Opana: Indications, Dosage, Precautions, Adverse Effects
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Opana - Product Information

Manufacture: Endo Pharmaceuticals Inc.
Country: United States
Condition: Opiate Adjunct, Pain
Class: Analgesics
Form: Tablets
Ingredients: Oxymorphone hydro chloride, Lactose monohydrate, Magnesium stearate, Starch, Corn, FD&C blue no. 2

Indications and Usage

OPANA is indicated for the relief of moderate to severe acute pain where the use of an opioid is appropriate.

Dosage and Administration

Selection of patients for treatment with OPANA should be governed by the same principles that apply to the use of similar opioid analgesics [see Indications and Usage]. 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 Agency for Healthcare Research and Quality, and the American Pain Society.

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

Individualization of Dosage

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. In the selection of the initial dose of OPANA, 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 analgesics and other medications;
  • The type and severity of the patient's pain;
  • The 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. Titrate dose to adequate pain relief (generally mild or no pain). 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. 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 family members of the potential common adverse reactions associated with changing opioid doses.

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.

Initiation of Therapy

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

Opioid-Naïve Patients

Patients who have not been receiving opioid analgesics should be started on OPANA in a dosing range of 10 to 20 mg every four to six hours depending on the initial pain intensity. If deemed necessary to initiate therapy at a lower dose (e.g., for renal or hepatic impairment or for geriatric patients), patients may be started with OPANA 5 mg. The dose should be titrated based upon the individual patient’s response to their initial dose of OPANA. This dose can then be adjusted to an acceptable level of analgesia taking into account the pain intensity and adverse reactions experienced by the patient.

Initiation of therapy with doses higher than 20 mg is not recommended because of potential serious adverse reactions.

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 Other Oral Opioids to Opana

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.

Maintenance of Therapy

During therapy, continual re-evaluation of the patient receiving OPANA is important, with special attention to the maintenance of pain control and the relative incidence of side effects associated with therapy. If the level of pain increases, effort should be made to identify the source of increased pain, while adjusting the dose [see Dosage and Administration].

Cessation of Therapy

When the patient no longer requires therapy with OPANA, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient [see Drug Abuse and Dependence].

Patients with Hepatic Impairment

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 side effects [see Warnings and Precautions].

Patients with Renal Impairment

There are 57% and 65% increases in oxymorphone bioavailability in patients with moderate and severe renal impairment, respectively; treated with extended-release oxymorphone tablets. Accordingly, OPANA should be administered cautiously and in reduced dosages to patients with creatinine clearance rates less than 50 mL/min.

Use with Central Nervous System Depressants

OPANA, 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 (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 and Drug Interactions]. When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced.

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

Geriatric Patients

Exercise caution in the selection of the starting dose of OPANA for an elderly patient by starting at the low end of the dosing range (e.g., 5 mg) [see Use in Specific Populations].

Dosage Forms and Strengths

The 5 mg dosage form is a blue, round, convex tablet debossed with E612 over 5 on one side and plain on the other.

The 10 mg dosage form is a red, round, convex tablet debossed with E613 over 10 on one side and plain on the other.

Contraindications

  • OPANA is contraindicated in patients with a known hypersensitivity to oxymorphone or to any of the other ingredients in OPANA, or with known hypersensitivity to morphine analogs such as codeine.
  • OPANA is contraindicated in patients with respiratory depression, except in monitored settings and in the presence of resuscitative equipment.
  • OPANA is contraindicated in patients with acute or severe bronchial asthma or hypercarbia.
  • OPANA is contraindicated in any patient who has or is suspected of having paralytic ileus [see Warning and Precautions].
  • OPANA is contraindicated in patients with moderate or severe hepatic impairment [see Warnings and Precautions].

Warnings and Precautions

Respiratory Depression

Respiratory depression is the chief hazard of OPANA. Respiratory depression may occur more frequently in elderly or debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia, when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.

Administer OPANA with extreme caution to patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression, or coma. In these patients, even usual therapeutic doses of oxymorphone may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Consider alternative non-opioid analgesics and use OPANA only under careful medical supervision at the lowest effective dose in such patients.

Misuse, Abuse, and Diversion of Opioids

OPANA contains oxymorphone, a mu opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine. Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

Oxymorphone can be abused in a manner similar to other opioid agonists, legal or illicit. This issue should be considered when prescribing or dispensing oxymorphone in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

OPANA tablets may be abused by crushing, chewing, snorting, or injecting the product. These practices pose a significant risk to the abuser that could result in overdose and death [see Drug Abuse and Dependence].

