Non-steroidal anti-inflammatory drugs (NSAIDs) review

Safety advisory - inconsistent information about the known risk of miscarriage

11 October 2016

Consumers and health professionals are advised that the TGA has completed a recent safety review of the known association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the increased risk of miscarriage. The review focused on ensuring that consistent information on this risk was available for all products.

NSAIDs are available in a variety of doses and formulations, and are widely used to treat pain, inflammation and fever. They can be used to treat the symptoms of arthritis, rheumatism, muscle strains, sprains, tendonitis and period pain.

NSAIDs include the following medications:

  • aspirin
  • celecoxib
  • diclofenac
  • etoricoxib
  • flurbiprofen
  • ibuprofen
  • indometacin (previously known as indomethacin)
  • ketoprofen
  • ketorolac trometamol
  • mefenamic acid
  • meloxicam
  • naproxen
  • parecoxib
  • piroxicam
  • sulindac.

All NSAIDs are available on prescription, while some are also available in lower dose over-the-counter forms that can be obtained without a prescription.

The TGA's review was not prompted by any new safety concerns but resulted from an observed inconsistency in the warning statements included in the Product Information (PI) documents of NSAIDs.

The recommendations of the review do not pertain to topical non-aspirin NSAID preparations such as gels, creams and sprays.

In summary, the review has confirmed that there is a known association between use of non-aspirin NSAIDs and increased risk of miscarriage, particularly when the medicine is taken close to the time of conception. The review also found that this association is widely acknowledged by professional medical organisations. However, warnings about this risk in PIs and labelling are not consistent across these products.

The review has confirmed there is insufficient evidence to demonstrate an association between aspirin and this risk at this time.

The review involved:

  • comparison of Australian PIs and international product information/reference documents for all NSAIDs
  • review of mandated warnings, published literature and therapeutic guidelines
  • analysis of adverse event reports from the TGA Adverse Drug Reactions System (ADRS) Database
  • obtaining expert advice from the Advisory Committee on the Safety of Medicines (ACSOM).

The full review is now available on the TGA website.

The meeting statement that contains the ACSOM advice regarding this issue is also available on the TGA website.

Non-aspirin NSAIDs that can be bought over-the-counter are required to have various advisory statements on their labels. The following advisory statement is used for non-aspirin NSAIDs (other than diclofenac when indicated for children, preparations used for dermal or external use and those indicated exclusively for period pain) in relation to the risk of use in pregnancy:

'Do not use [this product/insert name of product] during the first 6 months of pregnancy, except on doctor's advice. Do not use at all during the last 3 months of pregnancy.'

The TGA review found that this advisory statement does not address the use in women who have just conceived and are therefore unlikely to be aware that they are pregnant. This is relevant, as the data suggests that the risk is greatest when the medicine is taken close to the time of conception.

The review also found that NSAID products that are indicated exclusively for period pain should have the risk of use in pregnancy warning included on their labels. Treatment guidelines recommend taking these non-aspirin NSAIDs before a period begins in anticipation of period pain. Women who have conceived but are not yet aware of it may be exposed to increased risk of miscarriage if they self-treat for period pain in these situations.

Given that NSAIDs indicated exclusively for period pain have the same active ingredient as other NSAID products that are not indicated exclusively for period pain, there is also potential for consumers to use these products for other indications without being advised of the risk of use in pregnancy.

The TGA is now working with sponsors of non-aspirin NSAIDs to harmonise the warnings regarding the risk of use in pregnancy, including information about the potential increased risk of miscarriage when the medicine is taken close to the time of conception. The TGA is also working with sponsors to include a warning on the labels of all OTC non-aspirin NSAID products, including those indicated exclusively for period pain, that appropriately addresses this risk. See: Consultation: Non-steroidal anti-inflammatory drugs: proposed additional advisory statement.

Information for consumers

Use of non-aspirin NSAIDs is known to be associated with an increase in the risk of miscarriage, particularly when taken close to the time of conception. There are many other individual factors that can increase the risk of miscarriage, including advanced age, smoking, obesity and other medical conditions.

If you are pregnant, think you may be pregnant or are trying to become pregnant, consult a health professional before using these products and consider using an alternative medicine.

If you use any over-the-counter medicine, always read the label and follow the instructions.

If you have any questions or concerns about this issue, talk to your health professional.

Information for health professionals

Health professionals are reminded of the increased risk of miscarriage associated with treatment with non-aspirin NSAIDs, particularly if taken close to the time of conception.

Consider advising patients who may be pregnant or are trying to become pregnant of the increased risk associated with these medicines, including over-the-counter products.

See the TGA full review and the related advice in the ACSOM meeting statement for further information.

Reporting problems

Consumers and health professionals are encouraged to report problems with medicines or vaccines. Your report will contribute to the TGA's monitoring of these products.

The TGA cannot give advice about an individual's medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a medicine or vaccine.