FDA label 373589f7-8b10-4196-a4ce-f80ea3f086c2

WARNINGS None.

ADVERSE REACTIONS ELMIRON ® was evaluated in clinical trials in a total of 2627 patients (2343 women, 262 men, 22 unknown) with a mean age of 47 [range 18 to 88 with 581 (22%) over 60 years of age]. Of the 2627 patients, 128 patients were in a 3 month trial and the remaining 2499 patients were in a long term, unblinded trial. Deaths occurred in 6/2627 (0.2%) patients who received the drug over a period of 3 to 75 months. The deaths appear to be related to other concurrent illnesses or procedures, except in one patient for whom the cause was not known. Serious adverse events occurred in 33/2627 (1.3%) patients. Two patients had severe abdominal pain or diarrhea and dehydration that required hospitalization. Because there was not a control group of patients with interstitial cystitis who were concurrently evaluated, it is difficult to determine which events are associated with ELMIRON ® and which events are associated with concurrent illness, medicine, or other factors. Adverse Experience In Placebo-Controlled Clinical Trials of ELMIRON ® 100 mg Three Times a Day for 3 Months Body System/Adverse Experience ELMIRON ® n=128 Placebo n=130 CNS Overall Number of Patients Within a body system, the individual events do not sum to equal overall number of patients because a patient may have more than one event. 3 5 Insomnia 1 0 Headache 1 3 Severe Emotional Lability/Depression 2 1 Nystagmus/Dizziness 1 1 Hyperkinesia 1 1 GI Overall Number of Patients 7 7 Nausea 3 3 Diarrhea 3 6 Dyspepsia 1 0 Jaundice 0 1 Vomiting 0 2 Skin/Allergic Overall Number of Patients 2 4 Rash 0 2 Pruritus 0 2 Lacrimation 1 1 Rhinitis 1 1 Increased Sweating 1 0 Other Overall Number of Patients 1 3 Amenorrhea 0 1 Arthralgia 0 1 Vaginitis 1 1 Total Events 17 27 Total Number of Patients Reporting Adverse Events 13 19 The adverse events described below were reported in an unblinded clinical trial of 2499 interstitial cystitis patients treated with ELMIRON ® . Of the original 2499 patients, 1192 (48%) received ELMIRON ® for 3 months; 892 (36%) received ELMIRON for 6 months; and 598 (24%) received ELMIRON ® for one year, 355 (14%) received ELMIRON ® for 2 years, and 145 (6%) for 4 years. Frequency (1 to 4%): Alopecia (4%), diarrhea (4%), nausea (4%), headache (3%), rash (3%), dyspepsia (2%), abdominal pain (2%), liver function abnormalities (1%), dizziness (1%). Frequency (≤ 1%): Digestive: Vomiting, mouth ulcer, colitis, esophagitis, gastritis, flatulence, constipation, anorexia, gum hemorrhage. Hematologic: Anemia, ecchymosis, increased prothrombin time, increased partial thromboplastin time, leukopenia, thrombocytopenia. Hypersensitive Reactions: Allergic reaction, photosensitivity. Respiratory System: Pharyngitis, rhinitis, epistaxis, dyspnea. Skin and Appendages: Pruritus, urticaria. Special Senses: Conjunctivitis, tinnitus, optic neuritis, amblyopia, retinal hemorrhage. Post-Marketing Experience Rectal Hemorrhage ELMIRON ® was evaluated in a randomized, double-blind, parallel group, Phase 4 study conducted in 380 patients with interstitial cystitis dosed for 32 weeks. At a daily dose of 300 mg (n = 128), rectal hemorrhage was reported as an adverse event in 6.3% of patients. The severity of the events was described as "mild" in most patients. Patients in that study who were administered ELMIRON ® 900 mg daily, a dose higher than the approved dose, experienced a higher incidence of rectal hemorrhage, 15%. Liver Function Abnormality A randomized, double-blind, parallel group, phase 2 study was conducted in 100 men (51 ELMIRON ® and 49 placebo) dosed for 16 weeks. At a daily dose of 900 mg, a dose higher than the approved dose, elevated liver function tests were reported as an adverse event in 11.8% (n = 6) of ELMIRON ® treated patients and 2% (n = 1) of placebo treated patients.

