Safety alert: NSAIDs and miscarriage


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A TGA review has found medicine labelling is inconsistent regarding the association between non-aspirin NSAIDs and miscarriage

The safety review confirmed there is a known association between use of these medicines and increased risk of miscarriage, particularly when the medicine is taken close to the time of conception.

It found an observed inconsistency in the warning statements included in the Product Information (PI) documents of NSAIDs.

For example, a statement warning of the increased risk of miscarriage is at present included in the PI for only five non-aspirin NSAIDs.

NSAIDs that are not scheduled as an S4 are required to have an advisory statement on their medicine labels: “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.”

However the TGA points out that the current advisory statement does not address the use in women who have just conceived and are therefore unlikely to be aware that they are pregnant.

Label warnings for period pain-specific products are also currently not required to carry the pregnancy warning.

“This is of relevance as the data to support the increased risk of miscarriage with non-aspirin NSAID use suggests that the risk is greatest when the non-aspirin NSAID is taken at the time of conception,” says the TGA.

The TGA is therefore working with pharmaceutical companies to update PI warnings across all OTC non-aspirin NSAIDs, even those for period pain, to include an advisory statement on their packaging which appropriately addresses the risk of miscarriage.

These revised warnings only apply to oral products such as tablets, liquids and capsules. They do not apply to topical preparations such as gels, creams and sprays.

Based on the findings, the Australian Self-Medication Industry warns that people who are pregnant, think they may be pregnant or are trying to become pregnant should be advised to consult a health professional before using any OTC medicines, even NSAIDs.

In regards to aspirin, the TGA says there is currently insufficient evidence to support a causal association between aspirin use and an increased risk of miscarriage.

See the full review here.

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2 Comments

  1. Lyndsey Harper
    12/10/2016

    This is helpful especially for those who are trying to conceive like me. We’re trying and I’m waiting for a positive result on my free conceiveeasy PT. I hope it’ll happen for me soon.

    • Ron Batagol
      12/10/2016

      Safety review: Nonsteroidal anti-inflammatory drugs (NSAIDs) and spontaneous abortion
      Related information
      Safety advisory: Non-steroidal anti-inflammatory drugs (NSAIDs) review

      ACSOM meeting statement, Meeting 30, 20 November 2015

      Version 1.0, September 2016

      Link:https://www.tga.gov.au/alert/safety-review-nonsteroidal-anti-inflammatory-drugs-nsaids-and-spontaneous-abortion

      Ron’s comments in Medical Observer.

      I have no problem with TGA wanting to, as a matter of precautionary public health advice, to harmonise the warnings in the product information for NSAID products, regarding the data suggesting increased risk of spontaneous abortion, when taken around the time of conception.

      However health professionals advising patients need to also be aware that the studies suggesting the association, whilst demonstrating an association, thereby justifying cautionary patient advice, have not clearly demonstrated a causal link.

      Thus, in the article “Analgesics and pain relief in pregnancy and breastfeeding”, (1) the author, Dr.D.Kennedy notes that “A case-control and population-based observational cohort study from Scandinavia demonstrated an increased risk of spontaneous abortion with first trimester use of NSAIDs but with no evidence of other adverse pregnancy outcomes (2). The author noted that “major flaws in this study, however, were that it was prescription-based and retrospective and did not control for the indications of use of NSAIDs ,such as underlying fever or viral illness”.

      Also, a 2015 study by S.Daniel et.al. at Motherisk, Canada, “NSAIDs and spontaneous abortions – true effect or an indication bias?” (3) found that “the use of NSAIDs during the week before a spontaneous abortion is sharply increased”. They concluded that the increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage biases studies assessing the association between exposure to NSAIDs and spontaneous abortions.

      Ron Batagol,

      Pharmacist and Obstetric Medicines Information Consultant,

      Nunawading, Vic 3131

      References:

      1. Kennedy.D. Analgesics and pain relief in pregnancy and breastfeeding.Aust Prescr: 2011;34:101 Feb 2011DOI: 10.18773/austprescr.2011.007

      2. Nielsen G.L., Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs:population based observational study and case-control study. BMJ 2001; 322:266-70.

      3. Sharon Daniel,Gideon Koren,4 * Eitan Lunenfeld3 & Amalia Levy1* Departments of 1 Public Health, 2 Pediatrics and 3 Obstetrics and Gynecology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Soroka Medical Center, Beer-Sheva, Israel and 4 The Motherisk Program, Division of Clinical Pharmacology-Toxicology, Hospital for Sick Children, The University of Toronto, Toronto, Canada. .NSAIDs and spontaneous abortions – true effect or an indication bias?

      British Journal of Clinical Pharmacology 2015;DOI:10.1111/bcp.Safety review: Nonsteroidal anti-inflammatory drugs (NSAIDs) and spontaneous abortion
      Related information
      Safety advisory: Non-steroidal anti-inflammatory drugs (NSAIDs) review

      ACSOM meeting statement, Meeting 30

      I have no problem with TGA wanting to, as a matter of precautionary public health advice, to harmonise the warnings in the product information for NSAID products, regarding the data suggesting increased risk of spontaneous abortion, when taken around the time of conception.

      However health professionals advising patients need to also be aware that the studies suggesting the association, whilst demonstrating an association, thereby justifying cautionary patient advice, have not clearly demonstrated a causal link.

      Thus, in the article “Analgesics and pain relief in pregnancy and breastfeeding”, (1) the author, Dr.D.Kennedy notes that “A case-control and population-based observational cohort study from Scandinavia demonstrated an increased risk of spontaneous abortion with first trimester use of NSAIDs but with no evidence of other adverse pregnancy outcomes (2). The author noted that “major flaws in this study, however, were that it was prescription-based and retrospective and did not control for the indications of use of NSAIDs ,such as underlying fever or viral illness”.

      Also, a 2015 study by S.Daniel et.al. at Motherisk, Canada, “NSAIDs and spontaneous abortions – true effect or an indication bias?” (3) found that “the use of NSAIDs during the week before a spontaneous abortion is sharply increased”. They concluded that the increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage biases studies assessing the association between exposure to NSAIDs and spontaneous abortions.

      Ron Batagol,

      Pharmacist and Obstetric Medicines Information Consultant,

      Nunawading, Vic 3131

      References:

      1. Kennedy.D. Analgesics and pain relief in pregnancy and breastfeeding.Aust Prescr: 2011;34:101 Feb 2011DOI: 10.18773/austprescr.2011.007

      2. Nielsen G.L., Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs:population based observational study and case-control study. BMJ 2001; 322:266-70.

      3. Sharon Daniel,Gideon Koren,4 * Eitan Lunenfeld3 & Amalia Levy1* Departments of 1 Public Health, 2 Pediatrics and 3 Obstetrics and Gynecology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Soroka Medical Center, Beer-Sheva, Israel and 4 The Motherisk Program, Division of Clinical Pharmacology-Toxicology, Hospital for Sick Children, The University of Toronto, Toronto, Canada. .NSAIDs and spontaneous abortions – true effect or an indication bias?

      British Journal of Clinical Pharmacology 2015;DOI:10.1111/bcp.12653

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