HERNEXEOS zongertinib 60 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Zongertinib is used to treat certain types of non-small cell lung cancer (NSCLC). Zongertinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.
Read the full MedlinePlus article ↗- Hernexeos is a targeted cancer treatment specifically for adults with a type of lung cancer called non-squamous non-small cell lung cancer (NSCLC) that either can't be removed by s...
- What exactly is Hernexeos being used to treat in my case?
- Good news — you can take Hernexeos with or without food, whichever is easiest for you. The important thing is to swallow the tablet whole with water. Don't split, crush, or chew it...
- Can I take this pill with food, or does it need to be on an empty stomach?
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $366.18 | $10,985.54 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Hernexeos 60 mgthis 00597-9257-59 | Boehringer | 30 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11608343 ↗ | Drug substance | U-4245 | Jul 21, 2041 |
| US 12171739 ↗ | Drug substance | — | Nov 15, 2026 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Aug 8, 2030 |
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00597-9257-59 You're viewing this | 1 BOTTLE, PLASTIC in 1 CARTON (0597-9257-59) / 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC | 2026-01-06 | Active |
| 00597-9257-86 | 1 BOTTLE, PLASTIC in 1 CARTON (0597-9257-86) / 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC | 2025-08-08 | Active |
Pack size FAQ
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE HERNEXEOS is indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test [see Dosage and Administration (2.1) ] . This indication is approved under accelerated approval based on objective response rate and duration of response [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
HERNEXEOS is a kinase inhibitor indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test. ( 1 ) This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Select patients for treatment with HERNEXEOS based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations. ( 2.1 ) The recommended dosage of HERNEXEOS is based on body weight: ( 2.2 ) Patients weighing less than 90 kg: 120 mg ( 2.2 ) Patients weighing 90 kg or greater: 180 mg ( 2.2 ) Take HERNEXEOS orally once daily with or without food until disease progression or unacceptable toxicity. ( 2.2 )
2.1Patient Selection Select patients for treatment of unresectable or metastatic NSCLC based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations in tumor or plasma specimens [see Clinical Studies (14) ] . If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-authorized tests for HER2 (ERBB2) tyrosine kinase domain activating mutations is available at: http://www.fda.gov/CompanionDiagnostics.
2.2Recommended Dosage and Administration The recommended dosage of HERNEXEOS is based on body weight: Patients weighing less than 90 kg: 120 mg Patients weighing 90 kg or greater: 180 mg Take HERNEXEOS orally once daily with or without food until disease progression or unacceptable toxicity. Swallow HERNEXEOS tablets whole with water. Do not split, crush, or chew tablets.
Missed Dose If a dose is missed within 12 hours, take the dose. If a dose is missed by more than 12 hours, skip the missed dose and take the next scheduled dose. Vomited Dose If a dose is vomited, do not take an additional dose.
Take the next dose at the regularly scheduled time.
2.3Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are presented in Table 1. Table 1 Recommended HERNEXEOS Dose Reductions for Adverse Reactions Current HERNEXEOS Dose First Reduction Second Reduction 180 mg 120 mg 60 mg 120 mg 60 mg Permanently discontinue Permanently discontinue HERNEXEOS in patients who are unable to tolerate 60 mg once daily. The recommended dosage modifications for adverse reactions are presented in Table 2.
Table 2 Recommended HERNEXEOS Dosage Modifications for Adverse Reactions Adverse Reaction Severity* Dosage Modification ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal *Based on Common Terminology Criteria for Adverse Events (CTCAE) version
5.0Hepatotoxicity [see Warnings and Precautions (5.1) ] Grade 3 or 4 ALT and/or AST without increased total bilirubin Interrupt HERNEXEOS until recovered to ≤ Grade 1 or baseline. Resume HERNEXEOS at reduced dose level. Grade 3 total bilirubin Interrupt HERNEXEOS until recovered to ≤ Grade 1 or baseline.
Resume HERNEXEOS at reduced dose level. Grade 4 total bilirubin Permanently discontinue HERNEXEOS. ALT or AST ≥ 3× ULN with total bilirubin ≥ 2× ULN Permanently discontinue HERNEXEOS.
