Hertraz Adverse Reactions

Summary of the Safety Profile: As per the published literature, amongst the most serious and/or common adverse reactions reported in trastuzumab usage to date are cardiac dysfunction, infusion-related reactions, haematotoxicity (in particular neutropenia), infections and pulmonary adverse reactions.
Tabulated List of Adverse Reactions: In this section, the following categories of frequency have been used: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
As per the published literature, presented in Table 13 are adverse reactions that have been reported in association with the use of intravenous trastuzumab alone or in combination with chemotherapy in pivotal clinical trials and in the post-marketing setting.
All the terms included are based on the highest percentage seen in pivotal clinical trials. (See Table 13a and 13b.)

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Cardiac Dysfunction: As per the published literature, congestive heart failure, NYHA II-IV is a common adverse reaction associated with the use of trastuzumab and has been associated with a fatal out come (see Precautions). Signs and symptoms of cardiac dysfunction such as dyspnoea, orthopnoea, increased cough, pulmonary oedema, S3 gallop, or reduced ventricular ejection fraction, have been observed in patients treated with trastuzumab (see Precautions).
As per the published literature on another trastuzumab product, in 3 pivotal clinical trials of adjuvant trastuzumab given in combination with chemotherapy, the incidence of grade 3/4 cardiac dysfunction (specifically symptomatic Congestive Heart Failure) was similar in patients who were administered chemotherapy alone (ie did not receive trastuzumab) and in patients who were administered trastuzumab sequentially to a taxane (0.3-0.4 %). The rate was highest in patients who were administered trastuzumab concurrently with a taxane (2.0 %). In the neoadjuvant setting, the experience of concurrent administration of trastuzumab and low dose anthracycline regimen is limited (see Precautions).
When trastuzumab was administered after completion of adjuvant chemotherapy NYHA class III-IV heart failure was observed in 0.6 % of patients in the one-year arm after a median follow-up of 12 months. After a median follow-up of 8 years the incidence of severe CHF (NYHA III & IV) following 1 year of trastuzumab therapy (combined analysis of the two trastuzumab treatment arms) was 0.89 %, and the rate of mild symptomatic and asymptomatic left ventricular dysfunction was 6.35 %. Reversibility of severe CHF (defined as a sequence of at least two consecutive LVEF values ≥ 50 % after the event) was evident for 70 % of trastuzumab-treated patients. Reversibility of mild symptomatic and asymptomatic left ventricular dysfunction was demonstrated for 83.1 % of trastuzumab-treated patients. Approximately 10 % of cardiac endpoints occurred after completion of trastuzumab.
As per the published literature on another trastuzumab product, in the pivotal metastatic trials of intravenous trastuzumab, the incidence of cardiac dysfunction varied between 9 % and 12 % when it was combined with paclitaxel compared with 1 %-4 % for paclitaxel alone. For monotherapy, the rate was 6 %-9 %. The highest rate of cardiac dysfunction was seen in patients receiving trastuzumab concurrently with anthracycline/cyclophosphamide (27 %), significantly higher than for anthracycline/cyclophosphamide alone (7 %-10 %). In a subsequent trial with prospective monitoring of cardiac function, the incidence of symptomatic CHF was 2.2 % in patients receiving trastuzumab and docetaxel, compared with 0 % in patients receiving docetaxel alone. Most of the patients (79 %) who developed cardiac dysfunction in these trials experienced an improvement after receiving standard treatment for CHF.
Infusion Reactions, Allergic-Like Reactions and Hypersensitivity: As per the published literature on another trastuzumab product, it is estimated that approximately 40 % of patients who are treated with trastuzumab will experience some form of infusion-related reaction. However, the majority of infusion-related reactions are mild to moderate in intensity (NCI-CTC grading system) and tend to occur earlier in treatment, i.e. during infusions one, two and three and lessen in frequency in subsequent infusions. Reactions include chills, fever, dyspnoea, hypotension, wheezing, bronchospasm, tachycardia, reduced oxygen saturation, respiratory distress, rash, nausea, vomiting and headache (see Precautions). The rate of infusion-related reactions of all grades varied between studies depending on the indication, the data collection methodology, and whether trastuzumab was given concurrently with chemotherapy or as monotherapy.
Severe anaphylactic reactions requiring immediate additional intervention can occur usually during either the first or second infusion of trastuzumab (see Precautions) and have been associated with a fatal outcome.
Anaphylactoid reactions have been observed in isolated cases.
Haematotoxicity: As per the published literature, febrile neutropenia occurred very commonly. Commonly occurring adverse reactions included anaemia, leukopenia, thrombocytopenia and neutropenia. The frequency of occurrence of hypoprothrombinemia is not known. The risk of neutropenia may be slightly increased when trastuzumab is administered with docetaxel following anthracycline therapy.
Pulmonary Events: As per the published literature, severe pulmonary adverse reactions occur in association with the use of trastuzumab and have been associated with a fatal outcome. These include, but are not limited to, pulmonary infiltrates, acute respiratory distress syndrome, pneumonia, pneumonitis, pleural effusion, respiratory distress, acute pulmonary oedema and respiratory insufficiency (see Precautions).
Seek medical attention immediately at the first sign of any adverse drug reaction.