Summary Safety Review - Imatinib Mesylate (GLEEVEC and generics) - Assessing the Risk of Decline in Kidney Function During Long-Term Treatment
March 7, 2016
Imatinib mesylate (Gleevec and generics)
Potential Safety Issue
Decline in kidney function during long-term treatment
- Imatinib is a drug used to treat cancer (chemotherapy). It is most commonly used to treat several solid tumours or blood cancers, such as chronic myelogenous leukemia (CML).
- Health Canada's safety review was carried out after new published literature was identified that suggested imatinib may be linked with decline in kidney function during long-term treatment.
- Health Canada's safety review concluded that at this time there is sufficient evidence to consider a potential link between imatinib and decline in kidney function during long-term treatment.
A safety review was carried out by Health Canada to evaluate the risk of decline in kidney function linked with long-term treatment with imatinib. This safety review was triggered by new published medical literature.
A decline in kidney function during long-term treatment means a progressive loss of kidney function over time. In most people, gradual decline in kidney function occurs naturally with age or as a result of other medical conditions, such as diabetes or hypertension. A progressive loss of kidney function can lead to chronic kidney disease or renal impairment or severe renal impairment (renal failure).
By contrast, acute renal failure occurs suddenly and quickly, and is a known risk with many cancer drugs. The current Canadian prescribing information for imatinib already warns of the potential risk of acute renal failure and Tumour Lysis Syndrome.
Use in Canada
- Imatinib is a chemotherapy (cancer) drug belonging to a class of cancer drugs called Tyrosine Kinase Inhibitors (TKIs). It is most commonly used to treat a type of blood cancer called chronic myelogenous leukemia (CML), but also used to treat other blood cancers or solid tumours.
- The typical starting dose for adult patients with CML is 400 mg/day. For patients with advanced CML, the starting dose is 600 mg/day.
Safety Review Findings
- At the time of the review, Health Canada had received 30 reports of decreased or abnormal kidney function linked with imatinib
Footnote1. The manufacturer found an additional 63 reports worldwide of decreased kidney function linked with imatinib. The study of these cases provided limited evidence of a causal relationship. In some of these reports, patients either had some risk factors that could explain the cause of renal impairment or there was insufficient information to assess the link.
- Information from six clinical trials suggested that patients on long-term treatment with imatinib gradually lost some of their kidney function at a rate that may be faster than normal. The progressive loss of kidney function was greatest in the first year of therapy.
- Over time, gradual losses of kidney function linked with imatinib treatment may contribute to the development or worsening of some kidney diseases.
Conclusions and Actions
- Health Canada's safety review concluded that at this time there is sufficient evidence to consider a potential causal link between imatinib and decline in kidney function during long-term treatment.
- In order to reduce this risk, Health Canada is working with the manufacturer of Gleevec to include additional safety information on decline in kidney function into the Canadian Product Monograph:
- Long term treatment with Gleevec may result in decline in renal function. Patients treated with imatinib in clinical studies had a decrease over time in estimated glomerular filtration rate (eGFR). Monitoring for renal function should be undertaken before initiating therapy and periodically thereafter.
- Health Canada will continue to monitor safety information involving imatinib mesylate, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.
The analysis that was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
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