Since 1994, Merck has been aware of unresolved sexual dysfunction in men who stopped taking finasteride

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In a clinical trial that ended in 1994, Merck documented a patient who had developed ‘Impotence’ while taking finasteride, and still had this problem several weeks after he stopped taking the drug. In a later trial, the company reported another such case. After Propecia was approved in 1997, Merck received postmarketing reports of men who had not recovered from sexual dysfunction after discontinuing finasteride. This post summarizes these cases as described in official Merck documents: the New Drug Application for Propecia submitted to FDA in 1997; and a safety update submitted to the Swedish Medical Products Agency in 2006.

Key points

  • Between 1998 and 2001, a patient discontinued a Phase 3 trial of finasteride due to a drug-related sexual adverse experience (AE). Six months after discontinuation, the sexual AE was unresolved. There were also 16 men whose drug-related sexual AEs were unresolved at the conclusion of the trial.
  • As of November 2006, Merck had recorded 100 reports of a drug-related sexual adverse experience (AE) associated with finasteride, where the therapy had been discontinued and the AE was unresolved. There were an additional 278 reports of possible concern with incomplete information.
  • In Phase 2 clinical trials of finasteride (at a higher dose of 5 mg/day), a patient had an unresolved sexual AE 27 days after discontinuing the trial.

Merck’s adverse event database: Hundreds of reports of unresolved sexual adverse events

As of 2006, Merck had received hundreds of reports of unresolved sexual dysfunction associated with finasteride. Merck included this table in its 2006 safety update to the Swedish Medical Products Agency:

Merck Periodic Safety Update Report to Swedish Medical Products Agency, 30 Nov 2006, p. 5 (data from 1998–6 Nov 2006)

The table shows there were 200 cases of sexual adverse experiences associated with finasteride which were not recovered. Of these, 100 had discontinued the medication. There were an additional 63 cases which were not recovered and it was unknown whether therapy had been discontinued. There were a further 215 cases where it was unknown whether they had recovered or not.

5-year extension study of Propecia: an unresolved sexual adverse event after discontinuation

There was a patient in years 3–5 of the Phase 3 extension studies, who had unresolved sexual dysfunction six months after discontinuing the trial due to a drug-related sexual adverse event. We know this because of a 2006 report Merck submitted to the Swedish regulatory authority:

Merck Periodic Safety Update Report to Swedish Medical Products Agency, 30 Nov 2006, p. 2

It appears Merck did not explicitly acknowledge this patient in the Supplemental New Drug Application it submitted in 2001; however, deep in the filing, on page 101, in vertical orientation, the word “all” was struck from the phrase “Resolution occurred in all men who discontinued therapy with PROPECIA due to [sexual] side effects…”

Merck Supplemental New Drug Application (NDA) submitted to FDA, p. 101

Merck’s report to the Swedish authority indicates (without an explicit statement) that 16 of 48 men who remained in the study and had drug-related sexual AEs did not have resolution of those AEs at the conclusion of the trial. No further follow-up information on these 16 men is provided.

Phase 2 pilot study: Unresolved impotence after discontinuation

This Phase 2 trial (#047) of finasteride for male pattern baldness was conducted from July 1992 to April 1994. A 35-year-old man had onset of Impotence on day 123 after starting finasteride 5 mg/day. Merck designated this a non-serious adverse event (AE) which was “Possibly” drug-related.

Trial #047 (p. 22 of PDF)

The table obfuscates the length of time the adverse event was still present after discontinuation. The data has been converted into a timeline:

  • Day 1: Patient begins finasteride 5 mg/day
  • Day 123 (~4 months from start of trial): Onset of Impotence
  • Day 170 (~5.5 months from start of trial): Discontinues finasteride
  • Day 197 (27 days after discontinuation): Impotence “Still present” *

* Day of onset (123) plus duration of adverse event (74) = 197. To calculate duration after discontinuation: Date of last assessment (197) – date of drug discontinuation (170) = 27 days.

No further follow-up information is provided. Despite this participant’s experience, Merck’s Conclusions on this trial included the statement: “Finasteride 5 mg/d was generally well tolerated by young men with MPB.”

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