Opana
FDA Label NDC 16590-747

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.

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.

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.

OPANA ER is NOT intended for use as a prn analgesic.

OPANA ER Tablets are to be swallowed whole and are not to be broken, chewed, dissolved, or crushed. Taking 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 (oxymorphone hydrochloride) extended-release, is a semi-synthetic opioid analgesic supplied in 5 mg, 10 mg, 20 mg, and 40 mg tablet strengths for oral administration. The tablet strength describes the amount of oxymorphone hydrochloride per tablet. The tablets contain the following inactive ingredients: hypromellose, iron oxide black, methylparaben, propylene glycol, silicified microcrystalline cellulose, sodium stearyl fumarate, TIMERx^® -N, titanium dioxide, and triacetin. The 5 mg, 10 mg and 20 mg tablets also contain macrogol, and polysorbate 80. In addition, the 5 mg tablets contain iron oxide red. The 10 mg tablets contain FD and C yellow No. 6. The 20 mg tablets contain FD and C blue No. 1, FD and C yellow No. 6, and D and C yellow No. 10. The 40 mg tablets contain FD and C yellow No. 6, D and C yellow No. 10, and lactose monohydrate.

Chemically, oxymorphone hydrochloride is 4, 5α -epoxy-3, 14-dihydroxy-17-methylmorphinan-6-one hydrochloride, a white or slightly off-white, odorless powder, which is sparingly soluble in alcohol and ether, but freely soluble in water. The molecular weight of oxymorphone hydrochloride is 337.80. The pK_a1 and pK_a2 of oxymorphone at 37°C are 8.17 and 9.54, respectively. The octanol/aqueous partition coefficient at 37°C and pH 7.4 is 0.98.

The structural formula for oxymorphone hydrochloride is as follows:

The tablet strengths, 5, 10, 20 and 40 mg, describe the amount of oxymorphone hydrochloride per tablet.

Oxymorphone is an opioid agonist whose principal therapeutic action is analgesia. Other members of the class known as opioid agonists include substances such as morphine, oxycodone, hydromorphone, fentanyl, codeine, hydrocodone, and tramadol. In addition to analgesia, other pharmacological effects of opioid agonists include anxiolysis, euphoria, feelings of relaxation, respiratory depression, constipation, miosis, and cough suppression. Like all pure opioid agonist analgesics, with increasing doses there is increasing analgesia, unlike with mixed agonist/antagonists or non-opioid analgesics, where there is a limit to the analgesic effect with increasing doses. With pure opioid agonist analgesics, there is no defined maximum dose; the ceiling to analgesic effectiveness is imposed only by side effects, the more serious of which may include somnolence and respiratory depression.

The precise mechanism of the analgesic action is unknown. However, specific CNS (central nervous system) opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and play a role in the analgesic effects of this drug. In addition, opioid receptors have also been identified within the PNS (peripheral nervous system). The role that these receptors play in these drugs’ analgesic effects is unknown.

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

Opioids depress the cough reflex by direct effect on the cough center in the medulla oblongata. Antitussive effects may occur with doses lower than those usually required for analgesia. Opioids 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 OVERDOSAGE: Signs and Symptoms).

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

Opioids produce peripheral vasodilation which may result in orthostatic hypotension. Release of histamine can occur and may contribute to opioid-induced hypotension. Manifestations of histamine release may include orthostatic hypotension, pruritus, flushing, red eyes, and sweating. Animal studies have shown that oxymorphone has a lower propensity to cause histamine release than other opioids.

Opioids have been shown to have a variety of effects on the secretion of hormones. Opioids inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon in humans and other species, rats and dogs. Thyroid stimulating hormone (TSH) has been shown to be both inhibited and stimulated by opioids.

Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown.

Studies in healthy volunteers reveal predictable relationships between OPANA ER dosage and plasma oxymorphone concentrations.

