Dosage Form: tablet, extended release
FULL PRESCRIBING INFORMATION
Potential for Abuse
Opana ER contains oxymorphone, which is a morphine-like opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. (9)
Oxymorphone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Opana ER in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. (9.2)
Proper Patient Selection
Opana ER is an extended-release oral formulation of oxymorphone indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. (1)
Limitations of Use
Opana ER is NOT intended for use as an as needed analgesic. (1)
Opana ER tablets are to be swallowed whole and are not to be cut, broken, chewed, dissolved, or crushed. Taking cut, broken, chewed, dissolved, or crushed Opana ER tablets leads to rapid release and absorption of a potentially fatal dose of oxymorphone. (2)
Patients must not consume alcoholic beverages, or prescription or non-prescription medications containing alcohol, while on Opana ER therapy. The co-ingestion of alcohol with Opana ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone. (2 )
Indications and Usage for Opana ER
Opana ER is indicated for the relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for an extended period of time.
Limitations of Usage
Opana ER is not intended for use as an as needed analgesic.
Opana ER is not indicated for pain in the immediate post-operative period if the pain is mild, or not expected to persist for an extended period of time.
Opana ER is only indicated for post-operative use if the patient is already receiving the drug prior to surgery or if the post-operative pain is expected to be moderate or 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).
Opana ER Dosage and Administration
Safe Administration Instructions
Opana ER tablets must be swallowed whole and are not to be cut, broken, chewed, dissolved, or crushed. Taking cut, broken, chewed, dissolved, or crushed Opana ER tablets leads to rapid release and absorption of a potentially fatal dose of oxymorphone.
Patients must not consume alcoholic beverages, or prescription or non-prescription medications containing alcohol, while on Opana ER therapy. The co-ingestion of alcohol with Opana ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone.
Opana ER tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)].
Opana ER must be taken on an empty stomach, at least one hour prior to or two hours after eating [see Clinical Pharmacology (12.3)].
While symmetric (same dose AM and PM), around-the-clock, every 12 hours dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different dose given in AM than in PM) dosing, tailored to their pain pattern. It is usually appropriate to treat a patient with only one extended-release opioid for around-the-clock therapy.
Selection of patients for treatment with Opana ER should be governed by the same principles that apply to the use of other extended-release opioid analgesics [see Indications and Usage (1)]. Physicians should individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis, combination products, and chronic opioid therapy in a progressiveplan of pain management such as outlined by the World Health Organization, the American Pain Society and the Federation of State Medical Boards Model Guidelines. Healthcare professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring [see Boxed Warning].
Initiating Therapy with Opana ER
It is necessary to adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. In the selection of the initial dose of Opana ER, attention should be given to the following:
- total daily dose, potency and specific characteristics of the opioid the patient has been taking previously;
- relative potency estimate used to calculate the equivalent oxymorphone dose needed;
- patient’s degree of opioid tolerance;
- age, general condition, and medical status of the patient;
- concurrent non-opioid analgesics and other medications;
- type and severity of the patient’s pain;
- balance between pain control and adverse experiences;
- risk factors for abuse or addiction, including a prior history of abuse or addiction.
Once therapy is initiated, frequently assess pain relief and other opioid effects. Base the titration of the total daily Opana ER dose upon the amount of supplemental opioid utilization, severity of the patient’s pain, and the patient’s ability to tolerate the opioid. Titrate dose to generally mild or no pain with the regular use of no more than two doses of supplemental analgesia, i.e. “rescue,” per 24 hours, and tolerable side effects. Patients who experience breakthrough pain may require dosage adjustment.
If signs of excessive opioid-related adverse experiences are observed, the next dose may be reduced. If this adjustment leads to inadequate analgesia, a supplemental dose of immediate-release opioid, or a non-opioid analgesic may be administered. Adjust dosing to obtain an appropriate balance between pain relief and opioid-related adverse experiences. If significant adverse events occur before the therapeutic goal of mild or no pain is achieved, the events should be treated aggressively. If adverse events are adequately managed, continue upward titration to an acceptable level of pain control.
During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient and the caregiver/family. Advise patients and caregivers/family members of the potential adverse reactions.
The dosing recommendations below, therefore, can only be considered as suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.
Titrate dose to adequate pain relief (generally mild or no pain).
