Hernexeos (zongertinib)

If adverse events occur during therapy, temporary interruption, dosage reduction, and/or discontinuance of zongertinib may be necessary. For patients receiving 180 mg once daily, an initial reduction to 120 mg once daily is recommended. If further dosage reduction is necessary, the dosage should be reduced to 60 mg once daily. For patients receiving 120 mg once daily, a reduction to 60 mg once daily is recommended. If a dosage of 60 mg once daily is not tolerated, zongertinib should be permanently discontinued.

The recommended dosage modifications for adverse reactions are present in Table 1.

Table 1: Recommended Dosage Modification for Zongertinib Adverse Reactions

Adverse Reaction Dosage Modification Based on Severity Hepatotoxicity Grade 3 or 4 ALT and/or AST without increased total bilirubin: Interrupt until recovery to <=Grade 1 or baseline. Resume at reduced dose level. Grade 3 total bilirubin: Interrupt until recovery to <=Grade 1 or baseline. Resume at reduced dose level. Grade 4 total bilirubin: Permanently discontinue. ALT or AST >=3 times ULN with total bilirubin >=2 times ULN: Permanently discontinue. Left Ventricular Dysfunction LVEF 40 to 50% and decrease from baseline of 10 to 19%: Interrupt until recovery to <=Grade 1 or within 10% from baseline. If recovery to <=Grade 1 in <=4 weeks, resume at same dose level. If not recovered to <=Grade 1 within 4 weeks, permanently discontinue. LVEF 20 to 39% or >=20% decrease from baseline: Interrupt until recovery to <=Grade 1 or within 10% from baseline. If recovery to <=Grade 1 in <=4 weeks, resume at reduced dose level. If not recovered to <=Grade 1 within 4 weeks, permanently discontinue. Symp tomatic congestive heart failure: Permanently discontinue. Interstitial Lung Grade 2: Withhold until resolution. Disease/Pneumonitis Resume at reduced dose level. Permanently discontinue for recurrent ILD/pneumonitis. Grade 3 or Grade 4: Permanently discontinue. Diarrhea Grade 2: Maintain dose. Initiate anti-diarrheal treatment. Grade 2 lasting >=2 days despite anti-diarrheal treatment: Interrupt until recovery to <=Grade 1. Resume at reduced dose level. Grade 3 or Grade 4: Interrupt until recovery to <=Grade 1. Resume at re duced dose level. Permanently discontinue if diarrhea does not resolve to <=Grade 1 within 14 days, despite optimal supportive care (including anti-diarrheal treatment) and treatment interruption. Other Adverse Reactions Grade 3: Interrupt until recovery to <=Grade 1 or baseline. Resume at reduced dose level. Grade 4: Permanently discontinue.

Concomitant use of strong CYP3A inducers with zongertinib should be avoided. If concomitant use cannot be avoided, the zongertinib dose should be increased based on body weight. For patients weighing <90 kg, increase the zongertinib dose from 120 mg to 240 mg; for patients weighing >=90 kg, increase the zongertinib dose from 180 mg to 360 mg.

Seven to 14 days after discontinuation of a CYP3A inducer, the zongertinib dose that was taken prior to initiating the CYP3A inducer should be resumed.

No dosing information is available for this tab.

No dosing information is available for this tab.

Zongertinib is a substrate of cytochrome P-450 (CYP) isoenzyme 3A and an inhibitor of breast cancer resistance protein (BCRP).

