These Highlights Do Not Include All The Information Needed To Use Oxymorphone Hydrochloride Extended-release Tablets Safely And Effectively. See Full Prescribing Information For Oxymorphone Hydrochloride Extended-release Tablets.

Limitations of Usage:

• Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see Warnings and Precautions (5.1)], reserve Oxymorphone Hydrochloride Extended-Release Tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated or would be otherwise inadequate to provide sufficient management of pain.
• Oxymorphone Hydrochloride Extended-Release Tablets are not indicated as an as-needed (prn) analgesic.

Indications and Usage (1)                           04/2023

Dosage and Administration (2.1, 2.3)         04/2023

Warnings and Precautions (5.6)                 04/2023

Oxymorphone Hydrochloride Extended-Release Tablets contain oxymorphone, a substance with a high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1)].

Misuse is the intentinal use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than to other activities and obligations), and possible tolerance or physical dependence.

Misuse and abuse of Oxymorphone Hydrochloride Extended-Release Tablets increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of Oxymorphone Hydrochloride Extended-Release Tablets with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.

All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of Oxymorphone Hydrochloride Extended-Release Tablets abuse include those with a history of prolonged use of any opioid, including products containing oxymorphone, those with a history of drug or alcohol abuse, or those who use Oxymorphone Hydrochloride Extended-Release Tablets in combination with other abused drugs.

“Drug seeking" behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Pre-occupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.

Oxymorphone Hydrochloride Extended-Release Tablets, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Oxymorphone Hydrochloride Extended-Release Tablets

Abuse of Oxymorphone Hydrochloride Extended-Release Tablets poses a risk of overdose and death. This risk is increased with concurrent use of Oxymorphone Hydrochloride Extended-Release Tablets with alcohol and/or other CNS depressants. Taking cut, broken, chewed, crushed or dissolved Oxymorphone Hydrochloride Extended-Release Tablets enhance drug release and increases the risk of overdose and death.

Oxymorphone Hydrochloride Extended-Release Tablets is approved for oral use only. Inappropriate intravenous, intramuscular, or subcutaneous use of Oxymorphone Hydrochloride Extended-Release Tablets can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism.

Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Oxymorphone Hydrochloride Extended-Release Tablets, USP are for oral use and contain oxymorphone, a semi-synthetic opioid analgesic. Oxymorphone Hydrochloride Extended-Release Tablets, USP are supplied in 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg and 40 mg tablet strengths for oral administration. The tablet strength describes the amount of oxymorphone hydrochloride per tablet.

The tablets contain the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, hypromellose, xanthan gum, magnesium stearate, polyvinyl alcohol - partially hydrolyzed, polyethylene glycol, talc, and titanium dioxide. The 5 mg, 7.5 mg, 10 mg, 20 mg and 40 mg tablets contain FD&C Yellow No. 6 Aluminum Lake. In addition, the 5 mg tablets contain FD&C Blue No. 2 and D&C Red No. 27. The 7.5 mg tablets contain FD&C Blue No. 2 and FD&C Red No. 40. The 10 mg tablets contain FD&C Red No. 40. The 20 mg tablets contain D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1, and FD&C Blue No. 2. The 30 mg tablets contain Iron Oxide Yellow and Iron Oxide Black. The 40 mg tablets contain D&C Yellow No. 10 Aluminum Lake.

The chemical name of oxymorphone hydrochloride is 4,5α-epoxy-3, 14-dihydroxy-17-methylmorphinan-6-one hydrochloride. Oxymorphone hydrochloride, USP is a white or slightly off-white, odorless powder, which is sparingly soluble in alcohol and ether, but freely soluble in water. The molecular weight of oxymorphone hydrochloride is 337.80. The pKa1 and pKa2 of oxymorphone at 37°C are 8.17 and 9.54, respectively. The octanol/aqueous partition coefficient at 37°C and pH 7.4 is 0.98.

The structural formula for oxymorphone hydrochloride is as follows:

Risk Summary

There is no information regarding the presence of oxymorphone in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Oxymorphone Hydrochloride Extended-Release Tablets.

Clinical Considerations

Monitor infants exposed to Oxymorphone through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

Both tolerance and physical dependence can develop during use of opioid therapy.

Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e. a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use.

Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets in a patient physically dependent on opioids. Rapid tapering of Oxymorphone Hydrochloride Extended-Release Tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

When discontinuing Oxymorphone Hydrochloride Extended-Release Tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of Oxymorphone Hydrochloride Extended-Release Tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see Dosage and Administration (2.5) and  Warnings and Precautions (5.15)].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)].

Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets in a patient physically dependent on opioids. When discontinuing Oxymorphone Hydrochloride Extended-Release Tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of Oxymorphone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration (2.5) and  Drug Abuse and Dependence (9.3)].

Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) and partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full 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 [see Drug Interactions (7)].

The safety and effectiveness of Oxymorphone Hydrochloride Extended-Release Tablets in patients below the age of 18 years have not been established. Two open-label studies were conducted in a total of 42 pediatric patients between the ages of 7 to 17 years requiring continuous, around the clock opioid treatment. The available safety and efficacy data were inconclusive for chronic use of Oxymorphone Hydrochloride Extended-Release Tablets. Limited data from one of the studies suggested that Oxymorphone Hydrochloride Extended-Release Tablets is not recommended for post-surgical pain.

Of the total number of subjects in clinical studies of Oxymorphone Hydrochloride Extended-Release Tablets, 27% were 65 and over, while 9% were 75 and over. No overall differences in effectiveness were observed between these subjects and younger subjects. There were several adverse events that were more frequently observed in subjects 65 and over compared to younger subjects. These adverse events included dizziness, somnolence, confusion and nausea. On average, age greater than 65 years was associated with an increase in oxymorphone AUC and C_max. Initiate dosing with Oxymorphone Hydrochloride Extended-Release Tablets in patients 65 years of age and over using the 5 mg dose and frequently reevaluate the patient for signs of respiratory and central nervous system depression when initiating and titrating Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.2)]. For patients on prior opioid therapy, start at 50% of the starting dose for a younger patient on prior opioids and titrate slowly.

Oxymorphone is known to be substantially excreted by the kidney and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because the elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.

