FDA label 9a2b6bfb-1333-4eea-83eb-6e1f2ec791fe

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and INTERACTION WITH ALCOHOL WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and INTERACTION WITH ALCOHOL See full prescribing information for complete boxed warning . Oxymorphone hydrochloride extended-release tablets expose users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk before prescribing, and monitor regularly for development of these behaviors or conditions. ( 5.1 ) Serious life-threatening or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow oxymorphone hydrochloride extended-release tablets whole to avoid exposure to a potentially fatal dose of oxymorphone. ( 5.2 ) Accidental ingestion of oxymorphone hydrochloride extended-release tablets, especially in children, can result in fatal overdose of oxymorphone. ( 5.2 ) Prolonged use of oxymorphone hydrochloride extended-release tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. ( 5.3 ) Instruct patients not to consume alcohol or any product containing alcohol while taking oxymorphone hydrochloride extended-release tablets because co-ingestion can result in fatal plasma oxymorphone levels. ( 5.4 ) Addiction, Abuse, and Misuse Oxymorphone hydrochloride extended-release tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing oxymorphone hydrochloride extended-release tablets, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1) ]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of oxymorphone hydrochloride extended-release tablets. Monitor for respiratory depression, especially during initiation of oxymorphone hydrochloride extended-release tablets or following a dose increase. Instruct patients to swallow oxymorphone hydrochloride extended-release tablets whole; crushing, chewing, or dissolving oxymorphone hydrochloride extended-release tablets can cause rapid release and absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions (5.2) ]. Accidental Ingestion Accidental ingestion of even one dose of oxymorphone hydrochloride extended-release tablets, especially by children, can result in a fatal overdose of oxymorphone [see Warnings and Precautions (5.2) ]. Neonatal Opioid Withdrawal Syndrome Prolonged use of oxymorphone hydrochloride extended-release tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.3) ]. Interaction with Alcohol Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking oxymorphone hydrochloride extended-release tablets. The co-ingestion of alcohol with oxymorphone hydrochloride extended-release tablets may result in increased plasma levels and a potentially fatal overdose of oxymorphone [see Warnings and Precautions (5.4) ].

5 WARNINGS AND PRECAUTIONS ​ See Boxed WARNINGS Interaction with CNS depressants: Concomitant use may cause profound sedation, respiratory depression, and death. If coadministration is required, consider dose reduction of one or both drugs because of additive pharmacological effects. ( 5.4 ) Elderly, cachectic, and debilitated patients and those with chronic pulmonary disease: Monitor closely because of increased risk for life-threatening respiratory depression. ( 5.5 , 5.6 ) Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions: If symptoms occur, stop administrations immediately, discontinue permanently, and do not rechallenge with any other oxymorphone formulation. ( 5.7 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.8 ) Hypotensive effect: Monitor during dose initiation and titration. ( 5.10 ) Patients with head injury or increased intracranial pressure: Monitor for sedation and respiratory depression. Avoid use of oxymorphone hydrochloride extended-release tablets in patients with impaired consciousness or coma susceptible to intracranial effects of CO 2 retention. ( 5.11 ) Use with caution in patients who have difficulty swallowing or have underlying G1 disorders that may predispose them to obstruction. ( 5.12 ) 5.1 Addiction, Abuse, and Misuse Oxymorphone hydrochloride extended-release tablets contain oxymorphone, a Schedule II controlled substance. As an opioid, oxymorphone hydrochloride extended-release tablets expose users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9) ]. As modified-release products such as oxymorphone hydrochloride extended-release tablets deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of oxymorphone present. