Zongertinib

Zongertinib is a prescription medicine for the treatment of unresectable or metastatic Non-Small Cell Lung Cancer (NSCLC) in adults with tumors HER2 (ERBB2) tyrosine kinase domain (TKD)-activating mutations and who have received prior systemic therapy.

Zongertinib is available under the following different brand names: Hernexeos

Common side effects of Zongertinib include:

• diarrhea
• rash 
• fatigue 
• nausea
• hepatotoxicity
• decreased white blood cell count
• increased liver function tests
• decreased potassium levels

Serious side effects of Zongertinib include:

• symptoms of liver problems may include skin or the white part of the eyes turning yellow, bleeding or bruising more easily than normal, feeling very tired, dark or brown (tea colored) urine, loss of appetite, right upper quadrant pain, nausea or vomiting
• symptoms of heart problems may include tachycardia, shortness of breath, dizziness, loss of consciousness, tiredness, coughing, feeling lightheaded, swelling of the legs, ankles or feet
• symptoms of lung problems may include trouble breathing, shortness of breath, cough, or fever

Rare side effects of Zongertinib 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

Oral tablet

• 60 mg

Non-Small Cell Lung Cancer (NSCLC)

Adult dosage

• Adults weighing 90 kg and more: 180 mg orally daily
• Adults weighing less than 90 kg: 120 mg orally daily
• Continue therapy until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, 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 without first checking with your doctor, healthcare provider, or pharmacist.

Drug interaction overview

Zongertinib is a CYP3A4 substrate and a BCRP inhibitor

• Strong CYP3A inducers
  • Avoid coadministration; increase dosage if concomitant use cannot be avoided
  • Concomitant use may decrease zongertinib exposure, which may reduce efficacy
• BCRP substrates
  • Follow BCRP substrate recommendations for use with BCRP inhibitors
  • Concomitant use may increase exposure to the BCRP substrate, which may increase the risk of adverse effects

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Hepatotoxicity
  • Can cause severe and life-threatening hepatotoxicity (eg, drug-induced liver injury)
  • Evaluate liver function tests (LFTs) (e.g., ALT, AST, and TB) before starting therapy, every 2 weeks during the first 12 weeks, and then monthly thereafter as clinically indicated
  • Increase LFT monitoring in patients who develop transaminase elevations
  • Hold, reduce dosage, or permanently discontinue, based on severity
• Left ventricular dysfunction (LVD)
  • Can cause severe LVD and decreased left ventricular ejection fraction (LVEF)
  • Median time to decreased LVEF onset: 9 weeks (range, 2.9 to 63)
  • Has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50%
  • Evaluate LVEF before starting therapy, at regular intervals during therapy, and as clinically indicated
  • Hold, reduce dosage, or permanently discontinue, based on severity
• Interstitial lung disease (ILD)/pneumonitis
  • Can cause severe and life-threatening ILD/pneumonitis; 1 patient died with unresolved pneumonitis more than 30 days after discontinuing therapy
  • Median time to ILD/pneumonitis onset: 19 weeks (range, 6 to 65)
  • Monitor for new or worsening symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever)
  • Hold, reduce dosage, or permanently discontinue, based on severity
• Embryo-fetal toxicity
  • May cause fetal harm if administered during pregnancy
  • Advise pregnant patients and females of reproductive potential of fetal risk
  • Effective contraceptive use recommended during and after therapy in females of reproductive potential

Pregnancy and Lactation

• Pregnancy
  • May cause fetal harm when administered during pregnancy, based on findings from animal studies and its mechanism of action
  • There are no available data on use in pregnant patients to inform drug-associated risk
  • Advise pregnant patients and females of reproductive potential of fetal risk
  • Verify pregnancy status before starting therapy in females of reproductive potential
• Contraception requirements
  • Females of reproductive potential should use effective contraception during therapy and for 2 weeks after the last dose
• Infertility
  • May impair fertility in females and males, based on data from animal studies
  • Fertility was reversible in female animals; the effect on testes in male animals was not reversible within a 4-week recovery period
• Lactation
  • No data on the presence of zongertinib or its metabolites in human milk or effects on breastfed children or on milk production
  • Due to the potential for serious adverse reactions in breastfed children, avoid breastfeeding during therapy and for 2 weeks after the last dose