Off-label prescribing driving pregabalin use 

A sharp rise in the uptake of pregabalin is believed to be driven by GPs and other specialists prescribing it outside of its TGA approved indications.

About 1.4 million scripts were issued to 295,000 patients in the first 12 months after the anticonvulsant was listed on the PBS in March 2013 for refractory neuropathic pain, in line with expectations based on the estimated prevalence of the condition.

The PBAC had predicted the number would reach 2.4 million (350,000 patients) five years after listing, but instead figures hit 2.4 million (433,000 patients) at the end of the second year, and rose to almost 3.4 million scripts in 2015-16 – with over 90% written by GPs.

This rang alarm bells for the PBAC  drug utilisation sub-committee (DUSC) which in a report described its concerns that pregabalin was being prescribed for conditions other than neuropathic pain, including acute pain and fibromyalgia which it said was “outside the PBS restriction”.

This interpretation of the data was rejected by the drug’s sponsor Pfizer (Lyrica*), who at the time asserted there was no evidence to support the conclusions.

On the back of the report the PBAC asked NPS Medicine Wise to run an education program for prescribers on appropriate use of pregabalin and its PBS subsidised indication.

Speaking to the limbic Dr Andrew Boyden, an NPS Medicine Wise medical advisor, said there was a need to “raise awareness about what neuropathic pain is”.

“A lot of prescribing might be leaking out into areas which isn’t true neuropathic pain, but doctors are maybe assuming or believing, quite understandably, that there is a neuropathic component.

The reality is a lot of back pain and radiating pain that is not necessarily neuropathic and possibly we are getting prescribing in these areas.”

“Pregabalin is indicated for neuropathic pain but is generally ineffective for other sorts of pain… It’s understandable GPs are wanting to help people with their chronic pain but maybe the awareness of what is actually a correct diagnosis of neuropathic pain for which the drug is indicated may not be as high as it could be.”

He added that some clinicians may not be aware that the evidence suggests the effectiveness of pregabalin is in the order of seven patients needing to be treated to obtain benefit in one patient (a 30-50% reduction in pain).

“It’s interesting pregabalin has become such a popular medication in recent times because the national guidelines still recommend the older agents as a first line agent for neuropathic pain.”

Dr Michael Vagg, a pain specialist in Melbourne and a member of the Faculty of Pain Medicine, believes that a change in the definition of neuropathic pain in 2008 could be contributing to the confusion.

The new definition put forward by the International Association for the Study of Pain describes neuropathic pain as a “direct consequence of a lesion or disease affecting the somatosensory system” rather than a “dysfunction of the nervous system”.

“There is evidence that pregabalin is effective for treating other types of pain, but a lot of the studies predate the changes in the definition of neuropathic pain” he told the limbic.

He said a lack of training for GPs in how to manage chronic pain, a shortage of comprehensive pain services to refer to and substitute medicines on the PBS could also be compounding the issue.

“There are too few alternatives to using pregabalin, apart from strong opioids,” said Dr Vagg, a clinical senior lecturer in musculoskeletal medicine at Deakin University School of Medicine.

“Other first line treatments like amitriptyline, nortriptyline and duloxetine are anti-depressant drugs that are as effective for treating neuropathic pain but are not listed on the PBS for this indication.

“If you are a GP you’re going to see pregabalin before you see anything else.  A lot (of GPs) feel stuck if they don’t want to use opioids.”

A bigger problem than initial prescribing of pregabalin is  continuing the medication when it’s not working, he said.

“Maybe they [GPs] are scared to de-prescribe because they feel as though it sends a message there is nothing else that can be done.”

Meanwhile, addiction medicine expert Dr Adrian Reynolds said with the “indiscriminate” prescribing for pain comes the growing risk of misuse of pregabalin, which induces euphoria in therapeutic doses.

“We are seeing a small but increasing number of patients presenting to addiction medicine services with evidence of problems including addiction to these medicines,” said Dr Reynolds, who is the president of the Royal College of Physicians’ Chapter[of Addiction Medicine.

“This drug is starting cause problems at a population level and if doctors aren’t picking up on it in a timely way and changing their practice, then you need to consider a regulatory response alongside another mechanisms, including clinical governance and undergraduate and postgraduate education and training.”

A spokesperson for Pfizer said the company “supports the appropriate use of Lyrica (pregabalin) according to its registered indications in Australia”.

“We also take the safety of our medicines very seriously and the Lyrica product information contains information advising clinicians that patients should be carefully evaluated for a history of substance abuse and observed for signs of Lyrica misuse or abuse.”

*Pfizer’s patent for Lyrica expired in July this year.

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