Left Ventricular Dysfunction [see Warnings and Precautions (5.2) ] LVEF 40 to 50% and decrease from baseline of 10 to 19% Interrupt HERNEXEOS until recovered to ≤ Grade 1 or within 10% from baseline. If recovered to ≤ Grade 1 in ≤ 4 weeks, resume HERNEXEOS at the same dose level. If not recovered to ≤ Grade 1 within 4 weeks, permanently discontinue HERNEXEOS.
LVEF 20 to 39% or ≥ 20% decrease from baseline Interrupt HERNEXEOS until recovered to ≤ Grade 1 or within 10% from baseline. If recovered to ≤ Grade 1 in ≤ 4 weeks, resume HERNEXEOS at the reduced dose level. If not recovered to ≤ Grade 1 within 4 weeks, permanently discontinue HERNEXEOS.
Symptomatic Congestive Heart Failure Permanently discontinue HERNEXEOS. Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.3) ] Grade 2 Withhold HERNEXEOS until resolution. Resume HERNEXEOS at reduced dose level.
Permanently discontinue HERNEXEOS for recurrent ILD/pneumonitis. Grade 3 or Grade 4 Permanently discontinue HERNEXEOS. Diarrhea [see Adverse Reactions (6.1) ] Grade 2 Maintain HERNEXEOS dose.
Initiate anti-diarrheal treatment. Grade 2 lasting ≥ 2 days despite anti-diarrheal treatment Interrupt…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 60 mg tablets: yellow, oval, biconvex, film-coated tablets, debossed with "L6" on one side and the Boehringer Ingelheim company symbol on the other side. Each tablet contains 60 mg of zongertinib. Tablets: 60 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hepatotoxicity : Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to administration, every 2 weeks during the first 12 weeks, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on severity. ( 5.1 ) Left Ventricular Dysfunction : Monitor LVEF at baseline prior to administration and at regular intervals during treatment and as clinically indicated.
Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on severity. ( 5.2 ) Interstitial Lung Disease/Pneumonitis : Monitor for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on severity.
( 5.3 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.4 )
5.1Hepatotoxicity HERNEXEOS can cause severe and life-threatening hepatotoxicity, including drug induced liver injury. In the pooled safety population [see Adverse Reactions (6.1) ], based on adverse reaction data, hepatotoxicity occurred in 27% of patients treated with HERNEXEOS. Grade 3 drug induced liver injury occurred in 1.4% and Grade 4 in 0.3% of patients treated with HERNEXEOS.
Grade 3 hepatic failure occurred in 0.3% of patients treated with HERNEXEOS. Based on laboratory data, 37% of patients treated with HERNEXEOS experienced increased alanine aminotransferase (ALT), including 4.9% Grade 3 and 1% Grade 4. Increased aspartate aminotransferase (AST) occurred in 31% of patients treated with HERNEXEOS, including 3.8% Grade 3 and 0.7% Grade 4.
Increased bilirubin occurred in 20% of patients treated with HERNEXEOS, including 1% Grade 3 and 0.3% Grade 4. HERNEXEOS was interrupted for an adverse reaction of hepatotoxicity in 8% of patients, the dose was reduced in 3.8% and permanently discontinued in 1%. Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to administration of HERNEXEOS, every 2 weeks during the first 12 weeks, and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations.
Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on the severity of the adverse reaction [see Dosage and Administration (2.3) ].
5.2Left Ventricular Dysfunction HERNEXEOS can cause severe left ventricular dysfunction. Decreases in left ventricular ejection fraction (LVEF) have occurred with anti-HER2 therapies, including HERNEXEOS. Treatment with HERNEXEOS has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.
In the pooled safety population [see Adverse Reactions (6.1) ], LVEF decrease occurred in 6% of patients treated with HERNEXEOS, including 1.7% Grade 3. Two patients with Grade 3 LVEF decrease required permanent discontinuation of HERNEXEOS. The median time to onset of decreased LVEF was 12 weeks (range: 2.9 to 63 weeks).
Before initiating HERNEXEOS, evaluate LVEF and monitor at regular intervals during treatment and as clinically indicated. Interrupt, reduce the dose, or permanently discontinue HERNEXEOS based on the severity of the adverse reaction [see Dosage and Administration (2.3) ].
5.3Interstitial Lung Disease/Pneumonitis HERNEXEOS can cause severe and life-threatening interstitial lung disease (ILD)/pneumonitis. In the pooled safety population [see Adverse Reactions (6.1) ], ILD/pneumonitis occurred in 2.1% of patients treated with HERNEXEOS. The median time to first onset of ILD/pneumonitis was 13 weeks (range: 1.4 to 65 weeks).