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed oxymorphone hydrochloride extended-release tablets and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient's risk for opioid abuse or addiction, abuse, or misuse prior to prescribing oxymorphone hydrochloride extended-release tablets, and monitor all patients receiving oxymorphone hydrochloride extended-release tablets for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol addiction or abuse) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the prescribing of oxymorphone hydrochloride extended-release tablets for the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as oxymorphone hydrochloride extended-release tablets, but use in such patients necessitates intensive counseling about the risks and proper use of oxymorphone hydrochloride extended-release tablets along with intensive monitoring for signs of addiction, abuse, and misuse. Abuse, or misuse of oxymorphone hydrochloride extended-release tablets by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the oxymorphone and can result in overdose and death [see Overdosage (10) ] . Opioid agonists such as oxymorphone hydrochloride extended-release tablets are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing oxymorphone hydrochloride extended-release tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17) ] . Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified-release opioids, even when used as recommended. Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status [see Overdosage (10) ] . Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of oxymorphone hydrochloride extended-release tablets, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with oxymorphone hydrochloride extended-release tablets and following dose increases. To reduce the risk of respiratory depression, proper dosing and titration of oxymorphone hydrochloride extended-release tablets are essential [see Dosage and Administration (2 ) ]. Overestimating the oxymorphone hydrochloride extended-release tablets dose when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental ingestion of even one dose of oxymorphone hydrochloride extended-release tablets, especially by children, can result in respiratory depression and death due to an overdose of oxymorphone. 5.3 Neonatal Opioid Withdrawal Syndrome Prolonged use of oxymorphone hydrochloride extended-release tablets during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. 5.4 Interactions with Central Nervous System Depressants Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on oxymorphone hydrochloride extended-release tablets therapy. The co-ingestion of alcohol with oxymorphone hydrochloride extended-release tablets may result in increased plasma levels and a potentially fatal overdose of oxymorphone [see Clinical Pharmacology (12.3) ]. Hypotension, profound sedation, coma, respiratory depression, and death may result if oxymorphone hydrochloride extended-release tablets are used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of oxymorphone hydrochloride extended-release tablets in a patient taking a CNS depressant, assess the duration use of the CNS depressant and the patient's response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient's use of alcohol or illicit drugs that cause CNS depression. If the decision to begin oxymorphone hydrochloride extended-release tablets is made, start with oxymorphone hydrochloride extended-release tablets 5 mg every 12 hours, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant [see Drug Interactions (7.2) ] . 5.5 Use in Elderly, Cachectic, and Debilitated Patients Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely, particularly when initiating and titrating oxymorphone hydrochloride extended-release tablets and when oxymorphone hydrochloride extended-release tablets are given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.2) ] . 5.6 Use in Patients with Chronic Pulmonary Disease Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression for respiratory depression, particularly when initiating therapy and titrating with oxymorphone hydrochloride extended-release tablets, as in these patients, even usual therapeutic doses of oxymorphone hydrochloride extended-release tablets may decrease respiratory drive to the point of apnea [see Warnings and Precautions (5.2) ] . Consider the use of alternative non-opioid analgesics in these patients if possible. 5.7 Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions Potentially life-threatening hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients treated with oxymorphone hydrochloride extended-release tablets in the postmarket setting. The most commonly described clinical features in these reports were swelling of the face, eyes, mouth, lips, tongue, hands, and/or throat; dyspnea; hives, pruritus, and/or rash; and nausea/vomiting. If anaphylaxis or other hypersensitivity occurs, stop administration of oxymorphone hydrochloride extended-release tablets immediately, discontinue oxymorphone hydrochloride extended-release tablets permanently, and do not rechallenge with any formulation of oxymorphone. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction [see Patient Counseling Information ( 17 )] . 5.8 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one 1 month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. 5.9 Use in Patients with Hepatic Impairment A study of oxymorphone hydrochloride extended-release tablets in patients with hepatic disease indicated greater plasma concentrations than those with normal hepatic function [see Clinical Pharmacology (12.3)] . Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with moderate or severe hepatic impairment. In patients with mild hepatic impairment reduce the starting dose to the lowest dose and monitor for signs of respiratory and central nervous system depression [see Dosage and Administration ( 2.5 )] . 5.10 Hypotensive Effect Oxymorphone hydrochloride extended-release tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g. phenothiazines or general anesthetics) [see Drug Interactions (7.2) ] . Monitor these patients for signs of hypotension after initiating or titrating the dose of oxymorphone hydrochloride extended-release tablets. In patients with circulatory shock, oxymorphone hydrochloride extended-release tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of oxymorphone hydrochloride extended-release tablets in patients with circulatory shock. 5.11 Use in Patients with Head Injury or Increased Intracranial Pressure Monitor patients taking oxymorphone hydrochloride extended-release tablets who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with oxymorphone hydrochloride extended-release tablets. Oxymorphone hydrochloride extended-release tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of oxymorphone hydrochloride extended-release tablets in patients with impaired consciousness or coma. 5.12 Difficulty in Swallowing and Risk for Obstruction in Patients at Risk for a Small Gastrointestinal Lumen There have been post-marketing reports of difficulty in swallowing oxymorphone hydrochloride extended-release tablets. These reports included choking, gagging, regurgitation and tablets stuck in the throat. Instruct patients not to pre-soak, lick or otherwise wet oxymorphone hydrochloride extended-release tablets prior to placing in the mouth, and to take one tablet at a time with enough water to ensure complete swallowing immediately after placing in the mouth. There have been rare post-marketing reports of cases of intestinal obstruction, some of which have required medical intervention to remove the tablet. Patients with underlying GI disorders such as esophageal cancer or colon cancer with a small gastrointestinal lumen are at greater risk of developing these complications. Consider use of an alternative analgesic in patients who have difficulty swallowing and patients at risk for underlying GI disorders resulting in a small gastrointestinal lumen. 5.13 Use in Patients with Gastrointestinal Conditions Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with paralytic ileus. Avoid the use of oxymorphone hydrochloride extended-release tablets in patients with other GI obstruction. The oxymorphone in oxymorphone hydrochloride extended-release tablets may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause increases in the serum amylase. 5.14 Use in Patients with Convulsive or Seizure Disorders The oxymorphone in oxymorphone hydrochloride extended-release tablets may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during oxymorphone hydrochloride extended-release tablets therapy. 5.15 Avoidance of Withdrawal Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy with an opioid agonist analgesic, including oxymorphone hydrochloride extended-release tablets. In these patients, mixed agonists/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms. When discontinuing oxymorphone hydrochloride extended-release tablets, gradually taper the dose [see Dosage and Administration ( 2.3 )] . Do not abruptly discontinue oxymorphone hydrochloride extended-release tablets. 5.16 Driving and Operating Machinery Oxymorphone hydrochloride extended-release tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of oxymorphone hydrochloride extended-release tablets and know how they will react to the medication.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1) ] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3) ] Interactions with Other CNS Depressants [see Warnings and Precautions (5.4) ] Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.8 )] Hypotensive Effect [see Warnings and Precautions (5.10) ] Gastrointestinal Effects [see Warnings and Precautions (5.12 , 5.13) ] Seizures [see Warnings and Precautions (5.14) ] Adverse reactions in ≥2% of patients in placebo-controlled trials: nausea, constipation, dizziness, somnolence, vomiting, pruritus, headache, sweating increased, dry mouth, sedation, diarrhea, insomnia, fatigue, appetite decreased, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Impax Laboratories, Inc. at 1-800-934-6729 or FDA at 1-800-FDA-1088 or www.fda.gov / medwatch. 