Opana Er

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 is an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine and other opioids.

OPANA ER, like morphine and other opioids used in analgesia, can be abused and is subject to criminal diversion.

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 leads to the rapid release and absorption of a potentially fatal dose 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 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 (seeBOXED 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 Patients Conversion from OPANA to OPANA ER

Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as OPANA ER, every 12 hours. 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 Ratioa

Oxymorphone 10 mg 1 Hydrocodone 20 mg 0.5 Oxycodone 20 mg 0.5 Methadone 20 mg 0.5 Morphine 30 mg 0.333

aRatio 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 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 of 10 mg every 12 hours every 3-7 days, until adequate pain relief and acceptable side effects have been achieved (see Individualization of Dose). Individualization of Dose

Once therapy is initiated, pain relief and other opioid effects should be frequently assessed. In clinical practice, titration of the total daily OPANA ER dose should be based upon the amount of supplemental opioid utilization, severity of the patient’s pain, and the patient’s ability to tolerate the opioid. Patients should be titrated 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.

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 OPANA, another immediate-release opioid, or a non-opioid analgesic may be administered. Dose adjustments should be made 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 under control, upward titration should continue 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. Patients and caregivers/family members should be advised of the potential side effects.

Patients with Hepatic Impairment

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).

Patients with Renal Impairment

There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively (seeCLINICAL 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.

Use with CNS Depressants

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 (seePRECAUTIONS: General and PRECAUTIONS: Drug-Drug Interactions).

Geriatrics

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects (seeCLINICAL 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.

Maintenance of Therapy and Supplemental Analgesia

The intent of the titration period is to establish a patient-specific every 12 hours dose that will maintain adequate analgesia with acceptable side effects for as long as pain relief is necessary. During titration and before a stable dose is achieved, OPANA or other immediate-release medications can be used as supplemental analgesia between dosings. Should pain recur, the dose can be incrementally increased to re-establish pain control. The method of therapy adjustment outlined above should be employed to re-establish pain control.

During chronic therapy with OPANA ER, the continued need for around-the-clock opioid therapy should be reassessed periodically.

Cessation of Therapy

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 (seeCLINICAL 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).

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 is an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine and other opioids.

OPANA ER, like morphine and other opioids used in analgesia, can be abused and is subject to criminal diversion.

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 leads to the rapid release and absorption of a potentially fatal dose 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 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 Patients Conversion from OPANA to OPANA ER

Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as OPANA ER, every 12 hours. 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).
      

Individualization of Dose

Once therapy is initiated, pain relief and other opioid effects should be frequently assessed. In clinical practice, titration of the total daily OPANA ER dose should be based upon the amount of supplemental opioid utilization, severity of the patient’s pain, and the patient’s ability to tolerate the opioid. Patients should be titrated 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.

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 OPANA, another immediate-release opioid, or a non-opioid analgesic may be administered. Dose adjustments should be made 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 under control, upward titration should continue 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. Patients and caregivers/family members should be advised of the potential side effects.

Patients with Hepatic Impairment

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).

Patients with Renal Impairment

There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively (see CLINICAL PHARMACOLOGY 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.

Use with CNS Depressants

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).

Geriatrics

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.

Maintenance of Therapy and Supplemental Analgesia

The intent of the titration period is to establish a patient-specific every 12 hours dose that will maintain adequate analgesia with acceptable side effects for as long as pain relief is necessary. During titration and before a stable dose is achieved, OPANA or other immediate-release medications can be used as supplemental analgesia between dosings. Should pain recur, the dose can be incrementally increased to re-establish pain control. The method of therapy adjustment outlined above should be employed to re-establish pain control.

During chronic therapy with OPANA ER, the continued need for around-the-clock opioid therapy should be reassessed periodically.

Cessation of Therapy

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).

2.1 Safe Administration Instructions

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.

While symmetric (same dose AM and PM), around-the-clock, every 12 hours dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different dose given in AM than in PM) dosing, tailored to their pain pattern. It is usually appropriate to treat a patient with only one extended-release opioid for around-the-clock therapy.

Selection of patients for treatment with OPANA ER should be governed by the same principles that apply to the use of other extended-release opioid analgesics [see Indications and Usage (1)]. Physicians should individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis, combination products, and chronic opioid therapy in a 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].

2.2 Initiating Therapy with OPANA ER

It is necessary to adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. In the selection of the initial dose of OPANA ER, attention should be given to the following:

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

Once therapy is initiated, frequently assess pain relief and other opioid effects. Base the titration of the total daily OPANA ER dose upon the amount of supplemental opioid utilization, severity of the patient’s pain, and the patient’s ability to tolerate the opioid. Titrate dose to generally mild or no pain with the regular use of no more than two doses of supplemental analgesia, i.e. “rescue,” per 24 hours. 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 OPANA ER 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 OPANA ER is 5 mg every 12 hours. Thereafter, titrate the dose individually at increments of 5-10 mg every 12 hours every 3-7 days, to a level that provides adequate analgesia and minimizes side effects under the close supervision of the prescribing physician.

Opioid-Experienced Patients
Conversion from OPANA to OPANA ER
Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as OPANA ER, every 12 hours.

Conversion from Parenteral Oxymorphone to OPANA ER
Given OPANA ER’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to OPANA ER by administering 10 times the patient's total daily parenteral oxymorphone dose as OPANA ER in two equally divided doses (e.g., [IV dose x 10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to OPANA ER
For conversion from other opioids to OPANA ER, physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion ratios are only approximate. 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. Gradually adjust the initial dose of OPANA ER 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. There is substantial patient variation in the relative potency of different opioid drugs and formulations.

