Enhertu Special Precautions

In order to prevent medicinal product errors, it is important to check the vial labels to ensure that the medicinal product being prepared and administered is Enhertu (trastuzumab deruxtecan) and not trastuzumab or trastuzumab emtansine.
Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
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, dyspnoea, 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, preferably a computed tomography (CT) scan. 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 5 (see Dosage & Administration). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate 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 patients with moderate or severe renal impairment may be at increased risk of developing ILD/pneumonitis and should be monitored carefully (see Dosage & Administration).
Neutropenia: Cases of neutropenia, including febrile neutropenia with a fatal outcome, 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).
Left ventricular ejection fraction decrease: Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies. Standard cardiac function testing (echocardiogram or MUGA [multigated acquisition] scanning) should be performed to assess LVEF 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 Table 5 under Dosage & Administration).
Patients with moderate or severe hepatic impairment: There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. As metabolism and biliary excretion are the primary routes of elimination of the topoisomerase I inhibitor, DXd, Enhertu should be administered with caution in patients with moderate and severe hepatic impairment (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Effects on ability to drive and use machines: Enhertu may have a minor influence on the ability to drive and use machines. Patients should be advised to use caution when driving or operating machinery in case they experience fatigue, headache or dizziness during treatment with Enhertu (see Adverse Reactions).
Use in Pregnancy: Embryo-foetal toxicity: Enhertu can cause foetal harm when administered to a pregnant woman. In post-marketing 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, DXd, can also cause embryo-foetal 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 foetus. 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).