- Registration Date 2022-10-14
- Hit 1154
Summary
Adverse event reports submitted to the TGA suggest there is a lack of awareness that vitamin B6, which is present in many multivitamin and mineral supplements, can cause peripheral neuropathy. In response, the TGA has strengthened labelling requirements so products containing daily doses over 10mg of vitamin B6 must carry a warning about peripheral neuropathy.
What’s new in this article
Until recently, only products containing vitamin B daily doses of more than 50 mg have been required to carry a warning about this risk. However, a review by the TGA found that peripheral neuropathy can occur at doses less than 50 mg, and when people are taking multiple products containing vitamin B6. The risk appears to vary between individuals, with no minimum dose, duration of use or specific patient risk factors identified.
To raise awareness, the TGA has updated regulations so that all products containing a daily dose of vitamin B6 above 10 mg require a warning about peripheral neuropathy. To limit exposure to excessive doses, the maximum permitted daily dose of vitamin B6 in products has also been reduced from 200 mg to 100 mg for adults, with lower daily dose limits in place for children depending on their age.
What should health professionals do
Healthcare professionals should consider vitamin B6 toxicity in patients presenting with symptoms of peripheral neuropathy. A review of the patient’s vitamin B6 intake is recommended paying close attention to potential sources such as multivitamins and magnesium and zinc products, particularly when taken in combination.
Background
Peripheral neuropathy is a known side effect of vitamin B6 and is characterised by tingling, burning, or numbness, usually in the hands or feet. Delayed diagnosis and continued exposure can lead to progression of neuropathy.
Because of this risk, medicines containing daily doses of vitamin B6 over 50 mg or equivalent have been required to carry the following statement:
“WARNING - Stop taking this medication if you experience tingling, burning or numbness and see your healthcare practitioner as soon as possible. (Contains vitamin B6)”
Vitamin B6 is a water-soluble, essential nutrient found in food. In this form, it is not associated with peripheral neuropathy. Vitamin B6 is commonly present in off-the-shelf products (listed medicines) such as multivitamin and mineral preparations and vitamin B complexes, often in combination with magnesium or zinc.
There are currently three forms of vitamin B6 available in products:
- pyridoxine hydrochloride
- pyridoxal 5-phosphate
- pyridoxal 5-phosphate monohydrate.
When included as active ingredients, pharmaceutical companies must list these names on the label. Using the common name ‘vitamin B6’ is optional except when it is required as part of the peripheral neuropathy warning statement.
Adverse events reported to the TGA and overseas
Adverse event reports submitted to the TGA suggest there is a lack of awareness that vitamin B6 can cause peripheral neuropathy. This is particularly the case when symptoms have developed in patients consuming one or more products that do not carry a warning because they contain less than 50 mg of vitamin B6.
Up to 5 August 2022, the TGA had received 32 adverse event reports with sufficient information to establish a possible causal association between peripheral neuropathy and products containing vitamin B6.
In many cases, people reported they were unaware they had consumed vitamin B6 as the product they were taking was a magnesium supplement.
Of these 32 cases:
- 22 (69%) reported elevated vitamin B6 blood levels with peripheral neuropathy symptoms
- 21 (66%) involved daily doses of 50 mg of vitamin B6 or less
- 9 (28%) involved multiple medicines containing vitamin B6, some of which did not have a label warning because they contained less than 50 mg of vitamin B6.
The TGA is also aware of similar reports overseas, which indicate that peripheral neuropathy may occur at a daily dose of less than 50 mg of vitamin B6, or in people taking more than one product containing vitamin B6.
Changes to label warnings for vitamin B6 products
A public consultation highlighted that there is no minimum dose, minimum duration of use, form of vitamin B6 or identified patient risk factors that are established for peripheral neuropathy. The risk appears to vary depending on individual differences in people. Some cases of peripheral neuropathy associated with vitamin B6 were also from what appears to be excessive intake, or simultaneous consumption of multiple medicines containing vitamin B6.
In response, the TGA has made the following regulatory changes:
- Products containing
vitamin B6 in daily doses above 10 mg
now require a label warning about the risk of peripheral neuropathy. - Products must not provide more than 100 mg of vitamin B6 per day for adults (previously 200 mg), with lower daily dosage limits for children depending on the age group.
A transition period applies until 1 March 2023. This means all listed medicines that contain vitamin B6 must comply with these new requirements after that date.
The TGA continues to monitor any emerging evidence and reports of adverse events related to this issue, including whether the new requirements are sufficient to mitigate the risk of peripheral neuropathy.
A safety advisory on peripheral neuropathy and vitamin B6 was published in May 2020.
What to report? You don't need to be certain, just suspicious!
The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.
We particularly request reports of:
- all suspected reactions to new medicines (look for the Black Triangle in PI and CMI documents - this symbol identifies medicines that are new or being used differently)
- all suspected medicines interactions
- suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.
Reports may be submitted:
-
online
at -
by fax
to 02 6232 8392 -
by email
to
For more information about reporting, visit www.tga.gov.au or contact the TGA's Pharmacovigilance Branch ADR.Reports@tga.gov.au.
Disclaimer
Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.
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Medicines Safety Update is written by staff from the Pharmacovigilance Branch.
Editor: Ms Elspeth Kay
Deputy Editor: Dr Fiona Mackinnon
Contributors: Cathy Beckhouse, Antoinette Schulz and Claire Larter
Division Risk Information Division
Written by Risk Information Division