Zanidatamab

Zanidatamab is a bispecific HER2-directed antibody indicated for previously treated, unresectable, or metastatic HER2-positive biliary tract cancer (BTC).

• Zanidatamab is available under the following different brand names: Ziihera, zanidatamab-hrii

Common side effects of Zanidatamab include:

• diarrhea
• infusion-related reaction 
• abdominal pain 
• fatigue

Serious side effects of Zanidatamab include:

• heart problem symptoms include new or worsening shortness of breath, irregular heartbeat, feeling more tired than usual, sudden weight gain, swelling of your ankles or feet, dizziness or feeling light-headed, loss of consciousness
• infusion-related reaction symptoms include shortness of breath or trouble breathing, flushing, fever, nausea or vomiting, chills, dizziness or feeling lightheaded, rash, chest discomfort 
• diarrhea
• harm to the unborn baby

Rare side effects of Zanidatamab include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injection, powder for reconstitution

• 300 mg single-dose vial

BTC

Adult dosage

• 20 mg/kg IV every 2 weeks until disease progression or unacceptable toxicity

Premedication

• Give acetaminophen, antihistamine (e.g., diphenhydramine), and corticosteroid (e.g., hydrocortisone) 30-60 minutes before each dose

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Zanidatamab has no noted severe interactions with any other drugs
• Zanidatamab has no noted serious interactions with any other drugs
• Zanidatamab has no noted moderate interactions with any other drugs
• Zanidatamab has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Zanidatamab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Zanidatamab?”

Cautions

• Left ventricular dysfunction (LVD)
  • Median time to first LVD event: 5.6 months (range, 1.6-18.7); LVD resolved in 70% of patients
  • Assess left ventricular ejection fraction (LVEF) before starting and at regular intervals during therapy
  • Safety not established in patients with baseline LVEF less than 50%
  • Hold or permanently discontinue based on LVD severity
• Infusion-related reactions (IRR)
  • IRRs reported with the first dose in approximately one-quarter of patients; almost all cases were resolved within 1 day
  • Administer premedications before each dose
  • Monitor for signs and symptoms of IRR during and as clinically indicated after infusion
  • Ensure medications and emergency equipment are available for immediate use to treat IRRs
  • Hold, slow infusion rate, and permanently discontinue based on severity
  • Administer appropriate medical management
• Diarrhea
  • Severe diarrhea reported
  • Perform diagnostic testing to exclude other causes and administer antidiarrheal treatment as clinically indicated
  • Hold, reduce dose, or permanently discontinue based on severity
• Pneumonitis
  • Pneumonitis rarely reported
  • Permanently discontinue for confirmed Grade of 2 and more pneumonitis
  • Electrolyte imbalance/laboratory abnormality
• Grade 4
  • Hold or permanently discontinue
  • Initiate appropriate medical therapy and monitor as clinically indicated

Pregnancy and Lactation

• Not recommended during pregnancy
• Can cause fetal harm when administered to pregnant patients, based on mechanism of action
• No human or animal data regarding use in pregnancy
• In literature reports, HER2-directed antibody uses during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death
• Advise pregnant patients of potential fetal risks
• Females of reproductive potential
  • Obtain a pregnancy test before starting therapy
  • Advise use of effective contraception during therapy and for 4 months after the last dose
• Clinical considerations
  • Monitor for oligohydramnios during pregnancy or in patients who received therapy within 4 months before conception
  • If oligohydramnios occurs, perform fetal testing appropriate for gestational age and consistent with the local standard of care
• Lactation
  • There are no data on the presence of the drug in human milk, its effects on breastfed children, or milk production
  • Published data suggest human IgG is present in human milk but does not enter neonatal or infant circulation in substantial amounts
  • Consider the developmental and health benefits of breastfeeding along with the patient’s clinical need for therapy and any potential adverse effects on breastfed children from therapy or underlying maternal condition
  • Also, consider that the half-life is approximately 21 days and the washout period is 4 months