The efficacy and safety of Oxymorphone Hydrochloride Extended-Release Tablets have been evaluated in double-blind, controlled clinical trials in opioid-naïve and opioid-experienced patients with moderate to severe pain including low back pain.

Oxymorphone Hydrochloride Extended-Release Tablets are contraindicated in patients with:

• Significant respiratory depression [see Warnings and Precautions (5.3)]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.6)]
• Hypersensitivity (e.g. anaphylaxis) to oxymorphone, any other ingredients in Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.7), Adverse Reactions (6)].
• Moderate and severe hepatic impairment [see Warnings and Precautions (5.9),  Clinical Pharmacology (12.3)]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12)]

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 )]
• Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.3 )]
• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4)]
• Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions (5.6)]
• Anaphylaxis and Angioedema [see Warnings and Precautions (5.8 )]
• Adrenal Insufficiency [see Warnings and Precautions (5.9)]
• Severe Hypotension [see Warnings and Precautions (5.11)]
• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.13)] 
• Seizures [see Warnings and Precautions (5.14)]
• Withdrawal [see Warnings and Precautions (5.15)]

Table 5 includes clinically significant drug interactions with Oxymorphone Hydrochloride Extended-Release Tablets.

Table 5: Clinically Significant Drug Interactions with Oxymorphone Hydrochloride Extended-Release Tablets

Patients with moderate to severe renal impairment were shown to have an increase in oxymorphone bioavailability compared to the subjects with normal renal function [see Clinical Pharmacology (12.3)]. Start opioid-naïve patients with the 5 mg dose of Oxymorphone Hydrochloride Extended-Release Tablets and titrate slowly while closely regularly evaluate for respiratory and central nervous system depression [see Dosage and Administration (2.6)]. For patients on prior opioid therapy, start at 50% of the dose for a patient with normal renal function on prior opioids and titrate slowly.

CNS Depressant/Alcohol Interaction

Additive pharmacodynamic effects may be expected when Oxymorphone Hydrochloride Extended-Release Tablets are used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

Effects on the Central Nervous System

Oxymorphone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.

Oxymorphone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Effects on the Gastrointestinal Tract and on Other Smooth Muscle

Oxymorphone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.

Effects on the Cardiovascular System

Oxymorphone produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Release of histamine can occur and may contribute to opioid-induced hypotension. Manifestations of histamine release and/ or peripheral vasodilation may include pruritis, flushing, red eyes, sweating, and/or orthostatic hypotension.

Effects on the Endocrine System

Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions (6.2)]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.

Use of opioids for an extended period of time 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 [see Adverse Reactions (6.2)].

Effects on the Immune System

Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.

Concentration-Efficacy Relationships

The minimum effective plasma concentration of oxymorphone varies widely among patients, especially among patients who have been previously treated with opioid agonists. The minimum effective analgesic concentration of oxymorphone for any individual patient may increase over time due to an increase in pain, development of a new pain syndrome and/or development of analgesic tolerance [see Dosage and Administration (2.1, 2.3, 2.4)].

Concentration-Adverse Reaction Relationships

There is a relationship between increasing oxymorphone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see Dosage and Administration (2.1, 2.3, 2.4)] .

Patients with mild hepatic impairment have an increase in oxymorphone bioavailability compared to the subjects with normal hepatic function. In opioid-naïve patients with mild hepatic impairment, initiate Oxymorphone Hydrochloride Extended-Release Tablets using the 5 mg dose and regularly evaluate closely for respiratory and central nervous system depression. Oxymorphone Hydrochloride Extended-Release Tablets are contraindicated for patients with moderate and severe hepatic impairment [see Dosage and Administration (2.6), Contraindications (4) , Warnings and Precautions (5.9) and  Clinical Pharmacology (12.3)]. For patients on prior opioid therapy, start at the 50% of the dose for that a patient with normal hepatic function on prior opioids and titrate slowly.

Oxymorphone Hydrochloride Extended-Release Tablets are indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate.

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)]. Regularly evaluate these patients for signs of hypotension after initiating or titrating the dosage 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.

Oxymorphone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxymorphone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with oxymorphone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.

The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

Oxymorphone Hydrochloride Extended-Release Tablets contain oxymorphone, a Schedule II controlled substance.

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one 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.

• Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. (5.6)
• Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly Cachectic or Debilitated Patients: Regularly evaluate closely particularly during initiation and titration. (5.7) 
• Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions: If symptoms occur, stop administration immediately, discontinue permanently, and do not rechallenge with any other oxymorphone formulation. (5.8)
• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. (5.9)
• Severe Hypotension: Regularly evaluate during dose initiation and titration. Avoid use of oxymorphone hydrochloride extended-release tablets in patients with circulatory shock. (5.11)
• Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury or Impaired Consciousness: Monitor for sedation and respiratory depression. Avoid use of Oxymorphone Hydrochloride Extended-Release Tablets in patients with impaired consciousness or coma. (5.12)

• Oxymorphone Hydrochloride Extended-Release Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. (2.1) 
• Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of Oxymorphone Hydrochloride Extended-Release Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. (2.1, 5) 
• Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. (2.1, 5) 
• Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating. (2.1)
• Discuss availability of naloxone with the patient and caregiver and assess each patient’s need for access to naloxone, both when initiating and renewing treatment with Oxymorphone Hydrochloride Extended-Release Tablets. Consider prescribing naloxone based on the patient’s risk factors for overdose (2.2 , 5.1 , 5.2 , 5.3).
• For opioid-naïve and opioid non-tolerant patients, initiate treatment with 5 mg tablets orally every 12 hours. (2.3)
• To convert to Oxymorphone Hydrochloride Extended-Release Tablets from another opioid, use available conversion factors to obtain estimated dose. (2.3)
• Dose can be increased every 3 to 7 days, using increments of 5 mg to 10 mg every 12 hours (i.e., 10 mg to 20 mg per day). (2.4)
• Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. (2.5, 5.15) 
• Mild Hepatic Impairment: For opioid-naïve patients, initiate treatment with 5 mg and titrate slowly. For patients on prior opioid therapy, reduce starting dose by 50% and titrate slowly. Monitor for signs of respiratory and central nervous system depression. (2.6)  
• Renal Impairment: For opioid-naïve patients, initiate treatment with 5 mg and titrate slowly. For patients on prior opioid therapy, reduce starting dose by 50% and titrate slowly. Monitor for signs of respiratory and central nervous system depression. (2.7)
• Geriatric Patients: Initiate dosing with 5 mg, titrate slowly, and monitor for signs of respiratory and central nervous system depression. (2.8)