The minimum effective plasma concentration of oxymorphone for analgesia varies widely among patients, especially among patients who have been previously treated with agonist opioids. As a result, patients need to be individually titrated to achieve a balance between therapeutic and adverse effects. The minimum effective analgesic concentration of oxymorphone for any individual patient may increase over time due to an increase in pain, progression of disease, development of a new pain syndrome and/or potential development of analgesic tolerance.

OPANA ER is associated with typical opioid-related adverse experiences. There is a general relationship between increasing opioid plasma concentration and increasing frequency of adverse experiences such as nausea, vomiting, CNS effects, and respiratory depression.

As with all opioids, the dose must be individualized (see DOSAGE AND ADMINISTRATION). The effective analgesic dose for some patients will be too high to be tolerated by other patients.

The AUC was unchanged in one study and increased by approximately 18% in the other study in fed subjects following the administration of OPANA ER. Examination of the AUC suggests that most of the difference between fed and fasting conditions occurs in the first four hours after dose administration. After oral dosing with a single dose of 40 mg, a peak oxymorphone plasma level of 2.8 ng/ml is achieved at 1 hour in fasted subjects and a peak of 4.25 ng/ml is achieved at 2 hours in fed subjects and that beyond the 12 hour time point, there is very little difference in the curves. As a result, OPANA ER should be dosed at least one hour prior to or two hours after eating (see DOSAGE AND ADMINISTRATION).

The steady-state plasma concentrations of oxymorphone, 6-OH-oxymorphone, and oxymorphone-3-glucuronide are approximately 40% higher in elderly subjects (≥ 65 years of age) than in young subjects (18 to 40 years of age). On average, age greater than 65 years was associated with a 1.4-fold increase in oxymorphone AUC and a 1.5-fold increase in C_max. This observation does not appear related to a difference in body weight, metabolism, or excretion of oxymorphone (see PRECAUTIONS: Geriatric Use).

The liver plays an important role in the pre-systemic clearance of orally administered oxymorphone. Accordingly, the bioavailability of orally administered oxymorphone may be markedly increased in patients with moderate to severe liver disease. The disposition of oxymorphone was compared in 6 patients with mild, 5 patients with moderate, and one patient with severe hepatic impairment and 12 subjects with normal hepatic function. The bioavailability of oxymorphone was increased by 1.6-fold in patients with mild hepatic impairment and by 3.7-fold in patients with moderate hepatic impairment. In one patient with severe hepatic impairment, the bioavailability was increased by 12.2-fold. The half-life of oxymorphone was not significantly affected by hepatic impairment (see DOSAGE AND ADMINISTRATION: Patients with Hepatic Impairment).

12-Week Study in Opioid-Experienced Patients with Low Back Pain

Patients currently on chronic opioid therapy entered a 4-week, open-label titration phase with OPANA ER dosed every 12 hours at an approximated equianalgesic dose of their pre-study opioid medication. Of the patients who were able to stabilize within the Open‑Label Titration Period, the mean±SD VAS score at Screening was 69.5±17.0 mm and at Baseline (beginning of Double-Blind Period) were 23.9±12.1 mm and 22.2±10.8 mm for the oxymorphone ER and placebo groups, respectively. Stabilized patients entered a 12‑week double-blind treatment phase with placebo or their stabilized dose of OPANA ER. The mean±SD stabilized doses were 80.9±59.3 mg and 93.3±61.3 mg for the OPANA ER and placebo groups, respectively; total daily doses ranged from 20-260 mg. During the first 4 days of double-blind treatment, patients were allowed an unlimited number of OPANA 5 mg tablets, every 4-6 hours as supplemental analgesia; thereafter the number of OPANA was limited to two tablets per day. This served as a tapering method to minimize opioid withdrawal symptoms in placebo patients. Fifty seven percent of patients were titrated to a stabilized dose within approximately 4 weeks of OPANA ER dose titration. Seventy percent of patients treated with OPANA ER and 26% of patients treated with placebo completed the 12-week treatment. OPANA ER provided superior analgesia compared to placebo . The analgesic effect of OPANA ER was maintained throughout the double-blind treatment period in 80 % of patients who completed the study. These patients reported a decrease, no change, or a ≤10 mm increase in VAS score from Day 7 until the end of the study.

