The South African Health Products Regulatory Authority (SAHPRA) has confirmed that paracetamol remains a safe and recommended option for treating pain and fever during pregnancy, and that no scientific evidence links it to attention-deficit hyperactivity disorder (ADHD) and autism.
It added that it would continue to monitor emerging evidence on the medication’s safety, and that healthcare professionals are encouraged to provide counselling to patients about the side effects of paracetamol, as detailed in the product’s professional information and patient information leaflet (https://pi-pil-repository.sahpra.org.za/).
They are urged to report any suspected adverse drug reactions related to paracetamol and other health products to SAHPRA via the eReporting link available on the SAHPRA website (www.sahpra.org.za) or complete an ADR reporting form.
Alternatively, reporting can be done via the Med Safety App, downloadable through Google Play or the Apple App Store.
Meanwhile, the FDA’s move to ask pharmaceutical company GSK to update the label for the now-generic drug leucovorin that it stopped selling more than 28 years ago – after claiming an agency review of the literature shows it might help with autism – has raised questions about which data back the effort, how it will actually be used by patients and doctors, and who will supply the pill.
One expert has scathingly described the decision as “not normal”.
Typically, reports Endpoints News, the FDA only asks companies to re-label a drug when there are concerns about its safety or efficacy, narrowing its usage. Aside from cancer, where the FDA has a programme to review older oncology drug labels, it’s unprecedented for the agency to independently push to expand the use of a medication into a new disease.
And in this case, it’s still unclear on which data, exactly, the FDA is relying.
A Health department spokesperson told Endpoints that an “analysis across 23 publications from 2009-2024 demonstrated the effectiveness for cerebral folate deficiency (CFD)”, the neurological condition with developmental delays associated with autism.
“The analysis shows that overall, 85% of patients experienced some type of clinical benefit including improved speech/communication capabilities,” according to the spokesperson, who didn’t, however, provide links or names of the studies. The analysis hasn’t been published by the government yet, either.
Last week President Donald Trump and HHS Secretary Robert F. Kennedy Jr controversially unveiled the new indication for leucovorin and claimed that, despite conflicting evidence, the use of Tylenol during pregnancy may cause or contribute to autism.
“For the FDA to decide based on a non-public review of some unclear past literature of dubious quality that a drug works for a certain indication that was never part of a drug’s original indication and then tell the public that the drug works for that purpose and THEN tell the manufacturer (which seemingly hasn’t made the drug in 25 years) to identify the right dose and conditions for use for some future labelling update is absolutely not normal,” Harvard Medical School Professor Aaron Kesselheim told Endpoints.
“It is in a different universe from normal.”
GSK told Endpoints it would update the label for the drug at the FDA’s request, but it has no plans to restart manufacturing of leucovorin, which it once sold under the brand name Wellcovorin.
There are also questions about what dose of the drug patients would get, since generic companies offer various doses and formulations. In addition, there are also unregulated supplements purporting to contain the active ingredient in leucovorin.
GSK also said it did not know what dose of the drug would be recommended by the FDA.
Patricia Zettler, Professor at Ohio State University and former FDA lawyer, said: “The FDA seems to be asking the NDA sponsor to add an indication to this drug, and from what we can tell from what is public, FDA is basing that request on information which seems quite different from what the agency would normally consider to be ‘substantial evidence’ of effectiveness, even for rare diseases.”
Research into whether leucovorin can help with autism has been promising and is ongoing, Richard Frye, a paediatric neurologist, told Endpoints. Frye wrote a book on the use of folate in autism and made national news earlier this year when he treated a boy with non-verbal autism with leucovorin.
“It is a promising treatment,” Frye said, but it’s not a cure. He noted the label update may make physicians more willing to prescribe leucovorin for autism, but said he found it “a little surprising” that the FDA “released this without any guidance for physicians, especially as there are so many different forms of the generic drugs and supplements on the market, with various dosages and formulations and varying potential effects on autism symptoms”.
Frye said he recommends parents use versions of the drug made by the generics company West-Ward Pharmaceuticals, a US subsidiary of Hikma, but they ran out of supplies last March and it’s unclear if the company intends to replenish them. West-Ward did not immediately respond to a request for comment.
Other generics and supplements that are currently marketed as leucovorin aren’t optimal, and some “have excipients that can cause kids to regress”, Frye said.
See more from MedicalBrief archives:
SA expert groups dismiss Trump’s paracetamol link to autism
Kennedy to ‘reveal causes of autism’ this month