New Safety Information: Interaction of Proton Pump Inhibitors (PPIs) with Methotrexate

Starting date:
October 19, 2012
Posting date:
October 19, 2012
Type of communication:
Information Update
Subcategory:
Medical Device
Source of recall:
Health Canada
Identification number:
RA-15076

Health Canada is informing Canadians and Canadian health care practitioners that the labelling for methotrexate and Proton Pump Inhibitors is being updated to include information on a potential interaction between these products. The new information will be in the "Warnings and Precautions" section of the methotrexate and the PPIs labelling.

Methotrexate is used at high doses in the treatment of cancer and at much lower dose in the treatment of autoimmune diseases. Proton pump inhibitors are acid reducers used in the treatment of heartburn or acid indigestion.

The use of high-dose methotrexate and of PPIs at the same time by patients may increase the amount of methotrexate in the blood leading to side effects. The possible risks to health include kidney failure, low red blood cell count, inflammation of the digestive tract, irregular heartbeat, muscle pain, infections, and diarrhea.

While a definite association between PPI use and an increase in methotrexate has not been confirmed, there have been a number of studies suggesting a possible interaction between PPIs and methotrexate. The potential for an increased risk of methotrexate side effects is very likely, which is why Health Canada is informing Canadians and Canadian health care practitioners of this change in labelling.

Health Canada will continue to evaluate the scientific evidence as it emerges and take appropriate action as needed.

Patients should not stop taking their medication unless they have been advised to do so by their health care professional. Patients using PPIs and methotrexate should consult with their doctor if they have any concerns about their health or these products.

Health care practitioners are reminded that PPIs , in general, should be prescribed at the lowest dose and for the shortest duration of therapy appropriate to the condition being treated. As noted in the drug labels, a temporary withdrawal of the PPI may be considered by the healthcare practitioner in some patients receiving treatments with high-dose methotrexate.

Drug labels, also known as "Product Monographs," contain important prescribing and safety information for health professionals and patients, and are available by search of Health Canada's Drug Product Database.

How to report side effects to health products

To report suspected adverse reaction (side effect) to these or other health products, please contact Health Canada's Canada Vigilance Program toll-free at 1-866-234-2345, or complete a Canada Vigilance Reporting Form and send to us using one of these methods:

PPI drugs currently marketed in Canada

The following proton pump inhibitors are available in Canada:

  • Dexlansoprazole (sold under the brand name Dexilant)
  • Esomeprazole (sold under the brand name Nexium and its generic equivalent)
  • Omeprazole (sold under the brand name Losec and its generic equivalents)
  • Lansoprazole (sold under the brand name Prevacid and its generic equivalents)
  • Pantoprazole (sold under the brand names Pantoloc and Panto IV, and their generic equivalent(s)
  • Pantoprazole/magnesium (sold under the brand name Tecta)
  • Rabeprazole (sold under the brand name Pariet and its generic equivalents)

PPIs are also available in combination with other drugs, for example: Vimovo (contains esomeprazole and naproxen).

Advisory

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