All 200 pharma firms selling 5-ARIs in the EU must address ‘causal relationship’ between drugs’ use and patients
considering, attempting or committing suicide
Oct. 11, 2024
Dear Friends:
Depending on how deadly regulators across the pond find finasteride to be, the drug could be in for a continental shelving come February.
Countdown to D-Day
Last week, the European Medicines Agency (EMA) launched an investigation into reported links between finasteride therapy and suicidality. (According to the US National Institutes of Health, suicidality is defined as “Thoughts of death or suicide, planning or preparing suicide, attempting suicide, and completing suicide.”)
The five-month procedure, being directed by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), will assess all available data on this growing public-health concern, while weighing its impact on the benefit-risk balance of both finasteride and fellow 5-alpha reductase inhibitor (5-ARI) dutasteride.
Upon completion of its probe, the EMA, a scientific agency of the European Union (EU) in charge of evaluating and supervising pharmaceutical products, will “issue a recommendation on whether the marketing authorisations for these medicines should be maintained, varied, suspended or withdrawn” across the European Economic Area (EEA).
A total of 30 nations—27 EU member states, along with Iceland, Liechtenstein and Norway—make up the EEA, while 200 pharmaceutical companies are authorized by the EMA to market finasteride and dutasteride in those nations.
Each company, aka marketing authorization holder (MAH), has been directed to respond by December 10 to a series of questions that dig into the suicide trend from an epidemiological and economic point of view. The sought data, literature, and input for finasteride products (both oral and topical formulations), and for dutasteride, include:
▪ Sections of the summary of product characteristics (SmPC), package leaflet (PL) and labelling (inner and/or outer packaging) pertaining to suicidality and other psychiatric disorders.
▪ An analysis of all relevant non-clinical data, clinical trials data, pharmaco-epidemiological studies, and published literature on suicidality following finasteride or dutasteride.
▪ A discussion of “the causal relationship between suicidal ideation and/or suicide and treatment with finasteride or dutasteride.”
▪ A discussion on the characterization of possible risk factors including age, dose, administration route, treatment duration, and personal psychiatric history.
▪ Risk-minimisation measures for psychiatric disorders implemented in each member state, and proposals for new measures to further minimize suicidality.
▪ Annual sales figures.
The deadline for the PRAC formulating its recommendations is February 2025, at which point the committee will share them with the Co-ordination Group for Mutual Recognition and Decentralised Procedures—Human (CMDh), which in turn will adopt a final position.
Although the EMA isn’t a drug-regulatory authority, which means it can’t legally oblige member states to do anything, all its recommendations are handed over to the European Commission (EC), a politically independent arm of the EU responsible for drafting new legislation. And according to the agency itself, the EC “follows the opinion of EMA in almost all cases.”
Fifth time a charm?
If this investigation yields changes to the product literature, market suspension, or market withdrawal, it will mark the fifth time in 16 years that the EMA has taken steps to inform the public of adverse, and persistent, reactions to finasteride that have emerged in the post-marketing population:
▪ 2009: “Persistence of sexual dysfunction after discontinuation of treatment” added to the Propecia (finasteride 1 mg) SmPC.
▪ 2010: “Depressed mood” added to the SmPC.
▪ 2017: “Depressed mood” replaced by “depression” in the SmPC, and a warning section added regarding mood alterations, including “depression and, less frequently, suicidal ideation.”
▪ 2018: “Anxiety” added to the SmPC.
World powers converge
The EMA’s move comes just six months after one former EU member launched its own probe, which itself followed on the heels of four other nations calling out finasteride’s potential dangers:
• United Kingdom: April 2024. The Medicines and Healthcare Products Regulatory Agency issued a Drug Safety Update alerting health care pros that finasteride patients risk developing psychiatric and/or sexual side effects that can persist post-treatment.
• Canada: January 2024. Health Canada informed health care pros that “The Warnings and Precautions and Patient Medication Information sections of the Canadian product monographs [aka, labels] for Propecia and Proscar (finasteride 5 mg) have been updated with the risk of mood alterations [including] depressed mood, depression, self-harm injury [and] suicidal ideation.”
• Japan: August 2023. The Pharmaceuticals and Medical Devices Agency published a disproportionality analysis of suicidality ADRs associated with finasteride and dutasteride. For suicidal ideation, the expected number of ADRs was 43, but the actual number was 470 (+993%). For completed suicide, expected ADRs was 40, but the actual number was 148 (+270%).
• France: December 2022. The National Agency for the Safety of Medicines and Health Products (ANSM) mandated that a red-box warning be added to all finasteride 1 mg products. It reads: “This medication can cause side effects, including psychiatric and/or sexual disorders.”
