23 August 2018

TGA to probe pregabalin after abuse warning

Addiction Drugs Pain

A rapid rise in overdoses and deaths associated with abuse of pregabalin since the pain and epilepsy medication was PBS-listed in 2013 has prompted an investigation by the TGA.

A study led by Dr Rose Cairns has confirmed 88 deaths in NSW alone since the drug was introduced in 2005, including 82 deaths since 2013.

“We had been noticing a rise in the misuse and abuse of pregabalin,” Dr Cairns, a Senior Specialist at the NSW Poisons Information Centre, said.

“In addition, international studies had appeared indicating that pregabalin had an abuse potential, which was a bit different to what was thought when it was introduced.”

Dr Cairns said many Australian doctors might not have been aware of the danger of off-label use of pregabalin, which is marketed in Australia as Lyrica and licensed for treatment of neuropathic pain and epilepsy.

“What we are trying to highlight is that it does have an abuse potential, and prescribers need to be aware of that, especially when patients have a substance-abuse history.”

Pregabalin dispensings showed an increase of nearly three-fold in the three years to 2016, according to the study, published in the journal, Addiction.

Intentional poisonings recorded in the NSW data set rose steeply following the PBS listing, with 376 cases in 2016, taking the total to 1158.

From analyses of two toxicology databases, the study concluded that one in seven Australian patients who were prescribed the drug were at a high risk of misusing it.

The high-risk group was more likely to be younger, male, and be co-prescribed benzodiazepines or opioids.  They tended to have more individual prescribers and high pregabalin strengths prescribed.

This group accounted for just over 50% of the pregabalin dispensed by volume, the study found.

However, the profile of most Australian patients who were dispensed pregabalin in 2016-17 was very different: nearly 60% were female, with a median age of 62.

Dr Cairns said the intentional poisoning cases included a range of behaviours: deliberate self-harm; recreational use for a euphoric effect; and off-label use, including patients prescribed the drug for pain consuming larger doses to combat anxiety or sleeplessness.

In Europe, the drug is also approved for generalised anxiety disorder, and in the US for fibromyalgia.

Internationally, there have been numerous reports of misuse and abuse of pregabalin, the study report says.

“Euphoria is a documented side effect of pregabalin, and tolerance and withdrawal have been reported. There are reports of drug users taking large doses of pregabalin for euphoric and dissociative effects.”

Dr Cairns also noted evidence from overseas of off-label use for conditions including anxiety, post traumatic stress disorder, and treating other substance abuse.

“We are advocating for (avoidance of) extensive off-label use,” she said.

In the UK, the drug is currently being considering for rescheduling as a controlled substance, a step supported by the British Medical Association.

In January, the association wrote to the UK government’s drugs legislation team addressing concerns about pregabalin and gabapentin, another gabapentinoid drug.

“Our members have raised particular concerns about their impact in prisons, where when misused they are associated with addiction, trading, overdose and bullying, both on the wings and in consultation rooms.

“We also have concerns about the pressure put on clinicians in out of hours and urgent care services for repeat prescription.”

The TGA is investigating the misuse and abuse of pregabalin in Australia and has been liaising with the NSW Poisons Information Centre, a spokeswoman for the federal health department said.

“It is anticipated that the issue will be referred to the Advisory Committee on Medicines, prior to any regulatory action being implemented in Australia,” she said.

Around 3.9 million PBS and RPBS prescriptions for pregabalin, including co-payment prescriptions, were dispensed in Australia in 2016-17.