CONVERSION RATIOS TO OPANA ER  aRatio 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 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 of 10 mg every 12 hours every 3-7 days, until adequate pain relief and acceptable side effects have been achieved [see Dosage and Administration (2.1)].  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.  Opioid  Approximate Equivalent Dose  Oral
Conversion Ratioa  Oral  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

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

2.3 Patients with Hepatic Impairment

Start patients with mild hepatic impairment with the lowest dose and titrate slowly while carefully monitoring side effects. OPANA ER is contraindicated in patients with moderate or severe hepatic impairment [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)].

2.4 Patients with Renal Impairment

There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively [see Clinical Pharmacology (12.3)]. Accordingly, in patients with creatinine clearance rates less than 50 mL/min, start OPANA ER with the lowest dose and titrate slowly while carefully monitoring side effects.

2.5 Use with Central Nervous System Depressants

In patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, start OPANA ER at 1/3 to 1/2 of the usual dose because respiratory depression, hypotension, and profound sedation, coma or death may result [see Warnings and Precautions (5.4) and Drug Interactions (7.2)].

Although no specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, OPANA ER is not recommended for use in patients who have received MAO inhibitors within 14 days [see Drug Interactions (7.6)].

2.6 Geriatrics Patients

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects. Exercise caution in the selection of the starting dose of OPANA ER for an elderly patient by starting at the low end of the dosing range and slowly titrating to adequate analgesia [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.5)].

2.7 Maintenance of Therapy

During chronic therapy with OPANA ER, periodically reassess the continued need for around-the-clock opioid therapy. Continue to assess patients for their clinical risks for opioid abuse, addiction, or diversion particularly with high-dose formulations. If patients need to titrate while on maintenance therapy, follow the same method outlined in Initiating Therapy with OPANA ER.

2.8 Cessation of Therapy

When the patient no longer requires therapy with OPANA ER tablets, gradually taper doses to prevent signs and symptoms of withdrawal in the physically dependent patient.

2.1   Safe Administration Instructions

OPANA ER tablets must be swallowed whole and are not to be cut, broken, chewed, dissolved, or crushed.  Taking cut, broken, chewed, dissolved, or crushed OPANA ER tablets leads to rapid release and absorption of a potentially fatal dose of oxymorphone. 

Patients must not consume alcoholic beverages, or prescription or non-prescription medications containing alcohol, while on OPANA ER therapy.  The co-ingestion of alcohol with OPANA ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone.

OPANA ER tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)].

OPANA ER must be taken on an empty stomach, at least one hour prior to or two hours after eating [see Clinical Pharmacology (12.3)].

While symmetric (same dose AM and PM), around-the-clock, every 12 hours dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different dose given in AM than in PM) dosing, tailored to their pain pattern.  It is usually appropriate to treat a patient with only one extended-release opioid for around-the-clock therapy.

Selection of patients for treatment with OPANA ER should be governed by the same principles that apply to the use of other extended-release opioid analgesics [see Indications and Usage (1)].  Physicians should individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis, combination products, and chronic opioid therapy in a progressiveplan of pain management such as outlined by the World Health Organization, the American Pain Society and the Federation of State Medical Boards Model Guidelines.  Healthcare professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring [see Boxed Warning].

2.2  Initiating Therapy with OPANA ER

It is necessary to adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. In the selection of the initial dose of OPANA ER, attention should be given to the following:

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

Once therapy is initiated, frequently assess pain relief and other opioid effects. Base the titration of the total daily OPANA ER dose upon the amount of supplemental opioid utilization, severity of the patient’s pain, and the patient’s ability to tolerate the opioid.  Titrate dose to generally mild or no pain with the regular use of no more than two doses of supplemental analgesia, i.e. “rescue,” per 24 hours, and tolerable side effects. Patients who experience breakthrough pain may require dosage adjustment.

If signs of excessive opioid-related adverse experiences are observed, the next dose may be reduced.  If this adjustment leads to inadequate analgesia, a supplemental dose of immediate-release opioid,  or a non-opioid analgesic may be administered. Adjust dosing to obtain an appropriate balance between pain relief and opioid-related adverse experiences.  If significant adverse events occur before the therapeutic goal of mild or no pain is achieved, the events should be treated aggressively.  If adverse events are adequately managed, continue upward titration to an acceptable level of pain control.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient and the caregiver/family. Advise patients and caregivers/family members of the potential adverse reactions.

The dosing recommendations below, therefore, can only be considered as suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.

Titrate dose to adequate pain relief (generally mild or no pain).

Opioid-Naïve Patients
The initial dose for patients who are not opioid-experienced and who are being initiated on chronic around-the-clock opioid therapy with OPANA ER is 5 mg every 12 hours.  Thereafter, titrate the dose individually at increments of 5-10 mg every 12 hours every 3-7 days, to a level that provides adequate analgesia and tolerable side effects under the close supervision of the prescribing physician.

Opioid-Experienced Patients
Conversion from OPANA to OPANA ER
Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as OPANA ER, every 12 hours. 

Conversion from Parenteral Oxymorphone to OPANA ER
Given OPANA ER’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to OPANA ER by administering 10 times the patient's total daily parenteral oxymorphone dose as OPANA ER in two equally divided doses (e.g., [IV dose x 10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to OPANA ER
For conversion from other opioids to OPANA ER, physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion ratios are only approximate. 

