Oxymorphone Hydrochloride Extended-Release Tablets, 7.5 mg and 15 mg These highlights do not include all the information needed to use Oxymorphone hydrochloride safely and effectively. See full prescribing information for Oxymorphone hydrochloride. | Oxymorphone hydrochloride

09:53 EDT 1st August 2014 | BioPortfolio
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Potential for Abuse

Oxymorphone hydrochloride extended-release tablets contain 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 oxymorphone hydrochloride extended-release tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. ( 9.2 )

Proper Patient Selection

Oxymorphone hydrochloride extended-release tablets are 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

Oxymorphone hydrochloride extended-release tablets are NOT intended for use as an as needed analgesic. ( 1 )

Oxymorphone hydrochloride extended-release tablets are to be swallowed whole and are not to be broken, chewed, dissolved, or crushed. Taking broken, chewed, dissolved, or crushed oxymorphone hydrochloride extended-release 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 oxymorphone hydrochloride extended-release tablet 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. ( 2 )

Oxymorphone hydrochloride extended-release tablets are 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

Oxymorphone hydrochloride extended-release tablets are not intended for use as an as needed analgesic.

Oxymorphone hydrochloride extended-release tablets are 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.

Oxymorphone hydrochloride extended-release tablets are 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).

Oxymorphone hydrochloride extended-release tablets are to be swallowed whole and are not to be broken, chewed, dissolved, or crushed. Taking broken, chewed, dissolved, or crushed oxymorphone hydrochloride extended-release 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 oxymorphone hydrochloride extended-release tablet 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.

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 oxymorphone hydrochloride extended-release tablets 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 progressive plan 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].

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 oxymorphone hydrochloride extended-release tablets, attention should be given to the following:

Once therapy is initiated, frequently assess pain relief and other opioid effects. Base the titration of the total daily oxymorphone hydrochloride extended-release tablet 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. 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 an 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. Once 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).

Administer oxymorphone hydrochloride extended-release tablets on an empty stomach, at least one hour prior to or two hours after eating [see Clinical Pharmacology (12.3)].

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 oxymorphone hydrochloride extended-release tablets is 5 mg every 12 hours. Thereafter, titrate the dose individually at increments of 5 to 10 mg every 12 hours every 3 to 7 days, to a level that provides adequate analgesia and minimizes side effects under the close supervision of the prescribing physician.

Opioid-Experienced Patients

Conversion from Oxymorphone Hydrochloride Tablets to Oxymorphone Hydrochloride Extended-Release Tablets

Patients receiving oxymorphone hydrochloride tablets may be converted to oxymorphone hydrochloride extended-release tablets by administering half the patient's total daily oral oxymorphone hydrochloride tablets dose as oxymorphone hydrochloride extended-release tablets, every 12 hours.

Conversion from Parenteral Oxymorphone to Oxymorphone Hydrochloride Extended-Release Tablets

Given oxymorphone hydrochloride extended-release tablet’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to oxymorphone hydrochloride extended-release tablets by administering 10 times the patient's total daily parenteral oxymorphone dose as oxymorphone hydrochloride extended-release tablets 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 Oxymorphone Hydrochloride Extended-Release Tablets

For conversion from other opioids to oxymorphone hydrochloride extended-release tablets, physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion ratios are only approximate. In general, it is safest to start the oxymorphone hydrochloride extended-release tablets therapy by administering half of the calculated total daily dose of oxymorphone hydrochloride extended-release tablets (see conversion ratio table below) in 2 divided doses, every 12 hours. Gradually adjust the initial dose of oxymorphone hydrochloride extended-release tablets until adequate pain relief and acceptable side effects have been achieved.

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 oxymorphone hydrochloride extended-release tablets. In a Phase 3 clinical trial with an open-label titration period, patients were converted from their current opioid to oxymorphone hydrochloride extended-release tablets using the following table as a guide. There is substantial patient variation in the relative potency of different opioid drugs and formulations.

