FDA label c00a9dd4-45c6-4de5-bfb7-9abdaac6bbcd

5 WARNINGS AND PRECAUTIONS AVODART reduces serum prostate-specific antigen (PSA) concentration by approximately 50%. However, any confirmed increase in PSA while on AVODART may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for untreated men. (5.1) AVODART may increase the risk of high-grade prostate cancer. (5.2, 6.1) Assess patients to rule out other urological diseases, including prostate cancer, prior to prescribing AVODART. (5.3) Women who are pregnant or could become pregnant should not handle AVODART Capsules due to potential risk to a male fetus. (5.4, 8.1) Patients should not donate blood until 6 months after their last dose of AVODART. (5.5) 5.1 Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection In clinical studies, AVODART reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment. This decrease was predictable over the entire range of PSA values in patients with symptomatic BPH, although it may vary in individuals. AVODART may also cause decreases in serum PSA in the presence of prostate cancer. To interpret serial PSAs in men taking AVODART, a new PSA baseline should be established at least 3 months after starting treatment and PSA monitored periodically thereafter. Any confirmed increase from the lowest PSA value while on AVODART may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5 alpha-reductase inhibitor. Noncompliance with AVODART may also affect PSA test results. To interpret an isolated PSA value in a man treated with AVODART for 3 months or more, the PSA value should be doubled for comparison with normal values in untreated men. The free-to-total PSA ratio (percent free PSA) remains constant, even under the influence of AVODART. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving AVODART, no adjustment to its value appears necessary. Coadministration of dutasteride and tamsulosin resulted in similar changes to serum PSA as dutasteride monotherapy. 5.2 Increased Risk of High-grade Prostate Cancer In men aged 50 to 75 years with a prior negative biopsy for prostate cancer and a baseline PSA between 2.5 ng/mL and 10.0 ng/mL taking AVODART in the 4-year Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, there was an increased incidence of Gleason score 8-10 prostate cancer compared with men taking placebo (AVODART 1.0% versus placebo 0.5%) [see Indications and Usage (1.3), Adverse Reactions (6.1)] . In a 7-year placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg, PROSCAR), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%). 5 alpha-reductase inhibitors may increase the risk of development of high-grade prostate cancer. Whether the effect of 5 alpha-reductase inhibitors to reduce prostate volume, or study-related factors, impacted the results of these studies has not been established. 5.3 Evaluation for Other Urological Diseases Lower urinary tract symptoms of BPH can be indicative of other urological diseases, including prostate cancer. Patients should be assessed to rule out prostate cancer and other urological diseases prior to treatment with AVODART and periodically thereafter. 5.4 Exposure of Women—Risk to Male Fetus AVODART Capsules should not be handled by a woman who is pregnant or who could become pregnant. Dutasteride is absorbed through the skin and could result in unintended fetal exposure. If a woman who is pregnant or who could become pregnant comes in contact with leaking dutasteride capsules, the contact area should be washed immediately with soap and water [see Use in Specific Populations (8.1)] . 5.5 Blood Donation Men being treated with AVODART should not donate blood until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of dutasteride to a pregnant female transfusion recipient. 5.6 Effect on Semen Characteristics The effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in normal volunteers aged 18 to 52 (n = 27 dutasteride, n = 23 placebo) throughout 52 weeks of treatment and 24 weeks of post-treatment follow-up. At 52 weeks, the mean percent reductions from baseline in total sperm count, semen volume, and sperm motility were 23%, 26%, and 18%, respectively, in the dutasteride group when adjusted for changes from baseline in the placebo group. Sperm concentration and sperm morphology were unaffected. After 24 weeks of follow-up, the mean percent change in total sperm count in the dutasteride group remained 23% lower than baseline. While mean values for all semen parameters at all time-points remained within the normal ranges and did not meet predefined criteria for a clinically significant change (30%), 2 subjects in the dutasteride group had decreases in sperm count of greater than 90% from baseline at 52 weeks, with partial recovery at the 24-week follow-up. The clinical significance of dutasteride’s effect on semen characteristics for an individual patient’s fertility is not known.

