 4 weeks.

Treatment may be resumed if LVEF returns to the normal range and the absolute decrease is ≤15 percentage points within 4-8 weeks.

Permanent discontinuation is required if LVEF does not recover to within 15 percentage points of the pre-treatment baseline.

Infusion-Related Reactions

For mild (Grade 1) reactions: Reduce the infusion rate by 50%. For moderate (Grade 2) reactions: Immediately stop the infusion, and resume at 50% of the original rate after symptomatic treatment.

For severe (Grade 3) reactions: Immediately stop the infusion and do not restart within the same cycle. Subsequent infusions should be administered at 50% of the original rate; permanently discontinue if the reaction recurs.

For life-threatening (Grade 4) reactions: Immediately discontinue the drug and permanently terminate treatment.

Medication in Special Populations for Ziihera (Zanidatamab-hrii)

Pregnant Women and Women of Reproductive Age

Ziihera has embryo-fetal toxicity; use during pregnancy may cause fetal harm.

Verify the pregnancy status of women of childbearing potential before initiating treatment.

Women of childbearing age must use effective contraception during treatment and for 4 months after the last dose.

Lactating Women

There are no data on the presence of zanidatamab-hrii in human milk.

During treatment, weigh the developmental and health benefits of breastfeeding against the mother’s clinical need for the drug.

Pediatric Patients

The efficacy of Ziihera in pediatric patients has not been established, and it is not currently recommended for this population.