Summary Safety Review - Sulfamethoxazole-Trimethoprim - Risk of Drug-induced Immune Thrombocytopenia
Review decision
A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.
Issued: 2014-11-18
issue
A safety review was conducted to evaluate the available information regarding the potential risk of drug-induced immune thrombocytopenia, also known as a low number of platelets in the blood, with products containing sulfamethoxazole and/or trimethoprim (SMX-TMP). The review was prompted by the ongoing assessment of information regarding these products and a United States Food and Drug Administration (U.S. FDA) announcement of changes to the prescribing information for Bactrim and Bactrim DS, both SMX-TMP containing products.
Background
Approved use of sulfamethoxazole-trimethoprim in Canada
Sulfamethoxazole (SMX) and trimethoprim (TMP) are different antibiotics that can be used alone or in combination. When used separately, these antibiotics only stop the growth of bacteria. However, when combined together, these antibiotics kill the bacteria. It can lead to a better outcome for the patient. SMX-TMP containing products are used for the treatment of various infections such as bladder, lung, and ear infections. These products have been on the Canadian market since 1973.
Thrombocytopenia
Thrombocytopenia is a reduced number of platelets in the blood. Platelets are blood cells that play an important role in blood clotting. Severe bleeding may happen when the blood contains a low number of platelets. Drugs can cause thrombocytopenia by different mechanisms. For example, thrombocytopenia can be due to an allergic reaction to the drug, called hypersensitivity reaction. SMX-TMP use can trigger the immune system to produce antibodies that will destroy the platelets. This is called drug-induced immune thrombocytopenia.
Objective
To review the available evidence concerning the risk of developing drug-induced immune thrombocytopenia while taking SMX-TMP containing medications. The evidence considered included Canadian patient reports of thrombocytopenia while taking SMX-TMP, medical and scientific literature, and what is known about the use of SMX-TMP containing products both in Canada and internationally. The current strategies to minimize the risk were also considered, including a review of the product information available to health care professionals and patients.
Key findings
Use of SMX-TMP in Canada1
SMX-TMP containing products are widely used in Canada. At the time of the review, Health Canada estimated the number of prescriptions for these drugs at about 1,000,000 per year for the past 6 years.
Canadian reports of Thrombocytopenia associated with SMX-TMP
At the time of the review, Health Canada had received 130 adverse reaction reports of thrombocytopenia with the use of SMX-TMP containing products. More than half of these reported thrombocytopenia without any other blood disorder. A fatal outcome was reported for 12 of these cases.
Scientific reports
A number of case reports of thrombocytopenia associated with SMX-TMP have been published over the years. A search of the medical literature identified three population studies. The analysis of these studies showed an increased risk of thrombocytopenia with the use of SMX-TMP. The risk appears to be increased in some patients such as those who have the Acquired Immune Deficiency Syndrome (AIDS).
Taking into account the studies and case reports, it is possible that SMX/TMP can contribute to the development of drug-induced immune thrombocytopenia in some patients. Overall, the incidence of this reaction appears to be very low.
International data
The U.S. prescribing information includes a warning on the risk of immune thrombocytopenia and a contraindication in patients allergic to SMX-TMP or with a history of drug-induced thrombocytopenia.
Conclusions and actions
Considering the evidence regarding the risk of thrombocytopenia, the possible mechanism of SMX-TMP induced immune thrombocytopenia, and widespread use of these products in Canada, Health Canada is currently working with the manufacturers to update the prescribing information for SMX-TMP containing products. This will inform health professionals and patients of the potential risk of drug-induced immune thrombocytopenia with SMX-TMP containing products. The prescribing information will include a new contraindication indicating that SMX-TMP containing products should not be used in patients with a known hypersensitivity including a history of drug-induced immune thrombocytopenia.
References
- Garbe E, Andersohn F, Bronder E, et al. Drug-induced immune thrombocytopaenia: results from the Berlin Case-Control Surveillance Study. Eur J Clin Pharmacol 2012;68(5):821-32.
- Ten Berg MJ, Huisman A, Souverein PC, et al. Drug-induced thrombocytopenia: a population study. Drug Saf 2006;29(8):713-21.
Footnotes
- IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place.
- This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review.