6 ADVERSE REACTIONS The most common adverse reactions, reported in ≥1% of patients treated with AVODART and more commonly than in patients treated with placebo, are impotence, decreased libido, ejaculation disorders, and breast disorders. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trial of another drug and may not reflect the rates observed in practice. From clinical trials with AVODART as monotherapy or in combination with tamsulosin: The most common adverse reactions reported in subjects receiving AVODART were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), and ejaculation disorders. The most common adverse reactions reported in subjects receiving combination therapy (AVODART plus tamsulosin) were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving combination therapy (11%) compared with those receiving AVODART (2%) or tamsulosin (4%) as monotherapy. Study withdrawal due to adverse reactions occurred in 4% of subjects receiving AVODART, and 3% of subjects receiving placebo in placebo-controlled trials with AVODART. The most common adverse reaction leading to study withdrawal was impotence (1%). In the clinical trial evaluating the combination therapy, study withdrawal due to adverse reactions occurred in 6% of subjects receiving combination therapy (AVODART plus tamsulosin) and 4% of subjects receiving AVODART or tamsulosin as monotherapy. The most common adverse reaction in all treatment arms leading to study withdrawal was erectile dysfunction (1% to 1.5%). Monotherapy: Over 4,300 male subjects with BPH were randomly assigned to receive placebo or 0.5-mg daily doses of AVODART in three identical 2-year, placebo-controlled, double-blind, Phase 3 treatment studies, each followed by a 2-year open-label extension. During the double-blind treatment period, 2,167 male subjects were exposed to AVODART, including 1,772 exposed for 1 year and 1,510 exposed for 2 years. When including the open-label extensions, 1,009 male subjects were exposed to AVODART for 3 years and 812 were exposed for 4 years. The population was aged 47 to 94 years (mean age: 66 years) and greater than 90% were Caucasian. Table 1 summarizes clinical adverse reactions reported in at least 1% of subjects receiving AVODART and at a higher incidence than subjects receiving placebo. Table 1. Adverse Reactions Reported in ≥1% of Subjects Over a 24-Month Period and More Frequently in the Group Receiving AVODART Than the Placebo Group (Randomized, Double-Blind, Placebo-Controlled Studies Pooled) by Time of Onset a Includes breast tenderness and breast enlargement. Adverse Reaction Adverse Reaction Time of Onset Months 0-6 Months 7-12 Months 13-18 Months 19-24 AVODART (n) (n = 2,167) (n = 1,901) (n = 1,725) (n = 1,605) Placebo (n) (n = 2,158) (n = 1,922) (n = 1,714) (n = 1,555) Impotence AVODART 4.7% 1.4% 1.0% 0.8% Placebo 1.7% 1.5% 0.5% 0.9% Decreased libido AVODART 3.0% 0.7% 0.3% 0.3% Placebo 1.4% 0.6% 0.2% 0.1% Ejaculation disorders AVODART 1.4% 0.5% 0.5% 0.1% Placebo 0.5% 0.3% 0.1% 0.0% Breast disorders a AVODART 0.5% 0.8% 1.1% 0.6% Placebo 0.2% 0.3% 0.3% 0.1% Long-Term Treatment (Up to 4 Years): High-grade Prostate Cancer: The REDUCE trial was a randomized, double-blind, placebo-controlled trial that enrolled 8,231 men aged 50 to 75 years with a serum PSA of 2.5 ng/mL to 10 ng/mL and a negative prostate biopsy within the previous 6 months. Subjects were randomized to receive placebo (N = 4,126) or 0.5-mg daily doses of AVODART (N = 4,105) for up to 4 years. The mean age was 63 years and 91% were Caucasian. Subjects underwent protocol-mandated scheduled prostate biopsies at 2 and 4 years of treatment or had “for-cause biopsies” at non-scheduled times if clinically indicated. There was a higher incidence of Gleason score 8-10 prostate cancer in men receiving AVODART (1.0%) compared with men on placebo (0.5%) [see Indications and Usage (1.3), Warnings and Precautions (5.2)]. In a 7-year placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg, PROSCAR), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%). No clinical benefit has been demonstrated in patients with prostate cancer treated with AVODART. Reproductive and Breast Disorders: In the 3 pivotal placebo-controlled BPH trials with AVODART, each 4 years in duration, there was no evidence of increased sexual adverse reactions (impotence, decreased libido, and ejaculation disorder) or breast disorders with increased duration of treatment. Among these 3 trials, there was 1 case of breast cancer in the dutasteride group and 1 case in the placebo group. No cases of breast cancer were reported in any treatment group in the 4-year CombAT trial or the 4-year REDUCE trial. The relationship between long-term use of dutasteride and male breast neoplasia is currently unknown. Combination With Alpha-Blocker Therapy (CombAT): Over 4,800 male subjects with BPH were randomly assigned to receive 0.5-mg AVODART, 0.4-mg tamsulosin, or combination therapy (0.5-mg AVODART plus 0.4-mg tamsulosin) administered once daily in a 4-year double-blind study. Overall, 1,623 subjects received monotherapy with AVODART; 1,611 subjects received monotherapy with tamsulosin; and 1,610 subjects received combination therapy. The population was aged 49 to 88 years (mean age: 66 years) and 88% were Caucasian. Table 2 summarizes adverse reactions reported in at least 1% of subjects in the combination group and at a higher incidence than subjects receiving monotherapy with AVODART or tamsulosin. Table 2. Adverse Reactions Reported Over a 48-Month Period in ≥1% of Subjects and More Frequently in the Coadministration Therapy Group than the Groups Receiving Monotherapy With AVODART or Tamsulosin (CombAT) by Time of Onset Adverse Reaction Adverse Reaction Time of Onset Year 1 Year 2 Year 3 Year 4 Months 0-6 Months 7-12 Combination a (n = 1,610) (n = 1,527) (n = 1,428) (n = 1,283) (n = 1,200) AVODART (n = 1,623) (n = 1,548) (n = 1,464) (n = 1,325) (n = 1,200) Tamsulosin (n = 1,611) (n = 1,545) (n = 1,468) (n = 1,281) (n = 1,112) Ejaculation disorders b Combination 7.8% 1.6% 1.0% 0.5% <0.1% AVODART 1.0% 0.5% 0.5% 0.2% 0.3% Tamsulosin 2.2% 0.5% 0.5% 0.2% 0.3% Impotence c Combination 5.4% 1.1% 1.8% 0.9% 0.4% AVODART 4.0% 1.1% 1.6% 0.6% 0.3% Tamsulosin 2.6% 0.8% 1.0% 0.6% 1.1% Decreased libido d Combination 4.5% 0.9% 0.8% 0.2% 0.0% AVODART 3.1% 0.7% 1.0% 0.2% 0.0% Tamsulosin 2.0% 0.6% 0.7% 0.2% <0.1% Breast disorders e Combination 1.1% 1.1% 0.8% 0.9% 0.6% AVODART 0.9% 0.9% 1.2% 0.5% 0.7% Tamsulosin 0.4% 0.4% 0.4% 0.2% 0.0% Dizziness Combination 1.1% 0.4% 0.1% <0.1% 0.2% AVODART 0.5% 0.3% 0.1% <0.1% <0.1% Tamsulosin 0.9% 0.5% 0.4% <0.1% 0.0% a Combination = AVODART 0.5 mg once daily plus tamsulosin 0.4 mg once daily. b Includes anorgasmia, retrograde ejaculation, semen volume decreased, orgasmic sensation decreased, orgasm abnormal, ejaculation delayed, ejaculation disorder, ejaculation failure, and premature ejaculation. c Includes erectile dysfunction and disturbance in sexual arousal. d Includes libido decreased, libido disorder, loss of libido, sexual dysfunction, and male sexual dysfunction. e Includes breast enlargement, gynecomastia, breast swelling, breast pain, breast tenderness, nipple pain, and nipple swelling. Cardiac Failure: In CombAT, after 4 years of treatment, the incidence of the composite term cardiac failure in the combination therapy group (12/1,610; 0.7%) was higher than in either monotherapy group: AVODART, 2/1,623 (0.1%) and tamsulosin, 9/1,611 (0.6%). Composite cardiac failure was also examined in a separate 4-year placebo-controlled trial evaluating AVODART in men at risk for development of prostate cancer. The incidence of cardiac failure in subjects taking AVODART was 0.6% (26/4,105) compared with 0.4% (15/4,126) in subjects on placebo. A majority of subjects with cardiac failure in both studies had co-morbidities associated with an increased risk of cardiac failure. Therefore, the clinical significance of the numerical imbalances in cardiac failure is unknown. No causal relationship between AVODART, alone or in combination with tamsulosin, and cardiac failure has been established. No imbalance was observed in the incidence of overall cardiovascular adverse events in either study. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of AVODART. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to AVODART. Immune System Disorders: Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema. Neoplasms: Male breast cancer.

<table width="532.000" ID="id_8cf5d6be-5c64-4028-bb90-bad116810323"> <caption ID="id_4589a3a5-7285-4940-9be6-23a45e330520">Table 1. Adverse Reactions Reported in &#x2265;1% of Subjects Over a 24-Month Period and More Frequently in the Group Receiving AVODART Than the Placebo Group (Randomized, Double-Blind, Placebo-Controlled Studies Pooled) by Time of Onset</caption> <col width="29.9%"/> <col width="17.5%"/> <col width="16.5%"/> <col width="17.5%"/> <col width="18.6%"/> <tfoot ID="id_7b37abab-2a38-4ca8-bcdb-881627fc835c"> <tr> <td align="left" valign="top" colspan="5" rowspan="1" styleCode="Lrule Botrule Rrule"> ^a Includes breast tenderness and breast enlargement.</td> </tr> </tfoot> <tbody> <tr ID="id_5d9120e0-3eff-4e13-b7ec-829a343bea5e"> <td align="center" valign="bottom" rowspan="2" styleCode="Lrule Toprule Rrule">Adverse Reaction</td> <td align="center" valign="bottom" colspan="4" rowspan="1" styleCode="Botrule Rrule">Adverse Reaction Time of Onset</td> </tr> <tr ID="id_a28a20f6-890e-49eb-8b72-fd3dcac4f751"> <td align="center" valign="bottom" rowspan="1" styleCode="Lrule Rrule">Months 0-6</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">Months 7-12</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">Months 13-18</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">Months 19-24</td> </tr> <tr ID="id_70de6877-2744-4d45-83a2-8eee8d513164"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> AVODART (n)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">(n = 2,167)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">(n = 1,901)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">(n = 1,725)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">(n = 1,605)</td> </tr> <tr ID="id_9bfbb024-787f-4275-9a94-683f162f7bfa"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Botrule Rrule"> Placebo (n)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">(n = 2,158)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">(n = 1,922)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">(n = 1,714)</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">(n = 1,555)</td> </tr> <tr ID="id_f74e87f5-0f8c-4492-989e-16edbc1629a2"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule">Impotence</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_711a2a4d-3aea-4789-8ad4-c06bd78e6de8"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">4.7%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1.4%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1.0%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.8%</td> </tr> <tr ID="id_261ee321-e3fa-4405-a88d-9877a492e11a"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Botrule Rrule"> Placebo</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">1.7%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">1.5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.9%</td> </tr> <tr ID="id_1565d133-905d-4e95-9578-3fad7e2258cd"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule">Decreased libido</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_a4f1161c-6643-44b1-b9b7-ee5d5553e003"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">3.0%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.7%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.3%</td> </tr> <tr