Usual Adult Dose for Pain

The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time; each patient should be managed individually.

ORAL:
Use as first Opioid Analgesic:

• Initial dose: 10 to 20 mg orally every 4 to 6 hours as needed for pain

Maximum initial dose: 20 mg

Conversion from Other Oral Opioids to Oral Oxymorphone:

• Determine equipotent dose using published potency tables; it is safest to start therapy by administering one-half the calculated total daily oxymorphone requirement in 4 to 6 equally divided oral doses every 4 to 6 hours and gradually adjust dose as needed.

Comments:

• Dose conversion should be done carefully and with close monitoring due to large patient variability in regards to opioid analgesic response.
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
• Monitor closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and with each dose increase.
• Due to risks of addiction, abuse, and misuse, even at recommended doses, reserve use for patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products) have not been tolerated, or are not expected to be tolerated, or have not provided adequate analgesia, or are not expected to provide adequate analgesia.

Use: For the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Usual Adult Dose for Chronic Pain

The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time; each patient should be managed individually.

Use as the First Opioid Analgesic or for those who are NOT Opioid Tolerant:
Initial dose: Extended-release tablets: 5 mg orally every 12 hours

CONVERSION DOSES:
Immediate-Release Oxymorphone to Extended-Release Oxymorphone Tablets: Administer same total daily dose

• Initial dose: One-half total daily immediate-release requirement as extended-release tablet orally every 12 hours

From Other Oral Opioids to Oxymorphone Extended-Release Tablets:

• Discontinue all other around-the-clock opioid drugs when oxymorphone extended-release therapy is initiated.
• Published potency tables can be used to estimate a patient's 24-hour oral oxymorphone requirement; however, due to substantial inter-patient variability, the conversion should then underestimate a patient's 24-hour requirement and provide rescue medication as the dose is titrated.
• Alternatively, the following conversion factors (CF) may be used to convert selected oral opioids to the extended-release oxymorphone tablet: Oxymorphone, CF=1; Hydrocodone, CF=0.5; Oxycodone, CF=0.5; Methadone, CF= 0.5, Morphine, CF=0.333
• As an example: Sum the total daily dose of prior oral opioid; multiply that sum by the CF to obtain 24-hour oral oxymorphone requirement; divide by 2 to calculate approximate starting dose to be given every 12 hours, round down, if necessary.
• These CFs cannot be used to convert from oxymorphone extended-release tablets to the selected oral opioid as doing so will result in overestimation of the oral opioid dose and may result in fatal respiratory depression

TITRATION AND MAINTENANCE:
Maintenance Dose: Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions; dose adjustments may be made in 5 to 10 mg increments every 12 hours, every 3 to 7 days.
Breakthrough Pain: If the level of pain increases after dose stabilization, attempt to identify the source before increasing dose; rescue medication with appropriate immediate-release analgesia may be helpful

Comments:

• An opioid tolerant patient is one who has been receiving for 1-week or longer at least: oral morphine 60 mg/day, fentanyl transdermal patch 25 mcg per hour, oral oxycodone 30 mg/day, oral hydromorphone 8 mg/day, oral oxymorphone 25 mg/day, or an equianalgesic dose of another opioid
• When converting from methadone, close monitoring is of particular importance due to methadone's long half-life.
• Dose conversion should be done carefully and with close monitoring due to large patient variability in regards to opioid analgesic response.
• Upon cessation of therapy in the physically dependent patient, individually taper reassessing frequently to manage pain and withdrawal symptoms.

Use: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Renal Dose Adjustments

Moderate to severe renal impairment: Use with caution starting at the lowest dose and titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

Extended-release tablets:
Opioid-naive with CrCl less than 50 mL/min: Initial dose: 5 mg orally every 12 hours
Opioid-experienced with CrCl less than 50 mL/min: Initial dose: 50% lower than starting dose for patients with normal function, titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

Liver Dose Adjustments

Moderate to severe hepatic impairment: Use is contraindicated
Mild hepatic impairment: titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

Extended-release tablets:
Opioid-naive with mild hepatic impairment: Initial dose: 5 mg orally every 12 hours
Opioid-experienced with mild hepatic impairment: Initial dose: 50% lower than starting dose for patients with normal function, titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

Dose Adjustments

Elderly:
Immediate-release: Use with caution starting at the lowest dose and titrate slowly while monitoring for side effects.
Extended-release tablets:
Initial dose: 5 mg orally every 12 hours; titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

Use with CNS depressants:

• This drug should be started at one-third to one-half of the usual dose in patients concurrently receiving other CNS depressants.

