TGA - Therapeutic Goods Administration

12/02/2019 | News release | Distributed by Public on 12/01/2019 23:37

Safety review of coumarin in topical listed medicines

Coumarin is a naturally occurring chemical found in a number of food products such as cinnamon and tonka bean. Coumarin is currently permitted for use in listed medicine; however, it is only permitted for use as an active homoeopathic ingredient (with a maximum concentration of 0.001%). During a review of listed sunscreen products, the TGA became aware that coumarin was being used as a fragrance in sunscreen and other topical listed medicines however was not on the Therapeutic Goods (Permissible Ingredients) Determination ('the Determination'). Therefore, the TGA conducted a preliminary safety review to determine whether coumarin was appropriate for use in listed medicines and sunscreens as a fragrance ingredient.

The review was unable to establish a safe concentration limit for the topical use of coumarin, and identified some safety concerns such as liver injury, skin sensitisation, and populations at greater risk such as children and pregnant/breastfeeding women. In March 2019, the TGA sought comments from sponsors of medicines containing coumarin, fragrance suppliers, dermatologists and industry associations to provide additional relevant information (particularly safety data or safety reports) to assist the TGA in finalising the safety profile of coumarin. A total of 7 submissions were received.

Additional data was provided which addressed some of the safety concerns in the preliminary safety review. This information has been considered and used to finalise the safety review.

Safety review

How to access a pdfor Worddocument

Summary of feedback

Health professionals supported the conclusions of the report regarding the possibility of liver injury, reproductive toxicity and skin sensitisation. They also supported the TGA's proposal to limit coumarin to a concentration of 0.001% when used in listed medicines. Industry stakeholders generally acknowledged the possibility of liver injury but did not support that a unique limit, that was not aligned with international fragrance standards, was appropriate for listed medicines. Industry stakeholders provided additional evidence for consideration and also raised other concerns which have been addressed in the final safety review. The following key recommendations were proposed by industry stakeholders:

  • Any limit for topical listed medicines should be aligned with the International Fragrance Association's (IFRA) standard.
  • The report consider additional data provided.
  • A compliance transition period is provided for existing products.

TGA response

The TGA thanks all parties for the feedback provided.

The additional data provided has been considered and incorporated into the final safety review. In particular, data for reproductive and developmental toxicity was able to address the safety concerns regarding coumarin in pregnancy and breastfeeding. However, concerns regarding the use of coumarin in children remains outstanding. As sunscreens may be used by the entire family, sunscreens containing coumarin will need to specify they should only be used by adults. This requirement will also apply to any other topical listed medicines.

The safety review establishes that the appropriate tolerable daily limit for coumarin exposure from all sources (including diet, cosmetic products and sunscreens) is 0.1 mg/kg bodyweight. The IFRA standard proposes a limit of 0.3% coumarin in products for use on the body. A sunscreen containing coumarin at this level would provide 6 mg/kg bodyweight of coumarin (60-times the tolerable daily limit) when used as recommended[1] for a full-day. A sunscreen containing 0.001% coumarin used in the same way would provide 0.02 mg/kg bodyweight (this is 20% of the tolerable daily limit). In the absence of a reliable estimation of Australian intake of coumarin from dietary and cosmetic sources, this lower limit is considered to be more appropriate for low risk listed medicines. As such, the requirements for listed medicines will specify that topical products may not exceed a concentration of 0.001% coumarin.

Sponsors of existing listed medicines and sunscreens will have until 2 March 2021 to bring their products into compliance. This transition time will align with the March 2020 low-negligible risk changes to the Permissible Ingredients Determination.

Outcome

Requirements to the effect of the following will be introduced into the Determination in March 2020 (at the same time as the low-negligible risk changes to the Permissible Ingredients Determination).

Ingredient name Purpose Specific requirements
COUMARIN E, H

Only for use as an active homeopathic ingredient or excipient ingredient.

When used as an active homoeopathic ingredient, the concentration of coumarin in the medicine must be no more than 0.001%.

When used as an excipient, must only be used in topical medicines for dermal application.

The requirements specified in paragraph (a) below apply to medicines that contain the ingredient that are:

  • listed in the Register on or after 2 March 2020; or
  • supplied after 2 March 2021.

a) When used as an excipient:

  • the concentration of coumarin in the medicine must not be more than 0.001%; and
  • the label of the medicine must specify that the product should only be used by adults.