The following table provides approximate equivalent doses, which may be used as a guideline for conversion.  The conversion ratios and approximate equivalent doses in this conversion table are only to be used for the conversion from current opioid therapy to OPANA ER.  

In general, it is safest to start the OPANA ER therapy by administering 50% of the calculated total daily dose, calculated below, of OPANA ER (see conversion ratio table below) in 2 divided doses, every 12 hours. Gradually adjust the initial dose of OPANA ER until adequate pain relief and acceptable side effects have been achieved.

        Calculating the total daily dose of OPANA ER:

        Step 1    Calculate the total daily dose of the opioid.

        Step 2    Multiply the total daily dose for the opioid by the conversation ratio in Table 1 to calculate the total daily oxymorphone dose. 

Table 1:  Oral Opioid Conversion Ratios to OPANA ER

Oral Opioid

Oral Conversion Ratio

Oxymorphone

1

Hydrocodone

0.5

Oxycodone

0.5

Methadone a

0.5

Morphine

0.333

Step 3    Adjust the total daily dose of oxymorphone for the individual patient.

Step 4    Divide the total daily oxymorphone dose in half to determine the OPANA ER dose to be administered every 12 hours.

For patients on a regimen of mixed opioids, calculate the approximate oral oxymorphone dose for each opioid, sum the totals, and divide in half to estimate the total daily oxymorphone dose. The dose of OPANA ER can be gradually adjusted, preferably at increments of 10 mg every 12 hours every 3-7 days, until adequate pain relief and acceptable side effects have been achieved [see Dosage and Administration (2.1)].

aIt is extremely important to monitor all patients closely when converting from methadone to other opioid agonists including OPANA ER. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and accumulates in the plasma.

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

2.3   Patients with Hepatic Impairment

Start patients with mild hepatic impairment with the lowest dose and titrated slowly while carefully monitoring side effects. OPANA ER is contraindicated in patients with moderate or severe hepatic impairment [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)].

2.4   Patients with Renal Impairment

There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively [see Clinical Pharmacology (12.3)].  Accordingly, in patients with creatinine clearance rates less than 50 mL/min, start OPANA ER with the lowest dose and titrate slowly while carefully monitoring side effects.

2.5   Use with Central Nervous System Depressants

In patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, start OPANA ER at 1/3 to 1/2 of the usual dose because respiratory depression, hypotension, and profound sedation, coma or death may result [see Warnings and Precautions (5.4) and Drug Interactions (7.2)]. 

Although no specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, OPANA ER is not recommended for use in patients who have received MAO inhibitors within 14 days [see Drug Interactions (7.6)].

2.6   Geriatric Patients

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects.  Exercise caution in the selection of the starting dose of OPANA ER for an elderly patient by starting at the low end of the dosing range and slowly titrating to adequate analgesia [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.5)].

2.7   Maintenance of Therapy

During chronic therapy with OPANA ER, periodically reassess the continued need for around-the-clock opioid therapy.  Continue to assess patients for their clinical risks for opioid abuse, addiction, or diversion particularly with high-dose formulations.  If patients need to titrate while on maintenance therapy, follow the same method outlined in Initiating Therapy with OPANA ER .

2.8  Cessation of Therapy

When the patient no longer requires therapy with OPANA ER tablets, gradually taper doses to prevent signs and symptoms of withdrawal in the physically dependent patient.

2.1   Safe Administration Instructions

OPANA ER tablets must be swallowed whole and are not to be cut, broken, chewed, dissolved, or crushed.  Taking cut, broken, chewed, dissolved, or crushed OPANA ER tablets leads to rapid release and absorption of a potentially fatal dose of oxymorphone. 

Patients must not consume alcoholic beverages, or prescription or non-prescription medications containing alcohol, while on OPANA ER therapy.  The co-ingestion of alcohol with OPANA ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone.

OPANA ER tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)].

OPANA ER must be taken on an empty stomach, at least one hour prior to or two hours after eating [see Clinical Pharmacology (12.3)].

While symmetric (same dose AM and PM), around-the-clock, every 12 hours dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different dose given in AM than in PM) dosing, tailored to their pain pattern.  It is usually appropriate to treat a patient with only one extended-release opioid for around-the-clock therapy.

Selection of patients for treatment with OPANA ER should be governed by the same principles that apply to the use of other extended-release opioid analgesics [see Indications and Usage (1)].  Physicians should individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis, combination products, and chronic opioid therapy in a progressiveplan of pain management such as outlined by the World Health Organization, the American Pain Society and the Federation of State Medical Boards Model Guidelines.  Healthcare professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring [see Boxed Warning].

2.2  Initiating Therapy with OPANA ER

It is necessary to adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. In the selection of the initial dose of OPANA ER, attention should be given to the following:

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

Once therapy is initiated, frequently assess pain relief and other opioid effects. Base the titration of the total daily OPANA ER dose upon the amount of supplemental opioid utilization, severity of the patient’s pain, and the patient’s ability to tolerate the opioid.  Titrate dose to generally mild or no pain with the regular use of no more than two doses of supplemental analgesia, i.e. “rescue,” per 24 hours, and tolerable side effects. Patients who experience breakthrough pain may require dosage adjustment.

If signs of excessive opioid-related adverse experiences are observed, the next dose may be reduced.  If this adjustment leads to inadequate analgesia, a supplemental dose of immediate-release opioid,  or a non-opioid analgesic may be administered. Adjust dosing to obtain an appropriate balance between pain relief and opioid-related adverse experiences.  If significant adverse events occur before the therapeutic goal of mild or no pain is achieved, the events should be treated aggressively.  If adverse events are adequately managed, continue upward titration to an acceptable level of pain control.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient and the caregiver/family. Advise patients and caregivers/family members of the potential adverse reactions.

