Pronunciation: zye HAYR rah
Generic name: zanidatamab-hrii
Dosage form: infusion
Drug class: HER2 inhibitors

Medically reviewed by Melisa Puckey, BPharm. Last updated on Nov 26, 2024.

What is Ziihera?

Ziihera (zanidatamab-hrii) is a targeted treatment used to treat HER2-positive biliary tract cancer (BTC) that has already been treated but has spread to other parts of the body (metastasized) or cannot be removed by surgery. Ziihera is a bispecific HER2-directed antibody, which means it targets two cancer-causing proteins (HER2) on the tumor cells.  Ziihera is not a chemotherapy. Ziihera (zanidatamab-hrii) is given as an intravenous infusion once every 2 weeks.

Ziihera mechanism of action by binding to two extracellular sites on HER2 leads to a reduction of the receptor on the tumor cell surface and induces complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis, which results in tumor growth inhibition and tumor cell death.

Ziihera FDA approval was granted for the treatment of adults who have a type of bile duct  (cholangiocarcinoma) or gallbladder cancer called biliary tract cancer (BTC), which has been confirmed to be human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+). The biliary tract cancer must have been previously treated and is not able to be removed by surgery or has spread to other parts of your body (metastatic). Ziihera FDA approval was based on positive results from the HERIZON-BTC-01, which showed an objective response rate (ORR) of 52% with a median duration of response (DOR) of 14.9 months. Ziihera was approved under accelerated approval, and continued approval for this indication is dependent on clinical benefit in further trial results.

Ziihera side effects

Common Ziihera side effects

Common Ziihera side effects are diarrhea (50%) , infusion-related reactions (35%), stomach pain (29%), nausea (18%), vomiting (15%), tiredness (24%), rash (19%), and reduced appetite (16%). These side effects occurred in 15% or more patients in a clinical trial. Ziihera can also affect laboratory results, causing reduced hemoglobin and lymphocytes and other laboratory abnormalities.

Serious side effects and warnings

Ziihera may cause serious side effects, including:

Left Ventricular Dysfunction: a decrease in left ventricular ejection fraction (LVEF) may occur in some patients, assess left ventricular ejection fraction (LVEF) before starting treatment and at regular intervals during treatment. 

Infusion-Related Reactions (IRRs):  IRR were reported in 31% of 233 patients treated with Ziihera as a single agent in clinical studies. Premedicate before each infusion. Stop the infusion, decrease the infusion rate, and/or permanently discontinue based on infusion-related reactions severity.

Diarrhea: This medicine can cause severe diarrhea. If diarrhea occurs, use antidiarrheal treatment as clinically indicated. Diagnostic tests should be done as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue this medicine based on severity of diarrhea.

Toxic to an unborn baby: Based on the way Ziihera works it can cause fetal harm when administered to a pregnant woman. Females who are able to become pregnant should use birth control (contraception) during treatment with Ziihera and for 4 months after the last dose. 

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088

Related/similar drugs

Before taking this medicine

Before taking this medicine, tell your healthcare provider about all of your medical conditions, including if you:  

• have or have had any heart problems  

Pregnancy

Tell your healthcare provider if you are planing a pregnacy, are pregnant, or become pregnant. Ziihera can be toxic to an unborn baby and cause fetal harm. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with Ziihera to make sure you are not pregnant. Females who are able to become pregnant should use birth control (contraception) during treatment with Ziihera and for 4 months after the last dose to ensure they do not get pregnant.

Breastfeeding

Tell  your healthcare providers if you are breastfeeding or plan to breastfeed. It is not known if Ziihera passes into your breastmilk.  Discuss with your healthcare provider about the best way to feed your baby if you receive treatment with this medicine. 

How will I receive this medicine?

Ziihera is given as an infusion into your vein (IV infusion) every 2 weeks. 

Your first and second infusions will be given over 120 to 150 minutes and if you tolerate the first and second infusions well, then your third and fourth infusions may be given to you over 90 minutes. Each additional infusion may be given to you over 60 minutes.  

Your healthcare provider: 

• will give you acetaminophen, an antihistamine, and a corticosteroid medicine 30 to 60 minutes before each treatment to help prevent infusion-related reactions or make them less severe. 
• may slow down, temporarily stop, or permanently stop your treatment with ZIIHERA if you have certain side effects.
• may do certain tests to check you for some side effects. 
• will decide how many treatments you need.

 If you miss a dose, call your healthcare provider as soon as possible to reschedule your appointment.

Ziihera doing information

The recommended Ziihera dose is 20 mg/kg, given as an intravenous infusion once every 2 weeks.

The dosage should be modified for adverse reactions. Permanently discontinue Ziihera in patients who cannot tolerate 15 mg/kg.

Do not administer as an intravenous push or bolus.  Do not co-administer Ziihera and other intravenous drugs through the same intravenous line. 

What other drugs will affect Ziihera?

Other drugs may affect Ziihera, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. 

Storage

Store in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) in the original carton until time of reconstitution. 

Do not freeze. 

Ingredients

Active ingredient: zanidatamab-hrii 

Inactive ingredients: polysorbate 20, sodium succinate, succinic acid, and sucrose.

Company

Distributor Ziihera Jazz Pharmaceuticals, Inc. Palo Alto, CA 94304 

Manufactured Ziihera Jazz Pharmaceuticals Ireland Limited Fifth Floor, Waterloo Exchange Waterloo Road, Dublin 4 Dublin, Ireland D04 E5W7.

Ziihera Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Ziihera.

Further information

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

Medical Disclaimer