<table width="80%" ID="i3690822a-4c72-4045-8f67-bf0c9624e9d3"> <caption>Adverse Experience In Placebo-Controlled Clinical Trials of ELMIRON^&#xAE; 100 mg Three Times a Day for 3 Months</caption> <col width="50%" align="left" valign="middle"/> <col width="25%" align="center" valign="top"/> <col width="25%" align="center" valign="top"/> <thead> <tr> <th styleCode="Lrule">Body System/Adverse Experience</th> <th>ELMIRON^&#xAE; n=128</th> <th styleCode="Rrule">Placebo n=130</th> </tr> </thead> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule"> <content styleCode="bold">CNS</content> Overall Number of Patients<footnote ID="ta1">Within a body system, the individual events do not sum to equal overall number of patients because a patient may have more than one event.</footnote> </td> <td>3</td> <td styleCode="Rrule">5</td> </tr> <tr> <td styleCode="Lrule"> Insomnia</td> <td>1</td> <td styleCode="Rrule">0</td> </tr> <tr> <td styleCode="Lrule"> Headache</td> <td>1</td> <td styleCode="Rrule">3</td> </tr> <tr> <td styleCode="Lrule"> Severe Emotional Lability/Depression</td> <td>2</td> <td styleCode="Rrule">1</td> </tr> <tr> <td styleCode="Lrule"> Nystagmus/Dizziness</td> <td>1</td> <td styleCode="Rrule">1</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Hyperkinesia</td> <td>1</td> <td styleCode="Rrule">1</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> <content styleCode="bold">GI</content> Overall Number of Patients<footnoteRef IDREF="ta1"/> </td> <td>7</td> <td styleCode="Rrule">7</td> </tr> <tr> <td styleCode="Lrule"> Nausea</td> <td>3</td> <td styleCode="Rrule">3</td> </tr> <tr> <td styleCode="Lrule"> Diarrhea</td> <td>3</td> <td styleCode="Rrule">6</td> </tr> <tr> <td styleCode="Lrule"> Dyspepsia</td> <td>1</td> <td styleCode="Rrule">0</td> </tr> <tr> <td styleCode="Lrule"> Jaundice</td> <td>0</td> <td styleCode="Rrule">1</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Vomiting</td> <td>0</td> <td styleCode="Rrule">2</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> <content styleCode="bold">Skin/Allergic</content> Overall Number of Patients<footnoteRef IDREF="ta1"/> </td> <td>2</td> <td styleCode="Rrule">4</td> </tr> <tr> <td styleCode="Lrule"> Rash</td> <td>0</td> <td styleCode="Rrule">2</td> </tr> <tr> <td styleCode="Lrule"> Pruritus</td> <td>0</td> <td styleCode="Rrule">2</td> </tr> <tr> <td styleCode="Lrule"> Lacrimation</td> <td>1</td> <td styleCode="Rrule">1</td> </tr> <tr> <td styleCode="Lrule"> Rhinitis</td> <td>1</td> <td styleCode="Rrule">1</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Increased Sweating</td> <td>1</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> <content styleCode="bold">Other</content> Overall Number of Patients<footnoteRef IDREF="ta1"/> </td> <td>1</td> <td styleCode="Rrule">3</td> </tr> <tr> <td styleCode="Lrule"> Amenorrhea</td> <td>0</td> <td styleCode="Rrule">1</td> </tr> <tr> <td styleCode="Lrule"> Arthralgia</td> <td>0</td> <td styleCode="Rrule">1</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Vaginitis</td> <td>1</td> <td styleCode="Rrule">1</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule">Total Events</td> <td>17</td> <td styleCode="Rrule">27</td> </tr> <tr> <td styleCode="Lrule">Total Number of Patients</td> <td/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule">Reporting Adverse Events</td> <td>13</td> <td styleCode="Rrule">19</td> </tr> </tbody> </table>