OPANA 40mg.

BOXED WARNING

Oxymorphone is an opioid agonist and therefore has abuse potential and risk of fatal overdose from respiratory failure. Addiction may occur in patients who obtain oxymorphone illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. To discourage abuse, the smallest appropriate quantity of oxymorphone should be dispensed, and proper disposal instructions for unused drug should be given to patients.

Oxymorphone is contraindicated in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) in unmonitored care settings or in the absence of resuscitative equipment. Receipt of moderate oxymorphone doses in these patients may significantly decrease pulmonary ventilation. Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if concurrent use is necessary, use the lowest effective dosages and minimum treatment durations needed. Monitor patients closely for signs or symptoms of respiratory depression and sedation. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to oxymorphone, as even usual therapeutic doses of oxymorphone may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with oxymorphone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. Oxymorphone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a “sighing” breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxymorphone. In animal studies with rats and rabbits, reduced fetal weight was noted when oxymorphone was given during organogenesis at doses up to 4.9- and 48.8-times the adult human dose of 20 mg/day based on body surface area, respectively. In a pre- and post-natal study in rats, oxymorphone given during gestation and lactation at a dose approximately 2.4-times an adult human dose of 20 mg/day was associated with increased neonatal death (postnatal day 0 to 1). Decreased pup survival over the first week of life, reduced pup birth weight, and reduced postnatal weight gain occurred with doses 4.9-times the adult human dose. Oxymorphone is not recommended for use in women during and immediately prior to labor and obstetric delivery as opioid agonists may cause respiratory depression in the newborn. Oxymorphone can prolong the duration of labor by temporarily reducing the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation. Further, prolonged maternal use of opioids, such as oxymorphone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.

Like all opioid analgesics, oxymorphone is associated with significant potential for overdose or poisoning; proper patient selection and counseling is recommended. Extended-release oxymorphone is not intended for use in the management of pain following surgery, acute pain, or on an as-needed basis; it is intended only for patients requiring continuous, around-the-clock opioid analgesia for an extended period of time and requires an experienced clinician who is knowledgeable in the use of long-acting opioids for the management of chronic pain. Further, the misuse of oxymorphone tablets by crushing, chewing, snorting, or injecting the dissolved product (parenteral administration) poses a significant risk to the abuser and may result in overdose and death. Cases of thrombotic microangiopathy, many requiring hospitalization and plasmapheresis therapy, have been reported with parenteral abuse. Parenteral drug abuse is commonly associated with transmission of infectious diseases including hepatitis and HIV. Oxymorphone should be kept out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure or improper use may cause respiratory failure and a fatal overdose. Consumption with ethanol will result in additive CNS depressant effects. Advise patients to avoid ethanol ingestion and ethanol intoxication, including the ingestion of alcohol contained in prescription or non-prescription medications, during therapy.

DEA CLASS

Rx, schedule II

DESCRIPTION

Semi-synthetic opiate agonist
Used for the relief of moderate to severe acute and chronic pain
Available in multiple formulations

COMMON BRAND NAMES

Opana

HOW SUPPLIED

Opana/Oxymorphone/Oxymorphone Hydrochloride Oral Tab ER: 5mg, 7.5mg, 10mg, 15mg, 20mg, 30mg, 40mg
Opana/Oxymorphone/Oxymorphone Hydrochloride Oral Tab: 5mg, 10mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

With appropriate dosage titration, there is no maximum dose of oxymorphone.

With appropriate dosage titration, there is no maximum dose of oxymorphone.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Oxymorphone is contraindicated in patients with moderate and severe hepatic dysfunction.
Use oxymorphone cautiously in patients with mild hepatic impairment:
Immediate-release tablets and parenteral dosage forms: Start at the lowest dose (e.g., 5 mg PO) and titrate slowly while carefully monitoring for respiratory or CNS depression.
Extended-release tablets: For opioid-naive patients, start with the 5 mg PO dose. For patients previously on other opioids, start oxymorphone at 50% lower than the starting dose for a patient with normal hepatic function on prior opioids. Titrate slowly and monitor patients for respiratory or CNS depression.