No dose adjustment for CYP 3A4-or 2C9-mediated drug-drug interactions is required [see Clinical Pharmacology (12.3)].

CONVERSION RATIOS TO OXYMORPHONE HYDROCHLORIDE EXTENDED-RELEASE TABLETS
Approximate Equivalent Dose Oral
Opioid Oral Conversion Ratio a
a Ratio for conversion of oral opioid dose to approximate oxymorphone equivalent dose. Select opioid and multiply the dose by the conversion ratio to calculate the approximate oral oxymorphone equivalent.
● The conversion ratios and approximate equivalent doses in this conversion table are only to be used for the conversion from current opioid therapy to oxymorphone hydrochloride extended-release tablets.
● Sum the total daily dose for the opioid and multiply by the conversion ratio to calculate the oxymorphone total daily dose.
● For patients on a regimen of mixed opioids, calculate the approximate oral oxymorphone dose for each opioid and sum the totals to estimate the total daily oxymorphone dose. 
● The dose of oxymorphone hydrochloride extended-release tablets can be gradually adjusted, preferably at increments of 10 mg every 12 hours every 3 to 7 days, until adequate pain relief and acceptable side effects have been achieved [see Dosage and Administration (2.1)].
b It is extremely important to monitor all patients closely when converting from methadone to other opioid agonists. 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 tends to accumulate in the plasma. 
Oxymorphone 10 mg 1
Hydrocodone 20 mg 0.5
Oxycodone 20 mg 0.5
Methadone b 20 mg 0.5
Morphine 30 mg 0.333

Start patients with mild hepatic impairment with the lowest dose and titrate slowly while carefully monitoring side effects. Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with moderate or severe hepatic impairment [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)].

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 oxymorphone hydrochloride extended-release tablets with the lowest dose and titrate slowly while carefully monitoring side effects.

In patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, start oxymorphone hydrochloride extended-release tablets 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, oxymorphone hydrochloride extended-release tablets are not recommended for use in patients who have received MAO inhibitors within 14 days [see Drug Interactions (7.6)].

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 oxymorphone hydrochloride extended-release tablets 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)].

During chronic therapy with oxymorphone hydrochloride extended-release tablets, 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 Oxymorphone Hydrochloride Extended-Release Tablets.

When the patient no longer requires therapy with oxymorphone hydrochloride extended-release tablets, gradually taper doses to prevent signs and symptoms of withdrawal in the physically dependent patient.

Oxymorphone hydrochloride extended-release tablets are contraindicated in patients who have:

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 CO 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 CO 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:

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.

The following table 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 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.

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 Double-Blind
Titration Period Treatment Period
Oxymorphone Oxymorphone
Hydrochloride Hydrochloride
Extended-Release Extended-Release
Tablets 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 Oxymorphone
Hydrochloride Hydrochloride
Extended-Release Extended-Release
Tablets 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%
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
(N=1259) (N=461)
Nausea 33% 13%
Constipation 28% 13%
Dizziness (Excl Vertigo) 18% 8%
Somnolence 17% 2%
Vomiting 16% 4%
Pruritus 15% 8%
Headache 12% 6%
Sweating increased 9% 9%
Dry mouth 6% <1%
Sedation 6% 8%
Diarrhea 4% 6%
Insomnia 4% 2%
Fatigue 4% 1%
Appetite decreased 3% <1%
Abdominal pain 3% 2%

Oxymorphone is highly metabolized principally in the liver and undergoes reduction or conjugation with glucuronic acid to form both active and inactive metabolites [see Pharmacokinetics (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)].

The concomitant use of other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol may produce additive CNS depressant effects. Oxymorphone hydrochloride extended-release tablets 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)].

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 oxymorphone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxymorphone and/or may precipitate withdrawal symptoms.

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 or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

Oxymorphone hydrochloride extended-release tablets are 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.

