Merck Knew About Suicides Linked To Propecia (Finasteride) But Didn’t Update Label, Unsealed Documents Show
KAISER HEALTH NEWS – Internal records were made public in late January after a 2019 Reuters motion to unseal 11 documents.
A 2011 update of the popular anti-baldness treatment’s label didn’t include a warning about suicidal behavior even though the FDA had by then received reports of 10 suicides.
Since 2011, the FDA has received reports of another 100 deaths linked to the drug.
Reuters: Exclusive: Merck Anti-Baldness Drug Propecia Has Long Trail Of Suicide Reports, Records Show
Newly unsealed court documents and other records show that Merck & Co and U.S. regulators knew about reports of suicidal behavior in men taking the company’s anti-baldness treatment Propecia when they decided not to warn consumers of those potential risks in a 2011 update of the popular drug’s label.
Internal records from Merck were made public in late January, when a federal magistrate in Brooklyn, New York, granted a 2019 Reuters motion to unseal 11 documents filed in years of litigation alleging Propecia caused persistent sexual dysfunction and other harmful side effects. (Levine and Terhune, 2/3)
From Wikipedia, the free encyclopedia
Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat hair loss and benign prostatic hyperplasia in men.
It can also be used to treat excessive hair growth in women and as a part of hormone therapy for transgender women. It is taken by mouth.
Finasteride is a 5α-reductase inhibitor and therefore an antiandrogen. It works by decreasing the production of dihydrotestosterone (DHT) by about 70%, including in the prostate gland and the scalp.
Side effects from finasteride are rare, however some men experience sexual dysfunction, depression, and breast enlargement. In some men, sexual dysfunction may persist after stopping the medication. It may also hide the early symptoms of certain forms of prostate cancer.
Finasteride was patented in 1984 and approved for medical use in 1992. It is available as a generic medication. In 2017, it was the 86th-most commonly prescribed medication in the United States, with more than nine million prescriptions.
Finasteride is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate and for the treatment of male pattern hair loss (androgenetic alopecia) in men.
Physicians sometimes prescribe finasteride for the treatment of benign prostatic hyperplasia (BPH), informally known as an enlarged prostate.
Finasteride may improve the symptoms associated with BPH such as difficulty urinating, getting up during the night to urinate, hesitation at the start and end of urination, and decreased urinary flow.
It provides less symptomatic relief than alpha-1 blockers such as tamsulosin and symptomatic relief is slower in onset (six months or more of treatment with finasteride may be required to determine the therapeutic results of treatment).
Symptomatic benefits are mainly seen in those with prostate volume > 40 cm3. In long-term studies finasteride but not alpha-1 inhibitors reduce the risk of acute urinary retention (−57% at 4 years) and the need for surgery (−54% at 4 years).
If the drug is discontinued, any therapeutic benefits are reversed within about 6–8 months.
Scalp hair loss
Finasteride is also used to treat male pattern baldness (androgenic alopecia) in men, a condition that develops in up to 80% of Caucasian men.
In the United States, finasteride and minoxidil are the only two FDA approved drugs for the treatment of male pattern hair loss as of 2017. Treatment with finasteride slows further hair loss and provides about 30% improvement in hair loss after six months of treatment, with effectiveness persisting as long as the drug is taken.
Taking finasteride leads to a reduction in scalp and serum DHT levels; by lowering scalp levels of DHT, finasteride can maintain or increase the amount of terminal hairs in the anagen phase by inhibiting and sometimes reversing miniaturization of the hair follicle. Finasteride is most effective on the crown but can reduce hair loss in all areas of the scalp.
Finasteride has also been tested for pattern hair loss in women; however, the results were no better than placebo. Finasteride is less effective in the treatment of scalp hair loss than dutasteride.
In males over 55 years old finasteride decreases the risk of low grade prostate cancer but may increase the risk of high grade prostate cancer and has no effect on overall survival.
A 2010 review found a 25% reduction in the risk of prostate cancer with 5α-reductase inhibitor. A follow-up study of the Medicare claims of participants in a 10-year Prostate Cancer Prevention Trial suggests the reduction in prostate cancer is maintained even after discontinuation of treatment.
