Enhertu Special Precautions

Interstitial Lung Disease/Pneumonitis: Cases of interstitial lung disease (ILD) and/or pneumonitis have been reported with ENHERTU (see Adverse Reactions). Fatal outcomes have been observed.
Patients should be advised to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Patients should be monitored for signs and symptoms of ILD/pneumonitis. Evidence of ILD/pneumonitis should be promptly investigated. Patients with suspected ILD/pneumonitis should be evaluated by radiographic imaging. Consultation with a pulmonologist should be considered. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). ENHERTU should be withheld until recovery to Grade 0 and may be resumed according to instructions in Table 6 (see Dosage & Administration). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. ENHERTU should be permanently discontinued in patients who are diagnosed with symptomatic (Grade 2 or greater) ILD/pneumonitis (see Dosage & Administration). Patients with a history of ILD/pneumonitis or with moderate or severe renal impairment may be at increased risk of developing ILD/pneumonitis and should be monitored carefully (see Dosage & Administration).
In clinical studies (n=1590) across multiple tumor types, ILD occurred in 14.3% of patients treated with ENHERTU 5.4 mg/kg and above as determined by independent review. Most ILD cases were Grade 1 (3.7%) and Grade 2 (7.7%). Grade 3 cases occurred in 1.2% and Grade 4 cases occurred in 0.1% of patients. Grade 5 events occurred in 1.6% of patients. One patient had pre-existing ILD that worsened post treatment leading to Grade 5 ILD. Median time to first onset was 5.4 months (range: -0.5 to 23.3).
Neutropenia: Cases of neutropenia, including febrile neutropenia, were reported in clinical studies of ENHERTU.
Complete blood counts should be monitored prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction (see Dosage & Administration).
In clinical studies (n=1590) across multiple tumor types, neutropenia was reported in 37.9% of patients treated with ENHERTU 5.4 mg/kg and above and 21.1% had Grade 3 or 4 events. Median time to first onset was 22 days (range: 1 day to 24.8 months). Febrile neutropenia was reported in 2.0% of patients.
Left Ventricular Ejection Fraction Decrease: Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies. LVEF should be assessed prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. LVEF decrease should be managed through treatment interruption. ENHERTU should be permanently discontinued if LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed. ENHERTU should be permanently discontinued in patients with symptomatic congestive heart failure (CHF) (see Dosage & Administration).
In clinical studies (n=1590) across multiple tumor types in patients treated with ENHERTU 5.4 mg/kg and above, LVEF decrease was reported in 3.0% of patients, of which 0.4% were Grade 3. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.
Embryo-Fetal Toxicity: ENHERTU can cause fetal harm when administered to a pregnant woman. In postmarketing reports, use of trastuzumab, a HER2 receptor antagonist, during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Based on findings in animals and its mechanism of action, the topoisomerase I inhibitor component of ENHERTU can also cause embryo-fetal harm when administered to a pregnant woman (see Use in Pregnancy & Lactation).
The pregnancy status of females of reproductive potential should be verified prior to the initiation of ENHERTU. The patient should be informed of the potential risks to the fetus. Females of reproductive potential should be advised to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Male patients with female partners of reproductive potential should be advised to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU (see Use in Pregnancy & Lactation).