6.1 Clinical Trial 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 to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of oxymorphone hydrochloride extended-release tablets was evaluated in a total of 2011 patients in open-label and controlled clinical trials. The clinical trials enrolled of patients with moderate to severe chronic non-malignant pain, cancer pain, and post surgical pain. The most common serious adverse events reported with administration of oxymorphone hydrochloride extended-release tablets were chest pain, pneumonia and vomiting. Tables 1 and 2 list the most frequently occurring adverse reactions (in at least 5% of patients) from the placebo-controlled trials in patients with low back pain. Table 1: Treatment-Emergent Adverse Reactions Reported in ≥5% of Patients During the Open-Label Titration Period and Double-Blind Treatment Period by Preferred Term — Number (%) of Treated Patients (12-Week Study In Opioid-Naïve Patients with Low Back Pain) Open-Label Titration Period Double-Blind Treatment Period Oxymorphone Hydrochloride Extended-Release Tablets Oxymorphone Hydrochloride Extended-Release Tablets Placebo Preferred Term (N = 325) (N = 105) (N = 100) Constipation 26% 7% 1% Somnolence 19% 2% 0% Nausea 18% 11% 9% Dizziness 11% 5% 3% Headache 11% 4% 2% Pruritus 7% 3% 1% Table 2: Treatment-Emergent Adverse Reactions Reported in ≥5% of Patients During the Open-Label Titration Period and Double-Blind Treatment Period by Preferred Term — Number (%) of Treated Patients (12-Week Study In Opioid-Experienced Patients with Low Back Pain) Open-Label Titration Period Double-Blind Treatment Period Oxymorphone Hydrochloride Extended-Release Tablets Oxymorphone Hydrochloride Extended-Release Tablets Placebo Preferred Term (N = 250) (N = 70) (N = 72) Nausea 20% 3% 1% Constipation 12% 6% 1% Headache 12% 3% 0% Somnolence 11% 3% 0% Vomiting 9% 0% 1% Pruritus 8% 0% 0% Dizziness 6% 0% 0% The following table lists adverse reactions that were reported in at least 2% of patients in placebo-controlled trials (N=5). Table 3: Adverse Reactions Reported in Placebo-Controlled Clinical Trials with Incidence ≥2% in Patients Receiving Oxymorphone Hydrochloride Extended-Release Tablets. MedDRA Preferred Term Oxymorphone Hydrochloride Extended-Release Tablets (N=1259) Placebo (N=461) Nausea 33% 13% Constipation 28% 13% Dizziness (Excl Vertigo) 18% 8% Somnolence 17% 2% Vomiting 16% 4% Pruritus 15% 8% Headache 12% 6% Sweating increased 9% 9% Dry mouth 6% <1% Sedation 6% 8% Diarrhea 4% 6% Insomnia 4% 2% Fatigue 4% 1% Appetite decreased 3% <1% Abdominal pain 3% 2% The common (≥1% to <10%) adverse drug reactions reported at least once by patients treated with oxymorphone hydrochloride extended-release tablets in the clinical trials organized by MedDRA's (Medical Dictionary for Regulatory Activities) System Organ Class and not represented in Table 1 were: Eye disorders: vision blurred Gastrointestinal disorders: diarrhea, abdominal pain, dyspepsia General disorders and administration site conditions: dry mouth, appetite decreased, fatigue, lethargy, weakness, pyrexia, dehydration, weight decreased, edema Nervous system disorders: insomnia Psychiatric disorders: anxiety, confusion, disorientation, restlessness, nervousness, depression Respiratory, thoracic and mediastinal disorders: dyspnea Vascular disorders: flushing and hypertension Other less common adverse reactions known with opioid treatment that were seen <1% in the oxymorphone hydrochloride extended-release tablets trials include the following: Bradycardia, palpitation, syncope, tachycardia, postural hypotension, miosis, abdominal distention, ileus, hot flashes, allergic reactions, hypersensitivity, urticaria, oxygen saturation decreased, central nervous system depression, depressed level of consciousness, agitation, dysphoria, euphoric mood, hallucination, mental status changes, difficult micturition, urinary retention, hypoxia, respiratory depression, respiratory distress, clamminess, dermatitis, hypotension. 6.2 Post-marketing Experience The following adverse reactions have been identified during post approval use of oxymorphone hydrochloride extended-release tablets. 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. Nervous system disorder: amnesia, convulsion, memory impairment Serotonin syndrome, adrenal insufficiency Anaphylaxis, angioedema, and other hypersensitivity reactions Androgen deficiency: Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation.