Oxymorphone Hydrochloride Extended-Release Tablets USP, 5 mg dosage form is a purple, round, film-coated extended-release tablet debossed with "G71" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 7.5 mg dosage form is a gray, round, film-coated extended-release tablet debossed with "G75" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 10 mg dosage form is an orange, round, film-coated extended-release tablet debossed with "G72" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 15 mg dosage form is a white, round, film-coated extended-release tablet debossed with "G76" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 20 mg dosage form is a green, round, film-coated extended-release tablet debossed with "G73" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 30 mg dosage form is a brown, round, film-coated extended-release tablet debossed with "G77" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 40 mg dosage form is an orange, round, film-coated extended-release tablet debossed with "G74" on one side and blank on the other side.

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 2 and 3 list the most frequently occurring adverse reactions (in at least 5% of patients) from the placebo-controlled trials in patients with low back pain.

The Table 4 lists adverse reactions that were reported in at least 2% of patients in placebo-controlled trials (N=5).

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.

The following adverse reactions have been identified during post approval use of opioids. 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: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Oxymorphone Hydrochloride Extended-Release Tablets.

Androgen deficiency: Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see Clinical Pharmacology (12)].

Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and  Precautions (5.6) ]

Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).

• Pregnancy: May cause fetal harm. (8.1)
• Lactation: Not recommended. (8.2)

Oxymorphone Hydrochloride Extended-Release Tablet contains, oxymorphone, a Schedule II controlled substance. As an opioid, Oxymorphone Hydrochloride Extended-Release Tablets exposes users to the risks of addiction, abuse, and misuse. Because extended-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 [see Drug Abuse and Dependence (9)].

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Oxymorphone Hydrochloride Extended-Release Tablets. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing Oxymorphone Hydrochloride Extended-Release Tablets and reassess all patients receiving Oxymorphone Hydrochloride Extended-Release Tablets for the development of these behaviors and conditions. Risks are 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). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids 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 frequent reevaluation for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2) and Warnings and Precautions (5.3)].

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)].

Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. 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 careful storage of the drug during the course of treatment and proper disposal of unused drug. 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.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Storage and Disposal

Because of the risks associated with accidental ingestion, misuse and abuse, advise patients to store Oxymorphone Hydrochloride Extended-Release Tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving Oxymorphone Hydrochloride Extended-Release Tablets unsecured can pose a deadly risk to others in the home [see Warnings and Precautions (5.1, 5.3) and Drug Abuse and Dependence (9.2)].

Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused Oxymorphone Hydrochloride Extended-Release Tablets should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.

Oxymorphone Hydrochloride Extended-Release Tablets, USP are supplied as follows:

5 mg

Purple, round, film-coated extended-release tablets debossed with "G71" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1231-08

Bottles of 60                                                  NDC 0115-1231-13

Bottles of 100                                                NDC 0115-1231-01

Bottles of 1,000                                             NDC 0115-1231-03

7.5 mg

Gray, round, film-coated extended-release tablets debossed with "G75" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1315-08

Bottles of 60                                                  NDC 0115-1315-13

Bottles of 100                                                NDC 0115-1315-01

Bottles of 1,000                                             NDC 0115-1315-03

10 mg

Orange, round, film-coated extended-release tablets debossed with "G72" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1232-08

Bottles of 60                                                  NDC 0115-1232-13

Bottles of 100                                                NDC 0115-1232-01

Bottles of 1,000                                             NDC 0115-1232-03

15 mg

White, round, film-coated extended-release tablets debossed with "G76" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1316-08

Bottles of 60                                                  NDC 0115-1316-13

Bottles of 100                                                NDC 0115-1316-01

Bottles of 1,000                                             NDC 0115-1316-03

20 mg

Green, round, film-coated extended-release tablets debossed with "G73" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1233-08

Bottles of 60                                                  NDC 0115-1233-13

Bottles of 100                                                NDC 0115-1233-01

Bottles of 1,000                                             NDC 0115-1233-03

30 mg

Brown, round, film-coated extended-release tablets debossed with "G77" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1317-08

Bottles of 60                                                  NDC 0115-1317-13

Bottles of 100                                                NDC 0115-1317-01

Bottles of 1,000                                             NDC 0115-1317-03

40 mg

Orange, round, film-coated extended-release tablets debossed with "G74" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1234-08

Bottles of 60                                                  NDC 0115-1234-13

Bottles of 100                                                NDC 0115-1234-01

Bottles of 1,000                                             NDC 0115-1234-03



Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].



Dispense in tight container as defined in the USP, with a child-resistant closure (as required).



Store Oxymorphone Hydrochloride Extended-Release Tablets securely and dispose of properly [see Patient Counseling Information (17)].

Use of Oxymorphone Hydrochloride Extended-Release Tablets for an extended period of time during pregnancy can result in withdrawal 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. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for an extended period of time of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1) and Patient Counseling Information (17)].

Individually titrate Oxymorphone Hydrochloride Extended-Release Tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Oxymorphone Hydrochloride Extended-Release Tablets to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions as well as to reassess for the development of addiction, abuse, and misuse [see Warnings and Precautions (5.1, 5.15)]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During use of opioid therapy for an extended period of time, periodically reassess the continued need for the use of opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the Oxymorphone Hydrochloride Extended-Release Tablets dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3 days, Oxymorphone Hydrochloride Extended-Release Tablets dosage adjustments, preferably at increments of 5 mg to 10 mg every 12 hours, may be done every 3 to 7 days.

Patients who experience breakthrough pain may require a dose increase of Oxymorphone Hydrochloride Extended-Release Tablets, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing Oxymorphone Hydrochloride Extended-Release Tablets dose.

If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), the subsequent dose may be reduced [see Warnings and Precautions (5)]. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Serious, life-threatening, or fatal respiratory depression has been reported with the use of 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 (CO₂) 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. 