A significantly higher proportion of OPANA ER patients (79.7%) had at least a 30% reduction in pain score from screening to study endpoint compared to placebo patients (34.8%). Proportion of patients with various degrees of improvement from screening to study endpoint is shown in Figure 2.

Figure 2: Percent Reduction in Average Pain Intensity from Screening to Final Visit

OPANA ER is contraindicated in patients with moderate and severe hepatic impairment (see CLINICAL PHARMACOLOGY, PRECAUTIONS and DOSAGE AND ADMINISTRATION).

OPANA ER TABLETS are to be swallowed whole, and are not to be broken, chewed, crushed or dissolved. Taking broken, chewed, crushed or dissolved OPANA ER TABLETS could lead to the 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 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 WARNINGS and WARNINGS: Drug Abuse and Addiction).

Concerns about abuse, addiction, and diversion should not prevent the proper management of pain.

Healthcare professionals should contact their State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

OPANA ER contains oxymorphone, an opioid with an abuse liability similar to morphine and other opioid agonists and is a Schedule II controlled substance. OPANA ER and other opioids used in analgesia, can be abused and are subject to criminal diversion (see WARNINGS: Misuse, Abuse and Diversion of Opioids).

Drug addiction is characterized by a preoccupation with the procurement, hoarding, and abuse of drugs for non-medicinal purposes. Drug addiction is treatable, utilizing a multi-disciplinary 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. OPANA ER, 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.

Abuse of OPANA ER poses a risk of overdose and death. This risk is increased with concurrent abuse of OPANA ER with alcohol and other substances. In addition, 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.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms (see PRECAUTIONS: Usage in Pregnancy and PRECAUTIONS: Labor and Delivery).

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, or coma (see PRECAUTIONS: Drug-Drug Interactions).

A study of OPANA ER in patients with hepatic disease indicated greater plasma concentrations than those with normal hepatic function (see CLINICAL PHARMACOLOGY). OPANA ER should be used with caution in patients with mild impairment. These patients should be started with the lowest dose and titrated slowly while carefully monitoring for side effects. OPANA ER is contraindicated for patients with moderate and severe hepatic impairment (see CONTRAINDICATIONS, WARNINGS, and DOSAGE AND ADMINISTRATION).

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 (see DOSAGE AND ADMINISTRATION).

OPANA ER, like other opioids, decreases bowel motility. Ileus is a common post-operative complication, especially after intra-abdominal surgery with opioid analgesia. Caution should be taken to monitor for decreased bowel motility in post-operative patients receiving opioids. Standard supportive therapy should be implemented.

In general, OPANA ER should not be abruptly discontinued. However, OPANA ER, like other opioids, can be safely discontinued without the development of withdrawal symptoms by slowly tapering the daily dose (see DOSAGE AND ADMINISTRATION: Cessation of Therapy).

• Patients should be advised that OPANA ER contains oxymorphone, a morphine-like pain reliever, and should be taken only as directed.
  
  
• Patients should be advised that OPANA ER is designed to work properly only if swallowed whole. The extended-release tablets may release all their contents at once if broken, chewed or crushed, resulting in a risk of fatal overdose 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.
  
  
• Appropriate pain management requires changes in the dose to maintain best pain control. Patients should be advised of the need to contact their physician if pain control is inadequate, but not to change the dose of OPANA ER without consulting their physician.
  
  
• Patients should be advised to report episodes of breakthrough pain and adverse experiences occurring during therapy to their doctor. Individualization of dosage is essential to make optimal use of this medication.
  
  
• Patients should be cautioned that OPANA ER may cause drowsiness, dizziness, or lightheadedness, and may impair mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car, operating machinery, etc.
  
  
• Patients should not combine OPANA ER with alcohol or other central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, because additive effects may occur, resulting in serious injury or death.
  
