Source: FDA, National Drug Code (US) Revision Year: 2025
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-approved test, and who have received prior systemic therapy [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.
Select patients for treatment of unresectable or metastatic NSCLC based on the presence of HER2 (ERBB2) tyrosine kinase domain activating mutations in tumor specimens [see Clinical Studies (14)]. Information on FDA-approved tests for HER2 (ERBB2) tyrosine kinase domain activating mutations is available at: http://www.fda.gov/CompanionDiagnostics.
The recommended dosage of HERNEXEOS is based on body weight:
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.
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.
If a dose is vomited, do not take an additional dose. Take the next dose at the regularly scheduled time.
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 |
|---|---|---|
| Hepatotoxicity [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 HERNEXEOS until recovered to ≤ Grade 1. • Resume HERNEXEOS at reduced dose level. | |
| Grade 3 or Grade 4 | • Interrupt HERNEXEOS until recovered to ≤ Grade 1. • Resume HERNEXEOS at reduced dose level. • Permanently discontinue HERNEXEOS 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 [see Adverse Reactions (6.1)] | Grade 3 | • Interrupt HERNEXEOS until recovered to ≤ Grade 1 or baseline. • Resume HERNEXEOS at reduced dose level. |
| Grade 4 | • Permanently discontinue HERNEXEOS. |
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria for Adverse Events; ULN = upper limit of normal
Avoid concomitant use of strong CYP3A inducers with HERNEXEOS.
If concomitant use cannot be avoided, increase the HERNEXEOS dose based on body weight [see Drug Interactions (7.1)]:
After discontinuing a CYP3A inducer, resume the HERNEXEOS dose (7 to 14 days after discontinuing the CYP3A inducer) that was taken prior to initiating the CYP3A inducer.
Overdose in one patient who ingested 600 mg of HERNEXEOS resulting in nausea and vomiting.
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.
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