Opioid-Naïve Patients
The initial dose for patients who are not opioid-experienced and who are being initiated on chronic around-the-clock opioid therapy with Opana ER is 5 mg every 12 hours. Thereafter, titrate the dose individually at increments of 5-10 mg every 12 hours every 3-7 days, to a level that provides adequate analgesia and tolerable side effects under the close supervision of the prescribing physician.
Opioid-Experienced Patients
Conversion from OPANA to Opana ER
Patients receiving OPANA may be converted to Opana ER by administering half the patient's total daily oral OPANA dose as Opana ER, every 12 hours.
Conversion from Parenteral Oxymorphone to Opana ER
Given Opana ER’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to Opana ER by administering 10 times the patient's total daily parenteral oxymorphone dose as Opana ER in two equally divided doses (e.g., [IV dose x 10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.
Conversion from Other Oral Opioids to Opana ER
For conversion from other opioids to Opana ER, physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion ratios are only approximate.
The following table provides approximate equivalent doses, which may be used as a guideline for conversion. The conversion ratios and approximate equivalent doses in this conversion table are only to be used for the conversion from current opioid therapy to Opana ER.
- In general, it is safest to start the Opana ER therapy by administering 50% of the calculated total daily dose, calculated below, of Opana ER (see conversion ratio table below) in 2 divided doses, every 12 hours. Gradually adjust the initial dose of Opana ER until adequate pain relief and acceptable side effects have been achieved.
Calculating the total daily dose of Opana ER:
Step 1 Calculate the total daily dose of the opioid.
Step 2 Multiply the total daily dose for the opioid by the conversation ratio in Table 1 to calculate the total daily oxymorphone dose.
Table 1: Oral Opioid Conversion Ratios to Opana ER
Oral Opioid | Oral Conversion Ratio |
Oxymorphone | 1 |
Hydrocodone | 0.5 |
Oxycodone | 0.5 |
Methadone a | 0.5 |
Morphine | 0.333 |
Step 3 Adjust the total daily dose of oxymorphone for the individual patient.
Step 4 Divide the total daily oxymorphone dose in half to determine the Opana ER dose to be administered every 12 hours.
- For patients on a regimen of mixed opioids, calculate the approximate oral oxymorphone dose for each opioid, sum the totals, and divide in half to estimate the total daily oxymorphone dose.
- The dose of Opana ER can be gradually adjusted, preferably at increments of 10 mg every 12 hours every 3-7 days, until adequate pain relief and acceptable side effects have been achieved [see Dosage and Administration (2.1)].
aIt is extremely important to monitor all patients closely when converting from methadone to other opioid agonists including Opana ER. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and accumulates in the plasma.
No dose adjustment for CYP 3A4 or 2C9 mediated drug-drug interactions is required [see Clinical Pharmacology (12.3)].
Patients with Hepatic Impairment
Start patients with mild hepatic impairment with the lowest dose and titrated slowly while carefully monitoring side effects. Opana ER is contraindicated in patients with moderate or severe hepatic impairment [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)].
Patients with Renal Impairment
There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively [see Clinical Pharmacology (12.3)]. Accordingly, in patients with creatinine clearance rates less than 50 mL/min, start Opana ER with the lowest dose and titrate slowly while carefully monitoring side effects.
Use with Central Nervous System Depressants
In patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, start Opana ER at 1/3 to 1/2 of the usual dose because respiratory depression, hypotension, and profound sedation, coma or death may result [see Warnings and Precautions (5.4) and Drug Interactions (7.2)].
Although no specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, Opana ER is not recommended for use in patients who have received MAO inhibitors within 14 days [see Drug Interactions (7.6)].
Geriatric Patients
The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects. Exercise caution in the selection of the starting dose of Opana ER for an elderly patient by starting at the low end of the dosing range and slowly titrating to adequate analgesia [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.5)].
Maintenance of Therapy
During chronic therapy with Opana ER, periodically reassess the continued need for around-the-clock opioid therapy. Continue to assess patients for their clinical risks for opioid abuse, addiction, or diversion particularly with high-dose formulations. If patients need to titrate while on maintenance therapy, follow the same method outlined in Initiating Therapy with Opana ER .
Cessation of Therapy
When the patient no longer requires therapy with Opana ER tablets, gradually taper doses to prevent signs and symptoms of withdrawal in the physically dependent patient.
Dosage Forms and Strengths
The 5 mg dosage form is a pink, round, film-coated, biconvex extended-release tablet debossed with an “E” on one side and a “5” on the other side.
