Summary Safety Review - Phenylephrine and acetaminophen - Drug-drug interaction

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: 2016-11-23

Product

Phenylephrine and acetaminophen

Potential Safety Issue

Drug-drug interaction

Key Messages

  • Phenylephrine and acetaminophen are drugs often found together in non-prescription health products used to relieve symptoms from the common cold, flu and allergies.
  • This safety review was triggered by a report from the European Medicines Agency about the potential risk of an interaction between phenylephrine and acetaminophen and potential side effects when these two drugs are taken together.
  • Health Canada's safety review concluded that the evidence shows a drug-drug interaction between acetaminophen and phenylephrine which may lead to an increased amount of phenylephrine in the body; however, there is no evidence at this time to show that this is a significant risk to healthy consumers. Certain people may be at a greater risk of phenylephrine's side effects due to pre-existing health conditions, but this caution is already required to be on the labels of these products.
  • Health Canada will continue to monitor this safety issue and will publish a Health Product InfoWatch article to help raise awareness of the interaction among healthcare professionals and consumers.

Overview

Health Canada initiated a safety review following a report by the European Medicines Agency about the potential drug-drug interaction between phenylephrine and acetaminophen. These drugs are often found together in over-the-counter health products including those for treating cold, flu and allergies. People who have high blood pressure or heart disease may be more vulnerable to the side effects of phenylephrine if both of these drugs are taken together as there appears to be an interaction between them that leads to an increase of phenylephrine in the body (increased bioavailability).

Use in Canada

  • At the time of the review there were 66 non-prescription products on the Canadian market that combined both phenylephrine to treat congestion and acetaminophen for pain and fever relief due to the common cold, flu and allergies. All of these products are for use in adults and children 12 years and older only.
  • In Canada, all non-prescription, phenylephrine-containing products must include a warning statement to "ask a doctor before use if you have heart disease, high blood pressure, thyroid disease or diabetes."

Safety Review Findings

  • At the time of the review there was 1 Canadian reporta of increased blood pressure due to a possible drug interaction between phenylephrine and acetaminophen, which was further assessed. The individual had been taking an acetaminophen-phenylephrine combination product and was also taking another medication to treat his pre-existing high blood pressure. However, after adjustment of the blood pressure medication the blood pressure returned back to normal and he did not experience any further blood-pressure related side effects.
  • There is one published report in the scientific literature1 of a bleed in the brain (intracerebral hemorrhage) in a person taking multiple cough and cold medicines containing phenylephrine over a 30-day period. However, it could not be confirmed that this event was due to an interaction between phenylephrine and acetaminophen, given that there were multiple ingredients in the product, and the person had used multiple cough and cold medicines. Overall, the safety data reviewed by Health Canada were all lacking relevant information to determine if these side effects were due to a drug-drug interaction between phenylephrine and acetaminophen.
  • People who have high blood pressure or heart disease may be more vulnerable to the side effects of phenylephrine if both of these drugs are taken together as there appears to be an interaction between them that leads to an increase of phenylephrine in the body.

Conclusions and actions

  • Health Canada's safety review concluded that the evidence shows a drug-drug interaction between phenylephrine and acetaminophen which may lead to an increased amount of phenylephrine in the body; however, there is no evidence at this time to show that this is a significant risk to healthy consumers. Certain people may be at a greater risk of phenylephrine's side effects due to pre-existing health conditions, but this caution is already required to be on the labels of these products.
  • Health Canada will publish a Health Product InfoWatch article to help raise awareness of this drug interaction among healthcare professionals and consumers.
  • Health Canada continues to monitor the safety of non-prescription phenylephrine and acetaminophen combination products, 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.

Additional information

Canadian and international adverse reaction reports and what is known about the use of these products both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Tark BE, Messe SR, Balucani C, Levine SR. Intracerebral hemorrhage associated with oral phenylephrine use: A case report and review of the literature. J Stroke Cerebrovas Dis. 2014; 23(9): 2296-300.

Footnotes

  1. Canadian reports can be accessed through the Canada Vigilance Online Database

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