A woman who fears her daughter's death is linked to a change in her epilepsy medicine is urging vigilance among the 11,000 people being forced to switch drug brands by a Pharmac cost-saving drive.
Kate Randell* said her 23-year-old daughter Jane Randell* had just bought a house and was about to get married.
Her epilepsy was well-controlled for the past decade but she died suddenly on the morning of 20 September.
Pharmacy records and photographs taken by police investigating Jane's death showed she had switched brands of the anti-epileptic medicine lamotrigine - a practice some researchers believe increases seizure risk.
About 11,000 New Zealanders, most with epilepsy but some with mental health conditions, are switching to a generic form of lamotrigine called Logem.
Pharmac instigated the switch, which will save it $30 million over five years, by pulling funding for the two main brands, Lamictal and Arrow, used by 90 percent of New Zealanders with epilepsy.
The Centre for Adverse Reactions Monitoring (CARM) said there had been 26 reports of adverse reactions to lamotrigine since brand switch began in May. One of those reports was about Jane's death.
"Our lives have been turned upside down. I've lost my daughter," Kate said. "It has rippled out through our family and just broken us."
With a coroner's report still months away, Kate can't prove the brand switch led to a seizure and then a fall but she believes that was the case.
"I'm just devastated that the whole situation could have been so different had there been more information and more support out there."
Kate said Jane had used both Logem and Lamictal in recent years. She had taken Logem between 2015 until April this year. Pharmacy records show she was given Lamictal in June and July and then switched back to Logem. "So basically she has been on Logem, then she was given Lamictal and then she was put back on Logem again within a very short space of time."
Kate was angry at the lack of information and support offered during the brand switch. "I didn't know anything about it until after her death. I had no idea."
Pharmac documents obtained by RNZ - initially withheld for three months and only released after the intervention of the ombudsman - show how the drug-buying agency assessed the level of risk associated with the brand change.
Pharmac judged there was a "high" likelihood of "reports of break through seizures, mood destabilisation or adverse effects in one or more patients being attributed to the brand change".
The documents reveal the decision to go ahead with the switch went before the full Pharmac board rather than just the chief executive, partly because it was "considered contentious due to the perceived and potential clinical risks of a brand change in this population".
Medsafe warned Pharmac not to go ahead with the brand switch, saying it went against international best practice and posed a potential significant safety issue. "We note that we would be implementing a brand change without Medsafe's support," Pharmac said in the documents.
Brand switching often involves moving patients to cheaper generic drugs to free up money from Pharmac's capped budget to buy other medicines. It is a key part of the Pharmac model.
A paper from Pharmac's therapeutic group manager reveals the thinking behind the lamotrigine switch, describing it as an "opportunity for significant savings coupled with the need to meet budget and fund new investments".
It says "the outcome of this transaction will likely affect how we approach similar transactions" for other anti-epileptic drugs in the future, which could save more money.
The documents show Pharmac expected to reduce spending from nearly $9.5 million a year on lamotrigine to $910,000 by 2021.
But Kate said Pharmac needed to be more careful.
"It's not about money. It's about people's lives. It could have led disastrously to my daughter losing her life. It's unconfirmed but it could have. And we just don't want to see this happening to any anybody else, for another family to be suffering in the way that we are."
Kate said neither she nor her daughter had any idea Pharmac was making the brand switch.
She received a phone call on the morning of 20 September informing her Jane hadn't arrived at work.
"I just had this feeling and I dialled 111 and got an ambulance to go there. But as far as I understand she was already deceased by the time they arrived at the house."
Kate saw her daughter in the mortuary that afternoon and saw a head injury which she thought was the result of a fall during a seizure.
On 26 August, a few weeks before her death, Jane went to a pharmacy to pick up Lamictal but was given the generic Logem instead. It had a small sticker on the box saying it was the same medication; just a different size, shape and colour.
RNZ spoke to other patients and pharmacists who said the sticker was being used around the country to assure patients that the Logem generic is the same as the brand they were previously on.