However, 5α-reductase inhibitors have been found to increase the risk of developing certain rare but aggressive forms of prostate cancer (27% risk increase), although not all studies have observed this. No impact of 5-α-reductase inhibitor on survival has been found in people with prostate cancer.
Excessive hair growth
Finasteride has been found to be effective in the treatment of hirsutism (excessive facial and/or body hair growth) in women.
In a study of 89 women with hyperandrogenism due to persistent adrenarche syndrome, finasteride produced a 93% reduction in facial hirsutism and a 73% reduction bodily hirsutism after 2 years of treatment. Other studies using finasteride for hirsutism have also found it to be clearly effective.
Transgender hormone therapy
Finasteride is sometimes used in hormone replacement therapy for transgender women due to its antiandrogenic effects, in combination with a form of estrogen.
However, little clinical research of finasteride use for this purpose has been conducted and evidence of safety or efficacy is limited.
Moreover, caution has been recommended when prescribing finasteride to transgender women, as finasteride may be associated with side effects such as depression, anxiety, and suicidal ideation, symptoms that are particularly prevalent in the transgender population and in others at high risk already.
A 2010 Cochrane review concluded that adverse effects from finasteride are rare when used for BPH. When finasteride was originally approved for hair loss in 1997, the FDA reported that it appeared well tolerated, with the most common side effects being related to sexual function.
Finasteride is contraindicated in pregnancy. The Food and Drug Administration advises that donation of blood or plasma be deferred for at least one month after taking the last dose of finasteride.
The FDA has added a warning to 5α-reductase inhibitors concerning an increased risk of high-grade prostate cancer, as the treatment of BPH lowers PSA (prostate-specific antigen), which could mask the development of prostate cancer.
Although overall incidence of male breast cancer in clinical trials for finasteride 5 mg was not increased, there are post-marketing reports of breast cancer in association with its use, though available evidence does not provide clarity as to whether there is a causative relationship between finasteride and these cancers.
A 2018 meta-analysis found no higher risk of breast cancer with 5α-reductase inhibitors. Some men develop gynecomastia (breast development or enlargement) following finasteride usage.
The risk of gynecomastia with 5α-reductase inhibitors is low at about 1.5%. Depressive symptoms and suicidality have been reported.
Finasteride causes short-term sexual dysfunction in some men, which may persist in some men after stopping the medication. There are case reports of persistent diminished libido or erectile dysfunction after stopping the drug and the FDA has updated the label to inform people of these reports.
The 2010 Cochrane review found that compared with placebo, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder for the first year of treatment. The rates became indistinguishable from placebo after 2–4 years and these side effects usually got better over time.
A 2016 meta-analysis found that sexual dysfunction, including erectile dysfunction, loss of libido, and reduced ejaculate, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride. This adverse effect has been linked to lower quality of life and can cause stress in relationships.
Finasteride may cause persistent adverse sexual, neurological and physical effects in a subset of men.
This has been called post-finasteride syndrome, characterized by reported sexual and physical symptoms such as loss of libido, erectile dysfunction, ejaculatory disorders, reduction in penis size, penile curvature, reduced sensation, male breast enlargement, muscular atrophy, fatigue and severely dry skin.
People with post-finasteride syndrome may experience depression and anxiety, cognitive impairment and suicidal thoughts.
Post-finasteride syndrome may also have reduced levels of neurosteroids such as allopregnanolone in their cerebrospinal fluid. One study found that 1.4% developed persistent sexual dysfunction.
A 2019 Reuters investigation showed that Merck found evidence of persistent side effects in their original clinical trials and did not disclose it in their warning label. They uncovered court filings which demonstrated that Merck misrepresented Propecia’s safety record following clinical trials in the mid-late 1990s.
In one deposition, Charlotte Merritt, who oversaw regulatory activity for Propecia, acknowledged that Merck changed Propecia’s label for sexual adverse events in 2002, four years after Propecia hit the market. The label changed from “resolution occurred in all men who discontinued therapy with Propecia ” to “resolution occurred in men who discontinued therapy with Propecia”. Merritt testified that Merck eliminated the word “all” due to evidence from the clinical trials of adverse events that did not resolve following discontinuation of use.
In another deposition, Paul Howes, the head of marketing for Propecia acknowledged that Merck was aware that warnings of sexual side effects, particularly persistent to permanent side effects, would have a devastating impact on sales … READ MORE.