OPANA (oxymorphone hydrochloride 5 mg) Dailymed

• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals (2.1)
• Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. (2.2)
• Initiate treatment with 10 to 20 mg orally every four to six hours.
• OPANA should be taken on an empty stomach, at least one hour prior to or two hours after eating. (2.2)
• Conversion to OPANA:  Follow recommendations for conversion from other opioids or parenteral oxymorphone. (2.2)
• Do not stop OPANA abruptly in a physically dependent patient. (2.8)
• Mild Hepatic Impairment:  Initiate treatment with 5 mg and titrate slowly.  Monitor for signs of respiratory and central nervous system depression.  (2.3)
• Renal Impairment: Initiate treatment with 5 mg and titrate slowly.  Monitor for signs of respiratory and central nervous system depression.  (2.4)
• Geriatric Patients: Initiate dosing with 5 mg, titrate slowly, and monitor for signs of respiratory and central nervous system depression. (2.5)
• CNS Depressants: Initiate treatment with 1/3 to 1/2 the recommended starting dose, consider using a lower dosage of the concomitant CNS depressant, and monitor closely. (2.6, 5.5, 7)

2.1 Important Dosage and Administration Instructions

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].

Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, 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 and following dosage increases with OPANA and adjust the dosage accordingly [see Warnings and Precautions (5.2)].

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

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)].

2.2 Initial Dosage

Use of OPANA as the first Opioid Analgesic

Initiate treatment with OPANA in a dosing range of 10 to 20 mg every 4 to 6 hours as needed for pain.

Do not initiate treatment with doses higher than 20 mg because of the potential serious adverse reactions [see Clinical Studies (14.1)].

Conversion from Other Opioids to OPANA

There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of OPANA. It is safer to underestimate a patient’s 24-hour OPANA dosage than to overestimate the 24-hour OPANA dosage and manage an adverse reaction due to overdose.

For conversion from other opioids to OPANA, 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 OPANA therapy by administering half of the calculated total daily dose of OPANA in 4 to 6 equally divided doses, every 4-6 hours. The initial dose of OPANA can be gradually adjusted until adequate pain relief and acceptable side effects have been achieved.

Conversion from Parenteral Oxymorphone to OPANA

Given OPANA’s absolute oral bioavailability of approximately 10%, patients receiving parenteral oxymorphone may be converted to OPANA by administering 10 times the patient’s total daily parenteral oxymorphone dose as OPANA, in four or six equally divided doses (e.g., [IV dose x 10] divided by 4 or 6).  For example, approximately 10 mg of OPANA four times daily may be required to provide pain relief equivalent to a total daily IM dose of 4 mg oxymorphone.   Due to patient variability with regard to opioid analgesic response, upon conversion patients should be closely monitored to ensure adequate analgesia and to minimize side effects.

Conversion from OPANA to Extended-Release Oxymorphone

The relative bioavailability of OPANA compared to extended-release oxymorphone is unknown, so conversion to extended-release tablets must be accompanied by close observation for signs of excessive sedation and respiratory depression.

2.3 Dosage Modifications in Patients with Mild HepaticImpairment

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

Use OPANA with caution in patients with mild hepatic impairment, starting with the lowest dose (e.g., 5 mg) and titrating slowly while carefully monitoring for signs of respiratory and central nervous system depression [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

2.4 Dosage Modifications in Patients with RenalImpairment

Use OPANA with caution in patients with creatinine clearance rates less than 50 mL/min., starting with the lowest dose (e.g., 5 mg) and titrating slowly while carefully monitoring for signs of respiratory and central nervous system depression [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

2.5 Dosage Modifications in Geriatric Patients

Exercise caution in the selection of the starting dose of OPANA for an elderly patient by starting with the lowest dose (e.g., 5 mg) and titrate slowly while carefully monitoring for signs of respiratory and central nervous system depression [see Use in Specific Populations (8.5 )].

2.6 Dosage Modifications with Concomitant Use withCentral Nervous System Depressants

OPANA, like all opioid analgesics, should be started at one-third to one-half of the usual dose in patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, because respiratory depression, hypotension and profound sedation, coma or death may result [see Warnings and Precautions (5.4) and Drug Interactions (7)].  When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced.

2.7 Titrationand Maintenance of Therapy

Individually titrate OPANA to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving OPANA to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1)]. 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.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the OPANA dosage.  If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage.  Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.8 Discontinuation of OPANA

When a patient who has been taking OPANA regularly and may be physically dependent no longer requires therapy with OPANA, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue OPANA in a physically-dependent patient [see Warnings and Precautions (5.12), Drug Abuse and Dependence (9.2, 9.3)].

3 Dosage Forms And Strengths

Tablets 5 mg: blue, round, convex tablet debossed with E612 over 5 on one side and plain on the other.

Tablets 10 mg: red, round, convex tablet debossed with E613 over 10 on one side and plain on the other.


Tablets: 5 mg and 10 mg. (3)

4 Contraindications

OPANA is contraindicated in patients with:

• Significant respiratory depression [see Warnings and Precautions (5.2)]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.5)]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.10)]
• Hypersensitivity to oxymorphone (e.g., anaphylaxis, angioedema) or [see Warnings and Precautions (5.6), Adverse Reactions (6)]
• Moderate or severe hepatic impairment [see Warnings and Precautions (5.14)].

