Australia: Safety advisory: Non-steroidal anti-inflammatory drugs (NSAIDs) review - inconsistent information about the known risk of miscarriage (English Only)

Australia: Safety advisory: Non-steroidal anti-inflammatory drugs (NSAIDs) review - inconsistent information about the known risk of miscarriage (English Only)
The Therapeutic Goods Administration (TGA) advised that consumers and health professionals 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 medication aspirin, celecoxib, diclofenac, etoricoxib, flurbiprofen, ibuprofen, indometacin (previously known as indomethacin), ketoprofen, ketorolac trometamol, mefenamic acid, meloxicam, naproxen, parecoxib, piroxicam, and sulindac. In Australia, 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 full review is now 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 will also be working with sponsors to include a warning on the labels of products indicated exclusively for period pain that appropriately addresses this risk. 

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

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. 

Please refer to the following website in TGA for details: 

In Hong Kong, NSAID-containing products are registered pharmaceutical products with ingredients such as aspirin, diclofenac, ibuprofen, naproxen, indomethacin, mefenamic acid and piroxicam. With the exceptions such as ibuprofen, topical preparations containing certain NSAIDs such as diclofenac and piroxicam which are pharmacy only medicines, and aspirin which is an over-the-counter medicine, products containing NSAIDs are prescription only medicines. The risk of miscarriage is a known risk of NSAID, and is documented in reputable overseas drug literatures such as "Martindale: The Complete Drug Reference". So far, the Department of Health (DH) has received 16 cases of adverse drug reactions in connection with the use of NSAID, but none of them was related to miscarriage. DH will remain vigilant on the safety update on NSAID by other overseas drug regulatory authorities for consideration of any action deemed necessary. 

Ends/ Monday, October 11, 2016 
Issued at HKT 16:00