The dosing recommendations below, therefore, can only be considered as suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.

Titrate dose to adequate pain relief (generally mild or no pain).

Opioid-Naïve Patients
The initial dose for patients who are not opioid-experienced and who are being initiated on chronic around-the-clock opioid therapy with OPANA ER is 5 mg every 12 hours.  Thereafter, titrate the dose individually at increments of 5-10 mg every 12 hours every 3-7 days, to a level that provides adequate analgesia and tolerable side effects under the close supervision of the prescribing physician.

Opioid-Experienced Patients
Conversion from OPANA to OPANA ER
Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as OPANA ER, every 12 hours. 

Conversion from Parenteral Oxymorphone to OPANA ER
Given OPANA ER’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to OPANA ER by administering 10 times the patient's total daily parenteral oxymorphone dose as OPANA ER in two equally divided doses (e.g., [IV dose x 10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to OPANA ER
For conversion from other opioids to OPANA ER, physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion ratios are only approximate. 

The following table provides approximate equivalent doses, which may be used as a guideline for conversion.  The conversion ratios and approximate equivalent doses in this conversion table are only to be used for the conversion from current opioid therapy to OPANA ER.  

In general, it is safest to start the OPANA ER therapy by administering 50% of the calculated total daily dose, calculated below, of OPANA ER (see conversion ratio table below) in 2 divided doses, every 12 hours. Gradually adjust the initial dose of OPANA ER until adequate pain relief and acceptable side effects have been achieved.

        Calculating the total daily dose of OPANA ER:

        Step 1    Calculate the total daily dose of the opioid.

        Step 2    Multiply the total daily dose for the opioid by the conversation ratio in Table 1 to calculate the total daily oxymorphone dose. 

Table 1:  Oral Opioid Conversion Ratios to OPANA ER

Oral Opioid

Oral Conversion Ratio

Oxymorphone

1

Hydrocodone

0.5

Oxycodone

0.5

Methadone a

0.5

Morphine

0.333

Step 3    Adjust the total daily dose of oxymorphone for the individual patient.

Step 4    Divide the total daily oxymorphone dose in half to determine the OPANA ER dose to be administered every 12 hours.

For patients on a regimen of mixed opioids, calculate the approximate oral oxymorphone dose for each opioid, sum the totals, and divide in half to estimate the total daily oxymorphone dose. The dose of OPANA ER can be gradually adjusted, preferably at increments of 10 mg every 12 hours every 3-7 days, until adequate pain relief and acceptable side effects have been achieved [see Dosage and Administration (2.1)].

aIt is extremely important to monitor all patients closely when converting from methadone to other opioid agonists including OPANA ER. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and accumulates in the plasma.

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

2.3   Patients with Hepatic Impairment

Start patients with mild hepatic impairment with the lowest dose and titrated slowly while carefully monitoring side effects. OPANA ER is contraindicated in patients with moderate or severe hepatic impairment [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)].

2.4   Patients with Renal Impairment

There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively [see Clinical Pharmacology (12.3)].  Accordingly, in patients with creatinine clearance rates less than 50 mL/min, start OPANA ER with the lowest dose and titrate slowly while carefully monitoring side effects.

2.5   Use with Central Nervous System Depressants

In patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, start OPANA ER at 1/3 to 1/2 of the usual dose because respiratory depression, hypotension, and profound sedation, coma or death may result [see Warnings and Precautions (5.4) and Drug Interactions (7.2)]. 

Although no specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, OPANA ER is not recommended for use in patients who have received MAO inhibitors within 14 days [see Drug Interactions (7.6)].

2.6   Geriatric Patients

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects.  Exercise caution in the selection of the starting dose of OPANA ER for an elderly patient by starting at the low end of the dosing range and slowly titrating to adequate analgesia [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.5)].

2.7   Maintenance of Therapy

During chronic therapy with OPANA ER, periodically reassess the continued need for around-the-clock opioid therapy.  Continue to assess patients for their clinical risks for opioid abuse, addiction, or diversion particularly with high-dose formulations.  If patients need to titrate while on maintenance therapy, follow the same method outlined in Initiating Therapy with OPANA ER .

2.8  Cessation of Therapy

When the patient no longer requires therapy with OPANA ER tablets, gradually taper doses to prevent signs and symptoms of withdrawal in the physically dependent patient.

Enter section text here

2 DOSAGE AND ADMINISTRATION

2.1 Safe Administration Instructions

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.

While symmetric (same dose AM and PM), around-the-clock, every 12 hours dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different dose given in AM than in PM) dosing, tailored to their pain pattern. It is usually appropriate to treat a patient with only one extended-release opioid for around-the-clock therapy.

Selection of patients for treatment with OPANA ER should be governed by the same principles that apply to the use of other extended-release opioid analgesics [see Indications and Usage (1)]. Physicians should individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis, combination products, and chronic opioid therapy in a 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].

2.2 Initiating Therapy with OPANA ER It is necessary to adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. In the selection of the initial dose of OPANA ER, attention should be given to the following:

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

Once therapy is initiated, frequently assess pain relief and other opioid effects. Base the titration of the total daily OPANA ER dose upon the amount of supplemental opioid utilization, severity of the patient’s pain, and the patient’s ability to tolerate the opioid. Titrate dose to generally mild or no pain with the regular use of no more than two doses of supplemental analgesia, i.e. “rescue,” per 24 hours. 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 OPANA ER 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 OPANA ER is 5 mg every 12 hours. Thereafter, titrate the dose individually at increments of 5-10 mg every 12 hours every 3-7 days, to a level that provides adequate analgesia and minimizes side effects under the close supervision of the prescribing physician.