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 , 2.3) ]. Overestimating the Oxymorphone Hydrochloride Extended-Release Tablets dosage 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.

Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information (17)].

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.5)].

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with Oxymorphone Hydrochloride Extended-Release Tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see Patient Counseling Information (17)].

Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone [see Dosage and Administration (2.2), Warnings and Precautions (5.1, 5.3), Overdosage (10) and Patient Counseling Information (17)].

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 regularly evaluate for signs of respiratory and central nervous system depression [see Dosage and Administration (2.6)].

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.

Infertility

Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [Clinical Pharmacology (12.2) and Nonclinical Toxicology (13.1)].

The steady-state plasma concentrations of oxymorphone are higher in elderly subjects than in young subjects. Initiate dosing with Oxymorphone Hydrochloride Extended-Release Tablets in patients 65 years of age and over using the 5 mg dose and monitor closely for signs of respiratory and central nervous system depression when initiating and titrating Oxymorphone Hydrochloride Extended-Release Tablets to adequate analgesia [see Warnings and Precautions (5.3), Use in Specific Populations (8.5) and  Clinical Pharmacology (12.3)]. For patients on prior opioid therapy, start Oxymorphone Hydrochloride Extended-Release Tablets at 50% lower than the starting dose for a younger patient on prior opioids and titrate slowly.

Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect [see Dependence (9.3)]. Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior.

Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics. Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation (safely switching the patient to a different opioid moiety) [see Dosage and Administration (2.5); Warnings and  Precautions (5.15) ].

NDC 0115-1231-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 5 mg  CII 

Rx only

100 Tablets

NDC 0115-1232-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 10 mg  CII 

Rx only

100 Tablets

NDC 0115-1361-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 15 mg  CII 

Rx only

100 Tablets

NDC 0115-1233-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 20 mg  CII 

Rx only

100 Tablets

NDC 0115-1317-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 30 mg  CII 

Rx only

100 Tablets

NDC 0115-1234-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 40 mg  CII 

Rx only

100 Tablets

NDC 0115-1315-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 7.5 mg  CII 

Rx only

100 Tablets

Oxymorphone Hydrochloride Extended-Release Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks.

• Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions (5)]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of Oxymorphone Hydrochloride Extended-Release Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
• Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)].
• Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Oxymorphone Hydrochloride Extended-Release Tablets. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions (5)].

Instruct patients to swallow Oxymorphone Hydrochloride Extended-Release Tablets whole [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving Oxymorphone Hydrochloride Extended-Release Tablets will result in uncontrolled delivery of oxymorphone and can lead to overdose or death [see Warnings and Precautions (5.3)].

Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

Oxymorphone Hydrochloride Extended-Release Tablets are administered orally twice daily (every 12 hours).

In patients with creatinine clearance rates less than 50 mL/min, start Oxymorphone Hydrochloride Extended-Release Tablets in the opioid-naïve patient with the 5 mg dose. For patients on prior opioid therapy, start Oxymorphone Hydrochloride Extended-Release Tablets at 50% lower than the starting dose for a patient with normal renal function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.3) , Use in Specific Populations (8.7) and  Clinical Pharmacology (12.3)].

Oxymorphone Hydrochloride Extended-Release Tablets are contraindicated in patients with moderate or severe hepatic impairment.

In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose. For patients on prior opioid therapy, start Oxymorphone Hydrochloride Extended-Release Tablets at 50% lower than the starting dose for a patient with normal hepatic function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.3), Use in Specific Populations (8.6) and  Clinical Pharmacology (12.3)].

Oxymorphone Hydrochloride Extended-Release Tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. 

The oxymorphone in Oxymorphone Hydrochloride Extended-Release Tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Regularly evaluate patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

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)].

The oxymorphone in Oxymorphone Hydrochloride Extended-Release Tablets may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures occurring in other clinical settings associated with seizures. Regularly evaluate patients with a history of seizure disorders for worsened seizure control during Oxymorphone Hydrochloride Extended-Release Tablets therapy.

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

• Complete a REMS-compliant education program  offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
• Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG .
• Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
• Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities.

To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

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)].

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Oxymorphone Hydrochloride Extended-Release Tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions (7)].

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation).

If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2) and Warnings and Precautions (5.3)] .

Advise both patients and caregivers about the risks of respiratory depression and sedation when Oxymorphone Hydrochloride Extended-Release Tablets are used with benzodiazepine or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions (7) and  Patient Counseling Information (17)].

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.3) and Patient Counseling Information (17)].

Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program).

Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see Warnings and Precautions ( 5.1 , 5.3 , 5.5 )].

Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.

Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.

When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking Oxymorphone Hydrochloride Extended-Release Tablets, there are a variety of factors that should be considered, including the total daily dose of opioid (including Oxymorphone Hydrochloride Extended-Release Tablets) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist.

There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on Oxymorphone Hydrochloride Extended-Release Tablets who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.

It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.14) and Drug Abuse and Dependence (9.3)].

Addiction, Abuse, and Misuse

Because the use of Oxymorphone Hydrochloride Extended-Release Tablets exposes 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 and reassess all patients regularly for the development of these behaviors and 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, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of Oxymorphone Hydrochloride Extended-Release Tablets are essential [see Warnings and Precautions (5.2)]. Instruct patients to swallow Oxymorphone Hydrochloride Extended-Release tablets whole to avoid exposure to a potentially fatal dose of oxymorphone.

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)].

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 (5.3)].

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of Oxymorphone Hydrochloride Extended-Release Tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3), Drug Interactions (7)].

Neonatal Opioid Withdrawal Syndrome (NOWS)

If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions (5.4)].

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

Healthcare providers are strongly encouraged to complete a REMS compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings and Precautions (5.5)].

In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), Oxymorphone Hydrochloride Extended-Release Tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Regularly evaluate such patients for signs of sedation and respiratory depression, particularly when initiating therapy with Oxymorphone Hydrochloride Extended-Release Tablets.

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.

The use of Oxymorphone Hydrochloride Extended-Release Tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: Oxymorphone Hydrochloride Extended-Release Tablets treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.3)].

Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see Warnings and Precautions (5.3)].

Regularly evaluate patients, 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)  and  Drug Interactions (7)] . Alternatively, consider the use of non-opioid analgesics in these patients.