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Bcrp Inhibitors/Topotecan

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Inhibitors of the BCRP transporter may increase the intestinal absorption and hepatic uptake of topotecan.(1)

CLINICAL EFFECTS: The concurrent administration of topotecan with an inhibitor of BCRP may result in elevated levels of topotecan and signs of toxicity. These signs may include but are not limited to anemia, diarrhea, and thrombocytopenia.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of topotecan states that the use of topotecan and BCRP inhibitors should be avoided. If concurrent use is warranted, carefully monitor patients for adverse effects.(1)

DISCUSSION: In clinical studies, the combined use of elacridar (100 mg to 1000 mg), a BCRP and P-gp inhibitor, increased the area-under-curve (AUC) of topotecan approximately 2.5-fold.(1) BCRP inhibitors linked to this monograph include: capmatinib, clopidogrel, curcumin, danicopan, dasabuvir, elbasvir, enasidenib, ensitrelvir, febuxostat, fostamatinib, fostemsavir, glecaprevir, grazoprevir, lazertinib, oteseconazole, pacritinib, paritaprevir, pibrentasvir, pirtobrutinib, regorafenib, resmetirom, ritonavir, roxadustat, tafamidis, ticagrelor, tolvaptan, turmeric, vadadustat, velpatasvir, voxilaprevir, and zongertinib.(2,3)

P-Gp Or Bcrp Inhibitors/Ubrogepant (> 50 Mg)

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of ubrogepant.(1)

CLINICAL EFFECTS: The concurrent administration of ubrogepant with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of ubrogepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with P-gp or BCRP inhibitors. The dose of ubrogepant should not exceed 50 mg for initial dose. If a second dose of ubrogepant is needed, the dose should not exceed 50 mg.(1) For patients on concurrent therapy with vimseltinib and ubrogepant: the manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to ubrogepant.(3) For patients on daraxonrasib, the manufacturer of daraxonrasib states that it should be taken at least 4 hours apart from P-gp substrates.(4)

DISCUSSION: Ubrogepant is a substrate of P-gp and BCRP transporters. Use of P-gp or BCRP inhibitors may increase the exposure of ubrogepant. Clinical drug interaction studies with inhibitors of these transporters were not conducted. The US manufacturer of ubrogepant recommends dose adjustment if ubrogepant is coadministered with P-gp or BCRP inhibitors.(1) BCRP inhibitors linked to this monograph include: belumosudil, clopidogrel, curcumin, eltrombopag, febuxostat, fostemsavir, leniolisib, momelotinib, oteseconazole, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, oral tedizolid, turmeric, vadadustat, and zongertinib.(2,3,5) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, capmatinib, carvedilol, danicopan, daraxonrasib, daridorexant, imlunestrant, neratinib, osimertinib, propafenone, quinidine, selpercatinib, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, valbenazine, vimseltinib, and voclosporin.(2,3,5)

Select Bcrp Inhibitors/Aumolertinib

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Aumolertinib is a substrate for BCRP. Inhibitors of the BCRP transporter may increase the intestinal absorption and decrease hepatic elimination of aumolertinib.(1)

CLINICAL EFFECTS: Concurrent use with selected BCRP inhibitors may result in higher systemic concentrations of aumolertinib, which may increase the risk for cardiac failure, rhabdomyolysis, thrombosis, elevated LFTs, hyponatremia, hematologic toxicity, and QT prolongation, which may result in potentially life-threatening cardiac arrhythmias like torsade de pointes (TdP).(1)

PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Patients with risk factors for thrombosis may be at higher risk of adverse events, including those with advanced age, obesity (BMI >30), smoking, prolonged immobilization, heart failure, hypercoagulable state, history of venous thromboembolism, malignancy, and major surgery. The risk for rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of rhabdomyolysis.

PATIENT MANAGEMENT: The manufacturer of aumolertinib states concomitant administration of aumolertinib should be avoided with BCRP inhibitors.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting.