Opioid-Experienced Patients
Conversion from OPANA to OPANA ER
Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as OPANA ER, every 12 hours.

Conversion from Parenteral Oxymorphone to OPANA ER
Given OPANA ER’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to OPANA ER by administering 10 times the patient's total daily parenteral oxymorphone dose as OPANA ER in two equally divided doses (e.g., [IV dose x 10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to OPANA ER
For conversion from other opioids to OPANA ER, physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion ratios are only approximate. 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. Gradually adjust the initial dose of OPANA ER 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. There is substantial patient variation in the relative potency of different opioid drugs and formulations.

CONVERSION RATIOS TO OPANA ER


Approximate Equivalent Dose
Oral
Opioid
Oral
Conversion Ratioa
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
aRatio 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 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 of 10 mg every 12 hours every 3-7 days, until adequate pain relief and acceptable side effects have been achieved [see Dosage and Administration (2.1)].

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.


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

2.3 Patients with Hepatic Impairment
Start patients with mild hepatic impairment with the lowest dose and titrate slowly while carefully monitoring side effects. OPANA ER is contraindicated in patients with moderate or severe hepatic impairment [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)].

2.4 Patients with Renal Impairment
There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively [see Clinical Pharmacology (12.3)]. Accordingly, in patients with creatinine clearance rates less than 50 mL/min, start OPANA ER with the lowest dose and titrate slowly while carefully monitoring side effects.

2.5 Use with Central Nervous System Depressants In patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, start OPANA ER at 1/3 to 1/2 of the usual dose because respiratory depression, hypotension, and profound sedation, coma or death may result [see Warnings and Precautions (5.4) and Drug Interactions (7.2)].

Although no specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, OPANA ER is not recommended for use in patients who have received MAO inhibitors within 14 days [see Drug Interactions (7.6)].

2.6 Geriatrics Patients
The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects. Exercise caution in the selection of the starting dose of OPANA ER for an elderly patient by starting at the low end of the dosing range and slowly titrating to adequate analgesia [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.5)].

2.7 Maintenance of Therapy
During chronic therapy with OPANA ER, periodically reassess the continued need for around-the-clock opioid therapy. Continue to assess patients for their clinical risks for opioid abuse, addiction, or diversion particularly with high-dose formulations. If patients need to titrate while on maintenance therapy, follow the same method outlined in Initiating Therapy with OPANA ER.

2.8 Cessation of Therapy
When the patient no longer requires therapy with OPANA ER tablets, gradually taper doses to prevent signs and symptoms of withdrawal in the physically dependent patient.

Enter section text here

2 DOSAGE AND ADMINISTRATION

2.1 Safe Administration Instructions

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.

While symmetric (same dose AM and PM), around-the-clock, every 12 hours dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different dose given in AM than in PM) dosing, tailored to their pain pattern. It is usually appropriate to treat a patient with only one extended-release opioid for around-the-clock therapy.

Selection of patients for treatment with OPANA ER should be governed by the same principles that apply to the use of other extended-release opioid analgesics [see Indications and Usage (1)]. Physicians should individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis, combination products, and chronic opioid therapy in a 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].

2.2 Initiating Therapy with OPANA ER It is necessary to adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. In the selection of the initial dose of OPANA ER, attention should be given to the following:

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

Once therapy is initiated, frequently assess pain relief and other opioid effects. Base the titration of the total daily OPANA ER dose upon the amount of supplemental opioid utilization, severity of the patient’s pain, and the patient’s ability to tolerate the opioid. Titrate dose to generally mild or no pain with the regular use of no more than two doses of supplemental analgesia, i.e. “rescue,” per 24 hours. 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 OPANA ER 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 OPANA ER is 5 mg every 12 hours. Thereafter, titrate the dose individually at increments of 5-10 mg every 12 hours every 3-7 days, to a level that provides adequate analgesia and minimizes side effects under the close supervision of the prescribing physician.

Opioid-Experienced Patients
Conversion from OPANA to OPANA ER
Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as OPANA ER, every 12 hours.

Conversion from Parenteral Oxymorphone to OPANA ER
Given OPANA ER’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to OPANA ER by administering 10 times the patient's total daily parenteral oxymorphone dose as OPANA ER in two equally divided doses (e.g., [IV dose x 10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to OPANA ER
For conversion from other opioids to OPANA ER, physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion ratios are only approximate. 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. Gradually adjust the initial dose of OPANA ER 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. There is substantial patient variation in the relative potency of different opioid drugs and formulations.

CONVERSION RATIOS TO OPANA ER


Approximate Equivalent Dose
Oral
Opioid
Oral
Conversion Ratioa
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
aRatio 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 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 of 10 mg every 12 hours every 3-7 days, until adequate pain relief and acceptable side effects have been achieved [see Dosage and Administration (2.1)].

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.


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

2.3 Patients with Hepatic Impairment
Start patients with mild hepatic impairment with the lowest dose and titrate slowly while carefully monitoring side effects. OPANA ER is contraindicated in patients with moderate or severe hepatic impairment [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.3)].

2.4 Patients with Renal Impairment
There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively [see Clinical Pharmacology (12.3)]. Accordingly, in patients with creatinine clearance rates less than 50 mL/min, start OPANA ER with the lowest dose and titrate slowly while carefully monitoring side effects.

