FDA label 2c4b1ce3-43f4-4abc-b972-ebd5e531900c

WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, ACCIDENTAL EXPOSURE, AND INTERACTION WITH ALCOHOL Abuse Potential Oxymorphone hydrochloride extended-release tablets contains oxymorphone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit [see Warnings and Precautions (5.1) ]. Assess each patient’s risk for opioid abuse or addiction prior to prescribing oxymorphone hydrochloride extended-release tablets. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depressive disorder). Routinely monitor all patients receiving oxymorphone hydrochloride extended-release tablets for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and Dependence (9) ]. Life-threatening Respiratory Depression Respiratory depression, including fatal cases, may occur with use of oxymorphone hydrochloride extended-release tablets, even when the drug has been used as recommended and not misused or abused [see Warnings and Precautions (5.2) ]. Proper dosing and titration are essential and oxymorphone hydrochloride extended-release tablets should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. 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, dissolving, or chewing oxymorphone hydrochloride extended-release tablets can cause rapid release and absorption of a potentially fatal dose of oxymorphone. Accidental Exposure Accidental ingestion of oxymorphone hydrochloride extended-release tablets, especially in children, can result in a fatal overdose of oxymorphone [see Warnings and Precautions (5.3) ]. Interaction with Alcohol The co-ingestion of alcohol with oxymorphone hydrochloride extended-release tablets may result in an increase of plasma levels and potentially fatal overdose of oxymorphone [see Warnings and Precautions (5.4) ]. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while on oxymorphone hydrochloride extended-release tablets. WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, ACCIDENTAL EXPOSURE, AND INTERACTION WITH ALCOHOL See full prescribing information for complete boxed warning. Oxymorphone hydrochloride extended-release tablets contains oxymorphone, a Schedule II controlled substance. Monitor for signs of misuse, abuse, and addiction during oxymorphone hydrochloride extended-release tablet therapy. ( 5.1 , 9 ) Fatal respiratory depression may occur, with highest risk at initiation and with dose increases. Instruct patients on proper administration of oxymorphone hydrochloride extended-release tablets to reduce the risk. ( 5.2 ) Accidental ingestion of oxymorphone hydrochloride extended-release tablets can result in fatal overdose of oxymorphone, especially in children. ( 5.3 ) Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while taking oxymorphone hydrochloride extended-release tablets because of the risk of increased, and potentially fatal, plasma oxymorphone levels. ( 5.4 )

5 WARNINGS AND PRECAUTIONS See Boxed WARNINGS Elderly, cachectic, and debilitated patients, and patients with chronic pulmonary disease: Monitor closely because of increased risk of respiratory depression. ( 5.5 , 5.6 ) Interaction with CNS depressants: Consider dose reduction of one or both drugs because of additive effects. ( 5.7 , 7.2 ) Hypotensive effect: Monitor during dose initiation and titration. ( 5.9 ) 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. ( 5.10 ) Respiratory depression: Increased risk in elderly, debilitated patients, and those suffering from conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve. ( 5.2 ) 5.1 Abuse Potential Oxymorphone hydrochloride extended-release tablets contain oxymorphone, an opioid agonist and a Schedule II controlled substance. Oxymorphone can be abused in a manner similar to other opioid agonists, legal or illicit. Opioid agonists 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 in situations where there is concern about increased risks of misuse, abuse, or diversion. Concerns about abuse, addiction, and diversion should not, however, prevent the proper management of pain. Assess each patient’s risk for opioid abuse or addiction prior to prescribing oxymorphone hydrochloride extended-release tablets. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients at increased risk may still be appropriately treated with modified-release opioid formulations; however these patients will require intensive monitoring for signs of misuse, abuse, or addiction. Routinely monitor all patients receiving opioids for signs of misuse, abuse, and addiction because these drugs carry a risk for addiction even under appropriate medical use. Misuse or abuse of oxymorphone hydrochloride extended-release tablets by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the opioid and pose a significant risk that could result in overdose and death [see Overdosage (10) ]. 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 Respiratory depression is the primary risk of oxymorphone hydrochloride extended-release tablets. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with a “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. 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) ]. 