HYRNUO Film-coated tablet Ref.[116094] Active ingredients: Sevabertinib

Source: FDA, National Drug Code (US)  Revision Year: 2025 

1. Indications and Usage

HYRNUO is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1)], and who have received a prior systemic therapy.

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

2. Dosage and Administration

2.1 Patient Selection

Select patients for treatment of locally advanced or metastatic non-squamous NSCLC based on the presence of HER2 (ERBB2) TKD activating mutations in tumor specimens [see Clinical Studies (14)].

Information on FDA-approved tests is available at http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dosage

The recommended dosage of HYRNUO is 20 mg orally twice daily with food, until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3)]. Swallow tablets whole. Do not cut, crush, or chew tablets.

Missed Dose

If a dose is missed, take the missed dose as soon as you remember prior to the next scheduled dose. Do not take 2 doses at the same time to make up for the missed dose.

Vomited Dose

If a dose is vomited, do not take an additional dose. Resume dosing at the next scheduled time.

2.3 Dosage Modifications for Adverse Reactions

The recommended dosage reductions for adverse reactions are provided in Table 1.

Table 1. Recommended HYRNUO Dosage Reductions for Adverse Reactions:

Dose ReductionDosage Modification
First10 mg twice daily
Second10 mg once daily

Permanently discontinue HYRNUO in patients who are unable to tolerate 10 mg once daily.

The recommended dosage modifications for adverse reactions are provided in Table 2.

Table 2. Recommended HYRNUO Dosage Modifications for Adverse Reactions:

Adverse ReactionSeverity*Dosage Modification
Diarrhea [see
Warnings and
Precautions (5.1)]
Intolerable Grade 2 or
Grade 3
• Interrupt HYRNUO until recovery to
Grade ≤1.
• Resume HYRNUO at the same dose or
the next lower dose.
• For recurrence, resume HYRNUO at the
next lower dose.
Grade 4• Permanently discontinue HYRNUO.
Hepatotoxicity [see
Warnings and
Precautions (5.2)]
Grade 2, 3 or 4 ALT
and/or AST without
increased total
bilirubin or Grade 3
total bilirubin
• Interrupt HYRNUO until recovery to
Grade ≤1 or baseline.
• Resume HYRNUO at the next lower
dose.
ALT or AST ≥ 3× ULN
with total bilirubin
≥ 2× ULN or Grade 4
total bilirubin
• Permanently discontinue HYRNUO.
Interstitial lung
disease (ILD)/
pneumonitis
[see Warnings and
Precautions (5.3)]
Any Grade• Permanently discontinue HYRNUO.
Ocular toxicity [see
Warnings and
Precautions (5.4)]
Grade 2• Interrupt HYRNUO until recovery to
Grade ≤1.
• Resume HYRNUO at the next lower
dose.
• For recurrence, permanently discontinue
HYRNUO.
Grade 3 or Grade 4• Permanently discontinue HYRNUO.
Pancreatic Enzyme
Elevation [see
Warnings and
Precautions (5.5)]
Grade 3• Interrupt HYRNUO until recovery to
Grade ≤2 or baseline.
• Resume HYRNUO at the next lower
dose.
Grade 4• Permanently discontinue HYRNUO.
Other adverse
reactions [see
Adverse Reactions
(6.1)]
Intolerable or
recurrent Grade 2
or Grade 3
• Interrupt HYRNUO until recovery
to Grade ≤1.
• Resume HYRNUO at the same dose or
the next lower dose.
• For recurrence, resume HYRNUO at the
next lower dose.
Grade 4Permanently discontinue HYRNUO.

* Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.

2.4 Dosage Modifications for Strong CYP3A Inhibitors

Avoid concomitant use of strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dosage as shown in Table 3. After the CYP3A inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the HYRNUO dosage that was used prior to initiating the inhibitor [see Drug Interactions (7.1)].

Table 3. Recommended HYRNUO Dosage Modifications for Concomitant Use with Strong CYP3A Inhibitors:

Current DosageRecommended Dosage
20 mg twice daily10 mg twice daily
10 mg twice daily10 mg once daily
10 mg once dailyWithhold HYRNUO until strong CYP3A inhibitor is discontinued

16.2. Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

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