2.5 Use with Central Nervous System Depressants In patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, start OPANA ER at 1/3 to 1/2 of the usual dose because respiratory depression, hypotension, and profound sedation, coma or death may result [see Warnings and Precautions (5.4) and Drug Interactions (7.2)].

Although no specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, OPANA ER is not recommended for use in patients who have received MAO inhibitors within 14 days [see Drug Interactions (7.6)].

2.6 Geriatrics Patients
The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects. Exercise caution in the selection of the starting dose of OPANA ER for an elderly patient by starting at the low end of the dosing range and slowly titrating to adequate analgesia [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.5)].

2.7 Maintenance of Therapy
During chronic therapy with OPANA ER, periodically reassess the continued need for around-the-clock opioid therapy. Continue to assess patients for their clinical risks for opioid abuse, addiction, or diversion particularly with high-dose formulations. If patients need to titrate while on maintenance therapy, follow the same method outlined in Initiating Therapy with OPANA ER.

2.8 Cessation of Therapy
When the patient no longer requires therapy with OPANA ER tablets, gradually taper doses to prevent signs and symptoms of withdrawal in the physically dependent patient.

2.1  Initial Dosing

Initiate the dosing regimen for each patient individually, taking into account the patient"s prior analgesic treatment experience. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with OPANA ER [see Warnings and Precautions (5.2)].

Consider the following factors when selecting an initial dose of OPANA ER:

Total daily dose, potency, and any prior opioid the patient has been taking previously; Reliability of the relative potency estimate used to calculate the equivalent dose of oxymorphone needed (Note: potency estimates may vary with the route of administration); Patient"s degree of opioid experience and opioid tolerance; General condition and medical status of the patient; Concurrent medication; Type and severity of the patient"s pain.

OPANA ER tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)].

OPANA ER is administered at a frequency of twice daily (every 12 hours).  Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

Use of OPANA ER as the First Opioid Analgesic

Initiate Opana ER therapy with the 5 mg tablet twice daily (at 12-hour intervals).  Adjust the dose of OPANA ER in increments of 5-10 mg every 12 hours every 3 to 7 days.

Conversion from OPANA to OPANA ER

Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as OPANA ER, every 12 hours.

Conversion from Parenteral Oxymorphone to OPANA ER

The absolute oral bioavailability of OPANA ER is approximately 10%.  Convert patients receiving parenteral oxymorphone to OPANA ER by administering 10 times the patient"s total daily parenteral oxymorphone dose as OPANA ER in two equally divided doses (e.g., [IV dose x 10] divided by 2).  Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to OPANA ER

While there are useful tables of oral and parenteral equivalents, there is substantial inter-patient variability in the relative potency of different opioid drugs and formulations. As such, it is safer to underestimate a patient’s 24-hour oral oxymorphone dose and provide rescue medication (e.g. immediate-release oxymorphone) than to overestimate the 24-hour oral oxymorphone dose and manage an adverse reaction.  Consider the following general points:

In a Phase 3 clinical trial with an open-label titration period, patients were converted from their prior opioid to OPANA ER using the following table as a guide for the initial OPANA ER dose.  

The table is not a table of equianalgesic doses.  The conversion ratios in this table are only to be used for the conversion from oral therapy with one of the listed opioid analgesics to OPANA ER.   Do not use this table to convert from OPANA ER to another opioid. Doing so will result in an over-estimation of the dose of the new opioid and may result in fatal overdose.

For example, a patient receiving oxycodone at a total daily dose of 40 mg would then be converted to a total daily dose of 20 mg of oxymorphone (40 mg x 0.5), dosed as OPANA ER 10 mg twice daily.

CONVERSION RATIOS TO OPANA ER  Opioids  Total Daily Oral Dose  Oral Conversion Ratio  Oxymorphone  10 mg  1  Hydrocodone  20 mg  0.5  Oxycodone  20 mg  0.5  Methadone  20 mg  0.5  Morphine  30 mg  0.333 2.2  Titration and Maintenance of Therapy

Individually titrate OPANA ER to a dose that provides adequate analgesia and minimizes adverse reactions.  Continually reevaluate patients receiving OPANA ER to assess the maintenance of pain control and the relative incidence of adverse reactions.  During chronic therapy, especially for non-cancer-related pain (or pain associated with other terminal illnesses), periodically reassess the continued need for the use of opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the OPANA ER dose to decrease the level of pain.  Because steady-state plasma concentrations are approximated within 3 days, OPANA ER dosage adjustments, preferably at increments of 5-10 mg every 12 hours, may be done every 3 to 7 days.  Patients who experience breakthrough pain may require dosage adjustment or rescue medication with a small dose of an immediate-release medication (e.g. immediate-release oxymorphone). 

During chronic, around-the-clock opioid therapy, especially for non-cancer pain syndromes, reassess the continued need for around-the-clock opioid therapy periodically (e.g., every 6 to 12 months) as appropriate.

If signs of excessive opioid-related adverse reactions are observed, the next dose may be reduced.  Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3   Discontinuation of OPANA ER

When a patient no longer requires therapy with OPANA ER, use a gradual downward titration of the dose every two to four days, to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not abruptly discontinue OPANA ER. 

2.4   Administration of OPANA ER

Instruct patients to swallow OPANA ER tablets intact.  The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions (5.2)]. Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

2.5   Patients with Hepatic Impairment

OPANA ER is contraindicated in patients with moderate or severe hepatic impairment.