Limitations of Usage:

• Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see Warnings and Precautions (5.1)], reserve Oxymorphone Hydrochloride Extended-Release Tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated or would be otherwise inadequate to provide sufficient management of pain.
• Oxymorphone Hydrochloride Extended-Release Tablets are not indicated as an as-needed (prn) analgesic.

Indications and Usage (1)                           04/2023

Dosage and Administration (2.1, 2.3)         04/2023

Warnings and Precautions (5.6)                 04/2023

Oxymorphone Hydrochloride Extended-Release Tablets contain oxymorphone, a substance with a high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1)].

Misuse is the intentinal use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than to other activities and obligations), and possible tolerance or physical dependence.

Misuse and abuse of Oxymorphone Hydrochloride Extended-Release Tablets increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of Oxymorphone Hydrochloride Extended-Release Tablets with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.

All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of Oxymorphone Hydrochloride Extended-Release Tablets abuse include those with a history of prolonged use of any opioid, including products containing oxymorphone, those with a history of drug or alcohol abuse, or those who use Oxymorphone Hydrochloride Extended-Release Tablets in combination with other abused drugs.

“Drug seeking" behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Pre-occupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.

Oxymorphone Hydrochloride Extended-Release Tablets, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Oxymorphone Hydrochloride Extended-Release Tablets

Abuse of Oxymorphone Hydrochloride Extended-Release Tablets poses a risk of overdose and death. This risk is increased with concurrent use of Oxymorphone Hydrochloride Extended-Release Tablets with alcohol and/or other CNS depressants. Taking cut, broken, chewed, crushed or dissolved Oxymorphone Hydrochloride Extended-Release Tablets enhance drug release and increases the risk of overdose and death.

Oxymorphone Hydrochloride Extended-Release Tablets is approved for oral use only. Inappropriate intravenous, intramuscular, or subcutaneous use of Oxymorphone Hydrochloride Extended-Release Tablets can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism.

Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Oxymorphone Hydrochloride Extended-Release Tablets, USP are for oral use and contain oxymorphone, a semi-synthetic opioid analgesic. Oxymorphone Hydrochloride Extended-Release Tablets, USP are supplied in 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg and 40 mg tablet strengths for oral administration. The tablet strength describes the amount of oxymorphone hydrochloride per tablet.

The tablets contain the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, hypromellose, xanthan gum, magnesium stearate, polyvinyl alcohol - partially hydrolyzed, polyethylene glycol, talc, and titanium dioxide. The 5 mg, 7.5 mg, 10 mg, 20 mg and 40 mg tablets contain FD&C Yellow No. 6 Aluminum Lake. In addition, the 5 mg tablets contain FD&C Blue No. 2 and D&C Red No. 27. The 7.5 mg tablets contain FD&C Blue No. 2 and FD&C Red No. 40. The 10 mg tablets contain FD&C Red No. 40. The 20 mg tablets contain D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1, and FD&C Blue No. 2. The 30 mg tablets contain Iron Oxide Yellow and Iron Oxide Black. The 40 mg tablets contain D&C Yellow No. 10 Aluminum Lake.

The chemical name of oxymorphone hydrochloride is 4,5α-epoxy-3, 14-dihydroxy-17-methylmorphinan-6-one hydrochloride. Oxymorphone hydrochloride, USP is a white or slightly off-white, odorless powder, which is sparingly soluble in alcohol and ether, but freely soluble in water. The molecular weight of oxymorphone hydrochloride is 337.80. The pKa1 and pKa2 of oxymorphone at 37°C are 8.17 and 9.54, respectively. The octanol/aqueous partition coefficient at 37°C and pH 7.4 is 0.98.

The structural formula for oxymorphone hydrochloride is as follows:

Risk Summary

There is no information regarding the presence of oxymorphone in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Oxymorphone Hydrochloride Extended-Release Tablets.

Clinical Considerations

Monitor infants exposed to Oxymorphone through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

Both tolerance and physical dependence can develop during use of opioid therapy.

Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e. a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use.

Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets in a patient physically dependent on opioids. Rapid tapering of Oxymorphone Hydrochloride Extended-Release Tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

When discontinuing Oxymorphone Hydrochloride Extended-Release Tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of Oxymorphone Hydrochloride Extended-Release Tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see Dosage and Administration (2.5) and  Warnings and Precautions (5.15)].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)].

Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets in a patient physically dependent on opioids. When discontinuing Oxymorphone Hydrochloride Extended-Release Tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of Oxymorphone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration (2.5) and  Drug Abuse and Dependence (9.3)].

Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) and partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full 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 [see Drug Interactions (7)].

The safety and effectiveness of Oxymorphone Hydrochloride Extended-Release Tablets in patients below the age of 18 years have not been established. Two open-label studies were conducted in a total of 42 pediatric patients between the ages of 7 to 17 years requiring continuous, around the clock opioid treatment. The available safety and efficacy data were inconclusive for chronic use of Oxymorphone Hydrochloride Extended-Release Tablets. Limited data from one of the studies suggested that Oxymorphone Hydrochloride Extended-Release Tablets is not recommended for post-surgical pain.

Of the total number of subjects in clinical studies of Oxymorphone Hydrochloride Extended-Release Tablets, 27% were 65 and over, while 9% were 75 and over. No overall differences in effectiveness were observed between these subjects and younger subjects. There were several adverse events that were more frequently observed in subjects 65 and over compared to younger subjects. These adverse events included dizziness, somnolence, confusion and nausea. On average, age greater than 65 years was associated with an increase in oxymorphone AUC and C_max. Initiate dosing with Oxymorphone Hydrochloride Extended-Release Tablets in patients 65 years of age and over using the 5 mg dose and frequently reevaluate the patient for signs of respiratory and central nervous system depression when initiating and titrating Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.2)]. For patients on prior opioid therapy, start at 50% of the starting dose for a younger patient on prior opioids and titrate slowly.

Oxymorphone is known to be substantially excreted by the kidney and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because the elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.

The efficacy and safety of Oxymorphone Hydrochloride Extended-Release Tablets have been evaluated in double-blind, controlled clinical trials in opioid-naïve and opioid-experienced patients with moderate to severe pain including low back pain.