One patient was able to resume therapy after resolution of pneumonitis. Two patients required permanent discontinuation and one patient died with unresolved pneumonitis > 30 days a…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.2) ] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 20%) are diarrhea, rash, hepatotoxicity, fatigue, nausea, musculoskeletal pain, and upper respiratory tract infection. ( 6.1 ) The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma glutamyl transferase, decreased potassium, and decreased neutrophils.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to HERNEXEOS in 292 patients with unresectable or metastatic non-squamous NSCLC with HER2 (ERBB2) mutations who received HERNEXEOS as a single agent at 120 mg orally once daily until disease progression or unacceptable toxicity in Beamion LUNG-1 [see Clinical Studies (14) ] .
Among 292 patients who received HERNEXEOS, 59% of patients were exposed for 6 months or longer and 28% were exposed for greater than one year. In this pooled safety population, the most common (≥ 20%) adverse reactions were diarrhea (54%), rash (28%), hepatotoxicity (27%), fatigue (25%), nausea (23%), musculoskeletal pain (21%), and upper respiratory tract infection (20%). The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (10%), increased alanine aminotransferase (6%), increased aspartate aminotransferase (4.5%), increased gamma glutamyl transferase (2.8%), decreased potassium (2.4%), and decreased neutrophils (2.4%).
Beamion LUNG-1 The safety of HERNEXEOS was evaluated in Beamion LUNG-1 in 177 patients with unresectable or metastatic non-squamous NSCLC with HER2 tyrosine kinase domain (TKD) mutations; 72 patients had not received prior treatment; 105 patients had received prior platinum-based chemotherapy, and out of those patients, 34 patients had received prior treatment with a HER2-directed antibody drug conjugate (ADC) [see Clinical Studies (14) ] . Patients received HERNEXEOS as a single agent at 120 mg once daily until disease progression or unacceptable toxicity.
Among patients who received HERNEXEOS, 74% were exposed for 6 months or longer and 42% were exposed for greater than one year. The median age of patients who received HERNEXEOS was 63 years (range 30 to 88), 61% were female, 41% White, 48% Asian, and 0.6% Black or African American; 11% had unknown race data; 3.4% were of Hispanic or Latino ethnicity; and 38% had an Eastern Cooperative Oncology Group (ECOG) performance score of 0 and 62% had an ECOG performance score of 1. Serious adverse reactions occurred in 36% of patients receiving HERNEXEOS.
Serious adverse reactions in ≥ 2% of patients included pulmonary embolism (4%), dyspnea (3.4%), pneumonia (2.8%), hepatotoxicity, pleural effusion, and pericardial effusion (2.3%). Fatal adverse reactions occurred in one patient (0.6%) who received HERNEXEOS, due to pneumonia. Permanent discontinuation of HERNEXEOS due to an adverse reaction occurred in 6% of patients.
Adverse reactions which resulted in permanent discontinuation of HERNEXEOS were hepatotoxicity, decreased ejection fraction, anemia, increased blood alkaline phosphatase, diarrhea, dyspnea, increased gamma-glutamyl transferase, hemoptysis, pericardial effusion, pneumonitis, and pyrexia. Dos…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Strong CYP3A Inducers : Avoid concomitant use with strong CYP3A inducers. If concomitant use cannot be avoided, increase HERNEXEOS dose. ( 7.1 ) BCRP Substrates : Avoid concomitant use with certain BCRP substrates where minimal concentration increase may lead to serious adverse reactions and consider alternative therapies.
If concomitant use cannot be avoided, monitor patients closely for adverse reactions and follow recommendations provided in the BCRP substrate approved product labeling. For other BCRP substrates, monitor for increased adverse reactions and adjust the dosages of those substrates as clinically appropriate. ( 7.2 )
7.1Effects of Other Drugs on HERNEXEOS Avoid concomitant use of HERNEXEOS with strong CYP3A inducers. If concomitant use cannot be avoided, increase HERNEXEOS dose as recommended [see Dosage and Administration (2.4) ]. Zongertinib is a CYP3A substrate. Strong CYP3A inducers decrease zongertinib exposure [see Clinical Pharmacology (12.3) ] , which may reduce effectiveness of HERNEXEOS.