CrCl less than 50 mL/minute:
Immediate-release tablets and parenteral dosage forms: Use with caution. Start at the lowest dose (e.g., 5 mg PO) and titrate slowly while carefully monitoring for respiratory or CNS depression.
Extended-release tablets: For opioid-naive patients, start with the 5 mg PO dose. For patients previously on other opioids, start oxymorphone at 50% lower than the starting dose for a patient with normal renal function on prior opioids. Titrate slowly and monitor patients for respiratory or CNS depression.

ADMINISTRATION

Whether administering the extended-release or the immediate-release tablets, administer on an empty stomach either 1 hour before or 2 hours after eating.

Visually inspect for particulate matter and discoloration before administration whenever solution and container permit.
Parenteral oxymorphone should generally be administered by trained personnel.
For intravenous, intramuscular, or subcutaneous administration only.

Instruct patient on proper use of suppository (see Patient Information) and to avoid excessive handling of the suppository.

STORAGE

Numorphan:
– Refrigerate (between 36 and 46 degrees F)
Opana:
– Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

Although true opioid agonist hypersensitivity is rare, the use of oxymorphone is contraindicated in patients with oxymorphone hypersensitivity. Some oxymorphone formulations may contain lactose. Patients with lactase deficiency should take appropriate precautions with use.

Oxymorphone is an opioid agonist and therefore has abuse potential and risk of fatal overdose from respiratory failure. Addiction may occur in patients who obtain oxymorphone illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. To discourage abuse, the smallest appropriate quantity of oxymorphone should be dispensed, and proper disposal instructions for unused drug should be given to patients.

Oxymorphone is contraindicated in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) in unmonitored care settings or in the absence of resuscitative equipment. Receipt of moderate oxymorphone doses in these patients may significantly decrease pulmonary ventilation. Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if concurrent use is necessary, use the lowest effective dosages and minimum treatment durations needed. Monitor patients closely for signs or symptoms of respiratory depression and sedation. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to oxymorphone, as even usual therapeutic doses of oxymorphone may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with oxymorphone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. Oxymorphone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a “sighing” breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

Abrupt discontinuation of prolonged oxymorphone therapy can result in withdrawal symptoms. Gradually taper patients off prolonged oxymorphone therapy to avoid a withdrawal reaction. Generally, oxymorphone therapy can be decreased by 25% to 50% every 2 to 4 days with careful monitoring. Avoid use of partial agonists (e.g., buprenorphine), mixed agonist/antagonists (e.g., nalbuphine), or pure antagonists (e.g., naloxone) in patients physically dependent on opioids, as an acute withdrawal syndrome may precipitate. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and on the administered dose of the concomitant drug. If treatment of respiratory depression in an individual physically dependent on opioids is necessary, administer the opioid antagonist with extreme care; titrate the antagonist dose by using smaller than usual doses. In addition, the use of partial agonists or mixed agonist/antagonists in patients who have received or are receiving oxymorphone should be avoided as these medications may reduce the analgesic effect of oxymorphone.

Oxymorphone is contraindicated in patients with known or suspected GI obstruction, including paralytic ileus. Due to the effects of opioid agonists on the gastrointestinal tract, oxymorphone should be used cautiously in patients with GI disease such as ulcerative colitis (UC). Patients with UC or other inflammatory bowel disease may be more sensitive to constipation caused by opioid agonists. Opioid agonists may obscure the diagnosis or clinical course in patients with acute abdomen. Consider use of an alternative analgesic to oxymorphone extended-release tablets in patients with dysphagia and patients at risk for underlying GI disorders resulting in a small GI lumen as there are postmarketing reports of choking, gagging, regurgitation, tablets getting stuck in the throat, and intestinal obstruction. Opioid agonists may complicate cases of diarrhea secondary to poisoning or infectious diarrhea, as a reduction in GI motility may occur with use. Antimotility agents have been used successfully in these patients. If possible, opioid agonists should not be given until the toxic substance has been eliminated.

