Oxymorphone hydrochloride extended-release tablets are a semi-synthetic opioid analgesic indicated for the relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for an extended period of time.
Oxymorphone hydrochloride extended-release tablets are contraindicated in patients who have:
- significant respiratory depression
- or are suspected of having paralytic ileus
- acute or severe bronchial asthma or hypercarbia
- moderate and severe hepatic impairment [see Clinical Pharmacology (12.3), Warnings and Precautions (5.7),].
- known hypersensitivity to any of its components or the active ingredient, oxymorphone or with known hypersensitivity to morphine analogs such as codeine.
See Boxed WARNINGS
Oxymorphone hydrochloride extended-release tablets are to be swallowed whole, and are not to be broken, chewed, crushed or dissolved. Taking broken, chewed, crushed or dissolved oxymorphone hydrochloride extended-release tablets could lead to the rapid release and absorption of a potentially fatal dose of oxymorphone [see Boxed Warning ].
Patients must not consume alcoholic beverages, or prescription or non-prescription medications 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 Pharmacokinetics (12.3) ].
Instruct patients against use by individuals other than the patient for whom oxymorphone hydrochloride extended-release tablets were prescribed, as such inappropriate use may have severe medical consequences, including death.
Respiratory depression is the chief hazard of oxymorphone hydrochloride extended-release tablets. Respiratory depression is a potential problem in elderly or debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.
Administer oxymorphone hydrochloride extended-release tablets with extreme caution to patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression or coma. In these patients, even usual therapeutic doses of oxymorphone may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Consider alternative non-opioid analgesics and use oxymorphone hydrochloride extended-release tablets only under careful medical supervision at the lowest effective dose in such patients.
Oxymorphone hydrochloride extended-release tablets contain oxymorphone, a mu opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine. Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Oxymorphone can be abused in a manner similar to other opioid agonists, legal or illicit. This issue should be considered when prescribing or dispensing oxymorphone in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
Oxymorphone hydrochloride extended-release tablets may be abused by crushing, chewing, snorting or injecting the product. These practices will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death [see Drug Abuse and Dependence (9)].
Oxymorphone hydrochloride extended-release tablets may be targeted for theft and diversion. Healthcare professionals should contact their State Medical Board, State Board of Pharmacy, or State Control Board for information on how to detect or prevent diversion of this product, and security requirements for storing and handling of oxymorphone hydrochloride extended-release tablets.
Healthcare professionals should advise patients to store oxymorphone hydrochloride extended-release tablets in a secure place, preferably locked and out of the reach of children and other non-caregivers.
Concerns about abuse, misuse, diversion and addiction should not prevent the proper management of pain.
Patients receiving other opioid analgesics, general anesthetics, phenothiazines or other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with oxymorphone may experience respiratory depression, hypotension, profound sedation, coma and death [see Drug Interactions (7.2)]. Avoid concurrent use of alcohol and oxymorphone hydrochloride extended-release tablets [see Pharmacokinetics (12.3)].
In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the possible respiratory depressant effects of opioid analgesics and their potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO2 retention) may be markedly exaggerated. Furthermore, opioid analgesics can produce effects on papillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries.
Administer oxymorphone hydrochloride extended-release tablets with extreme caution to patients who may be particularly susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted.
Oxymorphone hydrochloride extended-release tablets may cause severe hypotension in a patient whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents that compromise vasomotor tone. Administer oxymorphone hydrochloride extended-release tablets with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.
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)]. Use oxymorphone hydrochloride extended-release tablets with caution in patients with mild impairment, starting with the lowest dose and titrating slowly while carefully monitoring for side effects [see Dosage and Administration (2.3)]. Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with moderate or severe hepatic impairment.
Use oxymorphone hydrochloride extended-release tablets with caution in the following conditions: adrenocortical insufficiency (e.g., Addison’s disease), prostatic hypertrophy or urethral stricture, severe impairment of pulmonary or renal function, and toxic psychosis.
Opioids may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings.
Oxymorphone hydrochloride extended-release decreases bowel motility. Opioids diminish propulsive peristaltic waves in the gastrointestinal tract. Monitor for decreased bowel motility in post-operative patients receiving opioids. The administration of oxymorphone hydrochloride extended-release may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with paralytic ileus.
Oxymorphone hydrochloride extended-release tablets are not indicated for pre-emptive analgesia (administration pre-operatively for the management of post-operative pain).
Oxymorphone hydrochloride extended-release tablets are only indicated for postoperative use in the patient if the patient is already receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time. Physicians should individualize treatment, moving from parenteral to oral analgesics as appropriate (see American Pain Society guidelines).
Patients who are already receiving oxymorphone hydrochloride extended-release tablets as part of ongoing analgesic therapy may be safely continued on the drug if appropriate dosage adjustments are made considering the procedure, other drugs given, and the temporary changes in physiology caused by the surgical intervention.
Oxymorphone hydrochloride extended-release tablets, like other opioids, may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis.
Opioid analgesics impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
The following serious adverse reactions are discussed elsewhere in the labeling:
- Respiratory depression [see Warnings and Precautions (5.2)]
- Misuse and abuse [see Warning and Precautions (5.3) and Drug Abuse and Dependence (9)]
- CNS depressant effects [see Warnings and Precautions (5.4)]
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 controlled clinical trials. The clinical trials consisted of patients with moderate to severe chronic non-malignant pain, cancer pain, and post surgical pain.
Tables 1 and 2 list the most frequently occurring adverse reactions (in at least 5% of patients) from the placebo-controlled trials in patients with low back pain.
|Titration Period||Treatment Period|
|Preferred Term||(N = 325)||(N = 105)||(N = 100)|
|Open-Label Titration Period||Double-Blind Treatment Period|
|Preferred Term||(N = 250)||(N = 70)||(N = 72)|
The following table lists adverse reactions that were reported in at least 2% of patients in placebo-controlled trials (N=5).
|MedDRA Preferred Term||Oxymorphone Hydrochloride|
|Dizziness (Excl Vertigo)||18%||8%|
The common (≥1% to <10%) adverse drug reactions reported at least once by patients treated with oxymorphone hydrochloride extended-release tablets in the clinical trials organized by MedDRA’s (Medical Dictionary for Regulatory Activities) System Organ Class and not represented in Table 1 were:
Eye disorders: vision blurred
Gastrointestinal disorders: diarrhea, abdominal pain, dyspepsia
General disorders and administration site conditions: dry mouth, appetite decreased, fatigue, lethargy, weakness, pyrexia, dehydration, weight decreased, edema
Nervous system disorders: insomnia
Psychiatric disorders: anxiety, confusion, disorientation, restlessness, nervousness, depression
Respiratory, thoracic and mediastinal disorders: dyspnea
Vascular disorders: flushing and hypertension
Other less common adverse reactions known with opioid treatment that were seen <1% in the oxymorphone hydrochloride extended-release tablets trials include the following: Bradycardia, palpitation, syncope, tachycardia, postural hypotension, miosis, visual disturbance, abdominal distention, ileus, feeling jittery, hot flashes, allergic reactions, hypersensitivity, urticaria, oxygen saturation decreased, central nervous system depression, depressed level of consciousness, agitation, dysphoria, euphoric mood, hallucination, mental impairment, mental status changes, difficult micturition, urinary retention, hypoxia, respiratory depression, respiratory distress, respiratory rate decreased, clamminess, dermatitis, hypotension.