Zenocutuzumab

Zenocutuzumab is a prescription medication indicated for the treatment of:

• advanced unresectable or metastatic neuregulin 1 (NRG1) fusion-positive non-small cell lung cancer (NSCLC)
• advanced unresectable or metastatic NRG1 fusion-positive pancreatic cancer

Zenocutuzumab is available under the following different brand names: Bizengri, zenocutuzumab-zbco.

Common side effects of Zenocutuzumab include:

• diarrhea 
• rash
• muscle or bone pain 
• constipation
• tiredness 
• vomiting
• nausea 
• abdominal pain
• shortness of breath 
• swelling of the breasts, face, ankles, or legs
• increased blood levels of liver enzymes and bilirubin 
• decreased blood levels of sodium, magnesium, and phosphate
• decreased red blood cell counts and platelet counts  
• increase in the time that it takes the blood to clot

Serious side effects of Zenocutuzumab include:

• infusion-related allergic and anaphylactic reaction symptoms include chills or shaking, itching or rash, nausea, vomiting, or diarrhea, shortness of breath or wheezing, fever, chest discomfort, cough, feeling light-headed, sudden swelling of the face, tongue, throat, or troubled swallowing, dizziness, back or neck pain, throat tightness or discomfort, feeling of numbness or tingling
• lung problem symptoms include trouble breathing, cough, shortness of breath, fever
• heart problems that may affect your heart’s ability to pump blood symptoms include shortness of breath, irregular heartbeat, coughing, sudden weight gain, tiredness, dizziness or feeling light-headed, swelling of the feet, ankles, or legs, loss of consciousness 
• harm to the unborn baby

Rare side effects of Zenocutuzumab 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 solution

• 375 mg/18.75 mL (20 mg/mL) single-dose vial

NSCLC

Adult dosage

• Premedication is required before each dose
• 750 mg IV every 2 weeks until disease progression or unacceptable toxicity

Pancreatic cancer

Adult dosage

• Premedication is required before each dose
• 750 mg IV every 2 weeks until disease progression or unacceptable toxicity

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.

• Zenocutuzumab has no noted severe interactions with any other drugs
• Zenocutuzumab has no noted serious interactions with any other drugs
• Zenocutuzumab has no noted moderate interactions with any other drugs
• Zenocutuzumab 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 Zenocutuzumab?”

Long-Term Effects

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

Cautions

• Infusion-related reactions (IRR)/hypersensitivity/anaphylactic reactions
• Life-threatening IRRs, hypersensitivity, and anaphylactic reactions may occur
• Median time to IRR onset: 63 min (range, 13-240) from the start of infusion; most IRRs occur with the first infusion
• Administer in a setting with emergency resuscitation equipment and staff trained to monitor for IRRs and administer emergency medications
• Monitor closely for signs and symptoms of IRR (e.g., chills, nausea, fever, and cough) during infusion and as clinically indicated; observe patients for at least 1 hour following completion of the first infusion
• Premedicate before each dose as recommended
  • Hold infusion, reduce infusion rate, or permanently discontinue based on severity
  • Administer symptomatic treatment as needed
• Interstitial lung disease (ILD)/pneumonitis
  • May be serious and life-threatening
  • Monitor for new or worsening pulmonary symptoms (e.g., dyspnea, cough, fever)
  • Immediately hold therapy for suspected ILD/pneumonitis; administer corticosteroids as clinically indicated
  • Permanently discontinue for confirmed Grade of 2 and more ILD/pneumonitis
• Left ventricular dysfunction (LVD)
  • Can cause LVD including left ventricular ejection fraction (LVEF)
  • Has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% at baseline
  • Evaluate LVEF before starting therapy and monitor LVEF at regular intervals during treatment as clinically indicated
  • Hold therapy, increase LVEF monitoring, or permanently discontinue based on LVD severity
• Permanently discontinue if symptomatic congestive heart failure (CHF) occurs

Pregnancy and Lactation

• Can cause fetal harm when administered during pregnancy, based on the mechanism of action
• No available data on pregnant patients or animals
• In animals (e.g., mice), HER2 and HER3 are critically important in embryo-fetal development including effects on cardiac, vascular, and neuronal development and embryo-lethality; HER3 is involved in mammary gland ductal morphogenesis
• Literature reports
  • Cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death reported with HER2-directed antibody treatment during pregnancy in humans
  • Case reports described oligohydramnios in pregnant patients who received HER2-directed antibody alone or in combination with chemotherapy
  • In some cases, the amniotic fluid index increased after the use of HER2-directed antibody was discontinued
• Females of reproductive potential
  • Inform of potential fetal risk
  • Verify pregnancy status before starting therapy
  • Advise use of effective contraception during therapy and for 2 months after the last dose
• Lactation
  • No data is available on the presence of zenocutuzumab in human milk, its effects on breastfed children, or milk production
  • Maternal IgG1 is known to be present in human milk
  • Effects of local gastrointestinal exposure and limited systemic exposure in breastfed children are not known
  • Consider the developmental and health benefits of breastfeeding with the mother’s clinical need for treatment and any potential adverse effects on the breastfed child from therapy or underlying maternal condition
  • The washout period is 2 months, based on the drug’s elimination half-life