The 7.5 mg dosage form is a gray, round, film-coated, biconvex extended-release tablet debossed with an “E” on one side and a “7 ½” on the other side.
The 10 mg dosage form is a light orange, round, film-coated, biconvex extended-release tablet debossed with an “E” on one side and a “10” on the other side.
The 15 mg dosage form is a white, round, film-coated, biconvex extended-release tablet debossed with an “E” on one side and a “15” on the other side.
The 20 mg dosage form is a light green, round, film-coated, biconvex extended-release tablet debossed with an “E” on one side and a “20” on the other side.
The 30 mg dosage form is a red, round, film-coated, biconvex extended-release tablet debossed with an “E” on one side and a “30” on the other side.
The 40 mg dosage form is a light yellow to pale yellow, round, film-coated, biconvex extended-release tablet debossed with an “E” on one side and a “40” on the other side.
Contraindications
Opana ER is contraindicated in patients who have:
- known hypersensitivity to any of its components or the active ingredient, oxymorphone or with known hypersensitivity to morphine analogs such as codeine.
- significant respiratory depression
- acute or severe bronchial asthma or hypercarbia
- or are suspected of having paralytic ileus
- moderate and severe hepatic impairment [see Clinical Pharmacology (12.3), Warnings and Precautions (5.7)].
Warnings and Precautions
Information Essential for Safe Administration
Opana ER tablets are to be swallowed whole, and are not to be cut, broken, chewed, crushed or dissolved. Taking cut, broken, chewed, dissolved, or crushed Opana ER 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 Opana ER therapy. The co-ingestion of alcohol with Opana ER 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 Opana ER was prescribed, as such inappropriate use may have severe medical consequences, including death.
Respiratory Depression
Respiratory depression is the chief hazard of Opana ER. 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 Opana ER 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 Opana ER only under careful medical supervision at the lowest effective dose in such patients.
Misuse, Abuse and Diversion of Opioids
Opana ER contains 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.
Opana ER tablets may be abused by crushing, chewing, snorting or injecting the product. These practices will result in the less controlled 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)].
Opana ER 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 Opana ER.
Healthcare professionals should advise patients to store Opana ER 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.
Interactions with Alcohol and other CNS Depressants
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 Opana ER [see Pharmacokinetics (12.3)].
Use in Patients with Head Injury and Increased Intracranial Pressure
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 Opana ER 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.
Hypotensive Effect
Opana ER 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 Opana ER with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.
Hepatic Impairment
A study of oxymorphone hydrochloride extended-release tablets in patients with hepatic disease indicated greater plasma concentrations than those with normal hepatic function [see Clinical Pharmacology (12)]. Use Opana ER 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)]. Opana ER is contraindicated in patients with moderate or severe hepatic impairment.
Special Risk Groups
Use Opana ER 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.
Gastrointestinal Effects
Opana ER 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 Opana ER may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Opana ER is contraindicated in patients with paralytic ileus.
Ambulatory Surgery and Post-Operative Use
Opana ER is not indicated for pre-emptive analgesia (administration pre-operatively for the management of post-operative pain).
Opana ER is 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 Opana ER 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.
Use in Pancreatic/Biliary Tract Disease
Opana ER, 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.
Driving and Operating Machinery
Opioid analgesics, including Opana ER, may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
Adverse Reactions
The following serious adverse reactions are discussed elsewhere in the labeling:
- Respiratory depression [see Warnings and Precautions (5.2)]
- Misuse and abuse [see Warnings and Precautions (5.3) and Drug Abuse and Dependence (9)]
- CNS depressant effects [see Warnings and Precautions (5.4)]
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of oxymorphone hydrochloride extended-release tablets was evaluated in a total of 2011 patients in 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.