Kate said Jane noticed she had been given different medication in August, and discussed it with her fiance.
"At no point was it discussed with her," Kate said. "Neither of them knew that there could possibly be repercussions of switching brands."
Kate was also concerned her daughter wasn't able to see a neurologist despite requesting an appointment. She began to feel unwell in the weeks leading up to her death but was told her annual appointment with the neurologist was still a few months away and she should see a GP instead.
She visited the GP on 11 September, and died just over a week later.
Ahead of the brand switch, Medsafe had warned Pharmac that all vulnerable patients should be referred for specialist oversight and advised "all patients are seen and counselled by their GP before changing brands".
Phamac rejected the advice, with its expert subcommittee saying it wasn't "clinically necessary" or practical with limited health resources.
Pharmac has continuously stressed Logem worked exactly the same way as the two brands it previously funded and that most people would not notice a difference.
The agency said people who needed their old brand for clinical reasons could apply to have it funded. So far it had received 59 applications and approved 27. It declined 10 applications on the grounds there was no clinical reason patients shouldn't try Logem and asked six applicants to supply more information.
Neurologist Dr John Fink was on the Pharmac expert committee that approved the brand switch.
He said about 50 percent of people on lamotrigine had changed brands at least once since they started on the drug and 4000 had changed brands two or more times. "So there's been a lot of brand switching of lamotrigine here in New Zealand over many years. And we just haven't seen the reality of significant concerns with it. It's appeared to be safe."
Even in people with good epilepsy control, 10 to 20 percent would have a seizure within a year and one in a 1000 would die regardless of brand changes or other factors, he said. "So that would be about 10 fatalities per year that we would expect, even if there's no change mandated by Pharmac."
Dr Fink believed the brand switch was ultimately worth the risk. "I think our assessment is that it is worth the $30 million. There's a number of studies out there which suggest there aren't any risks, that if there are risks they are small and we believe they can be managed."
Pharmac documents released under the Official Information Act referenced studies showing brand switching caused little impact on epilepsy patients but also referenced other studies saying there were increased risks.
The UK drug safety watchdog, the Medicines and Healthcare Products Regulatory Agency, said lamotrigine brands should only be switched on "clinical judgement".
The American Academy of Neurology also opposed generic substitution, saying "variation between name brand and generic drugs can be highly problematic for patients with epilepsy".
Phamac, however, said there were no clinical reasons why the change should cause problems.
It said the 'nocebo effect' - when people experience side effects because they believe their medicine is inferior - accounted for most issues patients had.
Documents show that prior to the brand switch, Pharmac thought it could use the lamotrigine change to research the nocebo effect. The agency would "consider utilising the lamotrigine brand change as an opportunity to get real world experience on whether counselling on the nocebo effect alter the acceptance of a brand change using lamotrigine as the pharmaceutical for this research".
The documents show there were suggestions the agency could publish "consumer stories" on its website "where a person receiving a funded generic medicines talks about their successful change from one brand to another. Lamotrigine could be one of the change examples."
In a statement to RNZ, Pharmac director of operations Lisa Williams said approximately 5180 people had now switched from another brand to Logem, and the agency was maintaining close contact with Medsafe about adverse event reports. It was aware that one report involved a fatality.
"For many people, epilepsy is a condition which can be well-managed and has little or no impact on their life. For others, ongoing seizures mean that epilepsy has a long-term impact. Like many medical conditions epilepsy can be a cause of sudden death, although this is not common and is of course utterly devastating for family and whānau."
Kate said Pharmac should be focused on disseminating patient safety information.
"Had we known before that there could be repercussions from a brand change we would have lived differently with my daughter until the change was fully done and she was well," she said.
"We don't know that she definitely had a seizure that morning - and we may not know for some time - but if she's not alone in this, if she is one of many people that are having their brand changed at this precise moment, it terrifies me that something bad could happen to somebody else."