General: In order to improve traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.
Left ventricular dysfunction: Decreases in LVEF have been reported with drugs that block HER2 activity, including pertzumab and trastuzumab. The incidence of symptomatic left ventricular systolic dysfunction (LVD [congestive heart failure]) was higher in patients treated with pertuzumab in combination with trastuzumab and chemotherapy compared to trastuzumb and chemotherapy. In the adjuvant setting, the majority of cases of symptomatic heart failure reported were in patients who received anthracycline-based chemotherapy (see Adverse Reactions). Patients who have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of LVEF decreases based on studies with intravenous pertuzumab in combination with trastuzumab and chemotherapy. Phesgo and/or intravenous pertuzumab and trastuzumab have not been studied in patients with: a pretreatment LVEF value of <55% (EBC) or <50% (MBC); a prior history of congestive heart failure (CHF); conditions that could impair left ventricular function such as uncontrolled hypertension, recent myocardial infarction, serious cardiac arrhythmia requiring treatment or a cumulative prior anthracycline exposure to >360 mg/m2 of doxorubicin or its equivalent. Intravenous pertuzumab in combination with trastuzumab and chemotherapy has not been studied in patients with decreases in LVEF <50% during prior trastuzumab adjuvant therapy. Assess LVEF prior to initiation of Phesgo and at regular intervals during treatment to ensure that LVEF is within normal limits (see Table 8 as follows). If the LVEF declines as indicated in Table 8 and has not improved, or has declined further at the subsequent assessment, discontinuation of Phesgo should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks. (See Table 8.)
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Injection/infusion-related reactions (IRRs): Phesgo has been associated with injection-related reactions. Injection-related reactions were defined as any systemic reaction with symptoms such as fever, chills, headache, likely due to a release of cytokines occurring within 24 hours of administration of Phesgo. Close observation of the patient during and for 30 minutes after administration of the loading dose and during and for 15 minutes following the administration of the maintenance dose of Phesgo is recommended. If a significant injection-related reaction occurs, the injection should be slowed down or paused and appropriate medical therapies should be administered. Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be considered in patients with severe injection-related reactions. This clinical assessment should be based on the severity of the preceding reaction and response to administered treatment for the adverse reaction (see Dosage & Administration). Although fatal outcomes resulting from injection-related reactions have not been observed with Phesgo, caution should be exercised as fatal infusion related-reactions have been associated with intravenous pertuzumab in combination with intravenous trastuzumab and chemotherapy.
Hypersensitivity reactions/anaphylaxis: Patients should be observed closely for hypersensitivity reactions. Although severe hypersensitivity reactions, including anaphylaxis and events with fatal outcomes, have not been observed in patients treated with Phesgo, caution should be exercised as these have been associated with intravenous pertuzumab in combination with trastuzumab and chemotherapy (see Adverse Reactions). Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. Phesgo is contraindicated in patients with known hypersensitivity to pertuzumab, trastuzumab, or to any of its excipients (see Contraindications).
Drug Abuse and Dependence: There is no evidence that Phesgo has the potential for drug abuse and dependence.
Ability to Drive and Use Machines: Phesgo has a minor influence on the ability to drive and use machines. Injection-related reactions and dizziness may occur during treatment with Phesgo (see previously mentioned and Adverse Reactions).
Renal Impairment: See Special Dosage Instructions: Renal Impairment under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Hepatic Impairment: The safety and efficacy of Phesgo in patients with hepatic impairment has not been studied.
Use in Children: The safety and efficacy of Phesgo in pediatric patients below 18 years of age have not been established.
Use in the Elderly: No overall differences in efficacy and safety of Phesgo was observed in patients ≥65 (n=26) and <65 years of age (n=222).
However, with intravenous pertuzumab in combination with trastuzumab, the incidence of the following all grade adverse events were at least 5% higher in patients patients ≥65 years of age (n=418) compared to patients <65 years of age (n=2926): decreased appetite, anemia, weight decreased, asthenia, dysgeusia, neuropathy peripheral, hypomagnesemia and diarrhea.