<table> <caption>Table 1: Treatment-Emergent Adverse Reactions Reported in &#x2265;5% of Patients During the Open-Label Titration Period and Double-Blind Treatment Period by Preferred Term &#x2014; Number (%) of Treated Patients (12-Week Study In Opioid-Na&#xEF;ve Patients with Low Back Pain)</caption> <col/> <col/> <col/> <col/> <thead> <tr> <th valign="top" styleCode=" Lrule Rrule "> </th> <th align="center" valign="top" styleCode=" Rrule "> Open-Label Titration Period</th> <th align="center" valign="top" colspan="2" styleCode=" Rrule "> Double-Blind Treatment Period</th> </tr> <tr> <th valign="top" styleCode=" Lrule Rrule "> </th> <th align="center" valign="top" styleCode=" Rrule "> Oxymorphone Hydrochloride Extended-Release Tablets</th> <th align="center" valign="top" styleCode=" Rrule "> Oxymorphone Hydrochloride Extended-Release Tablets</th> <th align="center" valign="top" styleCode=" Rrule "> Placebo</th> </tr> <tr> <th valign="top" styleCode=" Lrule Rrule "> Preferred Term</th> <th align="center" valign="top" styleCode=" Rrule "> (N = 325)</th> <th align="center" valign="top" styleCode=" Rrule "> (N = 105)</th> <th align="center" valign="top" styleCode=" Rrule "> (N = 100)</th> </tr> </thead> <tbody> <tr> <td valign="top" styleCode=" Lrule Rrule "> Constipation</td> <td align="center" valign="top" styleCode=" Rrule "> 26%</td> <td align="center" valign="top" styleCode=" Rrule "> 7%</td> <td align="center" valign="top" styleCode=" Rrule "> 1%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Somnolence</td> <td align="center" valign="top" styleCode=" Rrule "> 19%</td> <td align="center" valign="top" styleCode=" Rrule "> 2%</td> <td align="center" valign="top" styleCode=" Rrule "> 0%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Nausea</td> <td align="center" valign="top" styleCode=" Rrule "> 18%</td> <td align="center" valign="top" styleCode=" Rrule "> 11%</td> <td align="center" valign="top" styleCode=" Rrule "> 9%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Dizziness</td> <td align="center" valign="top" styleCode=" Rrule "> 11%</td> <td align="center" valign="top" styleCode=" Rrule "> 5%</td> <td align="center" valign="top" styleCode=" Rrule "> 3%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Headache</td> <td align="center" valign="top" styleCode=" Rrule "> 11%</td> <td align="center" valign="top" styleCode=" Rrule "> 4%</td> <td align="center" valign="top" styleCode=" Rrule "> 2%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Pruritus</td> <td align="center" valign="top" styleCode=" Rrule "> 7%</td> <td align="center" valign="top" styleCode=" Rrule "> 3%</td> <td align="center" valign="top" styleCode=" Rrule "> 1%</td> </tr> </tbody> </table>

<table> <caption>Table 2: Treatment-Emergent Adverse Reactions Reported in &#x2265;5% of Patients During the Open-Label Titration Period and Double-Blind Treatment Period by Preferred Term &#x2014; Number (%) of Treated Patients (12-Week Study In Opioid-Experienced Patients with Low Back Pain)</caption> <col/> <col/> <col/> <col/> <thead> <tr> <th valign="top" styleCode=" Lrule Rrule "> </th> <th align="center" valign="top" styleCode=" Rrule "> Open-Label Titration Period</th> <th align="center" valign="top" colspan="2" styleCode=" Rrule "> Double-Blind Treatment Period</th> </tr> <tr> <th valign="top" styleCode=" Lrule Rrule "> </th> <th align="center" valign="top" styleCode=" Rrule "> Oxymorphone Hydrochloride Extended-Release Tablets</th> <th align="center" valign="top" styleCode=" Rrule "> Oxymorphone Hydrochloride Extended-Release Tablets</th> <th align="center" valign="top" styleCode=" Rrule "> Placebo</th> </tr> <tr> <th valign="top" styleCode=" Lrule Rrule "> Preferred Term</th> <th align="center" valign="top" styleCode=" Rrule "> (N = 250)</th> <th align="center" valign="top" styleCode=" Rrule "> (N = 70)</th> <th align="center" valign="top" styleCode=" Rrule "> (N = 72)</th> </tr> </thead> <tbody> <tr> <td valign="top" styleCode=" Lrule Rrule "> Nausea</td> <td align="center" valign="top" styleCode=" Rrule "> 20%</td> <td align="center" valign="top" styleCode=" Rrule "> 3%</td> <td align="center" valign="top" styleCode=" Rrule "> 1%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Constipation</td> <td align="center" valign="top" styleCode=" Rrule "> 12%</td> <td align="center" valign="top" styleCode=" Rrule "> 6%</td> <td align="center" valign="top" styleCode=" Rrule "> 1%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Headache</td> <td