DISCUSSION: Based on in vitro data, aumolertinib is a substrate of BCRP.(1) BCRP inhibitors linked to this monograph include: asciminib, clopidogrel, darolutamide, elbasvir/grazoprevir, eltrombopag, enasidenib, febuxostat, fostemsavir, lazertinib, leniolisib, momelotinib, oteseconazole, regorafenib, rolapitant, roxadustat, tafamidis, ticagrelor, vadadustat, and zongertinib.(3,4)

Selected Inhibitors Of P-Gp Or Bcrp/Pazopanib

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of pazopanib.(1)

CLINICAL EFFECTS: The concurrent administration of pazopanib with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of pazopanib and signs of toxicity.(1)

PREDISPOSING FACTORS: The risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, and/or renal/hepatic dysfunction).(2)

PATIENT MANAGEMENT: The US manufacturer of pazopanib states concurrent use of P-gp inhibitors or BCRP inhibitors should be avoided.(1) Monitor patients for increased side effects from pazopanib. The manufacturer of daraxonrasib states P-gp substrates should be administered at least 4 hours apart from daraxonrasib.(5) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting.

DISCUSSION: Pazopanib is a substrate of P-gp and BCRP. Inhibitors of these transporters are expected to increase pazopanib levels.(1) BCRP inhibitors linked to this monograph include: asciminib, belumosudil, clopidogrel, cyclosporine, curcumin, darolutamide, eltrombopag, enasidenib, febuxostat, fostemsavir, grazoprevir, lazertinib, leflunomide, leniolisib, momelotinib, oteseconazole, pirtobrutinib, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, teriflunomide, tolvaptan, turmeric, vadadustat, and zongertinib.(1,3-5) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, capmatinib, carvedilol, cyclosporine, danicopan, daraxonrasib, daridorexant, diltiazem, flibanserin, fostamatinib, ginseng, glecaprevir/pibrentasvir, imlunestrant, isavuconazonium, ivacaftor, ledipasvir, neratinib, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, tezacaftor, ticagrelor, valbenazine, verapamil, vimseltinib, and voclosporin.(3,4)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Selected Inhibitors Of Bcrp/Cladribine Oral

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Inhibitors of BCRP may increase the absorption of cladribine.(1-2)

CLINICAL EFFECTS: The concurrent administration of cladribine with an inhibitor of BCRP may result in elevated levels of cladribine and signs of toxicity.(1-2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of cladribine states concurrent use of BCRP inhibitors should be avoided during the 4- to 5-day cladribine treatment.(1-2) Selection of an alternative concurrent medication with no or minimal transporter inhibiting proprieties should be considered. If this is not possible, dose reduction to the minimum mandatory dose of the BCRP inhibitor, separation in timing of administration, and careful patient monitoring is recommended.(1-2) Monitor for signs of hematologic toxicity. Lymphocyte counts should be monitored.

DISCUSSION: Cladribine is a substrate of BCRP. Inhibitors of this transporter are expected to increase cladribine levels.(1-2) BCRP inhibitors linked to this monograph include: capmatinib, clopidogrel, curcumin, danicopan, darolutamide, dasabuvir, eltrombopag, enasidenib, ensitrelvir, febuxostat, fostamatinib, fostemsavir, glecaprevir/pibrentasvir, grazoprevir, lazertinib, oteseconazole, pacritinib, paritaprevir, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, selpercatinib, sofosbuvir/velpatasvir/voxilaprevir, tafamidis, ticagrelor, tolvaptan, turmeric, vadadustat, and zongertinib.(1-4)

Zongertinib/Strong Cyp3a4 Inducers

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Strong CYP3A4 inducers may induce the metabolism of zongertinib.(1)

CLINICAL EFFECTS: Concurrent or recent use of a strong CYP3A4 inducer may result in decreased levels and effectiveness of zongertinib.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The manufacturer of zongertinib states that concomitant use of strong CYP3A4 inducers should be avoided.(1) If concurrent use cannot be avoided, increase the zongertinib dose based on body weight: - Less than 90 kg: increase from 120 mg to 240 mg dose - Greater than or equal to 90 kg: increase from 180 mg to 360 mg dose After stopping the CYP3A4 inducer, resume the prior zongertinib dose 7-14 days after stopping the CYP3A4 inducer.(1)