  
• Patients taking OPANA ER should be advised of the potential for severe constipation. Appropriate laxatives and/or stool softeners and other therapeutic approaches may be considered for use with the initiation of OPANA ER therapy.
  
  
• Patients should be advised not to adjust the dose of OPANA ER without consulting the prescribing professional.
  
  
• Patients should be advised that OPANA ER is a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
  
  
• Women of childbearing potential who become, or are planning to become pregnant should be advised to consult their physician regarding the effects of opioid analgesics and other drug use during pregnancy on themselves and their unborn child.
  
  
• If patients have been receiving treatment with OPANA ER for more than a few days to weeks and cessation of therapy is indicated, they should be counseled on the importance of safely tapering the dose and that abruptly discontinuing the medication could precipitate withdrawal symptoms. The physician should determine a dose schedule to accomplish a gradual discontinuation of the medication.
  
  
• As with any potent opioid, misuse of OPANA ER may result in serious adverse events. Patients should be instructed to keep OPANA ER in a secure place out of the reach of children and pets. Accidental consumption especially in children can result in overdose or death. When OPANA ER is no longer needed, the unused tablets should be destroyed by flushing down the toilet.

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: Metabolism).

When combined therapy with any of the above medications is contemplated, the dose of one or both agents should be reduced (see WARNINGS and DOSAGE AND ADMINISTRATION).

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 (see PRECAUTIONS).

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 ~6-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 83% maternal lethality.

There are no adequate and well-controlled studies in pregnant women. OPANA ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

OPANA ER should be used with caution in elderly patients. The plasma levels of oxymorphone are about 40% higher in elderly (≥65 years of age) than in younger subjects (see CLINICAL PHARMACOLOGY). Elderly patients should initially receive smaller starting doses of oxymorphone and dose titration should proceed cautiously.

Of the total number of subjects in clinical studies of OPANA ER, 27 percent were 65 and over, while 9 percent 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.

A study of OPANA ER in patients with hepatic disease indicated greater plasma concentrations than those with normal hepatic function (see CLINICAL PHARMACOLOGY). OPANA ER should be used with caution in patients with mild impairment. These patients should be started with the lowest dose and titrated slowly while carefully monitoring for side effects. OPANA ER is contraindicated for patients with moderate and severe hepatic impairment (see CONTRAINDICATIONS, WARNINGS, and DOSAGE AND ADMINISTRATION).

In a study of OPANA ER, patients with moderate to severe renal impairment were shown to have an increase in bioavailability ranging from 57-65% (see CLINICAL PHARMACOLOGY). These patients should be started cautiously with lower doses of OPANA ER and titrated slowly while carefully monitored for side effects (see DOSAGE AND ADMINISTRATION).

When normalized for body weight, gender differences were not observed (see CLINICAL PHARMACOLOGY). In clinical studies, the overall incidence rates for one or more adverse events were slightly higher among females than males for both OPANA ER subjects and placebo subjects.

Patients with mild hepatic impairment should be started with the lowest dose and titrated slowly while carefully monitoring side effects. OPANA ER is contraindicated in patients with moderate and severe hepatic dysfunction (see CLINICAL PHARMACOLOGY, CONTRAINDICATIONS and PRECAUTIONS).

There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively (see CLINICAL PHARMACOLOGY and PRECAUTIONS). Accordingly, in patients with creatinine clearance rate less than 50 mL/min, OPANA ER should be started with the lowest dose and titrated slowly while carefully monitoring side effects.

OPANA ER, like all opioid analgesics, should be started at 1/3 to 1/2 of the usual dose in patients who are concurrently receiving other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol because respiratory depression, hypotension, and profound sedation or coma may result. No specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, but caution in the use of any opioid in patients taking this class of drugs is appropriate (see PRECAUTIONS: General and PRECAUTIONS: Drug-Drug Interactions).

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects (see CLINICAL PHARMACOLOGY and PRECAUTIONS). In general, caution should be exercised in the selection of the starting dose of OPANA ER for an elderly patient usually starting at the low end of the dosing range and slowly titrating to adequate analgesia.

