Hyaluronidase/pertuzumab/trastuzumab Disease Interactions

Pulmonary toxicity, sometimes fatal has been reported with agents that block HER2 activity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest may be at increased risk of pulmonary toxicity and appear to have more severe toxicity. Patients should be monitored for pulmonary symptoms. Permanently discontinue treatment with these agents in patients diagnosed with interstitial lung disease or pneumonitis and institute appropriate care.

Decreases in left ventricular ejection fraction (LVEF) have been reported with agents that block HER2 activity. Patients who have received prior anthracyclines, those who received anthracycline after stopping therapy with agents that block HER2 activity, or patients who received prior radiotherapy to the chest area may be at higher risk of decreased LVEF. Therapy with these agents should be administered cautiously in patients with a previous history of heart conditions. Evaluate cardiac function before, during, and upon completion of treatment. Withhold or discontinue therapy with agents that block HER2 activity as appropriate, and for a confirmed clinically significant decrease in left ventricular function, or if the LVEF has not improved or has declined further. It is recommended to monitor overall cardiac function and LVEF by echocardiogram or MUGA scan as appropriate.

Peripheral neuropathy has been reported with the use of agents that block HER2 activity. Patients experiencing peripheral neuropathy may require temporary interruption, dose reduction, or treatment discontinuation of these agents. Withhold dosing temporarily for patients experiencing Grade 3 or 4 peripheral neuropathy until resolution. Close monitoring is recommended when using these agents in patients at risk, and all patients should be monitored on an ongoing basis for signs or symptoms of neurotoxicity.

Thrombocytopenia has been reported with the use of agents that block HER2 activity. Monitor platelet counts prior to initiation of therapy and prior to each dose. If appropriate modify the dose according to clinical guidelines. Patients with decreased platelet count and patients on anti-coagulant treatment should be closely monitored during treatment with these agents.

No dose adjustment of pertuzumab is necessary in patients with mild or moderate renal impairment. Caution should be exercised if pertuzumab is used in patients with severe renal impairment as there is limited pharmacokinetic data available. Clinical monitoring of renal function is recommended.