The safety of using oxymorphone in pregnancy has not been established with regard to possible adverse effects on fetal development. The use of oxymorphone hydrochloride extended-release tablets 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 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. Oxymorphone hydrochloride extended-release tablets 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 pregnant 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.

Opioids cross the placenta and may produce respiratory depression in neonates. Oxymorphone hydrochloride extended-release tablets are 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.

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 oxymorphone hydrochloride extended-release tablets are administered to a nursing woman. Infants exposed to oxymorphone hydrochloride extended-release 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.

Safety and effectiveness of oxymorphone hydrochloride extended-release tablets in pediatric patients below the age of 18 years have not been established.

Oxymorphone hydrochloride extended-release tablets should be used with caution in elderly patients [see Clinical Pharmacology 12.3)].

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.

In a PK study of oxymorphone hydrochloride extended-release, patients with mild hepatic impairment were shown to have an increase in bioavailability of 1.6 fold. Use oxymorphone hydrochloride extended-release tablets with caution in patients with mild impairment. Start these patients on the lowest dose and titrate slowly while carefully monitoring for side effects. Oxymorphone hydrochloride extended-release tablets are contraindicated for patients with moderate and severe hepatic impairment [see Contraindications (4), Warnings and Precautions (5.7), and Dosage and Administration (2.3)].

In a PK study of oxymorphone hydrochloride extended-release, patients with moderate to severe renal impairment were shown to have an increase in bioavailability ranging from 57 to 65% [see Clinical Pharmacology (12.3)]. Start these patients with the lowest dose of oxymorphone hydrochloride extended-release tablets and titrate slowly while monitored for side effects [see Dosage and Administration (2.4)].

Oxymorphone hydrochloride extended-release tablets contain oxymorphone, a mu opioid 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 Warning and Precautions (5.3)].

All patients treated with opioids 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 development and manifestations. Addiction is characterized by one or more of the following: impaired control over drug use, compulsive use, use for non-medical purposes, and continued use despite harm. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.

"Drug seeking" behavior is very common to addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Oxymorphone hydrochloride extended-release tablets, like other opioids, may be diverted for non-medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Oxymorphone hydrochloride extended-release tablets are intended for oral use only. Abuse of oxymorphone hydrochloride extended-release tablets pose a risk of overdose and death. This risk is increased with concurrent abuse of oxymorphone hydrochloride extended-release tablets with alcohol and other substances. Parenteral drug abuse is commonly associated with transmission of infectious disease such as hepatitis and HIV.

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

Opioid analgesics may cause physical dependence. Physical dependence results in withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an opioid antagonist or mixed opioid agonist/antagonist agent. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, or mixed agonist/antagonist analgesics (pentazocine, butorphanol, buprenorphine, nalbuphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). The development of physical dependence and tolerance is not unusual during chronic opioid therapy.

Oxymorphone hydrochloride extended-release tablets should not be abruptly discontinued [see Dosage and Administration (2.8)]. If oxymorphone hydrochloride extended-release tablets are abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other 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.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see Use in Specific Populations (8.1, 8.2)].

Acute overdosage with oxymorphone hydrochloride extended-release tablets are characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils and sometimes bradycardia and hypotension. In some cases, apnea, circulatory collapse, cardiac arrest and death may occur.

Oxymorphone hydrochloride extended-release tablets may cause 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 [see Clinical Pharmacology (12.2)].

In the treatment of oxymorphone hydrochloride extended-release tablet overdosage, primary attention should be given to the re-establishment of a patent airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arre

Manufacturer

Actavis Elizabeth LLC

Active Ingredients

Source

Drugs and Medications [667 Associated Drugs and Medications listed on BioPortfolio]

Opana [Endo Pharmaceuticals, Inc]

ENDO PHARMACEUTICALS 003466/September 2006 OPANA (Oxymorphone Hydrochloride) INJECTION 1mg/mL CII Opioid Analgesic Rx only

Oxymorphone hydrochloride [Endo Pharmaceuticals Inc.]