When the patient no longer requires therapy with OPANA ER tablets, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient (see CLINICAL TRIALS: 12-Week Study in Opioid-Naïve Patients with Low Back Pain and CLINICAL TRIALS: 12-Week Study in Opioid-Experienced Patients with Low Back Pain).

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

OPANA ER 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: Central Nervous System).

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). As with any opioid drug product, it is necessary to adjust the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience. Physicians should individualize treatment in every case (see DOSAGE AND ADMINISTRATION), using non-opioid analgesics, prn opioids and/or 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).

In the selection of the initial dose of OPANA ER, attention should be given to the following:

• The total daily dose, potency and specific characteristics of the opioid the patient has been taking previously;
• The relative potency estimate used to calculate the equivalent oxymorphone dose needed;
• The patient’s degree of opioid tolerance;
• The age, general condition, and medical status of the patient;
• Concurrent non-opioid analgesic and other medications;
• The type and severity of the patient's pain;
• The balance between pain control and adverse experiences;
• Risk factors for abuse, addiction or diversion, including a prior history of abuse, addiction or diversion.

The following dosing recommendations, 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.

OPANA ER should be administered on an empty stomach, at least one hour prior to or two hours after eating.


Initiation of Therapy

Opioid-Naïve Patients

It is suggested that patients who are not opioid-experienced being initiated on chronic around-the-clock opioid therapy be started with OPANA ER 5 mg every 12 hours. Thereafter, it is recommended that the dose be individually titrated, preferably at increments of 5-10 mg every 12 hours every 3-7 days, to a level that provides adequate analgesia and minimizes side effects under the close supervision of the prescribing physician (see CLINICAL TRIALS: 12-Week Study in Opioid-Naïve Patients with Low Back Pain).


Opioid-Experienced PatientsConversion 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. For example, a patient receiving 40 mg/day OPANA may require 20 mg OPANA ER every 12 hours.


Conversion from Parenteral Oxymorphone to OPANA ER

Given the 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 10/2). For example, approximately 20 mg of OPANA ER, every 12 hours, may be required to provide pain relief equivalent to a total daily dose of 4 mg of parenteral oxymorphone. Due to patient variability with regards to opioid analgesic response, upon conversion patients should be closely monitored to ensure adequate analgesia and to minimize 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. In general, it is safest to start the OPANA ER therapy by administering half of the calculated total daily dose of OPANA ER (see conversion ratio table below) in 2 divided doses, every 12 hours. The initial dose of OPANA ER can be gradually adjusted 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 OPANA ER. In a Phase 3 clinical trial with an open-label titration period, patients were converted from their current opioid to OPANA ER using the following table as a guide. In general, patients were able to successfully titrate to a stabilized dose of OPANA ER within 4 weeks (see Clinical TRIALS: 12-Week Study in Opioid-Experienced Patients with Low Back Pain). There is substantial patient variation in the relative potency of different opioid drugs and formulations.

                                    CONVERSION RATIOS TO OPANA ER
                                        Approximate Equivalent Dose



Opioid	Oral	Oral Conversion Ratio a
Oxymorphone	10 mg	1
Hydrocodone	20 mg	0.5
Oxycodone	20 mg	0.5
Methadone	20 mg	0.5
Morphine	30 mg	0.333

a - Ratio for conversion of oral opioid dose to approximate oxymorphone equivalent does. 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 Opana ER.
• 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 OPANA ER can be gradually adjusted, preferably at increments if 10 mg every 12 hours every 3-7 days, until adequate pain relief and acceptable side effects have achieved (see individualization of Dose).
  
      

OPANA ER contains oxymorphone, which is a controlled substance. Oxymorphone is controlled under Schedule II of the Controlled Substances Act. Oxymorphone, like all opioids, is liable to diversion and misuse and should be handled accordingly. Patients and their families should be instructed to flush any OPANA ER tablets that are no longer needed.