7.2Effects of HERNEXEOS on Other Drugs BCRP Substrates Avoid concomitant use of HERNEXEOS with certain BCRP substrates where minimal concentration changes may lead to serious adverse reactions. If coadministration cannot be avoided, monitor for increased adverse reactions and follow recommendations provided in the approved product labeling for the BCRP substrate. For other BCRP substrates, monitor for increased adverse reactions and adjust the dosages of those substrates as clinically appropriate.
Zongertinib is a BCRP inhibitor. HERNEXEOS increases exposure of BCRP substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ], HERNEXEOS can cause fetal harm when administered to a pregnant woman. There are no available data on the use of HERNEXEOS in pregnant women to inform a drug-associated risk. Oral administration of zongertinib to pregnant rats during the period of organogenesis caused structural abnormalities and alterations to growth at maternal exposures ≥ 19 times the human exposure based on AUC at the recommended dose [see Data ] .
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of 10, 30, or 60 mg/kg/day of zongertinib during the period of organogenesis (gestation day 7 to 18).
Zongertinib caused decreased fetal weights, delayed development of the urinary system, and kidney hydronephrosis at 60 mg/kg/day (approximately 19 times the human exposure based on AUC at the recommended dose). In an embryo-fetal development study in rabbits, there were no adverse embryo-fetal findings in pregnant animals administered oral doses of zongertinib up to 120 mg/kg/day (2.4 times the human exposure based on AUC at the recommended dose) during the period of organogenesis (gestation day 6 to 19). A literature-based assessment of the effects on reproduction demonstrated that mice expressing catalytically inactive HER2 die at mid-gestation due to cardiac dysfunction.
8.2Lactation Risk Summary There are no data on the presence of zongertinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with HERNEXEOS and for 2 weeks after the last dose.
8.3Females and Males of Reproductive Potential Based on findings from animal studies and its mechanism of action, HERNEXEOS can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating HERNEXEOS. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with HERNEXEOS and for 2 weeks after the last dose.
Infertility Females Based on findings from animal studies, HERNEXEOS may impair fertility in females. The effects in female animals were reversible [see Nonclinical Toxicology (13.1) ] . Males Based on findings from animal studies, HERNEXEOS may impair fertility in males of reproductive potential.
The effect on testes in animals was not reversible within a 4-week recovery period [see Nonclinical Toxicology (13.1) ] .
8.4Pediatric Use The safety and effectiveness of HERNEXEOS have not been established in pediatric patients.
8.5Geriatric Use Of the 292 patients with non-squamous NSCLC with HER2 (ERBB2) mutations who received HERNEXEOS in clinical studies, 47% were 65 years of age and older and 13% were 75 years and older. No overall differences in safety or effectiveness of HERNEXEOS were observed between older and younger adult patients.
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ], HERNEXEOS can cause fetal harm when administered to a pregnant woman. There are no available data on the use of HERNEXEOS in pregnant women to inform a drug-associated risk. Oral administration of zongertinib to pregnant rats during the period of organogenesis caused structural abnormalities and alterations to growth at maternal exposures ≥ 19 times the human exposure based on AUC at the recommended dose [see Data ] .
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of 10, 30, or 60 mg/kg/day of zongertinib during the period of organogenesis (gestation day 7 to 18).
Zongertinib caused decreased fetal weights, delayed development of the urinary system, and kidney hydronephrosis at 60 mg/kg/day (approximately 19 times the human exposure based on AUC at the recommended dose). In an embryo-fetal development study in rabbits, there were no adverse embryo-fetal findings in pregnant animals administered oral doses of zongertinib up to 120 mg/kg/day (2.4 times the human exposure based on AUC at the recommended dose) during the period of organogenesis (gestation day 6 to 19). A literature-based assessment of the effects on reproduction demonstrated that mice expressing catalytically inactive HER2 die at mid-gestation due to cardiac dysfunction.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of HERNEXEOS have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 292 patients with non-squamous NSCLC with HER2 (ERBB2) mutations who received HERNEXEOS in clinical studies, 47% were 65 years of age and older and 13% were 75 years and older. No overall differences in safety or effectiveness of HERNEXEOS were observed between older and younger adult patients.