Safe Reduction or Discontinuation of Therapy:

• Discontinuation/reduction plans should be individualized and take into consideration multiple factors such as type of pain, dose and duration of treatment, and patient specific physical and psychological attributes; patients should receive ongoing care and follow-up that addresses agreed upon and realistic goals.
• While there are no standard opioid tapering schedules suitable for all patients, good clinical practice dictates tapering in small increments (e.g., no greater than 10% to 25% of the total daily dose) at 2 to 4-week intervals; patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
• When an opioid analgesic is being discontinued due to a suspected substance use disorder, patients should be evaluated and treated, or referred for evaluation and treatment of a substance use disorder; treatment should include evidence-based approaches, such as medication assisted treatment.
• When discontinuing or reducing opioid doses in patients who have been receiving therapy for an extended period and/or at higher doses for chronic pain, a multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for all opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
ADDICTION, ABUSE, and MISUSE: This drug exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing, and monitor all patients regularly for the development of these behaviors or conditions.
REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.
LIFE-THREATENING RESPIRATORY DEPRESSION: Serious, life-threatening, or fatal respiratory depression may occur. Monitor for respiratory depression, especially during initiation or following a dose increase. Instruct patients to swallow extended-release tablets whole; crushing, chewing or dissolving can cause rapid release and absorption of a potentially fatal dose of oxymorphone.
ACCIDENTAL INGESTION: Accidental ingestion of even 1 dose of the extended-release tablet, especially by children, can result in a fatal overdose of oxymorphone.
NEONATAL OPIOID WITHDRAWAL SYNDROME: Prolonged use of this drug during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
INTERACTION WITH ALCOHOL: Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking this drug. The co-ingestion of alcohol with this drug may result in increased plasma levels and a potentially fatal overdose of oxymorphone.
RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use to cases when alternative treatment options are inadequate; limit dose and duration to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

CONTRAINDICATIONS:

• Significant respiratory depression
• Acute or severe bronchial asthma or hypercarbia
• Known hypersensitivity to this drug or product excipients
• Moderate or severe hepatic impairment
• Known or suspected paralytic ileus
• Known or suspected gastrointestinal obstruction (extended-release)

Safety and efficacy have not been established in patients younger than 18 years.

On June 8, 2017, The US FDA requested removal of Opana ER for risks related to abuse; Endo Pharmaceuticals has agreed to voluntarily withdraw this product from the market and will work with the FDA to coordinate an orderly removal in a manner to minimize treatment disruption and allow patients sufficient time to seek guidance from their healthcare professionals.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II

Dialysis

Data not available

Other Comments

Administration advice:

• 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

Oral:

• Take tablets on an empty stomach, at least 1 hour before or 2 hours after eating
• If a dose is missed, take it as soon as possible; if it is almost time for the next dose, skip the missed dose and return to the regular dosing schedule
• Extended-release tablets must be taken whole; do not cut, break, chew, dissolve, or crush
• Extended-release tablets should be taken 1 at a time with enough water to ensure complete swallowing; do not pre-soak, lick, or otherwise wet the tablet before placing in the mouth

General:

• This drug should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
• Because of the greater risk of overdose and death with extended-release formulations, the extended-release tablet should only be used in patients for whom alternative treatment options are ineffective, not tolerated, or would otherwise be inadequate to provide sufficient pain management.
• For patients receiving other opioid analgesics and switching to this drug or the extended-release tablet formulation, it is safer to underestimate a patient's 24-hour oral requirement and provide rescue medication than overestimate and manage an adverse reaction; there is substantial inter-patient variation in the relative potency of different opioid drugs that conversion tables are not able to capture.
• During chronic therapy, periodically reassess the continued need for opioid analgesics.
• The extended-release tablet should not be used as an as-needed pain medication.

Monitoring:

• Monitor closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dose increases.
• Monitor regularly for the development of addiction, abuse, and misuse.
• Monitor for signs of hypotension upon initiating therapy and following dose increases, especially in those whose blood pressure is compromised.
• Monitor for constipation and decreased bowel motility in post-operative patients.

Patient advice:

• Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
• Advise patients to store this drug safely out of the sight and reach of children; accidental use by a child is a medical emergency and can result in death.
• Advise patients that this drug, even when taken as recommended can result in addiction, abuse, and misuse; instruct patients not to share their drug with others and protect their drug from theft or misuse.
• Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest.
• Instruct patients not to consume alcoholic beverages, or prescription and non-prescription products that contain alcohol as this may result in increased oxymorphone levels.
• This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
• Patients should be instructed not to discontinue this drug without first discussing a tapering plan with their healthcare provider.
• Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.

Frequently asked questions

• Oxymorphone vs Hydromorphone - How do they compare?