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. Instruct patients against use by individuals other than the patient for whom oxymorphone hydrochloride extended-release tablets was prescribed and to keep oxymorphone hydrochloride extended-release tablets out of the reach of children, as such inappropriate use may result in fatal respiratory depression. To reduce the risk of respiratory depression, proper dosing and titration of oxymorphone hydrochloride extended-release tablets are essential [see Dosage and Administration (2.1 , 2.2) ]. Overestimating the oxymorphone hydrochloride extended-release tablets dose when converting patients from another opioid product can result in fatal overdose with the first dose. Respiratory depression has also been reported with use of modified-release opioids when used as recommended and not misused or abused. To further reduce the risk of respiratory depression, consider the following: Proper dosing and titration are essential and oxymorphone hydrochloride extended-release tablets should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Instruct patients to swallow oxymorphone hydrochloride extended-release tablets intact. The tablets are not to be crushed, dissolved, or chewed. The resulting oxymorphone dose may be fatal, particularly in opioid-naïve individuals. Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with respiratory depression and in patients with conditions that increase the risk of life-threatening respiratory depression [see Contraindications (4) ]. 5.3 Accidental Exposure Accidental consumption of oxymorphone hydrochloride extended-release tablets, especially in children, can result in a fatal overdose of oxymorphone. 5.4 Interaction with Alcohol The co-ingestion of alcohol with oxymorphone hydrochloride extended-release tablets can result in an increase of oxymorphone plasma levels and potentially fatal overdose of oxymorphone. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on oxymorphone hydrochloride extended-release tablet therapy [see Clinical Pharmacology (12.3) ]. 5.5 Elderly, Cachectic, and Debilitated Patients Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance compared to younger, healthier patients. Therefore, 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 Interactions with CNS Depressants and Illicit Drugs Hypotension, profound sedation, coma, or respiratory depression may result if oxymorphone hydrochloride extended-release tablets are used concomitantly with other 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 of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, consider the patient’s use, if any, of alcohol or illicit drugs that cause CNS depression. If oxymorphone hydrochloride extended-release tablet therapy is to be initiated in a patient taking a CNS depressant, start with a lower oxymorphone hydrochloride extended-release tablet dose than usual and 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) ]. 5.8 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) ]. 5.9 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. 5.10 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 CO 2 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 CO 2 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. 5.11 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. 5.12 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 tablet therapy. 5.13 Avoidance of Withdrawal Avoid the use of mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) 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/antagonists 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. 5.14 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: Respiratory Depression [see Warnings and Precautions (5.2) ] Chronic Pulmonary Disease [see Warnings and Precautions (5.6) ] Head Injuries and Increased Intracranial Pressure [see Warnings and Precautions (5.10) ] Interactions with Other CNS Depressants [see Warnings and Precautions (5.7) ] Hypotensive Effect [see Warnings and Precautions (5.9) ] Gastrointestinal Effects [see Warnings and Precautions (5.11) ] Seizures [see Warnings and Precautions (5.12) ] 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 Actavis at 1-800-432-8534 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 Oxymorphone Hydrochloride Extended-Release Tablets 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 Oxymorphone Hydrochloride Extended-Release Tablets 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 tablet 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

<table> <caption> 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-Na&#xEF;ve Patients with Low Back Pain)</caption> <col/> <col/> <col/> <col/> <thead> <tr> <td valign="top"> </td> <td align="center" valign="top"> <content styleCode="bold">Open-Label Titration Period</content> </td> <td align="center" valign="top" colspan="2"> <content styleCode="bold">Double-Blind Treatment Period</content> </td> </tr> <tr> <td valign="top"> </td> <td align="center" valign="top"> <content styleCode="bold">Oxymorphone Hydrochloride </content> </td> <td align="center" valign="top"> <content styleCode="bold">Oxymorphone Hydrochloride </content> </td> <td align="center" valign="top"> </td> </tr> <tr> <td valign="top"> </td> <td align="center" valign="top"> <content styleCode="bold">Extended-Release Tablets</content> </td> <td align="center" valign="top"> <content styleCode="bold">Extended-Release Tablets</content> </td> <td align="center" valign="top"> <content styleCode="bold">Placebo</content> </td> </tr> <tr> <td valign="top"> <content styleCode="bold">Preferred Term</content> </td> <td align="center" valign="top"> <content styleCode="bold">(N = 325)</content> </td> <td align="center" valign="top"> <content styleCode="bold">(N = 105)</content> </td> <td align="center" valign="top"> <content styleCode="bold">(N = 100)</content> </td> </tr> </thead> <tbody> <tr> <td valign="top"> Constipation</td> <td align="center" valign="top"> 26%</td> <td align="center" valign="top"> 7%</td> <td align="center" valign="top"> 1%</td> </tr> <tr> <td valign="top"> Somnolence</td> <td align="center" valign="top"> 19%</td> <td align="center" valign="top"> 2%</td> <td align="center" valign="top"> 0%</td> </tr> <tr> <td valign="top"> Nausea</td> <td align="center" valign="top"> 18%</td> <td align="center" valign="top"> 11%</td> <td align="center" valign="top"> 9%</td> </tr> <tr> <td valign="top"> Dizziness</td> <td align="center" valign="top"> 11%</td> <td align="center" valign="top"> 5%</td> <td align="center" valign="top"> 3%</td> </tr> <tr> <td valign="top"> Headache</td> <td align="center" valign="top"> 11%</td> <td align="center" valign="top"> 4%</td> <td align="center" valign="top"> 2%</td> </tr> <tr> <td valign="top"> Pruritus</td> <td align="center" valign="top"> 7%</td> <td align="center" valign="top"> 3%</td> <td align="center" valign="top"> 1%</td> </tr> </tbody> </table>