In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose.  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient with normal hepatic function on prior opioids and titrate slowly.  Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.6   Patients with Renal Impairment

In patients with creatinine clearance rates less than 50 mL/min, start OPANA ER in the opioid-naïve patient with the 5 mg dose.  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient with normal renal function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.7   Geriatric Patients

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects.  Initiate dosing with OPANA ER in patients 65 years of age and over using the 5 mg dose and monitor closely for signs of respiratory and central nervous system depression when initiating and titrating OPANA ER to adequate analgesia [see Warnings and Precautions (5.2), Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)].  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a younger patient on prior opioids and titrate slowly.

2.1  Initial Dosing

To avoid medication errors, prescribers and pharmacists must be aware that oxymorphone is available as both immediate-release 5 mg and 10 mg tablets and extended-release 5 mg and 10 mg tablets [see Dosage Forms and Strengths (3)].

OPANA ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Initiate the dosing regimen for each patient individually, taking into account the patient"s prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with OPANA ER [see Warnings and Precautions (5.2)].

OPANA ER tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)].  Crushing, chewing, or dissolving OPANA ER tablets will result in uncontrolled delivery of oxymorphone and can lead to overdose or death [see Warnings and Precautions (5.2)].

OPANA ER is administered at a frequency of twice daily (every 12 hours).  Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

Use of OPANA ER as the First Opioid Analgesic

Initiate treatment with OPANA ER with the 5 mg tablet orally every 12-hours.

Use of OPANA ER in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is OPANA ER 5 mg orally every 12 hours.  Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from OPANA to OPANA ER

Patients receiving OPANA may be converted to OPANA ER by administering half the patient"s total daily oral OPANA dose as OPANA ER, every 12 hours.

Conversion from Parenteral Oxymorphone to OPANA ER

The absolute oral bioavailability of OPANA ER is approximately 10%.  Convert patients receiving parenteral oxymorphone to OPANA ER by administering 10 times the patient"s total daily parenteral oxymorphone dose as OPANA ER in two equally divided doses (e.g., [IV dose x 10] divided by 2).  Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to OPANA ER

Discontinue all other around-the-clock opioid drugs when OPANA ER therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter- patient variability in the relative potency of different opioid drugs and products. As such, it is preferable to underestimate a patient’s 24-hour oral oxymorphone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxymorphone requirements which could result in adverse reactions.  In an OPANA ER clinical trial with an open-label titration period, patients were converted from their prior opioid to OPANA ER using Table 1 as a guide for the initial OPANA ER dose.

Consider the following when using the information in Table 1:

This is not a table of equianalgesic doses.  The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to OPANA ER.   This table cannot be used to convert from OPANA ER to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose.

CONVERSION FACTORS TO OPANA ER

Prior Oral Opioid

Approximate Oral Conversion Factor

Oxymorphone

1

Hydrocodone

0.5

Oxycodone

0.5

Methadone

0.5

Morphine

0.333

To calculate the estimated OPANA ER dose using Table 1:

For patients on a single opioid, sum the current total daily dose of the opioid and then multiply the total daily dose by the conversion factor to calculate the approximate oral oxymorphone daily dose. For patients on a regimen of more than one opioid, calculate the approximate oral oxymorphone dose for each opioid and sum the totals to obtain the approximate total oxymorphone daily dose. For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion

Always round the dose down, if necessary, to the appropriate OPANA ER strength(s) available.

Example conversion from a single opioid to OPANA ER:

Step 1:  Sum the total daily dose of the opioid oxycodone 20 mg BID
             20 mg former opioid 2 times daily = 40 mg total daily dose of former opioid

Step 2:  Calculate the approximate equivalent dose of oral oxymorphone based on the total daily dose of the current opioid using Table 1
             40 mg total daily dose of former opioid x 0.5 mg Conversion Factor = 20 mg of oral oxymorphone daily

Step 3:  Calculate the approximate starting dose of OPANA ER to be given every 12 hours. Round down, if necessary, to the appropriate
             OPANA ER TABLETS strengths available.
             10 mg OPANA ER every 12 hours

Conversion from Methadone to OPANA ER

Close monitoring is of particular importance 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 can accumulate in the plasma.

2.2  Titration and Maintenance of Therapy

Individually titrate OPANA ER to a dose that provides adequate analgesia and minimizes adverse reactions.  Continually reevaluate patients receiving OPANA ER to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, and misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the OPANA ER dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3 days, OPANA ER dosage adjustments, preferably at increments of 5-10 mg every 12 hours, may be done every 3 to 7 days. 

Patients who experience breakthrough pain may require a dose increase of OPANA ER, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing OPANA ER dose. 

If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced.  Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3   Discontinuation of OPANA ER

When a patient no longer requires therapy with OPANA ER, use a gradual downward titration of the dose every two to four days, to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not abruptly discontinue OPANA ER.

2.4   Administration of OPANA ER

Instruct patients to swallow OPANA ER tablets intact.  The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions (5.2)]. Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

2.5   Patients with Hepatic Impairment

OPANA ER is contraindicated in patients with moderate or severe hepatic impairment.

In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose.  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient with normal hepatic function on prior opioids and titrate slowly.  Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.6   Patients with Renal Impairment

In patients with creatinine clearance rates less than 50 mL/min, start OPANA ER in the opioid-naïve patient with the 5 mg dose.  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient with normal renal function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.7   Geriatric Patients

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects.  Initiate dosing with OPANA ER in patients 65 years of age and over using the 5 mg dose and monitor closely for signs of respiratory and central nervous system depression when initiating and titrating OPANA ER to adequate analgesia [see Warnings and Precautions (5.2), Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)].  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a younger patient on prior opioids and titrate slowly.