ID="id_72cdcad5-04ae-4c6d-b986-00fc67556b58"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Botrule Rrule"> Placebo</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">1.4%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.6%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.1%</td> </tr> <tr ID="id_0bd25c5c-9aba-4be1-953a-3db224307489"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule">Ejaculation disorders</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_8271a262-36ab-4469-bcb7-3f8cac30ad80"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1.4%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.1%</td> </tr> <tr ID="id_d28b52f5-133f-4018-91a8-9f0f03e2e17f"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Botrule Rrule"> Placebo</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.0%</td> </tr> <tr ID="id_11377466-05c3-4556-84e7-2f1085803642"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule">Breast disorders^a </td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule"/> </tr> <tr ID="id_99477d8d-95d4-48f7-a7ae-693d15ab6f48"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.8%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">1.1%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Rrule">0.6%</td> </tr> <tr ID="id_83a3e5e9-0674-4548-9a24-61ac35fcced3"> <td align="left" valign="top" rowspan="1" styleCode="Lrule Botrule Rrule"> Placebo</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.2%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.3%</td> <td align="center" valign="bottom" rowspan="1" styleCode="Botrule Rrule">0.1%</td> </tr> </tbody> </table>

<table border="single" width="477.000" ID="id_c6221878-5903-4e18-afce-21ff0849d5e0"> <caption ID="id_cadf77b9-9b05-4b20-a31a-f332be05a18f">Table 2. Adverse Reactions Reported Over a 48-Month Period in &#x2265;1% of Subjects and More Frequently in the Coadministration Therapy Group than the Groups Receiving Monotherapy With AVODART or Tamsulosin (CombAT) by Time of Onset</caption> <col width="21.8%"/> <col width="15.1%"/> <col width="17.8%"/> <col width="15.9%"/> <col width="14.3%"/> <col width="15.1%"/> <tbody> <tr ID="id_05704faa-db8b-43de-a3bd-7f586875d67c"> <td align="center" valign="bottom" rowspan="3" styleCode="Botrule Toprule Rrule Lrule">Adverse Reaction</td> <td align="center" valign="top" colspan="5" styleCode="Botrule Rrule">Adverse Reaction Time of Onset</td> </tr> <tr ID="id_b9165d3d-207a-4d94-bbbc-7ccec80313a2"> <td align="center" valign="top" colspan="2" styleCode="Lrule Rrule">Year 1</td> <td align="center" valign="bottom" rowspan="2" styleCode="Botrule Rrule">Year 2</td> <td align="center" valign="bottom" rowspan="2" styleCode="Botrule Rrule">Year 3</td> <td align="center" valign="bottom" rowspan="2" styleCode="Botrule Rrule">Year 4</td> </tr> <tr ID="id_39f965a2-815e-4805-880d-f9fe72f3ac60"> <td align="center" valign="top" styleCode="Lrule Botrule Rrule">Months 0-6</td> <td align="center" valign="top" styleCode="Botrule Rrule">Months 7-12</td> </tr> <tr ID="id_c8bcad2c-9746-40d8-99bf-cb1415dd4c2c"> <td align="left" valign="top" styleCode="Lrule Rrule"> Combination^a </td> <td align="center" valign="top" styleCode="Rrule">(n = 1,610)</td> <td align="center" valign="top" styleCode="Rrule">(n = 1,527)</td> <td align="center" valign="top" styleCode="Rrule">(n = 1,428)</td> <td align="center" valign="top" styleCode="Rrule">(n = 1,283)</td> <td align="center" valign="top" styleCode="Rrule">(n = 1,200)</td> </tr> <tr ID="id_ff860799-e0e3-4d02-90af-57f4c75e8295"> <td align="left" valign="top" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" styleCode="Rrule">(n = 1,623)</td> <td align="center" valign="bottom" styleCode="Rrule">(n = 1,548)</td> <td align="center" valign="bottom" styleCode="Rrule">(n = 1,464)</td> <td align="center" valign="bottom" styleCode="Rrule">(n = 1,325)</td> <td