align="center" valign="top" styleCode=" Rrule "> 12%</td> <td align="center" valign="top" styleCode=" Rrule "> 3%</td> <td align="center" valign="top" styleCode=" Rrule "> 0%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Somnolence</td> <td align="center" valign="top" styleCode=" Rrule "> 11%</td> <td align="center" valign="top" styleCode=" Rrule "> 3%</td> <td align="center" valign="top" styleCode=" Rrule "> 0%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Vomiting</td> <td align="center" valign="top" styleCode=" Rrule "> 9%</td> <td align="center" valign="top" styleCode=" Rrule "> 0%</td> <td align="center" valign="top" styleCode=" Rrule "> 1%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Pruritus</td> <td align="center" valign="top" styleCode=" Rrule "> 8%</td> <td align="center" valign="top" styleCode=" Rrule "> 0%</td> <td align="center" valign="top" styleCode=" Rrule "> 0%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Dizziness</td> <td align="center" valign="top" styleCode=" Rrule "> 6%</td> <td align="center" valign="top" styleCode=" Rrule "> 0%</td> <td align="center" valign="top" styleCode=" Rrule "> 0%</td> </tr> </tbody> </table>

<table> <caption>Table 3: Adverse Reactions Reported in Placebo-Controlled Clinical Trials with Incidence &#x2265;2% in Patients Receiving Oxymorphone Hydrochloride Extended-Release Tablets.</caption> <col/> <col/> <col/> <thead> <tr> <th valign="top" styleCode=" Lrule Rrule "> MedDRA Preferred Term</th> <th align="center" valign="top" styleCode=" Rrule "> Oxymorphone Hydrochloride Extended-Release Tablets (N=1259)</th> <th align="center" valign="top" styleCode=" Rrule "> Placebo (N=461)</th> </tr> </thead> <tbody> <tr> <td valign="top" styleCode=" Lrule Rrule "> Nausea</td> <td align="center" valign="top" styleCode=" Rrule "> 33%</td> <td align="center" valign="top" styleCode=" Rrule "> 13%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Constipation</td> <td align="center" valign="top" styleCode=" Rrule "> 28%</td> <td align="center" valign="top" styleCode=" Rrule "> 13%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Dizziness (Excl Vertigo)</td> <td align="center" valign="top" styleCode=" Rrule "> 18%</td> <td align="center" valign="top" styleCode=" Rrule "> 8%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Somnolence</td> <td align="center" valign="top" styleCode=" Rrule "> 17%</td> <td align="center" valign="top" styleCode=" Rrule "> 2%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Vomiting</td> <td align="center" valign="top" styleCode=" Rrule "> 16%</td> <td align="center" valign="top" styleCode=" Rrule "> 4%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Pruritus</td> <td align="center" valign="top" styleCode=" Rrule "> 15%</td> <td align="center" valign="top" styleCode=" Rrule "> 8%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Headache</td> <td align="center" valign="top" styleCode=" Rrule "> 12%</td> <td align="center" valign="top" styleCode=" Rrule "> 6%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Sweating increased</td> <td align="center" valign="top" styleCode=" Rrule "> 9%</td> <td align="center" valign="top" styleCode=" Rrule "> 9%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Dry mouth</td> <td align="center" valign="top" styleCode=" Rrule "> 6%</td> <td align="center" valign="top" styleCode=" Rrule "> &lt;1%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Sedation</td> <td align="center" valign="top" styleCode=" Rrule "> 6%</td> <td align="center" valign="top" styleCode=" Rrule "> 8%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Diarrhea</td> <td align="center" valign="top" styleCode=" Rrule "> 4%</td> <td align="center" valign="top" styleCode=" Rrule "> 6%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Insomnia</td> <td align="center" valign="top" styleCode=" Rrule "> 4%</td> <td align="center" valign="top" styleCode=" Rrule "> 2%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Fatigue</td> <td align="center" valign="top" styleCode=" Rrule "> 4%</td> <td align="center" valign="top" styleCode=" Rrule "> 1%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Appetite decreased</td> <td align="center" valign="top" styleCode=" Rrule "> 3%</td> <td align="center" valign="top" styleCode=" Rrule "> &lt;1%</td> </tr> <tr> <td valign="top" styleCode=" Lrule Rrule "> Abdominal pain</td> <td align="center" valign="top" styleCode=" Rrule "> 3%</td> <td align="center" valign="top" styleCode=" Rrule "> 2%</td> </tr> </tbody> </table>