Oxymorphone Hydrochloride Extended-Release Tablets are contraindicated in patients with:

• Significant respiratory depression [see Warnings and Precautions (5.3)]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.6)]
• Hypersensitivity (e.g. anaphylaxis) to oxymorphone, any other ingredients in Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.7), Adverse Reactions (6)].
• Moderate and severe hepatic impairment [see Warnings and Precautions (5.9),  Clinical Pharmacology (12.3)]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12)]

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 )]
• Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.3 )]
• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4)]
• Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions (5.6)]
• Anaphylaxis and Angioedema [see Warnings and Precautions (5.8 )]
• Adrenal Insufficiency [see Warnings and Precautions (5.9)]
• Severe Hypotension [see Warnings and Precautions (5.11)]
• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.13)] 
• Seizures [see Warnings and Precautions (5.14)]
• Withdrawal [see Warnings and Precautions (5.15)]

Table 5 includes clinically significant drug interactions with Oxymorphone Hydrochloride Extended-Release Tablets.

Table 5: Clinically Significant Drug Interactions with Oxymorphone Hydrochloride Extended-Release Tablets

Patients with moderate to severe renal impairment were shown to have an increase in oxymorphone bioavailability compared to the subjects with normal renal function [see Clinical Pharmacology (12.3)]. Start opioid-naïve patients with the 5 mg dose of Oxymorphone Hydrochloride Extended-Release Tablets and titrate slowly while closely regularly evaluate for respiratory and central nervous system depression [see Dosage and Administration (2.6)]. For patients on prior opioid therapy, start at 50% of the dose for a patient with normal renal function on prior opioids and titrate slowly.

CNS Depressant/Alcohol Interaction

Additive pharmacodynamic effects may be expected when Oxymorphone Hydrochloride Extended-Release Tablets are used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

Effects on the Central Nervous System

Oxymorphone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.

Oxymorphone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Effects on the Gastrointestinal Tract and on Other Smooth Muscle

Oxymorphone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.

Effects on the Cardiovascular System

Oxymorphone produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Release of histamine can occur and may contribute to opioid-induced hypotension. Manifestations of histamine release and/ or peripheral vasodilation may include pruritis, flushing, red eyes, sweating, and/or orthostatic hypotension.

Effects on the Endocrine System

Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions (6.2)]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.

Use of opioids for an extended period of time 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 [see Adverse Reactions (6.2)].

Effects on the Immune System

Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.

Concentration-Efficacy Relationships

The minimum effective plasma concentration of oxymorphone varies widely among patients, especially among patients who have been previously treated with opioid agonists. The minimum effective analgesic concentration of oxymorphone for any individual patient may increase over time due to an increase in pain, development of a new pain syndrome and/or development of analgesic tolerance [see Dosage and Administration (2.1, 2.3, 2.4)].

Concentration-Adverse Reaction Relationships

There is a relationship between increasing oxymorphone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see Dosage and Administration (2.1, 2.3, 2.4)] .

Patients with mild hepatic impairment have an increase in oxymorphone bioavailability compared to the subjects with normal hepatic function. In opioid-naïve patients with mild hepatic impairment, initiate Oxymorphone Hydrochloride Extended-Release Tablets using the 5 mg dose and regularly evaluate closely for respiratory and central nervous system depression. Oxymorphone Hydrochloride Extended-Release Tablets are contraindicated for patients with moderate and severe hepatic impairment [see Dosage and Administration (2.6), Contraindications (4) , Warnings and Precautions (5.9) and  Clinical Pharmacology (12.3)]. For patients on prior opioid therapy, start at the 50% of the dose for that a patient with normal hepatic function on prior opioids and titrate slowly.

Oxymorphone Hydrochloride Extended-Release Tablets are indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate.

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)]. Regularly evaluate these patients for signs of hypotension after initiating or titrating the dosage 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.

Oxymorphone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxymorphone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with oxymorphone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.

The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

Oxymorphone Hydrochloride Extended-Release Tablets contain oxymorphone, a Schedule II controlled substance.

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one 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.

• Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. (5.6)
• Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly Cachectic or Debilitated Patients: Regularly evaluate closely particularly during initiation and titration. (5.7) 
• Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions: If symptoms occur, stop administration immediately, discontinue permanently, and do not rechallenge with any other oxymorphone formulation. (5.8)
• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. (5.9)
• Severe Hypotension: Regularly evaluate during dose initiation and titration. Avoid use of oxymorphone hydrochloride extended-release tablets in patients with circulatory shock. (5.11)
• Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury or Impaired Consciousness: Monitor for sedation and respiratory depression. Avoid use of Oxymorphone Hydrochloride Extended-Release Tablets in patients with impaired consciousness or coma. (5.12)

• Oxymorphone Hydrochloride Extended-Release Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. (2.1) 
• Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of Oxymorphone Hydrochloride Extended-Release Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. (2.1, 5) 
• Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. (2.1, 5) 
• Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating. (2.1)
• Discuss availability of naloxone with the patient and caregiver and assess each patient’s need for access to naloxone, both when initiating and renewing treatment with Oxymorphone Hydrochloride Extended-Release Tablets. Consider prescribing naloxone based on the patient’s risk factors for overdose (2.2 , 5.1 , 5.2 , 5.3).
• For opioid-naïve and opioid non-tolerant patients, initiate treatment with 5 mg tablets orally every 12 hours. (2.3)
• To convert to Oxymorphone Hydrochloride Extended-Release Tablets from another opioid, use available conversion factors to obtain estimated dose. (2.3)
• Dose can be increased every 3 to 7 days, using increments of 5 mg to 10 mg every 12 hours (i.e., 10 mg to 20 mg per day). (2.4)
• Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. (2.5, 5.15) 
• Mild Hepatic Impairment: For opioid-naïve patients, initiate treatment with 5 mg and titrate slowly. For patients on prior opioid therapy, reduce starting dose by 50% and titrate slowly. Monitor for signs of respiratory and central nervous system depression. (2.6)  
• Renal Impairment: For opioid-naïve patients, initiate treatment with 5 mg and titrate slowly. For patients on prior opioid therapy, reduce starting dose by 50% and titrate slowly. Monitor for signs of respiratory and central nervous system depression. (2.7)
• Geriatric Patients: Initiate dosing with 5 mg, titrate slowly, and monitor for signs of respiratory and central nervous system depression. (2.8)

Oxymorphone Hydrochloride Extended-Release Tablets USP, 5 mg dosage form is a purple, round, film-coated extended-release tablet debossed with "G71" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 7.5 mg dosage form is a gray, round, film-coated extended-release tablet debossed with "G75" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 10 mg dosage form is an orange, round, film-coated extended-release tablet debossed with "G72" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 15 mg dosage form is a white, round, film-coated extended-release tablet debossed with "G76" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 20 mg dosage form is a green, round, film-coated extended-release tablet debossed with "G73" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 30 mg dosage form is a brown, round, film-coated extended-release tablet debossed with "G77" on one side and blank on the other side.