align="center" valign="bottom" styleCode="Rrule">(n = 1,200)</td> </tr> <tr ID="id_01396290-80b2-498b-8fd2-d18c0f65ac0c"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Tamsulosin</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">(n = 1,611)</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">(n = 1,545)</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">(n = 1,468)</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">(n = 1,281)</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">(n = 1,112)</td> </tr> <tr ID="id_897309bf-f4fc-4e35-b0b3-7378b41f2f89"> <td align="left" valign="top" styleCode="Lrule Rrule">Ejaculation disorders^b </td> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> </tr> <tr ID="id_1b5b652a-9a9c-4e4e-83b9-1df9279314a9"> <td align="left" valign="top" styleCode="Lrule Rrule"> Combination</td> <td align="center" valign="bottom" styleCode="Rrule">7.8%</td> <td align="center" valign="bottom" styleCode="Rrule">1.6%</td> <td align="center" valign="bottom" styleCode="Rrule">1.0%</td> <td align="center" valign="bottom" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" styleCode="Rrule">&lt;0.1%</td> </tr> <tr ID="id_e6ed669f-256a-499c-ae15-36a807740b9e"> <td align="left" valign="top" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" styleCode="Rrule">1.0%</td> <td align="center" valign="bottom" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" styleCode="Rrule">0.2%</td> <td align="center" valign="bottom" styleCode="Rrule">0.3%</td> </tr> <tr ID="id_4e564951-0ccd-4368-b34b-7e527dbcc9c2"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Tamsulosin</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.2%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.5%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.5%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.2%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.3%</td> </tr> <tr ID="id_891d72a3-da8d-4bc3-997f-aed14b697834"> <td align="left" valign="top" styleCode="Lrule Rrule">Impotence^c </td> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> </tr> <tr ID="id_6d441f74-4bfd-495b-af78-9b22abb21bef"> <td align="left" valign="top" styleCode="Lrule Rrule"> Combination</td> <td align="center" valign="bottom" styleCode="Rrule">5.4%</td> <td align="center" valign="bottom" styleCode="Rrule">1.1%</td> <td align="center" valign="bottom" styleCode="Rrule">1.8%</td> <td align="center" valign="bottom" styleCode="Rrule">0.9%</td> <td align="center" valign="bottom" styleCode="Rrule">0.4%</td> </tr> <tr ID="id_96ed7b52-4042-4391-83fd-275667678ad7"> <td align="left" valign="top" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" styleCode="Rrule">4.0%</td> <td align="center" valign="bottom" styleCode="Rrule">1.1%</td> <td align="center" valign="bottom" styleCode="Rrule">1.6%</td> <td align="center" valign="bottom" styleCode="Rrule">0.6%</td> <td align="center" valign="bottom" styleCode="Rrule">0.3%</td> </tr> <tr ID="id_1dc16916-b593-401f-b5cd-38c86b886884"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Tamsulosin</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.6%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.8%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">1.0%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.6%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">1.1%</td> </tr> <tr ID="id_2d614a75-8ab1-4f5b-9deb-1f68c3acacea"> <td align="left" valign="top" styleCode="Lrule Rrule">Decreased libido^d </td> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> </tr> <tr ID="id_aad58280-503e-47b9-a34c-ab174ac5155b"> <td align="left" valign="top" styleCode="Lrule Rrule"> Combination</td> <td align="center" valign="bottom" styleCode="Rrule">4.5%</td> <td align="center" valign="bottom" styleCode="Rrule">0.9%</td> <td align="center" valign="bottom" styleCode="Rrule">0.8%</td> <td align="center" valign="bottom" styleCode="Rrule">0.2%</td> <td