Table 1:Treatment-Emergent Adverse Events Reported in ≥5% of Patients During the Open-Label Titration Period and Double-Blind Treatment Period by Preferred Term —Number (%) of Treated Patients (12-Week Study In Opioid-Naïve Patients with Low Back Pain) | |||
Open-Label Titration Period | Double-Blind Treatment Period | ||
Oxymorphone Hydrochloride Extended-Release Tablets | Oxymorphone Hydrochloride Extended-Release Tablets | Placebo | |
Preferred Term | (N = 325) | (N = 105) | (N = 100) |
Constipation | 26% | 7% | 1% |
Somnolence | 19% | 2% | 0% |
Nausea | 18% | 11% | 9% |
Dizziness | 11% | 5% | 3% |
Headache | 11% | 4% | 2% |
Pruritus | 7% | 3% | 1% |
Table 2. Treatment-Emergent Adverse Events Reported in ≥5% of Patients During the Open-Label Titration Period and Double-Blind Treatment Period by Preferred Term —Number (%) of Treated Patients (12-Week Study In Opioid-Experienced Patients with Low Back Pain) | |||
Open-Label Titration Period | Double-Blind Treatment Period | ||
Oxymorphone Hydrochloride Extended-Release Tablets | Oxymorphone Hydrochloride Extended-Release Tablets | Placebo | |
Preferred Term | (N = 250) | (N = 70) | (N = 72) |
Nausea | 20% | 3% | 1% |
Constipation | 12% | 6% | 1% |
Headache | 12% | 3% | 0% |
Somnolence | 11% | 3% | 0% |
Vomiting | 9% | 0% | 1% |
Pruritus | 8% | 0% | 0% |
Dizziness | 6% | 0% | 0% |
The following table lists adverse reactions that were reported in at least 2% of patients in placebo-controlled trials (N=5).
Table 3: Adverse Reactions Reported in Placebo-Controlled Clinical Trials with Incidence ≥2% in Patients Receiving Oxymorphone Hydrochloride Extended-Release Tablets | ||
MedDRA Preferred Term | Oxymorphone Hydrochloride Extended-Release Tablets | Placebo |
Nausea | 33% | 13% |
Constipation | 28% | 13% |
Dizziness (Excl Vertigo) | 18% | 8% |
Somnolence | 17% | 2% |
Vomiting | 16% | 4% |
Pruritus | 15% | 8% |
Headache | 12% | 6% |
Sweating increased | 9% | 9% |
Dry mouth | 6% | <1% |
Sedation | 6% | 8% |
Diarrhea | 4% | 6% |
Insomnia | 4% | 2% |
Fatigue | 4% | 1% |
Appetite decreased | 3% | <1% |
Abdominal pain | 3% | 2% |
The common (≥1% to <10%) adverse drug reactions reported at least once by patients treated with oxymorphone hydrochloride extended-release tablets in the clinical trials organized by MedDRA’s (Medical Dictionary for Regulatory Activities) System Organ Class and not represented in Table 1:
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
Psychiatricdisorders: 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.
Drug Interactions
Drug-Drug Interactions
Oxymorphone is highly metabolized principally in the liver and undergoes reduction or conjugation with glucuronic acid to form both active and inactive metabolites [see Clinical Pharmacology (12.3)]. Clinical drug interaction studies with oxymorphone hydrochloride extended-release tablets showed no induction of CYP450 3A4 or 2C9 enzyme activity, indicating that no dose adjustment for CYP 3A4- or 2C9-mediated drug-drug interactions is required [see Clinical Pharmacology (12.3)].
Use with CNS Depressants
The concomitant use of other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol may produce additive CNS depressant effects. Opana ER should be started at 1/3 to 1/2 of the usual dose in patients who are concurrently receiving other central nervous system depressants because respiratory depression, hypotension, and profound sedation, coma and death may result, and titrated slowly as necessary for adequate pain relief.
When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced [see Dosage and Administration(2.5) and Warnings and Precautions (5.4)].
Interactions with Mixed Agonist/Antagonist Opioid Analgesics
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, or buprenorphine) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic, such as Opana ER. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of Opana ER and/or may precipitate withdrawal symptoms.
Cimetidine
CNS side effects have been reported (e.g., confusion, disorientation, respiratory depression, apnea, seizures) following coadministration of cimetidine with opioid analgesics; a causal relationship has not been established.
Anticholinergics
Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics including Opana ER may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
MAO Inhibitors
Opana ER is not recommended for use in patients who have received MAO inhibitors within 14 days, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. No specific interaction between oxymorphone and MAO inhibitors has been observed, but caution in the use of any opioid in patients taking this class of drugs is appropriate.
USE IN SPECIFIC POPULATIONS
Pregnancy
The safety of using oxymorphone in pregnancy has not been established with regard to possible adverse effects on fetal development. The use of Opana ER in pregnancy, in nursing mothers, or in women of child-bearing potential requires that the possible benefits of the drug be weighed against the possible hazards to the mother and the child.
Prolonged use of opioid analgesics including Opana ER during pregnancy may cause fetal-neonatal physical dependence.