<table> <caption> 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)</caption> <col/> <col/> <col/> <col/> <thead> <tr> <td valign="top"> </td> <td align="center" valign="top"> <content styleCode="bold">Open-Label Titration Period</content> </td> <td align="center" valign="top" colspan="2"> <content styleCode="bold">Double-Blind Treatment Period</content> </td> </tr> <tr> <td valign="top"> </td> <td align="center" valign="top"> <content styleCode="bold">Oxymorphone Hydrochloride </content> </td> <td align="center" valign="top"> <content styleCode="bold">Oxymorphone Hydrochloride </content> </td> <td align="center" valign="top"> </td> </tr> <tr> <td valign="top"> </td> <td align="center" valign="top"> <content styleCode="bold">Extended-Release Tablets</content> </td> <td align="center" valign="top"> <content styleCode="bold">Extended-Release Tablets</content> </td> <td align="center" valign="top"> <content styleCode="bold">Placebo</content> </td> </tr> <tr> <td valign="top"> <content styleCode="bold">Preferred Term</content> </td> <td align="center" valign="top"> <content styleCode="bold">(N = 250)</content> </td> <td align="center" valign="top"> <content styleCode="bold">(N = 70)</content> </td> <td align="center" valign="top"> <content styleCode="bold">(N = 72)</content> </td> </tr> </thead> <tbody> <tr> <td valign="top"> Nausea</td> <td align="center" valign="top"> 20%</td> <td align="center" valign="top"> 3%</td> <td align="center" valign="top"> 1%</td> </tr> <tr> <td valign="top"> Constipation</td> <td align="center" valign="top"> 12%</td> <td align="center" valign="top"> 6%</td> <td align="center" valign="top"> 1%</td> </tr> <tr> <td valign="top"> Headache</td> <td align="center" valign="top"> 12%</td> <td align="center" valign="top"> 3%</td> <td align="center" valign="top"> 0%</td> </tr> <tr> <td valign="top"> Somnolence</td> <td align="center" valign="top"> 11%</td> <td align="center" valign="top"> 3%</td> <td align="center" valign="top"> 0%</td> </tr> <tr> <td valign="top"> Vomiting </td> <td align="center" valign="top"> 9%</td> <td align="center" valign="top"> 0%</td> <td align="center" valign="top"> 1%</td> </tr> <tr> <td valign="top"> Pruritus</td> <td align="center" valign="top"> 8%</td> <td align="center" valign="top"> 0%</td> <td align="center" valign="top"> 0%</td> </tr> <tr> <td valign="top"> Dizziness</td> <td align="center" valign="top"> 6%</td> <td align="center" valign="top"> 0%</td> <td align="center" valign="top"> 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> <td valign="top"> <content styleCode="bold">MedDRA Preferred Term</content> </td> <td align="center" valign="top"> <content styleCode="bold">Oxymorphone Hydrochloride Extended-Release </content> </td> <td align="center" valign="top"> </td> </tr> <tr> <td valign="top"> </td> <td align="center" valign="top"> <content styleCode="bold">Tablets (N=1259)</content> </td> <td align="center" valign="top"> <content styleCode="bold">Placebo (N=461)</content> </td> </tr> </thead> <tbody> <tr> <td valign="top"> Nausea</td> <td align="center" valign="top"> 33%</td> <td align="center" valign="top"> 13%</td> </tr> <tr> <td valign="top"> Constipation</td> <td align="center" valign="top"> 28%</td> <td align="center" valign="top"> 13%</td> </tr> <tr> <td valign="top"> Dizziness (Excl Vertigo)</td> <td align="center" valign="top"> 18%</td> <td align="center" valign="top"> 8%</td> </tr> <tr> <td valign="top"> Somnolence</td> <td align="center" valign="top"> 17%</td> <td align="center" valign="top"> 2%</td> </tr> <tr> <td valign="top"> Vomiting </td> <td align="center" valign="top"> 16%</td> <td align="center" valign="top"> 4%</td> </tr> <tr> <td valign="top"> Pruritus </td> <td align="center" valign="top"> 15%</td> <td align="center" valign="top"> 8%</td> </tr> <tr> <td valign="top"> Headache </td> <td align="center" valign="top"> 12%</td> <td align="center" valign="top"> 6%</td> </tr> <tr> <td valign="top"> Sweating increased</td> <td align="center" valign="top"> 9%</td> <td align="center" valign="top"> 9%</td> </tr> <tr> <td valign="top"> Dry mouth</td> <td align="center" valign="top"> 6%</td> <td align="center" valign="top"> &lt;1%</td> </tr> <tr> <td valign="top"> Sedation</td> <td align="center" valign="top"> 6%</td> <td align="center" valign="top"> 8%</td> </tr> <tr> <td valign="top"> Diarrhea </td> <td align="center" valign="top"> 4%</td> <td align="center" valign="top"> 6%</td> </tr> <tr> <td valign="top"> Insomnia </td> <td align="center" valign="top"> 4%</td> <td align="center" valign="top"> 2%</td> </tr> <tr> <td valign="top"> Fatigue</td> <td align="center" valign="top"> 4%</td> <td align="center" valign="top"> 1%</td> </tr> <tr> <td valign="top"> Appetite decreased </td> <td align="center" valign="top"> 3%</td> <td align="center" valign="top"> &lt;1%</td> </tr> <tr> <td valign="top"> Abdominal pain</td> <td align="center" valign="top"> 3%</td> <td align="center" valign="top"> 2%</td> </tr> </tbody> </table>