align="center" valign="bottom" styleCode="Rrule">0.0%</td> </tr> <tr ID="id_5af054a8-0382-46d3-9c71-92477f282234"> <td align="left" valign="top" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" styleCode="Rrule">3.1%</td> <td align="center" valign="bottom" styleCode="Rrule">0.7%</td> <td align="center" valign="bottom" styleCode="Rrule">1.0%</td> <td align="center" valign="bottom" styleCode="Rrule">0.2%</td> <td align="center" valign="bottom" styleCode="Rrule">0.0%</td> </tr> <tr ID="id_9633e95c-0ad9-49b1-b7a9-99024e7368b4"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Tamsulosin</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.0%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.6%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.7%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.2%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">&lt;0.1%</td> </tr> <tr ID="id_fb424b14-0f10-4efc-8992-25cf93035714"> <td align="left" valign="top" styleCode="Lrule Rrule">Breast disorders^e </td> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> </tr> <tr ID="id_ead896d7-8e4b-4a5b-be7a-8d7791b93ef9"> <td align="left" valign="top" styleCode="Lrule Rrule"> Combination</td> <td align="center" valign="bottom" styleCode="Rrule">1.1%</td> <td align="center" valign="bottom" styleCode="Rrule">1.1%</td> <td align="center" valign="bottom" styleCode="Rrule">0.8%</td> <td align="center" valign="bottom" styleCode="Rrule">0.9%</td> <td align="center" valign="bottom" styleCode="Rrule">0.6%</td> </tr> <tr ID="id_c18deceb-e605-48ca-89bc-bbd9614351f1"> <td align="left" valign="top" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" styleCode="Rrule">0.9%</td> <td align="center" valign="bottom" styleCode="Rrule">0.9%</td> <td align="center" valign="bottom" styleCode="Rrule">1.2%</td> <td align="center" valign="bottom" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" styleCode="Rrule">0.7%</td> </tr> <tr ID="id_bb386960-65c8-4254-bf0d-2bf15b5cf2cc"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Tamsulosin</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.4%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.4%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.4%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.2%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.0%</td> </tr> <tr ID="id_b0e59f0d-6dfd-48a6-b6ea-5ae3565b504f"> <td align="left" valign="top" styleCode="Lrule Rrule">Dizziness</td> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> <td align="center" valign="bottom" styleCode="Rrule"/> </tr> <tr ID="id_448fc4a3-4b49-4112-ba8c-e7ae0f12c37a"> <td align="left" valign="top" styleCode="Lrule Rrule"> Combination</td> <td align="center" valign="bottom" styleCode="Rrule">1.1%</td> <td align="center" valign="bottom" styleCode="Rrule">0.4%</td> <td align="center" valign="bottom" styleCode="Rrule">0.1%</td> <td align="center" valign="bottom" styleCode="Rrule">&lt;0.1%</td> <td align="center" valign="bottom" styleCode="Rrule">0.2%</td> </tr> <tr ID="id_3f2a9e20-c085-44d2-81a1-e48505ad7a5b"> <td align="left" valign="top" styleCode="Lrule Rrule"> AVODART</td> <td align="center" valign="bottom" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" styleCode="Rrule">0.3%</td> <td align="center" valign="bottom" styleCode="Rrule">0.1%</td> <td align="center" valign="bottom" styleCode="Rrule">&lt;0.1%</td> <td align="center" valign="bottom" styleCode="Rrule">&lt;0.1%</td> </tr> <tr ID="id_fe414bd3-78c6-4c5d-8212-3404a877e577"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Tamsulosin</td> <td align="center" valign="bottom" styleCode="Rrule">0.9%</td> <td align="center" valign="bottom" styleCode="Rrule">0.5%</td> <td align="center" valign="bottom" styleCode="Rrule">0.4%</td> <td align="center" valign="bottom" styleCode="Rrule">&lt;0.1%</td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.0%</td> </tr> </tbody> </table>