DISCUSSION: Zongertinib area-under-curve (AUC) and maximum concentration (Cmax) decreased by 63% and 43%, respectively, following concomitant use of carbamazepine (strong CYP3A4 inducer) 600 mg once daily for 7 days.(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

P-Gp Or Bcrp Inhibitors/Ubrogepant (<= 50 Mg)

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of ubrogepant.(1)

CLINICAL EFFECTS: The concurrent administration of ubrogepant with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of ubrogepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with P-gp or BCRP inhibitors. The dose of ubrogepant should not exceed 50 mg for initial dose. If a second dose of ubrogepant is needed, the dose should not exceed 50 mg.(1) For patients on concurrent therapy with vimseltinib and ubrogepant: The manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to ubrogepant.(3) For patients on daraxonrasib, the manufacturer of daraxonrasib states that it should be taken at least 4 hours apart from P-gp substrates.(4)

DISCUSSION: Ubrogepant is a substrate of P-gp and BCRP transporters. Use of P-gp or BCRP inhibitors may increase the exposure of ubrogepant. Clinical drug interaction studies with inhibitors of these transporters were not conducted. The US manufacturer of ubrogepant recommends dose adjustment if ubrogepant is coadministered with P-gp or BCRP inhibitors.(1) BCRP inhibitors linked to this monograph include: belumosudil, clopidogrel, curcumin, eltrombopag, febuxostat, fostemsavir, leniolisib, momelotinib, oteseconazole, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, oral tedizolid, turmeric, vadadustat, and zongertinib.(2,3,5,6) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, capmatinib, carvedilol, danicopan, daraxonrasib, daridorexant, imlunestrant, neratinib, osimertinib, propafenone, quinidine, selpercatinib, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, valbenazine, vimseltinib, and voclosporin.(2,3,5,6)

Selected Bcrp Inhibitors/Atorvastatin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Atorvastatin is a substrate of the BCRP transporter.(1) Inhibitors of this transporter may increase intestinal absorption and hepatic uptake of BCRP substrates atorvastatin.(1)

CLINICAL EFFECTS: Administration of atorvastatin with BCRP inhibitors may result in elevated levels of atorvastatin, which could result in rhabdomyolysis.(1)

PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis.

PATIENT MANAGEMENT: Concurrent use of atorvastatin with BCRP inhibitors may result in increased risk of side effects associated with atorvastatin. Close monitoring would be prudent for statin related side effects including rhabdomyolysis. If concurrent therapy is deemed medically necessary, monitor patients for signs and symptoms of myopathy/rhabdomyolysis, including muscle pain/tenderness/weakness, fever, unusual tiredness, changes in the amount of urine, and/or discolored urine.

DISCUSSION: Atorvastatin is a BCRP substrate.(1) BCRP inhibitors linked to this monograph include: capmatinib, clopidogrel, curcumin, danicopan, encorafenib, fostamatinib, lazertinib, leflunomide, momelotinib, oteseconazole, pacritinib, pirtobrutinib, regorafenib, ritonavir, rolapitant, roxadustat, selpercatinib, sofosbuvir/velpatasvir/voxilaprevir, tafamidis, teriflunomide, tolvaptan, turmeric, vadadustat, velpatasvir, and zongertinib.(2,3)

Selected Bcrp Inhibitors/Rosuvastatin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Rosuvastatin is a substrate of the BCRP transporter.(1,2) Inhibitors of this transporter may increase intestinal absorption and hepatic uptake of BCRP substrates rosuvastatin.(1-8)

CLINICAL EFFECTS: Simultaneous use of BCRP inhibitors may result in increased levels and side effects from rosuvastatin, including rhabdomyolysis.(2,4)

PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. Patients on rosuvastatin with ABCG2 polymorphisms leading to decreased or poor BCRP transporter function may have increased rosuvastatin concentrations and risk of myopathy.