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.

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature].

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

OPANA ER tablets are supplied as follows:

5 mg
Pink, octagon shape, film coated, convex tablets with “E907” over “5” in black print on one side and plain on the other.
Bottles of 100 with child-resistant closure                                  NDC 63481-907-70
Unit-Dose package of 100 tablets (5 blister cards of 20
tablets, not child-resistant, for hospital use only)                         NDC 63481-907-75

10 mg
Light orange, octagon shape, film coated, convex tablets with “E674” over “10” in black print on one side and plain on the other.
Bottles of 100 with child-resistant closure                                  NDC 63481-674-70
Unit-Dose package of 100 tablets (5 blister cards of 20
tablets, not child-resistant, for hospital use only)                         NDC 63481-674-75

20 mg
Light green, octagon shape, film coated, convex tablets with “E617” over “20” in black print on one side and plain on the other.
Bottles of 100 with child-resistant closure                                  NDC 63481-617-70
Unit-Dose package of 100 tablets (5 blister cards of 20
tablets, not child-resistant, for hospital use only)                         NDC 63481-617-75

40 mg
Yellow, octagon shape, film coated, convex tablets with “E693” over “40” in black print on one side and plain on the other.
Bottles of 100 with child-resistant closure                                  NDC 63481-693-70
Unit-Dose package of 100 tablets (5 blister cards of 20
tablets, not child-resistant, for hospital use only)                         NDC 63481-693-75

Rx Only

CAUTION
DEA Order Form Required.

OPANA^® ER (Ō-pan-a)
(Oxymorphone Hydrochloride) Extended-Release Tablets
CII
Rx Only

OPANA ER Tablets, 5 mg
OPANA ER Tablets, 10 mg
OPANA ER Tablets, 20 mg
OPANA ER Tablets, 40 mg

Read the Patient Information that comes with OPANA ER before you start taking it and each time you get a new prescription. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment. Share the important information in this leaflet with members of your household.

What Is the Most Important Information I Should Know About OPANA ER?

• OPANA ER can cause trouble breathing (hypoventilation), which can lead to death, if used differently than the way you were told to use it by your healthcare provider (see “What are the possible side effects of OPANA ER?”).
  
  
• Swallow OPANA ER tablets whole. Do not break, crush, dissolve, or chew OPANA ER tablets before swallowing. If a tablet is broken, crushed, dissolved, or chewed, the full 12 hour dose can be taken into your body all at once. This is very dangerous. You could die from an overdose of the medicine. Use OPANA ER exactly the way your healthcare provider prescribes. If you cannot swallow tablets whole, tell your healthcare provider. You may need a different medicine.

What is OPANA ER?

• OPANA ER is a prescription medicine that contains the opioid (narcotic pain medicine) oxymorphone. OPANA ER is used to treat adults with constant pain (around the clock) that is moderate to severe and is expected to last for an extended period of time. OPANA ER is not for occasional (“as needed”) use.
  
  
• OPANA ER can cause physical dependence. Do not stop taking OPANA ER all of a sudden if you have been taking it for more than a few days. You could become sick with uncomfortable withdrawal symptoms because your body has become use to the medicine. Talk to your healthcare provider about slowly stopping OPANA ER to avoid getting sick with withdrawal symptoms. Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical dependence and drug addiction.
  
  
• OPANA ER is a controlled substance (CII) because it contains a narcotic painkiller that can be a target for people who abuse prescription medicines or street drugs. Keep your tablets in a safe place to protect them from being stolen. Never give your tablets to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others, even causing death, and is against the law.

Who Should Not Take OPANA ER?
Do not take OPANA ER if:

• You had surgery within the past day (24 hours) and you were not taking OPANA ER before your surgery.
  
  
• Your pain is mild or will go away in a few days.
  
  
• Your pain can be controlled by the occasional use of other pain medicines.
  
  
• You are having an asthma attack or have severe asthma, trouble breathing, or lung problems.
  