OPANA may be targeted for theft and diversion. Healthcare professionals should contact their State Medical Board, State Board of Pharmacy, or State Control Board for information on how to detect or prevent diversion of this product, and security requirements for storing and handling of OPANA.

Healthcare professionals should advise patients to store OPANA in a secure place, preferably locked and out of the reach of children and other non-caregivers.

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

Additive CNS Depressant Effects

The concomitant use of other CNS depressants including other opioids, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, and alcohol with oxymorphone may produce increased depressant effects including hypoventilation, hypotension, profound sedation, coma and death [see Drug Interactions].

Use in Patients with Head Injury and Increased Intracranial Pressure

In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the respiratory depressant effects of opioid analgesics and their potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO2 retention) may be markedly exaggerated. Furthermore, opioid analgesics can produce effects on papillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries.

Administer OPANA with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted.

Hypotensive Effect

OPANA, like all opioid analgesics, may cause severe hypotension in a patient whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents that compromise vasomotor tone. Administer OPANA with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.

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

Special Risk Groups

Use OPANA with caution in the following conditions: adrenocortical insufficiency (e.g., Addison’s disease), prostatic hypertrophy or urethral stricture, severe impairment of pulmonary or renal function, and toxic psychosis.

Opioids may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings.

Gastrointestinal Effects

Opioids diminish propulsive peristaltic waves in the gastrointestinal tract. Monitor for decreased bowel motility in post-operative patients receiving opioids. The administration of OPANA may obscure the diagnosis or clinical course in patients with acute abdominal conditions. OPANA is contraindicated in patients with paralytic ileus.

Use in Pancreatic/Biliary Tract Disease

OPANA, like other opioids, may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis.

Driving and Operating Machinery

Opioid analgesics impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Adverse Reactions

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Respiratory depression [see Warnings and Precautions]
  • Misuse and abuse [see Warnings and Precautions and Drug Abuse and Dependence]
  • CNS depressant effects [see Warnings and Precautions]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug;and may not reflect the rates observed in clinical practice.

Clinical Trials Experience

A total of 591 patients were treated with OPANA in controlled clinical trials. The clinical trials consisted of patients with acute post-operative pain (n=557) and cancer pain (n=34) trials.

The following table lists adverse reactions that were reported in at least 2% of patients receiving OPANA in placebo-controlled trials (acute post-operative pain (N=557)).

Table 1: Adverse Reactions Reported in Placebo-Controlled Trials
MedDRA Preferred Term OPANA (N=557) Placebo (N=270)
Nausea 19% 12%
Pyrexia 14% 8%
Somnolence 9% 2%
Vomiting 9% 7%
Pruritus 8% 4%
Headache 7% 4%
Dizziness (ExcudingVertigo) 7% 2%
Constipation 4% 1%
Confusion 3% <1%

The common (≥1% - >10%) adverse drug reactions reported at least once by patients treated with OPANA in the clinical trials organized by MedDRA’s (Medical Dictionary for Regulatory Activities) System Organ Class were and not represented in Table 1:

Cardiac disorders: tachycardia
Gastrointestinal disorders:
dry mouth, abdominal distention, and flatulence
General disorders and administration site conditions:
sweating increased
Nervous system disorders:
anxiety and sedation
Respiratory, thoracic and mediastinal disorders:
hypoxia
Vascular disorders:
hypotension

Other less common adverse reactions known with opioid treatment that were seen <1% in the OPANA trials includes the following:

Abdominal pain, ileus, diarrhea, agitation, disorientation, restlessness, feeling jittery, hypersensitivity, allergic reactions, bradycardia, central nervous system depression, depressed level of consciousness, lethargy, mental impairment, mental status changes, fatigue, depression, clamminess, flushing, hot flashes, dehydration, dermatitis, dyspepsia, dysphoria, edema, euphoric mood, hallucination, hypertension, insomnia, miosis, nervousness, palpitation, postural hypotension, syncope, dyspnea, respiratory depression, respiratory distress, respiratory rate decreased, oxygen saturation decreased, difficult micturition, urinary retention, urticaria, vision blurred, visual disturbances, weakness, appetite decreased, and weight decreased.

Post-marketing Experience

The following adverse reactions have been identified during post approval use of OPANA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous system disorder: amnesia, convulsion, memory impairment

Drug Interactions

Use with CNS Depressants

The concomitant use of other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol may produce additive CNS depressant effects. OPANA, 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 because respiratory depression, hypotension, and profound sedation, coma and death may result and titrated slowly as necessary for adequate pain relief.