PATIENT MANAGEMENT: Concurrent use of rosuvastatin with BCRP inhibitors may result in increased risk of side effects associated with rosuvastatin. If concurrent therapy is warranted, close monitoring would be prudent for statin related side effects including rhabdomyolysis. The Canadian manufacturer of clopidogrel states that the dose of rosuvastatin should not exceed 20 mg daily when used concomitantly with clopidogrel.(5) There is no recommendation for rosuvastatin dose adjustments from the Australian and US manufacturers of clopidogrel.(6,7) The Australian manufacturer of rosuvastatin states that the starting dose of rosuvastatin should not exceed 5 mg daily when used with agents that increase rosuvastatin exposure by 2-fold or more (e.g., clopidogrel, lopinavir-ritonavir, roxadustat). The maximum daily dose should be adjusted so that the expected rosuvastatin exposure does not exceed that obtained with the usual maximum daily dose.(8) Educate the patient of signs and symptoms of rhabdomyolysis.

DISCUSSION: Rosuvastatin is a BCRP substrate.(1,2) In a clinical study of 20 patients with stable coronary heart disease, single-dose clopidogrel 300 mg (a BCRP inhibitor) increased the area-under-curve (AUC) and maximum concentration (Cmax) of rosuvastatin by 2-fold and 1.3-fold, respectively. Multiple doses of clopidogrel 75 mg daily for 7 days increased rosuvastatin AUC by 1.4-fold but did not affect the Cmax.(4) In a pharmacokinetic study, concomitant use of lazertinib increased rosuvastatin Cmax by 2.2-fold and AUC by 2-fold.(3) BCRP inhibitors linked to this monograph include: clopidogrel, curcumin, encorafenib, lazertinib, ritonavir, rolapitant, roxadustat, tolvaptan, turmeric, and zongertinib.(2-9)

*None.

• Lactation

• Heart failure
• Interstitial lung disease
• Pregnancy

There are no moderate contraindications for this drug.

The most common adverse reactions (>=20%) reported with zongertinib are diarrhea, hepatotoxicity, rash, fatigue, and nausea.

The most common (>=2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased ALT, increased AST, decreased potassium, and increased gamma glutamyl transferase.

More Frequent

• Drug-induced hepatitis
• Dyspnea

Less Frequent

• Pneumonia
• Pulmonary thromboembolism

More Frequent

• Abnormal hepatic function tests
• Anemia
• Cough
• Diarrhea
• Elevated serum amylase
• Elevated serum lipase
• Fatigue
• Hyperbilirubinemia
• Hypercholesterolemia
• Hypertriglyceridemia
• Hypoalbuminemia
• Hypocalcemia
• Hypokalemia
• Hypomagnesemia
• Hyponatremia
• Increased creatine kinase level
• Leukopenia
• Lymphopenia
• Musculoskeletal pain
• Nail disorders
• Nausea
• Prolonged activated partial thromboplastin time
• Skin rash
• Thrombocytopenic disorder
• Upper respiratory infection
• Vomiting

Less Frequent

• Dry skin
• Peripheral neuropathy
• Stomatitis

No enhanced messaging available.

Safety and efficacy of zongertinib have not been established in pediatric patients.

There are no available human data on zongertinib use in pregnant women; however, based on animal studies, zongertinib can cause fetal harm when administered during pregnancy. When administered to pregnant rats, structural abnormalities and alterations to growth occurred at maternal exposures >=19 times the human exposure based on AUC at the recommended dose.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

It is not known whether zongertinib is distributed into human milk, or if the drug has any effects on the breastfed infant or on milk production.

Advise women not to breastfeed during treatment with zongertinib and for 2 weeks after the last dose.

Of the 260 patients with non-squamous non-small cell lung cancer (NSCLC) with human epidermal growth factor receptor (HER)2 (ERBB2) mutations who were treated with zongertinib, 46% were 65 years of age or older and 12% were 75 years of age or older. No overall differences in safety or efficacy were observed between elderly and younger patients.