2.1 Initial Dosing

To avoid medication errors, prescribers and pharmacists must be aware that oxymorphone is available as both immediate-release 5 mg and 10 mg tablets and extended-release 5 mg and 10 mg tablets [see Dosage Forms and Strengths].

OPANA ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Initiate the dosing regimen for each patient individually, taking into account the patient"s prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with OPANA ER [see Warnings and Precautions (5.2)].

OPANA ER tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling Information (17)].  Crushing, chewing, or dissolving OPANA ER tablets will result in uncontrolled delivery of oxymorphone and can lead to overdose or death [see Warnings and Precautions (5.2)].

OPANA ER is administered at a frequency of twice daily (every 12 hours).  Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

Use of OPANA ER as the First Opioid Analgesic

Initiate treatment with OPANA ER with the 5 mg tablet orally every 12-hours. 

Use of OPANA ER in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is OPANA ER 5 mg orally every 12 hours.  Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from OPANA to OPANA ER

Patients receiving OPANA may be converted to OPANA ER by administering half the patient"s total daily oral OPANA dose as OPANA ER, every 12 hours.

Conversion from Parenteral Oxymorphone to OPANA ER

The absolute oral bioavailability of OPANA ER is approximately 10%.  Convert patients receiving parenteral oxymorphone to OPANA ER by administering 10 times the patient"s total daily parenteral oxymorphone dose as OPANA ER in two equally divided doses (e.g., [IV dose x 10] divided by 2).  Due to patient variability with regards to opioid analgesic response, upon conversion monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to OPANA ER

Discontinue all other around-the-clock opioid drugs when OPANA ER therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter- patient variability in the relative potency of different opioid drugs and products. As such, it is preferable to underestimate a patient’s 24-hour oral oxymorphone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxymorphone requirements which could result in adverse reactions.  In an OPANA ER clinical trial with an open-label titration period, patients were converted from their prior opioid to OPANA ER using Table 1 as a guide for the initial OPANA ER dose.

Consider the following when using the information in Table 1:

This is not a table of equianalgesic doses.  The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to OPANA ER.   This table cannot be used to convert from OPANA ER to another opioid. Doing so will result in an over-estimation of the dose of the new opioid and may result in fatal overdose.

CONVERSION FACTORS TO OPANA ER

Prior Oral Opioid

Approximate Oral Conversion Factor

Oxymorphone

1

Hydrocodone

0.5

Oxycodone

0.5

Methadone

0.5

Morphine

0.333

To calculate the estimated OPANA ER dose using Table 1:

For patients on a single opioid, sum the current total daily dose of the opioid and then multiply the total daily dose by the conversion factor to calculate the approximate oral oxymorphone daily dose. For patients on a regimen of more than one opioid, calculate the approximate oral oxymorphone dose for each opioid and sum the totals to obtain the approximate total oxymorphone daily dose. For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion

Always round the dose down, if necessary, to the appropriate OPANA ER strength(s) available.

Example conversion from a single opioid to OPANA ER:

Step 1:  Sum the total daily dose of the opioid oxycodone 20 mg BID

             20 mg former opioid 2 times daily = 40 mg total daily dose of former opioid

Step 2:  Calculate the approximate equivalent dose of oral oxymorphone based on the total daily dose of the current opioid using Table 1

             40 mg total daily dose of former opioid x 0.5 mg Conversion Factor = 20 mg of oral oxymorphone daily

Step 3:  Calculate the approximate starting dose of OPANA ER to be given every 12 hours. Round down, if necessary, to the
              appropriate OPANA ER TABLETS strengths available.

              10 mg OPANA ER every 12 hours

Conversion from Methadone to OPANA ER

Close monitoring is of particular importance 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 can accumulate in the plasma.

2.2 Titration and Maintenance of Therapy

Individually titrate OPANA ER to a dose that provides adequate analgesia and minimizes adverse reactions.  Continually reevaluate patients receiving OPANA ER to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, and misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.  During chronic therapy, periodically reassess the continued need for the use of opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the OPANA ER dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3 days, OPANA ER dosage adjustments, preferably at increments of 5-10 mg every 12 hours, may be done every 3 to 7 days.                

Patients who experience breakthrough pain may require a dose increase of OPANA ER, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing OPANA ER dose. 

If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced.  Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3 Discontinuation of OPANA ER

When a patient no longer requires therapy with OPANA ER, use a gradual downward titration of the dose every two to four days, to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not abruptly discontinue OPANA ER.

2.4 Administration of OPANA ER

Instruct patients to swallow OPANA ER tablets intact.  The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions (5.2)]. Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

2.5 Patients with Hepatic Impairment

OPANA ER is contraindicated in patients with moderate or severe hepatic impairment.

In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose.  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient with normal hepatic function on prior opioids and titrate slowly.  Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.6 Patients with Renal Impairment

In patients with creatinine clearance rates less than 50 mL/min, start OPANA ER in the opioid-naïve patient with the 5 mg dose.  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient with normal renal function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.7 Geriatric Patients

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects.  Initiate dosing with OPANA ER in patients 65 years of age and over using the 5 mg dose and monitor closely for signs of respiratory and central nervous system depression when initiating and titrating OPANA ER to adequate analgesia [see Warnings and Precautions (5.2), Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)].  For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a younger patient on prior opioids and titrate slowly.