• Significant respiratory depression. (4)
• Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. (4)
• Known or suspected gastrointestinal obstruction, including paralytic ileus. (4)
• Known hypersensitivity to oxymorphone, any other ingredients in OPANA (4)
• Moderate or severe hepatic impairment (4)

5 Warnings And Precautions

• Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, particularly during initiation and titration. (5.2)
• Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions: If symptoms occur, stop administration immediately, discontinue permanently, and do not rechallenge with any oxymorphone formulation. (5.6)
• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. (5.7)
• Severe Hypotension: Monitor during dosage initiation and titration. Avoid use of OPANA in patients with circulatory shock. (5.8)
• Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation and respiratory depression. Avoid use of OPANA in patients with impaired consciousness or coma. (5.9)

5.1 Addiction, Abuse, and Misuse

OPANA contains oxymorphone, a Schedule II controlled substance. As an opioid, OPANA exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)].

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OPANA. Addiction can occur at recommended dosages and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing OPANA, and monitor all patients receiving OPANA for the development of these behaviors and conditions.  Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as OPANA, but use in such patients necessitates intensive counseling about the risks and proper use of OPANA along with intensive monitoring for signs of addiction, abuse, and misuse.

Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.  Consider these risks when prescribing or dispensing OPANA. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)].  Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

5.2 Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.  Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of OPANA, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of OPANA.

To reduce the risk of respiratory depression, proper dosing and titration of OPANA are essential [see Dosage and Administration (2)].  Overestimating the OPANA dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

Accidental ingestion of even one dose of OPANA, especially by children, can result in respiratory depression and death due to an overdose of oxymorphone.

5.3 Neonatal Opioid Withdrawal Syndrome

Prolonged use of OPANA during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly.  Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1), Patient Counseling Information (17)]. 

5.4 Risks from Concomitant Use withBenzodiazepines or Other CNS Depressants

Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on OPANA therapy. The co-ingestion of alcohol with OPANA may result in increased plasma levels and a potentially fatal overdose of oxymorphone [see Clinical Pharmacology (12.3)].

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OPANA with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone.  Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions (7)].

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use.  In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when OPANA is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).  Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined.  Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions (7), Patient Counseling Information (17)].

5.5 Life-Threatening Respiratory Depression in Patientswith Chronic Pulmonary Disease or in Elderly, Cachectic, or DebilitatedPatients

The use of OPANA in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: OPANA-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of OPANA [see Warnings and Precautions (5.2)].

Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see Warnings and Precautions (8.5)].

Monitor such patients closely, particularly when initiating and titrating OPANA and when OPANA is given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.2)]. Alternatively, consider the use of non-opioid analgesics in these patients.

5.6 Anaphylaxis, Angioedema, and OtherHypersensitivity Reactions

Potentially life-threatening hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients treated with OPANA in the postmarket setting.  The most commonly described clinical features in these reports were swelling of the face, eyes, mouth, lips, tongue, hands, and/or throat; dyspnea; hives, pruritus, and/or rash; and nausea/vomiting.  If anaphylaxis or other hypersensitivity occurs, stop administration of OPANA immediately, discontinue OPANA permanently, and do not rechallenge with any formulation of oxymorphone.  Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction [see Patient Counseling Information (17)]. 

5.7 Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.  If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids.  Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.  Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. 

5.8 Severe Hypotension

OPANA may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients.  There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Warnings and Precautions (5.4) and  Drug Interactions (7)].  Monitor these patients for signs of hypotension after initiating or titrating the dosage of OPANA. In patients with circulatory shock, OPANA may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of OPANA in patients with circulatory shock.

5.9 Risks of Use in Patients with IncreasedIntracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

In patients who may be susceptible to the intracranial effects of CO₂ retention (e.g., those with evidence of increased intracranial pressure or brain tumors), OPANA may reduce respiratory drive, and the resultant CO₂ retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with OPANA.

Opioids may also obscure the clinical course in a patient with a head injury.  Avoid the use of OPANA in patients with impaired consciousness or coma.

5.10Risksof Use in Patients with Gastrointestinal Conditions

OPANA is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The oxymorphone in OPANA may cause spasm of the sphincter of Oddi.  Opioids may cause increases in serum amylase.  Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

5.11 IncreasedRisk of Seizures in Patients with Seizure Disorders

The oxymorphone in OPANA may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures.  Monitor patients with a history of seizure disorders for worsened seizure control during OPANA therapy.

5.12 Withdrawal

Avoid the use of mixed agonist/antagonist (e.g, pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including OPANA.  In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)].

When discontinuing OPANA in a physically-dependent patient, gradually taper the dosage [see Dosage and Administration (2.8)]. Do not abruptly discontinue OPANA in these patients [see Drug Abuse and Dependence (9.3)].

5.13 Risks of Driving and Operating Machinery

OPANA may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.  Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of OPANA and know how they will react to the medication.

5.14 Hepatic Impairment

A study of extended-release oxymorphone tablets in patients with hepatic disease indicated greater plasma concentrations than in those with normal hepatic function [see Clinical Pharmacology (12.3)]. Use OPANA with caution in patients with mild impairment, starting with the lowest dose and titrating slowly while carefully monitoring for side effects [see Dosage and Administration (2.2, 2.3)]. OPANA is contraindicated in patients with moderate or severe hepatic impairment.