Teratogenic Effects
Pregnancy Category C
There are no adequate and well-controlled studies of oxymorphone in pregnant women. Opana ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [see Use in Specific Populations (8.2)].
Oxymorphone hydrochloride administration did not cause malformations at any doses evaluated during developmental toxicity studies in rats (≤25 mg/kg/day) or rabbits (≤50 mg/kg/day). These doses are ~3-fold and ~12-fold the human dose of 40 mg every 12 hours, based on body surface area. There were no developmental effects in rats treated with 5 mg/kg/day or rabbits treated with 25 mg/kg/day. Fetal weights were reduced in rats and rabbits given doses of ≥10 mg/kg/day and 50 mg/kg/day, respectively. These doses are ~1.2-fold and ~12-fold the human dose of 40 mg every 12 hours based on body surface area, respectively. There were no effects of oxymorphone hydrochloride on intrauterine survival in rats at doses ≤25 mg/kg/day, or rabbits at ≤50 mg/kg/day in these studies (see Non-teratogenic Effects, below). In a study that was conducted prior to the establishment of Good Laboratory Practices (GLP) and not according to current recommended methodology, a single subcutaneous injection of oxymorphone hydrochloride on gestation day 8 was reported to produce malformations in offspring of hamsters that received 15.5-fold the human dose of 40 mg every 12 hours based on body surface area. This dose also produced 20% maternal lethality.
Non-teratogenic Effects
Oxymorphone hydrochloride administration to female rats during gestation in a pre- and postnatal developmental toxicity study reduced mean litter size (18%) at a dose of 25 mg/kg/day, attributed to an increased incidence of stillborn pups. An increase in neonatal death occurred at ≥5 mg/kg/day. Post-natal survival of the pups was reduced throughout weaning following treatment of the dams with 25 mg/kg/day. Low pup birth weight and decreased postnatal weight gain occurred in pups born to oxymorphone-treated female rats given a dose of 25 mg/kg/day. This dose is ~3-fold higher than the human dose of 40 mg every 12 hours on a body surface area basis.
Labor and Delivery
Opioids cross the placenta and may produce respiratory depression in neonates. Opana ER is not recommended for use in women during and immediately prior to labor, when use of shorter acting analgesics or other analgesic techniques are more appropriate. Occasionally, opioid analgesics may prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor.
Neonates whose mothers received opioid analgesics during labor should be observed closely for signs of respiratory depression. A specific opioid antagonist, such as naloxone or nalmefene, should be available for reversal of opioid-induced respiratory depression in the neonate.
Upon delivery from a mother who received opioids for a long period of time, neonatal withdrawal may occur. Symptoms usually appear during the first days of life and may include convulsions, irritability, excessive crying, tremors, hyperactive reflexes, fever, vomiting, diarrhea, sneezing, yawning, and increased respiratory rate.
Nursing Mothers
It is not known whether oxymorphone is excreted in human milk. Because many drugs, including some opioids, are excreted in human milk, caution should be exercised when Opana ER is administered to a nursing woman. Infants exposed to Opana ER through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
Pediatric Use
Safety and effectiveness of Opana ER in pediatric patients below the age of 18 years have not been established.
Geriatric Use
Opana ER should be used with caution in elderly patients [see Clinical Pharmacology 12.3)].
Of the total number of subjects in clinical studies of extended-release oxymorphone 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.
Hepatic Impairment
In a PK study of extended-release oxymorphone tablets, patients with mild hepatic impairment were shown to have an increase in bioavailability of 1.6 fold. Use Opana ER with caution in patients with mild impairment. Start these patients on the lowest dose and titrate slowly while carefully monitoring for side effects. Opana ER is contraindicated for patients with moderate and severe hepatic impairment [see Contraindications(4), Warnings and Precautions (5.7), and Dosage and Administration(2.3)].
Renal Impairment
In a PK study of extended-release oxymorphone tablets, patients with moderate to severe renal impairment were shown to have an increase in bioavailability ranging from 57-65% [see Clinical Pharmacology (12.3)]. Start these patients with the lowest dose of Opana ER and titrate slowly while monitored for side effects [see Dosage and Administration (2.4)].
Drug Abuse and Dependence
Controlled Substance
Opana ER contains oxymorphone, a mu agonist and a Schedule II controlled substance with an abuse liability similar to morphine and other opioids. Oxymorphone can be abused and is subject to criminal diversion [see Warnings and Precautions (5.3)].
Abuse
All patients treated with opioids including Opana ER require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its deve
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