Hyrnuo therapy should be initiated and supervised by physicians experienced in the use of anti-cancer therapies. Patient selection The presence of HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations in tumour specimens must be confirmed using a validated test prior to initiation of therapy with Hyrnuo.
Posology Adults The recommended dose of Hyrnuo is 20 mg (two 10 mg tablets) taken twice a day until disease progression or unacceptable toxicity. If vomiting occurs after taking Hyrnuo, the patient must not take an additional dose. The next dose should be taken at its scheduled time.
Missed Dose If a dose of Hyrnuo is missed, the dose should be taken as soon as the patient remembers prior to the next scheduled dose, but not within 30 minutes of the next scheduled dose. The patient should not take two doses together to make up for a missed dose.
Dose Modifications due to Adverse Reactions Management of adverse reactions may require dose interruption, dose reduction and / or discontinuation of Hyrnuo. The recommended dose reduction levels are outlined in Table 1. Patients who are unable to tolerate 10 mg once daily should discontinue Hyrnuo treatment permanently.
8).
Table 2:
Recommended Dose Modifications for Hyrnuo for Adverse Reactions Adverse Reaction Severitya Recommended Hyrnuo dose modification and measures Diarrhoea Intolerable or - Withhold Hyrnuo until recovery to Grade ≤1. Adverse Reaction Severitya Recommended Hyrnuo dose modification and measures recurrent Grade 2 - Resume Hyrnuo at the same dose or the next lower dose as clinically appropriate.
Grade 3 - Withhold Hyrnuo until recovery to Grade ≤1. - For first occurrence, resume Hyrnuo at the same dose or the next lower dose. - For re-occurrence, resume Hyrnuo at the next lower dose. 4) Grade 4 - Permanently discontinue Hyrnuo.
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. 4) ALT or AST ≥ 3× ULN with total bilirubin ≥ 2× ULN or Grade 4 total bilirubin - Permanently discontinue Hyrnuo.
4) Any Grade - Permanently discontinue Hyrnuo. Intolerable or recurrent Grade 2 - Withhold Hyrnuo until recovery to Grade ≤1. - Resume Hyrnuo at the same dose or the next lower dose as clinically appropriate. Grade 3 - Withhold Hyrnuo until recovery to Grade ≤1.
- For first occurrence, resume Hyrnuo at the same dose or the next lower dose. - For re-occurrence, resume Hyrnuo at the next lower dose. 4) Grade 4 - Permanently discontinue Hyrnuo. Intolerable or recurrent Grade 2 - Withhold Hyrnuo until recovery to Grade ≤1.
- Resume Hyrnuo at the same dose or the next lower dose as clinically appropriate. 4) Grade 3 - Withhold Hyrnuo until recovery to Grade ≤1. - For first occurrence, resume Hyrnuo at the same dose or the next lower dose. Adverse Reaction Severitya Recommended Hyrnuo dose modification and measures - For re-occurrence, resume Hyrnuo at the next lower dose.
Grade 4 - Permanently discontinue Hyrnuo. Intolerable or recurrent Grade 2 - Withhold Hyrnuo until recovery to Grade ≤1. - Resume Hyrnuo at the same dose or the next lower dose as clinically appropriate. Grade 3 - Withhold Hyrnuo until recovery to Grade ≤1.
- For first occurrence, resume Hyrnuo at the same dose or the next lower dose. - For re-occurrence, resume Hyrnuo at the next lower dose. Other adverse reactions Grade 4 - Permanently discontinue Hyrnuo. 0 Dose Modifications due to concomitant use with strong CYP3A4 inhibitors Concomitant use of strong CYP3A4 inhibitors with Hyrnuo is not recommended.
5). 2), Hyrnuo should be temporarily withheld until treatment with the strong CYP3A4 inhibitor is completed. After the CYP3A4 inhibitor has been discontinued for 3 to 5 elimination half- lives, Hyrnuo should be resumed at the dose taken prior to initiating the inhibitor.
Table 3:
Recommended Dose Reductions of Hyrnuo for Concomitant Use of Strong CYP3A4 Inhibitors Current Hyrnuo Dosage Adjusted Hyrnuo Dosage Two 10 mg tablets twice daily (total daily dose of 40 mg) One 10 mg tablet twice daily (total daily dose of 20 mg) One 10 mg tablet twice daily (total daily dose of 20 mg) One 10 mg tablet once daily (total daily dose of 10 mg) One 10 mg tablet once daily (total daily dose of 10 mg) Withhold Hyrnuo Special populations Paediatric population Safety and efficacy of Hyrnuo in children and adolescents below 18 years of age have not been established.
2). Hepatic Impairment Use in patients with moderate and severe hepatic impairment is not recommended. 2). 5 to ≤3 x ULN and any AST) or severe (total bilirubin >3 x ULN and any AST) […]