🆘 Overdosage ▾
10 OVERDOSAGE Overdose in one patient who ingested 600 mg of HERNEXEOS resulted in nausea and vomiting.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Zongertinib is a kinase inhibitor of human epidermal growth factor receptor 2 (HER2). In vitro, zongertinib inhibited phosphorylation of HER2, downstream signaling of HER2 (phosphorylation of ERK), and proliferation of lung cancer cells harboring HER2 tyrosine kinase domain activating mutations. In vivo, zongertinib demonstrated anti-tumor activity in mouse xenograft models of NSCLC harboring HER2 tyrosine kinase domain activating mutations.
12.2Pharmacodynamics The exposure-response relationship and time-course of pharmacodynamic response of zongertinib have not been fully characterized. Cardiac Electrophysiology At 2.6 times the mean maximal concentration provided by the recommended dose of 120 mg, a mean increase in the QTc interval > 20 ms was not observed.
12.3Pharmacokinetics Zongertinib pharmacokinetics were observed at steady state in patients with advanced or metastatic solid tumors with HER2 aberrations at the approved recommended dosage and are presented as geometric mean (CV%), unless otherwise specified. Zongertinib maximum concentration (C max,ss ) is 3 (37%) µmol/L and the total systemic exposure (AUC) is 34 (34%) µmol*h/L following HERNEXEOS 120 mg orally daily. Zongertinib C max and AUC increase in an approximately dose proportional manner across the dose range of 60 mg (0.5 times the approved recommended dosage) to 360 mg (3 times the approved recommended dosage).
Zongertinib accumulation is approximately 1.5-fold for AUC and 1.3-fold for C max at the approved recommended dosage. Steady state is achieved within 2.5 days. Absorption Zongertinib median (min, max) time to maximum plasma concentration (T max ) is approximately 2 hours (min, max: 2, 6 hours).
Zongertinib absolute oral bioavailability is 76%. Effect of Food No clinically significant differences in zongertinib C max and AUC were observed following administration of a single 240 mg dose (2 times the approved recommended dose) with a high-fat meal (approximately 1,000 calories, approximately 50% fat). Distribution Zongertinib plasma protein binding is > 99%.
The apparent (oral) volume of distribution is 118 L (29%). Elimination Zongertinib effective half-life is 12 hours (21%) with an apparent (oral) clearance of 115 mL/min (31%). Metabolism Based on in vitro metabolite profiling, CYP-mediated oxidation pathways represent 48% to 62% (mainly CYP3A4 and CYP3A5), glucuronidation 13% to 25% (mainly UGT1A4), and glutathione conjugation 13% to 26% of total hepatic metabolism.
Unchanged zongertinib represented the majority (75%) of total radioactivity in plasma. Excretion After a single oral dose of radiolabeled zongertinib 60 mg to healthy participants, approximately 93% of the dose was recovered in feces (31% unchanged) and 1.3% in urine (0.2% unchanged). Specific Populations The apparent volume of distribution and clearance of zongertinib increase with increasing body weight (34 to 122 kg).
No clinically significant differences in the pharmacokinetics of zongertinib were observed based on age (30 to 88 years), sex, race (36% White, 49% Asian, 1.3% Black/African American), eGFR 60 to < 90 mL/min, or mild (defined as Child-Pugh A; AST > ULN and total bilirubin ≤ ULN; or total bilirubin > 1 to 1.5× ULN and any AST) and moderate (Child-Pugh B) hepatic impairment. The effect of eGFR 15 to < 60 mL/min, end-stage renal disease (eGFR < 15 mL/min) and severe hepatic impairment on the pharmacokinetics of zongertinib has not been studied.
Drug Interaction Studies CYP3A Inducers: Zongertinib AUC decreased by 63% and C max decreased by 43% following concomitant use of carbamazepine (strong CYP3A inducer) 600 mg once daily for 7 days. The effect of concomitant use of moderate CYP3A inducers on zongertinib C max and AUC are unknown. BCRP Substrates : Rosuvastatin (BCRP substrate) C max increased 3-fold and AUC 2.3-fold following concomitant use of HERNEXEOS 120 mg daily for 12 days.