Oxymorphone Hydrochloride Extended-Release Tablets USP, 40 mg dosage form is an orange, round, film-coated extended-release tablet debossed with "G74" on one side and blank on the other side.

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 2 and 3 list the most frequently occurring adverse reactions (in at least 5% of patients) from the placebo-controlled trials in patients with low back pain.

The Table 4 lists adverse reactions that were reported in at least 2% of patients in placebo-controlled trials (N=5).

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.

The following adverse reactions have been identified during post approval use of opioids. 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: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Oxymorphone Hydrochloride Extended-Release Tablets.

Androgen deficiency: Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see Clinical Pharmacology (12)].

Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and  Precautions (5.6) ]

Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).

• Pregnancy: May cause fetal harm. (8.1)
• Lactation: Not recommended. (8.2)

Oxymorphone Hydrochloride Extended-Release Tablet contains, oxymorphone, a Schedule II controlled substance. As an opioid, Oxymorphone Hydrochloride Extended-Release Tablets exposes users to the risks of addiction, abuse, and misuse. Because extended-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 [see Drug Abuse and Dependence (9)].

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Oxymorphone Hydrochloride Extended-Release Tablets. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing Oxymorphone Hydrochloride Extended-Release Tablets and reassess all patients receiving Oxymorphone Hydrochloride Extended-Release Tablets for the development of these behaviors and conditions. Risks are 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). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids 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 frequent reevaluation for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2) and Warnings and Precautions (5.3)].

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)].

Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. 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 careful storage of the drug during the course of treatment and proper disposal of unused drug. 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.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Storage and Disposal

Because of the risks associated with accidental ingestion, misuse and abuse, advise patients to store Oxymorphone Hydrochloride Extended-Release Tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving Oxymorphone Hydrochloride Extended-Release Tablets unsecured can pose a deadly risk to others in the home [see Warnings and Precautions (5.1, 5.3) and Drug Abuse and Dependence (9.2)].

Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused Oxymorphone Hydrochloride Extended-Release Tablets should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.

Oxymorphone Hydrochloride Extended-Release Tablets, USP are supplied as follows:

5 mg

Purple, round, film-coated extended-release tablets debossed with "G71" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1231-08

Bottles of 60                                                  NDC 0115-1231-13

Bottles of 100                                                NDC 0115-1231-01

Bottles of 1,000                                             NDC 0115-1231-03

7.5 mg

Gray, round, film-coated extended-release tablets debossed with "G75" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1315-08

Bottles of 60                                                  NDC 0115-1315-13

Bottles of 100                                                NDC 0115-1315-01

Bottles of 1,000                                             NDC 0115-1315-03

10 mg

Orange, round, film-coated extended-release tablets debossed with "G72" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1232-08

Bottles of 60                                                  NDC 0115-1232-13

Bottles of 100                                                NDC 0115-1232-01

Bottles of 1,000                                             NDC 0115-1232-03

15 mg

White, round, film-coated extended-release tablets debossed with "G76" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1316-08

Bottles of 60                                                  NDC 0115-1316-13

Bottles of 100                                                NDC 0115-1316-01

Bottles of 1,000                                             NDC 0115-1316-03

20 mg

Green, round, film-coated extended-release tablets debossed with "G73" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1233-08

Bottles of 60                                                  NDC 0115-1233-13

Bottles of 100                                                NDC 0115-1233-01

Bottles of 1,000                                             NDC 0115-1233-03

30 mg

Brown, round, film-coated extended-release tablets debossed with "G77" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1317-08

Bottles of 60                                                  NDC 0115-1317-13

Bottles of 100                                                NDC 0115-1317-01

Bottles of 1,000                                             NDC 0115-1317-03

40 mg

Orange, round, film-coated extended-release tablets debossed with "G74" on one side and blank on the other side.

Bottles of 30                                                  NDC 0115-1234-08

Bottles of 60                                                  NDC 0115-1234-13

Bottles of 100                                                NDC 0115-1234-01

Bottles of 1,000                                             NDC 0115-1234-03



Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].



Dispense in tight container as defined in the USP, with a child-resistant closure (as required).



Store Oxymorphone Hydrochloride Extended-Release Tablets securely and dispose of properly [see Patient Counseling Information (17)].

Use of Oxymorphone Hydrochloride Extended-Release Tablets for an extended period of time during pregnancy can result in withdrawal 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. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for an extended period of time of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1) and Patient Counseling Information (17)].

Individually titrate Oxymorphone Hydrochloride Extended-Release Tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Oxymorphone Hydrochloride Extended-Release Tablets to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions as well as to reassess for the development of addiction, abuse, and misuse [see Warnings and Precautions (5.1, 5.15)]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During use of opioid therapy for an extended period of time, periodically reassess the continued need for the use of opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the Oxymorphone Hydrochloride Extended-Release Tablets dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3 days, Oxymorphone Hydrochloride Extended-Release Tablets dosage adjustments, preferably at increments of 5 mg to 10 mg every 12 hours, may be done every 3 to 7 days.

Patients who experience breakthrough pain may require a dose increase of Oxymorphone Hydrochloride Extended-Release Tablets, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing Oxymorphone Hydrochloride Extended-Release Tablets dose.

If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), the subsequent dose may be reduced [see Warnings and Precautions (5)]. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Serious, life-threatening, or fatal respiratory depression has been reported with the use of 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 (CO₂) 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. 

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 , 2.3) ]. Overestimating the Oxymorphone Hydrochloride Extended-Release Tablets dosage 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.

Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information (17)].

