Hoffmann-La Roche, in consultation with Health Canada, has informed HealthCare Professionals of important new safety information regarding the use of Herceptin ( Trastuzumab ) during pregnancy.
Herceptin is a recombinant DNA-derived humanised monoclonal antibody that selectively targets the extracellular domain of the human epidermal growth factor receptor 2 protein ( HER-2 ). Overexpression of HER-2 protein is observed in 25%-30% of primary breast cancers. Trastuzumab has been shown, both in in-vitro assays and in animals, to inhibit the proliferation of human tumour cells that overexpress HER-2.
Herceptin is authorized for the treatment of:
patients with early stage breast cancer, whose tumours overexpress HER-2, following surgery and after chemotherapy.
patients with metastatic breast cancer whose tumours substantially overexpress HER-2.
In the post-marketing setting, cases of oligohydramnios during the second and third trimesters have been reported in pregnant women receiving Herceptin.
A review was completed of six reports of oligohydramnios that were reported between 2004 and August 2008. Four reports originated from literature articles. Two spontaneous reports concerned one twin pregnancy.
All mothers were exposed to Trastuzumab and at least one other chemotherapeutic agent during pregnancy. All had also received chemotherapy prior to Trastuzumab.
The mothers gave birth to viable infants who continued to develop normally up to five years after birth despite limited post-partum complications with no long-term effects.
In three cases, a decrease in amniotic fluid level was diagnosed seven weeks after the start of Trastuzumab.
A causal relationship to Trastuzumab could not be ruled out.
Spontaneous cases ( twins )
Not enough information was provided to assess a causal relationship to Trastuzumab.
Based on the information available a potential causal relationship to Trastuzumab cannot be excluded.
However from the limited information about oligohydramnios in 5 women exposed to Trastuzumab, the fetal outcome is not different than in women who have not been exposed to Trastuzumab.
Consistent with the product monograph, the recommendation remains that Herceptin should not be used during pregnancy unless the potential benefit for the mother outweighs the potential risk to the fetus.
If trastuzumab is administered during pregnancy, monitoring of the amniotic fluid is recommended.
The Herceptin Canadian Product Monograph has been updated to include the post marketing cases of oligohydramnios and provides the following information under Special Populations, Pregnant Women:
Reproduction studies have been conducted in cynomolgus monkeys at doses up to 25 times the weekly human maintenance dose of 2 mg/kg Herceptin and have revealed no evidence of impaired fertility or harm to the fetus. However, when assessing the risk of reproductive toxicity in humans, it is important to consider the significance of the rodent form of the HER2 receptor in normal embryonic development and the embryonic death in mutant mice lacking this receptor. Placental transfer of Herceptin during the early ( days 20-50 of gestation ) and late ( days 120-150 of gestation ) fetal development period was observed.
There are, however, no adequate and well-controlled studies in pregnant women and it is not known whether Herceptin can cause fetal harm when administered to a pregnant woman or whether it can affect reproductive capacity. In the post-marketing setting, cases of oligohydramnios during the second and third trimesters have been reported in pregnant women receiving Herceptin. Because animal reproduction studies are not always predictive of human response, Herceptin should not be used during pregnancy unless the potential benefit for the mother outweighs the potential risk to the fetus.
Source: Health Canada, 2009
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