Australia’s TGA plans to add liver injury warning to weight management ingredient

The TGA is proposing to add the warning: “I​n rare cases, Garcinia gummi-gutta may harm the liver. Stop use and see a doctor if you have yellowing skin/eyes or unusual: fatigue, nausea, appetite loss, abdominal pain, dark urine, or itching.”​

If implemented, companies will need to start doing so from March 1 next year, but there will also be a one-year transition grace period.

The TGA said that the proposal was made due to rising reports of liver injury associated with the ingredient as seen from literature reviews.

As of May 24, the TGA also received six cases of possible drug induced liver injury cases associated with Garcinia gummi-gutta ​or calcium hydroxycitrate – the calcium salt of hydroxycitric acid, which has been identified as the constituent of concern in liver injury.

All six cases involved products that are either not listed on TGA’s product database or did not include enough information to identify the Garcinia gummi-gutta​-containing product, said the TGA.

Four out of the six cases also involved the consumption of other suspected hepatotoxins.

“Only a small number of possible liver injury cases associated with HCA-containing ingredients have been reported to the TGA. ​

“While this may seem reassuring, it is possible that cases are going unreported. Notably, one published literature case resulting in liver transplant that occurred in Australia was not reported to the TGA,” ​the regulator said in its proposal.​

The dried outer layer of Garcinia gummi-gutta​ is consumed as part of a traditional Asian diet and in Ayurvedic medicine.

The ingredient has been permitted for use in Australia’s listed medicines, including complementary medicines or health supplements, since 2014.

As of May 16, there are 39 listed medicines containing Garcinia gummi-gutta. ​The majority claim to support weight management, metabolism, and / or energy levels.

The TGA is also proposing that the use of Garcinia gummi-gutta ​must be limited to its fruit peel.

This is on top of the existing restrictions which limit Garcinia gummi-gutta ​to only oral medicines. It is also not permitted for use in children, or in pregnant or lactating women.

The TGA’s proposal is currently open for public consultation​ until September 13.

Pregnancy related warnings ​

The TGA is also proposing to add pregnancy related warnings to complementary medicines containing the botanicals Ruta graveolens, ​also known as common rue, and Petroselinum crispum ​or parsley.

In the case of Ruta graveolens, ​it is proposing to add the warning: “Do not use if pregnant or likely to become pregnant, or during lactation.”​

There are currently nine products listed in TGA’s database that contain Ruta graveolens.​ Seven are for topical application and two are for oral administration.

The regulator said there were concerns around the botanical’s potential for inducing pregnancy termination and menstruation.

It could also potentially cause maternal death when used for inducing pregnancy termination, based on traditional herbal texts.

As of June 27, the TGA said it has not received adverse events reports related to pregnancy, except for skin reactions.

As for parsley (P. crispum​), it is proposing to add the warning: “Do not use if pregnant or likely to become pregnant”. ​

“P. crispum is consistently documented to induce abortion/miscarriage in traditional literature when used medicinally,”​ the TGA said.

This will apply to listed medicines containing dry parsley herb and the herb in the form of oil, powder, and its seed oil.

While the use of parsley in food in not a safety concern, it becomes an issue when it is used in preparations for medicinal purposes.

The TGA explained that this was because there might be increased exposure to certain constituents of concern due to their higher concentration.

One of these constituents is apiole, found primarily in the seed.

“The safety of P. crispum was considered by ACCM (Advisory Committee on Complementary Medicines) at their 34th meeting in March 2024. ​

“They agreed that there was sufficient evidence of risk to contraindicate the use of parsley in listed medicines during pregnancy, with the greatest risk being from parsley seed oil. ​

“They also advised that indications relating to pregnancy should not be permitted for these ingredients. The Committee recommended that the label warning should apply to both oral and topical use, given that essential oils can be absorbed through the skin,” ​the TGA said in the proposal.

As of July 5, there is one listed medicine containing parsley herb oil as an active ingredient. Two other listed medicines contain parsley seed oil as an active ingredient.

Another 52 medicines contain parsley as P. crispum​, with two using the ingredient as excipients and the remaining 50 as active ingredients.

Removals ​

On the other hand, the TGA is proposing to remove 1) Xanthium strumarium ​or rough cocklebur and 2) Xanthium sibiricum ​or Cang-er in Chinese from the list of ingredients identified as having low-risk.

Xanthium sibiricum​ is used as part of Traditional Chinese Medicine.

There are currently 16 listed medicines in Australia containing the two Xanthium ​species, with the majority using Xanthium sibiricum.​

There has been a case of adverse event involving Xanthium sibiricum ​in Australia back in April 2017.

A 26-year-old female was said to have experienced eye swelling and pruritic rash suspected to be caused by a medicine that contained the ingredient.

“While there is only one record of an adverse event occurring in Australia due to Xanthium-containing medicines, this does not necessarily mean these medicines are safe. ​

“It is likely that adverse events are under-reported, especially as Xanthium is included in complementary medicines often used without professional oversight,”​ the TGA said.