• USA: June 2022. In response to a Citizen Petition filed by the PFS Foundation, the Food and Drug Administration (FDA) ordered Organon & Co. (OGN), the Merck & Co. (MRK) spinoff that now owns Propecia and Proscar, to add “suicidal ideation and behavior” to the Prescribing Information of all finasteride 1 mg products.
(For a listing of all nations known to have issued PFS warnings, please consult our PFS Global Warning Map.)
French linchpin
Among the documents the EMA released in tandem with the announcement of its latest finasteride investigation is a filing from ANSM that set that investigation in motion. On September 13, Alexandre de la Volpilière, the agency’s interim director general, wrote:
Following serious spontaneous cases reported over time at [the] national level with finasteride 1 mg…ANSM has long been very concerned by the safety profile of finasteride 1 mg, especially regarding psychiatric disorders and sexual dysfunction which can persists after discontinuation of treatment.
He then enumerated four safety measures his own agency has taken, separate from the EMA, in the past four years:
• December 2019: Produced information sheet to better inform patients about the risk of psychiatric and sexual disorders. (PFS Foundation coverage, including English translations, here.)
• July 2022: Launched new section on the ANSM website to inform the public about risks including psychiatric and sexual disorders. (English here.)
• November 2022: Modified the outer packaging with a red-box warning and QR code, and updated the national patient information sheet with a warning that suicidal ideation can lead to completed suicide. (English here.)
• January 2023: Distributed “dear doctor” letter, to prescribers and non-prescribers alike, alerting them to the possible role of finasteride in patient reports of psychiatric or sexual disorders. (English here.)
“Despite these measures,” Volpilière continued, “cases of psychiatric disorders (including suicidal ideation) and sexual dysfunction (including long lasting sexual dysfunction that could lead to mood disorders) are still reported to” ANSM.
He also referenced a recent research project, which France undertook with 19 other EU member states, “examining 468 spontaneous cases of ‘suicide and suicidal ideation,’” 93 of which reported fatal outcomes, “presumably by suicide.” And in that same passage, he wrote:
Even though a causal association between finasteride and suicidal ideation has not been established, it was considered at least a reasonable possibility, given that known ADRs such as sexual disorders, including erectile dysfunction/impotence, depression, decreased libido, may lead to suicidal ideation.
Organon unenlightened?
In response to the EMA investigation, Organon, which is authorized to market Propecia and Proscar in 20 EEA nations, released this statement: “Nothing is more important to Organon than the safety of our medicines and the people who use them.”
Then they added: “Regulators around the world have reviewed the safety and efficacy data for these medicines prior to their approval.”
What Organon didn’t mention is that the FDA approved Proscar in 1993 and Propecia in 1997, meaning there now exists 31 years and 27 years, respectively, of postmarketing data on those drugs—after being used by tens of millions of men.
If Organon were to log onto the World Health Organization’s VigiBase database of adverse drug reactions and run a search for finasteride, they would find that among the 21,549 ADRs reported for the drug are 541 cases of suicidal ideation, 46 cases of suicide attempt, 105 cases of completed suicide, and 576 cases of death.
Then again, the company should already know that, because the majority of those ADRs were filed directly to Organon and its former parent company, Merck—and, as legally obliged, Organon and Merck reported them to the FDA, which in turn were aggregated by the WHO.
What’s more, 2024 recently earned the distinction of being the year in which an all-time record number of finasteride ADRs have been reported by the WHO—1,871 as of this week. That’s 75 more than the previous record year of 2015.
And there are still 11 weeks to go until year-end.
Finasteride was originally developed by Merck & Co., Inc., and first approved by the US Food and Drug Administration in 1993 as Proscar (5 mg, for enlarged prostate), and again in 1997, as Propecia (1 mg, for hair loss).
In June 2021, Merck spun off its Organon subsidiary as an independent public company (NYSE: OGN). Founded in the Netherlands in 1923, Organon bills itself as a “global health care company dedicated to making a world of difference for women, their families and the communities they care for.”
Among the Merck products Organon acquired in the deal were Proscar and Propecia. To report adverse events for either finasteride product, call the Organon Service Center at (844)674-3200, or email Service_Center@Organon.com.
Anyone living in the US who suffers from PFS should also report his or her symptoms to the US FDA. Anyone living outside the US who suffers from PFS should report his or her symptoms to the US FDA as well as to his or her local DRA, as directed on our Report Your Side Effects page.
If you or a loved one are suffering from PFS, and feeling depressed or unstable, please don’t hesitate to contact the PFS Foundation as soon as possible via our Patient Support hotline: social@pfsfoundation.org
Thank you.