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.5)].

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with Oxymorphone Hydrochloride Extended-Release Tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see Patient Counseling Information (17)].

Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone [see Dosage and Administration (2.2), Warnings and Precautions (5.1, 5.3), Overdosage (10) and Patient Counseling Information (17)].

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 regularly evaluate for signs of respiratory and central nervous system depression [see Dosage and Administration (2.6)].

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.

Infertility

Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [Clinical Pharmacology (12.2) and Nonclinical Toxicology (13.1)].

The steady-state plasma concentrations of oxymorphone are higher in elderly subjects than in young subjects. Initiate dosing with Oxymorphone Hydrochloride Extended-Release Tablets in patients 65 years of age and over using the 5 mg dose and monitor closely for signs of respiratory and central nervous system depression when initiating and titrating Oxymorphone Hydrochloride Extended-Release Tablets to adequate analgesia [see Warnings and Precautions (5.3), Use in Specific Populations (8.5) and  Clinical Pharmacology (12.3)]. For patients on prior opioid therapy, start Oxymorphone Hydrochloride Extended-Release Tablets at 50% lower than the starting dose for a younger patient on prior opioids and titrate slowly.

Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect [see Dependence (9.3)]. Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior.

Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics. Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation (safely switching the patient to a different opioid moiety) [see Dosage and Administration (2.5); Warnings and  Precautions (5.15) ].

NDC 0115-1231-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 5 mg  CII 

Rx only

100 Tablets

NDC 0115-1232-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 10 mg  CII 

Rx only

100 Tablets

NDC 0115-1361-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 15 mg  CII 

Rx only

100 Tablets

NDC 0115-1233-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 20 mg  CII 

Rx only

100 Tablets

NDC 0115-1317-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 30 mg  CII 

Rx only

100 Tablets

NDC 0115-1234-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 40 mg  CII 

Rx only

100 Tablets

NDC 0115-1315-01

Twice-A-Day (every 12 hours)

Oxymorphone Hydrochloride Extended-Release Tablets 7.5 mg  CII 

Rx only

100 Tablets

Oxymorphone Hydrochloride Extended-Release Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks.

• Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions (5)]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of Oxymorphone Hydrochloride Extended-Release Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
• Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)].
• Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Oxymorphone Hydrochloride Extended-Release Tablets. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions (5)].

Instruct patients to swallow Oxymorphone Hydrochloride Extended-Release Tablets whole [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving Oxymorphone Hydrochloride Extended-Release Tablets will result in uncontrolled delivery of oxymorphone and can lead to overdose or death [see Warnings and Precautions (5.3)].

Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

Oxymorphone Hydrochloride Extended-Release Tablets are administered orally twice daily (every 12 hours).

In patients with creatinine clearance rates less than 50 mL/min, start Oxymorphone Hydrochloride Extended-Release Tablets in the opioid-naïve patient with the 5 mg dose. For patients on prior opioid therapy, start Oxymorphone Hydrochloride Extended-Release Tablets at 50% lower than the starting dose for a patient with normal renal function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.3) , Use in Specific Populations (8.7) and  Clinical Pharmacology (12.3)].

Oxymorphone Hydrochloride Extended-Release Tablets are contraindicated in patients with moderate or severe hepatic impairment.

In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose. For patients on prior opioid therapy, start Oxymorphone Hydrochloride Extended-Release Tablets at 50% lower than the starting dose for a patient with normal hepatic function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.3), Use in Specific Populations (8.6) and  Clinical Pharmacology (12.3)].

Oxymorphone Hydrochloride Extended-Release Tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. 

The oxymorphone in Oxymorphone Hydrochloride Extended-Release Tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Regularly evaluate patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

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)].

The oxymorphone in Oxymorphone Hydrochloride Extended-Release Tablets may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures occurring in other clinical settings associated with seizures. Regularly evaluate patients with a history of seizure disorders for worsened seizure control during Oxymorphone Hydrochloride Extended-Release Tablets therapy.

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

• Complete a REMS-compliant education program  offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
• Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG .
• Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
• Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities.

To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

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)].

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Oxymorphone Hydrochloride Extended-Release Tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions (7)].

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation).

If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2) and Warnings and Precautions (5.3)] .

Advise both patients and caregivers about the risks of respiratory depression and sedation when Oxymorphone Hydrochloride Extended-Release Tablets are used with benzodiazepine or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions (7) and  Patient Counseling Information (17)].

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.3) and Patient Counseling Information (17)].

Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program).

Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see Warnings and Precautions ( 5.1 , 5.3 , 5.5 )].

Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.

Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.

When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking Oxymorphone Hydrochloride Extended-Release Tablets, there are a variety of factors that should be considered, including the total daily dose of opioid (including Oxymorphone Hydrochloride Extended-Release Tablets) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist.

There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on Oxymorphone Hydrochloride Extended-Release Tablets who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.

It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.14) and Drug Abuse and Dependence (9.3)].

Addiction, Abuse, and Misuse

Because the use of Oxymorphone Hydrochloride Extended-Release Tablets exposes 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 and reassess all patients regularly for the development of these behaviors and 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, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of Oxymorphone Hydrochloride Extended-Release Tablets are essential [see Warnings and Precautions (5.2)]. Instruct patients to swallow Oxymorphone Hydrochloride Extended-Release tablets whole to avoid exposure to a potentially fatal dose of oxymorphone.

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)].

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 (5.3)].

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of Oxymorphone Hydrochloride Extended-Release Tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3), Drug Interactions (7)].

Neonatal Opioid Withdrawal Syndrome (NOWS)

If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions (5.4)].

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

Healthcare providers are strongly encouraged to complete a REMS compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings and Precautions (5.5)].

In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), Oxymorphone Hydrochloride Extended-Release Tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Regularly evaluate such patients for signs of sedation and respiratory depression, particularly when initiating therapy with Oxymorphone Hydrochloride Extended-Release Tablets.

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.

The use of Oxymorphone Hydrochloride Extended-Release Tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: Oxymorphone Hydrochloride Extended-Release Tablets treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.3)].

Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see Warnings and Precautions (5.3)].

Regularly evaluate patients, 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)  and  Drug Interactions (7)] . Alternatively, consider the use of non-opioid analgesics in these patients.