Haematological disorders including leucocytosis, haemorrhage, thrombosis (common). 5. The sponsor states: The sponsor has included The evaluator has noted the carcinogenicity as potential risks change to the updated studies have ‘Epidemiological to the RMP. The sponsor’s response found considerable evidence is satisfactory. for an association between arsenic exposure and increased incidence of tumours, especially of the skin, lung and some internal organs. The mechanism of action is not fully understood, but it is likely to involve carcinogenic methylated metabolites such as dimethylarsinic acid (DMA).’ Carcinogenicity should be added as a potential risk. 6. The sponsor has provided The sponsor has included The evaluator has noted the search results regarding 'Off‐label use’ as missing change to the updated use of arsenic trioxide. A information in the RMP. The sponsor’s response few published research is satisfactory. papers reported use of arsenic trioxide for different types of leukaemia, multiple myeloma, aplastic anaemia and other cancers. ‘Off-label use’ should be added as missing information. 7. In regard to the proposed 7a. The sponsor has amended The evaluator has noted the routine risk minimisation the product information to read sponsor’s response. The activities, it is recommended as recommendations regarding to the Delegate that the draft the PI remain for the Use in Pregnancy PI document be revised as Delegate’s consideration. follows: Category X: Drugs which have such a high risk of causing Warning about pregnancy: permanent damage to the foetus arsenic trioxide is a category that they should not be used in X drug. The approved EU pregnancy or when there is a Summary of Product possibility of pregnancy. Characteristics (SmPC) for the innovator product PHENANSEN should not be given contains the following to patients who are pregnant. waring: Pregnancy test prior to the treatment with PHENANSEN and women of ‘Men should be considered. childbearing potential must use effective contraception In hamsters, rats and mice, during treatment with parenteral administration of TRISENOX.’ arsenite during the period of organogenesis produces In comparison, the Australian malformations, including neural PI advises: ‘PHENANSEN tube, eye, facial, genitourinary
Haematological disorders including leucocytosis, haemorrhage, thrombosis (common). 5. The sponsor states: ‘Epidemiological studies have found considerable evidence for an association between arsenic exposure and increased incidence of tumours, especially of the skin, lung and some internal organs. The mechanism of action is not fully understood, but it is likely to involve carcinogenic methylated metabolites such as dimethylarsinic acid (DMA).’ Carcinogenicity should be added as a potential risk. The sponsor has included carcinogenicity as potential risks to the RMP. The evaluator has noted the change to the updated The sponsor’s response is satisfactory. 6. The sponsor has provided search results regarding use of arsenic trioxide. A few published research papers reported use of arsenic trioxide for different types of leukaemia, multiple myeloma, aplastic anaemia and other cancers. ‘Off-label use’ should be added as missing information. The sponsor has included 'Off‐label use’ as missing information in the RMP. The evaluator has noted the change to the updated The sponsor’s response is satisfactory. 7. In regard to the proposed routine risk minimisation activities, it is recommended to the Delegate that the draft PI document be revised as follows: Warning about pregnancy: arsenic trioxide is a category X drug. The approved EU Summary of Product Characteristics (SmPC) for the innovator product contains the following waring: ‘Men and women of childbearing potential must use effective contraception during treatment with TRISENOX.’ In comparison, the Australian PI advises: ‘PHENANSEN 7a. The sponsor has amended the product information to read as Use in Pregnancy Category X: Drugs which have such a high risk of causing permanent damage to the foetus that they should not be used in pregnancy or when there is a possibility of pregnancy. PHENANSEN should not be given to patients who are pregnant. Pregnancy test prior to the treatment with PHENANSEN should be considered. In hamsters, rats and mice, parenteral administration of arsenite during the period of organogenesis produces malformations, including neural tube, eye, facial, genitourinary The evaluator has noted the sponsor’s response. The recommendations regarding the PI remain for the Delegate’s consideration.