As with other opioid agonists, oxymorphone may cause spasm of the sphincter of Oddi. Biliary effects due to opioid agonists have resulted in increased serum amylase concentrations. Oxymorphone should be used with caution in patients with biliary tract disease, including pancreatitis, or undergoing biliary tract surgery.

Use oxymorphone with caution in patients with CNS depression, toxic psychosis, head trauma, intracranial mass, or increased intracranial pressure. Monitor for signs of drowsiness and depressed respirations, particularly when initiating oxymorphone. Opioids may aggravate such conditions and alter neurologic parameters (e.g., level of consciousness, pupillary responses). Oxymorphone-induced hypoventilation can produce cerebral hypoxia, carbon dioxide retention, and raise CSF pressure. Avoid the use of oxymorphone in patients with impaired consciousness.

Opioid agonists, such as oxymorphone, produce cholinergic side effects (by stimulating medullary vagal nuclei) causing bradycardia and vasovagal syncope, and induce the release of histamine. In patients who are unable to maintain blood pressure due to hypovolemia or dehydration, or who concurrently receive other agents that compromise vasomotor tone (e.g., phenothiazines or general anesthetics), opioid agonists may induce peripheral vasodilatation and severe hypotension. These effects can cause problems in patients with cardiac disease (e.g., angina, heart failure). Oxymorphone should be used with caution in patients with cardiac arrhythmias or orthostatic hypotension. Oxymorphone should not be used in patients with circulatory shock.

Oxymorphone is contraindicated in patients with moderate or severe hepatic disease. Use oxymorphone cautiously in patients with mild hepatic impairment; start with the lowest dose and slowly titrate the dose while carefully monitoring for side effects. Greater oxymorphone plasma concentrations were observed in patients with hepatic disease compared to those with normal hepatic function.

Patients with moderate to severe renal impairment have been shown to have an increase in oxymorphone bioavailability. Use oxymorphone cautiously in patients with moderate to severe renal impairment; start with the lowest dose and slowly titrate the dose while carefully monitoring for side effects. Oxymorphone can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with prostatic hypertrophy, urethral stricture, bladder obstruction, pelvic tumors, or renal disease.

Neonates and infants < 6 months of age have highly variable clearance of opiate agonists. Therefore, infants younger than 6 months of age may be given opiate agonists but must be closely monitored for apnea until 24 hours after their last dose. Clinical practice guidelines suggest close monitoring of children up to 1 year of age. The safety and effectiveness of oxymorphone in neonates, infants, children, and adolescents have not been established.

Use oxymorphone with caution in geriatric or debilitated patients. Geriatric patients are more sensitive to the analgesic effects of oxymorphone, as they experience higher peak serum concentrations and a longer duration of pain relief. The plasma concentrations of oxymorphone are about 40% higher in patients 65 years of age and older as compared with younger adult patients. Sedation and respiratory depression may result from altered distribution or decreased elimination of the drug. Dizziness, somnolence, confusion, and nausea were more frequently observed in subjects 65 years of age and over compared to younger subjects during clinical studies. Initial doses may need to be reduced, and doses should be carefully titrated taking into account analgesic effects, adverse reactions, and concomitant drugs that may depress respiration. When using the extended-release tablets, initiate therapy using the 5 mg dose in opioid-naive geriatric patients; start geriatric patients on prior opioid therapy at 50% of the starting dose for a younger patient previously on opioids. According to the Beers Criteria, opiate agonists are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, with the exception of pain management due to recent fractures or joint replacement, since opiates can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an opiate must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Individuals receiving palliative care or those in hospice settings are excluded from the Beers Criteria; the balance of benefits and harms of medication management for these patients may differ from those of the general population of older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The Guidelines caution that opioids may cause constipation, nausea, vomiting, sedation, lethargy, weakness, confusion, dysphoria, physical and psychological dependency, hallucinations, and unintended respiratory depression, especially in individuals with compromised pulmonary function. These adverse effects can lead to other consequences such as falls. In addition, the initiation of longer-acting opioids (e.g., extended-release oxymorphone) is not recommended unless shorter-acting opioids have been unsuccessful, or titration of shorter-acting doses has established a clear daily dose of opioid analgesic that can be provided by using a long-acting form.

Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxymorphone. In animal studies with rats and rabbits, reduced fetal weight was noted when oxymorphone was given during organogenesis at doses up to 4.9- and 48.8-times the adult human dose of 20 mg/day based on body surface area, respectively. In a pre- and post-natal study in rats, oxymorphone given during gestation and lactation at a dose approximately 2.4-times an adult human dose of 20 mg/day was associated with increased neonatal death (postnatal day 0 to 1). Decreased pup survival over the first week of life, reduced pup birth weight, and reduced postnatal weight gain occurred with doses 4.9-times the adult human dose. Oxymorphone is not recommended for use in women during and immediately prior to labor and obstetric delivery as opioid agonists may cause respiratory depression in the newborn. Oxymorphone can prolong the duration of labor by temporarily reducing the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation. Further, prolonged maternal use of opioids, such as oxymorphone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.

There is no information available on the presence of oxymorphone in human milk, the effects on milk production, or the effects on the breast-fed infant. Because many drugs, including some opioids, are excreted in human milk, caution should be exercised when oxymorphone is administered to a woman who is breast-feeding because of the possibility of sedation, respiratory depression, and death in the infant. Non-opioid analgesics are preferred for pain control during breast-feeding. If breast-feeding continues during oxymorphone therapy, use lowest maternal dose and shortest duration possible to achieve the intended effect. The infant should be observed for possible sedation, respiratory depression, and changes in feeding patterns. Withdrawal symptoms may occur in infants whose mothers discontinue chronic opioid therapy. Alternative analgesics considered to be usually compatible with breast-feeding by previous American Academy of Pediatrics recommendations include acetaminophen, ibuprofen, and morphine.

Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression) and pose a reproductive risk. Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence, amenorrhea, or infertility. It is not known whether the effects on fertility are reversible. Monitor patients for symptoms of opioid-induced endocrinopathy. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.

Oxymorphone may impair the mental or physical abilities needed to perform potentially hazardous activities like driving a car or operating machinery. Advise any patient receiving oxymorphone to avoid driving or operating machinery unless they are tolerant to the effects of oxymorphone and know how the medication affects them.

Use oxymorphone with caution in patients with adrenal insufficiency (i.e., Addison’s disease), hypothyroidism, or myxedema. Such patients may be at increased risk of adverse events. Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH); however, the thyroid stimulating hormone may be either stimulated or inhibited by opioids. Rarely, adrenal insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency. In addition, chronic opioid use may lead to symptoms of hypogonadism, resulting from changes in the hypothalamic-pituitary-gonadal axis. Monitor patients for symptoms of opioid-induced endocrinopathy, particularly those receiving a daily dose equivalent to 100 mg or more of morphine. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.

Seizures can be precipitated by opioid agonists in patients with a preexisting seizure disorder. The incidence of these effects during oxymorphone therapy is not known, but appears to be rare at normal doses. Monitor patients with a history of seizure disorders for worsened seizure control during therapy.

Like all opioid analgesics, oxymorphone is associated with significant potential for overdose or poisoning; proper patient selection and counseling is recommended. Extended-release oxymorphone is not intended for use in the management of pain following surgery, acute pain, or on an as-needed basis; it is intended only for patients requiring continuous, around-the-clock opioid analgesia for an extended period of time and requires an experienced clinician who is knowledgeable in the use of long-acting opioids for the management of chronic pain. Further, the misuse of oxymorphone tablets by crushing, chewing, snorting, or injecting the dissolved product (parenteral administration) poses a significant risk to the abuser and may result in overdose and death. Cases of thrombotic microangiopathy, many requiring hospitalization and plasmapheresis therapy, have been reported with parenteral abuse. Parenteral drug abuse is commonly associated with transmission of infectious diseases including hepatitis and HIV. Oxymorphone should be kept out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure or improper use may cause respiratory failure and a fatal overdose. Consumption with ethanol will result in additive CNS depressant effects. Advise patients to avoid ethanol ingestion and ethanol intoxication, including the ingestion of alcohol contained in prescription or non-prescription medications, during therapy.