r, dyspnoea, hypotension, wheezing, bronchospasm, tachycardia, reduced oxygen saturation, respiratory distress, rash, nausea, vomiting and headache (see section 4.4). 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 section 4.4) and have been associated with a fatal outcome. Anaphylactoid reactions have been observed in isolated cases.
Haematotoxicity
Febrile neutropenia, leukopenia, anaemia, thrombocytopenia and neutropenia occurred very commonly. The frequency of occurrence of hypoprothrombinaemia is not known. The risk of neutropenia may be slightly increased when trastuzumab is administered with docetaxel following anthracycline therapy.
Pulmonary events
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 section 4.4).
Details of risk minimisation measures that are consistent with the EU Risk Management Plan are presented in “Warnings and precautions” (see section 4.4).
Immunogenicity
In the neoadjuvant-adjuvant EBC study (BO22227), at a median follow-up exceeding 70 months, 10.1% (30/296) of patients treated with trastuzumab intravenous developed antibodies against trastuzumab. Neutralising anti-trastuzumab antibodies were detected in post-baseline samples in 2 of 30 patients in the trastuzumab intravenous arm.
The clinical relevance of these antibodies is not known. The presence of anti-trastuzumab antibodies had no impact on the pharmacokinetics, efficacy (determined by pathological complete response [pCR] and event free survival [EFS]) and safety determined by occurrence of administration related reactions (ARRs) of trastuzumab intravenous.
There are no immunogenicity data available for trastuzumab in gastric cancer.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store
Ireland
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie
4.9 Overdose
There is no experience with overdose in human clinical trials. Single doses of trastuzumab alone greater than 10 mg/kg have not been administered in the clinical trials; a maintenance dose of 10 mg/kg q3w following a loading dose of 8 mg/kg has been studied in a clinical trial with MGC patients. Doses up to this level were well tolerated.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01XC03
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