Other Drugs: No clinically significa…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Zongertinib is a kinase inhibitor of human epidermal growth factor receptor 2 (HER2). In vitro, zongertinib inhibited phosphorylation of HER2, downstream signaling of HER2 (phosphorylation of ERK), and proliferation of lung cancer cells harboring HER2 tyrosine kinase domain activating mutations. In vivo, zongertinib demonstrated anti-tumor activity in mouse xenograft models of NSCLC harboring HER2 tyrosine kinase domain activating mutations.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 60 mg tablets: yellow, oval, biconvex, film-coated, debossed with "L6" on one side and the Boehringer Ingelheim company symbol on the other side. They are packaged in a bottle containing two silica gel desiccants and with a child-resistant closure, available as follows: Carton containing one bottle of 30 tablets each NDC: 0597-9257-59 Carton containing one bottle of 60 tablets each NDC: 0597-9257-86 Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Store in the original container to protect from moisture. Keep the bottle tightly closed. Do not remove the desiccants.
Once opened, use within 3 months. Discard any unused tablets 3 months after opening the bottle.
📦 Storage and Handling ▾
Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store in the original container to protect from moisture. Keep the bottle tightly closed. Do not remove the desiccants. Once opened, use within 3 months. Discard any unused tablets 3 months after opening the bottle.
📋 Description ▾
11 DESCRIPTION HERNEXEOS tablets for oral administration contain zongertinib, a kinase inhibitor. The chemical name of zongertinib is 2-Propenamide, N -[1-[8-[[3-methyl-4-[(1-methyl-1 H -benzimidazol-5-yl)oxy]phenyl] amino]pyrimido[5,4- d ]pyrimidin-2-yl]-4-piperidinyl]-. Its molecular formula is C 29 H 29 N 9 O 2 and the molecular weight is 535.6.
The structural formula is: Zongertinib is a yellow to dark yellow or orange solid. Zongertinib is slightly soluble at pH 1.2, and practically insoluble at pHs 3.6, 4.5, 5.4 and 6.8. Each film-coated tablet of HERNEXEOS contains 60 mg of zongertinib and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, mannitol, microcrystalline cellulose, and sodium stearyl fumarate.
In addition, the film-coating contains the following inactive ingredients: ferric oxide (yellow), glycerol mono and dicaprylocaprate, polyvinyl alcohol, sodium lauryl sulfate, talc, and titanium dioxide. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Hepatotoxicity Inform patients that HERNEXEOS can cause severe and life-threatening hepatotoxicity and that they will need to undergo lab tests to monitor liver enzymes during treatment [see Warnings and Precautions (5.1) ] . Advise patients to immediately contact their healthcare provider for signs and symptoms of hepatotoxicity.
Left Ventricular Dysfunction Inform patients that HERNEXEOS can cause severe left ventricular dysfunction. Advise patients to immediately contact their healthcare provider for new or worsening cardiovascular symptoms [see Warnings and Precautions (5.2) ]. Interstitial Lung Disease (ILD)/Pneumonitis Inform patients that HERNEXEOS can cause severe or life-threatening ILD/pneumonitis.
Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms [see Warnings and Precautions (5.3) ]. Diarrhea Inform patients that HERNEXEOS can cause diarrhea. Advise patients to immediately contact their healthcare provider for new or worsening diarrhea [see Adverse Reactions (6.1) ].
Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise females of reproductive potential to use effective contraception during treatment with HERNEXEOS and for 2 weeks after the last dose [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1 , 8.3) ] .
Lactation Advise women not to breastfeed during treatment with HERNEXEOS and for 2 weeks after the last dose [see Use in Specific Populations (8.2) ] . Infertility Advise females and males of reproductive potential that HERNEXEOS may impair fertility [see Use in Specific Populations (8.3) ] . Administration Instructions Instruct patients weighing less than 90 kg to take two 60 mg tablets once daily to achieve a complete 120 mg dose and instruct patients weighing 90 kg or greater to take three 60 mg tablets once daily to achieve a complete 180 mg dose [see Dosage and Administration (2.2) ] .
HERNEXEOS film-coated tablets can be taken with or without food [see Clinical Pharmacology (12.3) ]. Instruct patients to swallow HERNEXEOS tablets whole with water. Do not split, crush, or chew tablets.
Inform patients that if they miss a dose of HERNEXEOS within 12 hours, they should take it as soon as they remember. If a dose is missed by more than 12 hours, the patient should skip the missed dose and wait until the next scheduled dose [see Dosage and Administration (2.2) ] . If a dose is vomited, do not take an additional dose.
Take the next dose at the regularly scheduled time.