  
• You have liver problems.
  
  
• You are allergic to OPANA ER or anything in it. See the end of this leaflet for a complete list of ingredients in OPANA ER.

You have had severe allergic reactions to other narcotic pain medicines (such as morphine or codeine medicines). A severe allergic reaction includes a severe rash, hives, breathing problems, or dizziness.

OPANA ER is not for children under 18 years of age.

What Should I Tell My Healthcare Provider Before Starting OPANA ER?
Tell your healthcare provider about all of your medical problems, especially if you:

• have trouble breathing or lung problems
  
  
• have a head injury or brain problem
  
  
• have liver or kidney problems
  
  
• have adrenal gland problems, such as Addison’s disease
  
  
• have convulsions or seizures
  
  
• have thyroid problems
  
  
• have problems urinating or prostate problems
  
  
• have pancreas problems
  
  
• have a drinking problem or alcoholism
  
  
• have severe mental problems or hallucinations (see or hear things that are not really there)
  
  
• have past or present drug abuse or drug addiction problems
  
  
• are pregnant or plan to become pregnant. OPANA ER may harm your unborn baby.
  
  
• are breastfeeding. OPANA ER may pass through your milk and may harm your baby. You should not breastfeed while taking OPANA ER.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may cause serious problems when taken with OPANA ER, especially if they cause sleepiness (like sleeping pills, anxiety medicines, antihistamines, or tranquilizers).

Do not take any new medicines while using OPANA ER until you have talked to your healthcare provider or pharmacist and they have told you it is safe.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist.

How Should I Take OPANA ER?

• Follow your healthcare provider’s directions exactly. Your healthcare provider may change your dose based on your reactions to the medicine. Do not change your dose unless your healthcare provider tells you to change it. Do not take OPANA ER more often than prescribed.
  
  
• Swallow OPANA ER tablets whole. Do not break, crush, dissolve, or chew OPANA ER tablets before swallowing. If a tablet is broken, crushed, dissolved, or chewed, the full 12 hour dose can be taken into your body all at once. This is very dangerous. You could die from an overdose of the medicine. If you cannot swallow tablets whole, tell your healthcare provider. You may need a different medicine.
  
  
• Take OPANA ER every 12 hours or as instructed by your healthcare provider. OPANA ER should be taken on an empty stomach, at least one hour before or two hours after meals. Talk to your healthcare provider if you feel sick taking OPANA ER on an empty stomach.
  
  
• If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once unless your healthcare provider tells you to. If you are not sure about your dosing call your healthcare provider.
  
  
• If you take too much OPANA ER or overdose, call your local emergency number or poison control center right away.
  
  
• Talk to your healthcare provider often about your pain. Your healthcare provider can decide if you still need OPANA ER.
  
  
• If you have side effects that bother you or if you continue to have pain, call your healthcare provider.
  
  
• Stopping OPANA ER. If your healthcare provider decides you no longer need OPANA ER, ask how to slowly reduce the dose of your medicine so you don’t get uncomfortable (withdrawal) symptoms such as nausea, sweating, and pain. You should not stop taking OPANA ER all at once if you have been taking it for more than a few days without talking to your healthcare provider. OPANA ER can cause physical dependence. You can get sick with withdrawal symptoms if you stop OPANA ER all at once, because your body has become use to it.

After you stop taking OPANA ER, flush the unused tablets down the toilet. Safely dispose of OPANA ER out of the reach of children and pets.

What Should I Avoid While Taking OPANA ER?

• Do not drive, operate heavy machinery, or participate in any other possibly dangerous activities until you know how you react to this medicine. OPANA ER can make you sleepy. Ask your healthcare provider to tell you when it is okay to do these activities.
  
  
• Do not drink alcohol while using OPANA ER. It may increase the chance of having dangerous side effects including overdose and death.

