Published: 27 November 2018
Revised: 29 August 2023

Safety Information

Alert Communication

Artemisia annua (Sweet wormwood, Sweet Annie, Qing hao) extract marketed as Arthrem: risk of harm to the liver – statement under section 98 of the Medicines Act 1981

Products Affected
Information for consumers and caregivers
Information for healthcare professionals
Data Summary
What actions are Medsafe taking?
How to report adverse events
Further information

This alert communication updates a previous alert published on 15 February 2018: ‘Arthrem – potential risk of harm to the liver – statement under section 98 of the Medicines Act 1981’.

The Centre for Adverse Reactions Monitoring (CARM) has received a total of 25 reports of liver toxicity associated with the use of Artemisia annua extract marketed as Arthrem (as at 30 September 2018). CARM received 11 of these reports following publication of the previous alert.

Artemisia annua extract (also known as Sweet Wormwood, Sweet Annie or Qing hao) is marketed as a natural dietary supplement for maintaining and supporting joint health and mobility. Several products containing Artemisia annua extract are available in New Zealand.

Consumers should be aware that there is a potential risk of harm to the liver when taking products containing Artemisia annua extract.

Products Affected

The cases reported to CARM indicate use of Arthrem soft gel capsules (Promisia). Two cases also report use of GO Arthri-Remedy 1-A-Day soft gel capsules (GO Healthy).

GO Arthri-Remedy 1-A-Day was withdrawn after publication of the previous alert.

There are other products in New Zealand that contain Artemesia annua extract.

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Data Summary

CARM has received 25 reports of liver toxicity associated with the use of products containing Artemisia annua extract, up until 30 September 2018 (Table 1).

All of the reports identified Arthrem as the medicine suspected of causing the liver reaction. GO Arthri-Remedy 1-A-Day was co-suspected in two of the 25 reports.

The number of reports received by CARM suggests that the risk of liver toxicity associated with the use of this product is approximately 0.5 to 6.3 cases per 10 000 consumers.

The pattern of liver toxicity reported in the cases varied. A hepatocellular pattern was reported in 6 cases, a cholestatic pattern in 7 cases, and a mixed pattern in 3 cases. One case of hepatic cirrhosis was also reported. No information on the pattern of liver toxicity was available for the remaining 8 cases.

All of the patients stopped taking the product containing Artemisia annua extract when signs of liver toxicity developed. At the time the information was reported to CARM, most patients had already recovered from the hepatotoxicity, or were improving.

Arthrem has been studied in a 12-week pilot study¹ . During the study, one of 14 patients who took Arthrem 300 mg twice per day developed hepatitis, which was considered by the study investigators to be possibly related to Arthrem.

What actions are Medsafe taking?

Medsafe will continue to monitor the safety of Arthrem.

How to report adverse events

Online	Submit a CARM report Prescribers can also submit a report using the online reporting tool available in patient management software.
Paper	Download a consumer reporting form (Word Document, 61KB, 1 page) Download a healthcare professional reporting form (PDF, 292 KB, 2 pages) Submit completed forms by emailing CARMreport@health.govt.nz or mail (Medsafe, Ministry of Health, 133 Molesworth Street, Thorndon, Wellington, 6011).
Email	CARMreport@health.govt.nz

Medsafe cannot give advice about an individual’s medical condition. If you have any concerns about a medicine you are taking Medsafe encourages you to talk to your healthcare professional.

Further information

CARM has received 25 reports of patients who have experienced an adverse reaction to the liver after while taking a product containing Artemisia annua extract.

Table 1: Summary of Cases reported to CARM linking Arthrem with harm to the liver

CARM Report ID	Age & Sex	Medicines reported	Reactions Reported
119615	71 M	Arthrem * Pantoprazole Atorvastatin Cilazapril/ hydrochlorothiazide Fluoxetine Terazosin Finasteride Ibuprofen Febuxostat Lesinuride	Hepatic enzymes increased
120445	48 F	Arthrem * Diltiazem Cilazapril Nortriptyline Paracetamol Magnesium	Abdominal pain Fever Hepatic enzymes increased Nausea
122052	54 F	Arthrem *	Hepatitis Jaundice Pruritus
123150	76 F	Arthrem * Fish oil Glucosamine Turmeric Ibuprofen	Hepatitis Jaundice Pruritus
124405	67 F	Arthrem *	Hepatic function abnormal Jaundice Pruritus
124539	72 F	Arthrem *	Hepatic enzymes increased Jaundice
124873	55 F	Arthrem * Felodipine	Fever Hepatitis Jaundice Nausea
125378	62 M	Arthrem * Atorvastatin Omeprazole Candesartan	Hepatitis
125847	66 F	Arthrem *	Hepatic function abnormal Jaundice
125947	64 F	Arthrem *	Hepatic enzymes increased Nausea Vomiting
125969	76 F	Arthrem * Melatonin	Hepatic function abnormal Jaundice
125970	77 M	Arthrem *	Hepatic function abnormal Jaundice
126905	55 M	Arthrem * Metoprolol *	Hepatic enzymes increased Jaundice
126933	71 F	Arthrem * GO Arthri-Remedy *	Hepatic enzymes increased Jaundice
127445	65 M	Arthrem *	Anorexia Faeces pale Hepatic function abnormal Jaundice Pruritus
127447	60 M	Arthrem * Paracetamol/codeine Diclofenac	Abdominal pain Anorexia Jaundice Hepatic enzymes increased Vomiting
127451	58 F	Arthrem * GO Arthri-Remedy *	Hepatic function abnormal
127475	64 F	Arthrem *	Haematuria Hepatic enzymes increased Jaundice Pruritus Purpura
127492	69 F	Arthrem *	Jaundice Hepatic enzymes increased Pruritus Tiredness
127632	93 F	Arthrem Metoprolol Donepezil Pantoprazole Atorvastatin Isosorbide mononitrate Aspirin Timolol eye drops Levothyroxine	Hepatic enzymes increased
127841	71 M	Arthrem *	Hepatic function abnormal
128001	69 M	Arthrem *	Hepatic function abnormal
128048	81 M	Arthrem * Cilazapril Metoprolol Allopurinol Levothyroxine	Hepatic cirrhosis
128413	83 F	Arthrem *	Hepatic enzymes increased
128422	86 F	Arthrem *	Jaundice Hepatitis cholestatic Pruritus

* Medicine suspected to have caused the adverse reaction, as indicated by the reporter.

References

1. Stebbings S, Beattie E, McNamara D, et al. 2016. A pilot randomized, placebo-controlled clinical trial to investigate the efficacy and safety of an extract of Artemisia annua administered over 12 weeks, for managing pain, stiffness, and functional limitation associated with osteoarthritis of the hip and knee. Clinical Rheumatology 35: 1829-36