These highlights do not include all the information needed to use oxymorphone hydrochloride tablets safely and effectively. See full prescribing information for oxymorphone hydrochloride tablets. Oxym...

Oxymorphone hydrochloride [Roxane Laboratories, Inc]

These highlights do not include all the information needed to use Oxymorphone Hydrochloride Tablets safely and effectively. See full prescribing information for Oxymorphone Hydrochloride Tablets, CII....

Oxymorphone hydrochloride [Lake Erie Medical & Surgical Supply DBA Quality Care Products LLC]

These highlights do not include all the information needed to use Oxymorphone Hydrochloride Tablets safely and effectively. See full prescribing information for Oxymorphone Hydrochloride Tablets, CII....

Opana er [Rebel Distributors Corp]

OPANA ER(Oxymorphone Hydrochloride) Extended-Release Tablets5mg, 10mg, 20mg, and 40mgCIIRx Only

Clinical Trials [1003 Associated Clinical Trials listed on BioPortfolio]

Bioavailability of Oxymorphone Hydrochloride 40 mg Extended Release Tablets Under Fasted Conditions

The purpose of this study is to demonstrate the relative bioequivalence of oxymorphone hydrochloride extended-release tablets (Sandoz) with Opana extended release oxymorphone hydrochloride...

Bioavailability of Oxymorphone Hydrochloride 40 mg Extended Release Tablets Under Fed Conditions

The purpose of this study is to demonstrate the relative bioequivalence of oxymorphone hydrochloride extended release tablets (Sandoz) with Opana extended release oxymorphone hydrochloride...

A Pilot Study of Ultra Rapid Opioid Rotation and Titration of Oxymorphone

This project will explore the safety and feasibility of performing a successful intravenous patient controlled analgesia (IV PCA) Oxymorphone titration and conversion to oral ER Oxymorphon...

Effect of Extended-Release Oxymorphone Taking With or Without Food on Cognitive Functioning

The purpose of the study is to determine whether extended-release oxymorphone hydrochloride taken orally with a high-fat meal, generating an approximately 50% higher Cmax, impacts cognitiv...

Open-Label Safety and Tolerability of Oxymorphone IR and ER in Opioid Tolerant Pediatric Subjects

Patients will convert from current opioid to Oxymorphone ER and undergo titration. During the Titration Period, subjects will receive daily oxymorphone Extended Release tablets(s) every 1...

PubMed Articles [207 Associated PubMed Articles listed on BioPortfolio]

Clinical applications of oxymorphone.

Oxymorphone (14-hydroxydihydromorphinone), a pyridine ring unsubstituted pyridomorphinan, a semisynthetic opioid analgesic derived from thebaine, first developed in the year 1914 and has been availabl...

Pharmacokinetics of oxycodone hydrochloride and three of its metabolites after intravenous administration in Chinese patients with pain.

The aim of this study is to evaluate the pharmacokinetic profile of oxycodone and three of its metabolites, noroxycodone, oxymorphone and noroxymorphone after intravenous administration in Chinese pat...

Observations of Urinary Oxycodone and Metabolite Distributions in Pain Patients.

Oxycodone is an opioid analgesic metabolized to oxymorphone and noroxycodone by cytochrome P450 (CYP) 2D6 and 3A4/5, respectively. This was a retrospective study to evaluate sex, age, urinary pH and c...

Identification and determination of ketotifen hydrogen fumarate, azelastine hydrochloride, dimetindene maleate and promethazine hydrochloride by densitometric method.

Conditions for determination of: ketotifen hydrogen fumarate, azelastine hydrochloride, dimetindene maleate and promethazine hydrochloride by densitometric method in substances and pharmaceuticals wer...

Alkalimetric titrations of salts of organic bases in the Pharmacopoeia.

Modified methods - alkalimetry in ethanol 70% with a defined small volume of hydrochloric acid 0.01 mol/l added to the solution of the sample before the titration and alkalimetry in ethanol 70% or eth...

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