What are the Possible Side Effects of OPANA ER?
OPANA ER can cause trouble breathing.
Call your healthcare provider or get medical help right away if:

• your breathing slows down
  
  
• you have shallow breathing (little chest movement with breathing)
  
  
• you feel faint, dizzy, confused, or have any other unusual symptoms

These can be signs that you have taken too much OPANA ER (overdose) or the dose is too high for you, which can be dangerous and lead to death if not treated.

OPANA ER can cause your blood pressure to drop. This can make you feel dizzy if you get up too fast from sitting or lying down. Low blood pressure is also more likely to happen if you are taking other medicines that can also lower your blood pressure.

OPANA ER can cause physical dependence. Your body will get used to OPANA ER if you take it more than a few days. You can get sick with withdrawal symptoms if you stop taking OPANA ER all at once. You can avoid getting sick with withdrawal symptoms by stopping OPANA ER slowly. Your healthcare provider will tell you how to do this.

There is a chance of abuse or addiction with OPANA ER. Abuse or addiction is different than a physical dependence. If you have abused prescription medicines, street drugs or alcohol in the past, you may have a higher chance of developing abuse or addiction again while using OPANA ER. If you have more concerns, talk to your healthcare provider for more information about abuse and addiction.

The most common side effects of OPANA ER are nausea, constipation, dizziness, vomiting, itching, sleepiness, headache, increased sweating, and sedation. Some of these side effects may decrease with continued use. Talk to your healthcare provider if you continue to have these side effects.

These are not all the possible side effects of OPANA ER. For a complete list, ask your healthcare provider or pharmacist.

Constipation (decrease in the usual number of hard bowel movements) is a common side effect of opioid medicines, including OPANA ER. Talk to your healthcare provider or pharmacist about the use of laxatives (medicines to treat constipation) and stool softeners to prevent or treat constipation while taking OPANA ER.

How should I store OPANA ER?

• Store OPANA ER at room temperature between 59° to 86°F (15° to 30°C).
  
  
• Keep OPANA ER in a childproof container and store in a safe place to protect it from being stolen.
  
  
• Keep OPANA ER out of the reach of children. Accidental overdose in children is an emergency and can result in death.

General Information about OPANA ER

• Do not use OPANA ER for conditions for which it was not prescribed.
  
  
• Do not give OPANA ER to other people, even if they have the same symptoms you have. It may harm them, even causing death, and it is against the law.

This leaflet summarizes the most important information about OPANA ER. If you would like more information, talk with your healthcare provider. Also, you can ask your pharmacist or healthcare provider for information about OPANA ER that is written for healthcare professionals.

For additional information, please go to www.Endo.com or www.opana.com

What are the ingredients in OPANA ER?
Active Ingredient: oxymorphone hydrochloride
Inactive Ingredients: hypromellose, iron oxide black, methylparaben, propylene glycol, silicified microcrystalline cellulose, sodium stearyl fumarate, TIMERx^®-N, titanium dioxide, and triacetin. The 5 mg, 10 mg and 20 mg tablets also contain macrogol, and polysorbate 80. In addition, the 5 mg tablets contain iron oxide red. The 10 mg tablets contain FD and C yellow No. 6. The 20 mg tablets contain FD and C blue No. 1, FD and C yellow No. 6, and D and C yellow No. 10. The 40 mg tablets contain FD and C yellow No. 6, D and C yellow No.10, and lactose monohydrate.





CAUTION: Federal law prohibits dispensing without prescription.





Manufactured for:
Endo Pharmaceuticals Inc.
Chadds Ford, Pennsylvania 19317

Manufactured by:
Novartis Consumer Health Inc.
Lincoln, NE 68517

TIMERx^®-N is a registered Trademark of Penwest Pharmaceuticals Co., Danbury, Connecticut and is used herein pursuant to a license agreement between Penwest and Endo Pharmaceuticals.




                                                                 Copyright © Endo Pharmaceuticals Inc. 2006

                                                                                                                               413442/June, 2006

OPANA ER   C-II   5 MG  TABLETS

OPANA ER   C-II   10 MG   TABLETS

OPANA ER   C-II   40 MG   TABLETS