On June 9, 2011, the U.S. Food and Drug Administration (FDA) informed the public of new safety information for drugs called 5-alpha reductase inhibitors (5-ARIs). Men who take these drugs may have an increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer). The Warnings and Precautions section of the labels for all FDA-approved 5-ARIs have been revised to include information about this risk.
The following questions and answers address potential issues raised by this safety information.
Q1. What are 5-alpha reductase inhibitors (5-ARIs)?
A. 5-alpha-reductase inhibitors (5-ARIs) are a class of prescription medicines primarily used to treat the symptoms of benign prostatic hyperplasia (BPH) in men. BPH is a common condition in men older than 40 and is characterized by an enlarged prostate and symptoms such as frequent urination and difficulty emptying the bladder. Drugs in this class are finasteride (marketed as Proscar [finasteride 5 mg] and Propecia [finasteride 1 mg]) and dutasteride (marketed as Avodart). Dutasteride is also available in combination with tamsulosin under the brand name Jalyn.
Avodart, Jalyn, and Proscar are indicated for the treatment of BPH symptoms in men with an enlarged prostate. Avodart and Proscar are also approved to reduce the risk of urinary retention or surgery related to BPH. FDA believes that 5-ARIs remain safe and effective for their approved indications.
Propecia is only indicated for the treatment of male pattern hair loss in men.
Q2. What is high-grade prostate cancer?
A. High-grade prostate cancer is an aggressive type of prostate cancer, meaning it grows and spreads faster compared to low-grade prostate cancer.
High-grade prostate cancer is a serious disease, but accounts for a small portion of all diagnosed prostate cancers.
Q3. Why are the labels of all 5-alpha reductase inhibitors (5-ARIs) being revised?
A. The labels of all 5-alpha reductase inhibitors (5-ARIs) are being revised based on FDA's review of two large studies examining whether these drug products (Proscar, Avodart) reduce the risk of prostate cancer. The studies did find an overall reduction in the risk of lower-grade forms of prostate cancer, but both studies also showed an increased risk of high-grade prostate cancer.
As a result of these two studies, the labels of all FDA-approved 5-ARIs will be revised to include new information that these drug products may increase the risk of high-grade prostate cancer. The product labeling will also state that 5-ARIs are not approved for the prevention of prostate cancer.
Q4. What data are available on this safety issue?
A. The data that formed the basis for these labeling changes were based on two large, randomized controlled studies assessing the ability of 5-ARIs to reduce the rate of diagnosis of prostate cancer over a period of 7 years (Proscar) and 4 years (Avodart), respectively, in men at least 50 years of age. The Proscar trial evaluated the use of 5 mg doses of finasteride (Proscar) versus a placebo (sugar pill), and the Avodart trial evaluated the use of 0.5 mg doses of dutasteride (Avodart) versus a placebo, for the reduction of prostate cancer risk.
The trials demonstrated an overall reduction in prostate cancer diagnoses with finasteride and dutasteride treatment (see the Drug Safety Communication Data Summary for more information). This overall reduction was due to a decreased incidence of lower risk forms of prostate cancer. However, both the finasteride trial and the dutasteride trial showed an increased risk of high-grade prostate cancer.
It is important to note that neither trial evaluated 1 mg doses of finasteride (Propecia), used to treat male pattern hair loss.
Q5. Why is the labeling of Propecia being changed when this drug was not included in either study?
A. The labeling of Propecia is being changed to reflect the possibility of an increased risk of high-grade prostate cancer because Propecia contains 1 mg of finasteride. Although this is lower than the amount of finasteride in Proscar (5 mg), the active ingredient is the same.
It is still important to note that the applicability of the Avodart and Proscar studies to Propecia is currently unknown. The outcomes of both studies have been added to the Propecia labeling out of caution.
Men taking Propecia for hair loss should talk to their healthcare professional about the risks and benefits of this drug to determine the most appropriate treatment.
Q6. Does FDA believe the benefits of 5-alpha reductase inhibitors (5-ARIs) still outweigh their risks for the approved indications?
A. Yes. FDA believes that 5-ARIs remain safe and effective for their approved indications. Proscar and Avodart have been effective in controlling symptoms of benign prostatic hyperplasia (BPH), as well as in reducing the risks of acute urinary retention and the need for surgical intervention related to BPH. Healthcare professionals and patients are still encouraged to discuss the risks and benefits of 5-ARIs when deciding the best treatment for their disease.
FDA will continue its risk/benefit assessment of using 5-ARIs for the treatment for male pattern hair loss and will update the public when additional information is available.
Q7. What should men do if they are currently taking 5-alpha reductase inhibitors (5-ARIs)?
A. Men who are currently taking 5-alpha reductase inhibitors (5-ARIs) should consult a healthcare professional to discuss the risks and benefits of these medications. Men should not stop taking their medication unless directed to do so by a healthcare professional.
Q8. How should men taking 5-alpha reductase inhibitors (5-ARIs) be screened for prostate cancer?
A. There is no universally accepted screening test for prostate cancer, including high-grade prostate cancer. The most commonly used screening method is prostate-specific antigen (PSA) blood testing combined with a digital (finger) rectal exam. A PSA test checks for elevated serum PSA levels, which may indicate the presence of prostate cancer. A digital rectal exam involves a healthcare professional inserting a lubricated, gloved finger into the rectum to feel for enlargement, hardness or growths. For more information on prostate cancer screening, visit the National Cancer Institute's Prostate Cancer Screening and Testing website.
It is important to note that 5-alpha reductase inhibitors (5-ARIs) decrease serum PSA levels by approximately 50%. Any confirmed increase in PSA in men taking 5-ARIs, even if the value is within the normal range for men not taking 5-ARIs, should be evaluated by a healthcare professional. Men taking 5-ARIs should discuss the need for prostate cancer screening with a healthcare professional.
Q9. Are there other medications to treat benign prostatic hyperplasia (BPH) or male pattern baldness?
A. Yes. Another class of medications called alpha-blockers is approved to treat the symptoms of BPH. Medications in the alpha-blocker class include tamsulosin (Flomax), doxazosin (Cardura), terazosin (Hytrin), alfuzosin (Uroxatral), and silodosin (Rapaflo). However, 5-ARIs are the only medications that have been shown to reduce the risk of urinary retention or surgery related to an enlarged prostate.
Minoxidil is a topical product that is available over the counter in various formulations to treat male pattern hair loss.