When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced [see Dosage and Administration and Warnings and Precautions].

Interactions with Mixed Agonist/Antagonist Opioid Analgesics

Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, and buprenorphine) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as oxymorphone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxymorphone and/or may precipitate withdrawal symptoms in these patients.

Cimetidine

CNS side effects have been reported (e.g., confusion, disorientation, respiratory depression, apnea, seizures) following coadministration of cimetidine with opioid analgesics; a causal relationship has not been established.

Anticholinergics

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

MAO Inhibitors

Opana is not recommended for use in patients who have received MAO inhibitors within 14 days, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. No specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, but caution in the use of any opioid in patients taking this class of drugs is appropriate.

Use in Specific Populations

Pregnancy

The safety of using oxymorphone in pregnancy has not been established with regard to possible adverse effects on fetal development. The use of OPANA in pregnancy, in nursing mothers, or in women of child-bearing potential requires that the possible benefits of the drug be weighted against the possible hazards to the mother and the child.

Teratogenic Effects

Pregnancy Category C

There are no adequate and well-controlled studies of oxymorphone in pregnant women. In animal studies, oxymorphone caused decreased fetal and pup weights, an increase in stillbirth, and a decrease in postnatal pup survival at maternal oxymorphone doses equivalent to 0.4 to 4 times the human daily dose of 120 mg (Based on body surface area). OPANA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In embryo-fetal developmental toxicity studies, pregnant rats and rabbits received oxymorphone hydrochloride at doses up to about 2 times (rats) and 8 times (rabbits) total human daily dose of 120 mg(based on body surface area). No malformations occurred, but reduced fetal weights occurred at maternal doses of 0.8 (rat) and 4 (rabbit) times the total human daily dose of 120 mg (based on body surface area). There were no adverse developmental effects in rats that received 0.4 times or rabbits that received less than 4 times the total human dose. There were no effects of oxymorphone hydrochloride on intrauterine survival at doses in rats ≤2 times, or in rabbits at ≤8 times the human dose (see Non-teratogenic Effects, below). In a study conducted prior to the establishment of Good Laboratory Practices (GLP) and not according to current recommended methodology, a single subcutaneous injection of oxymorphone hydrochloride on gestation day 8 produced malformations in offspring of hamsters that received a dose equivalent to 10 times the total human daily dose of 120 mg (based on body surface area). This dose also produced 83% maternal lethality.

Non-teratogenic Effects

Oxymorphone hydrochloride administration to female rats during gestation in a pre- and postnatal developmental toxicity study reduced mean litter size (18%) at a dose of 25 mg/kg/day, attributed to an increase in the incidence of stillborn pups. An increase in neonatal death occurred at doses ≥5 mg/kg/day (0.4 times a total human daily dose of 120 mg, based on body surface area). Low pup birth weight, decreased post-natal weight gain, and reduced post-natal survival of pups occurred following treatment of the dams with 25 mg/kg/day (about 2 times a total human daily dose of 120 mg, based on body surface area).

Prolonged use of opioid analgesics during pregnancy may cause fetal-neonatal physical dependence. Neonatal withdrawal may occur. Symptoms usually appear during the first days of life and may include convulsions, irritability, excessive crying, tremors, hyperactive reflexes, fever, vomiting, diarrhea, sneezing, yawning, and increased respiratory rate.

Labor and Delivery

Opioids cross the placenta and may produce respiratory depression in neonates. OPANA is not recommended for use in women during and immediately prior to labor, when use of shorter acting analgesics or other analgesic techniques are more appropriate. Occasionally, opioid analgesics may prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Neonates whose mothers received opioid analgesics during labor should be observed closely for signs of respiratory depression. A specific opioid antagonist, such as naloxone or nalmefene, should be available for reversal of opioid-induced respiratory depression in the neonate.

Nursing Mothers

It is not known whether oxymorphone is excreted in human milk. Because many drugs, including some opioids, are excreted in human milk, caution should be exercised when OPANA is administered to a nursing woman. Infants exposed to OPANA through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

Pediatric Use

Safety and effectiveness of OPANA in pediatric patients below the age of 18 years have not been established.

Geriatric Use

OPANA should be used with caution in elderly patients.

Of the total number of subjects in clinical studies of OPANA, 31% were 65 and over, while 7% were 75 and over. No overall differences in effectiveness were observed between these subjects and younger subjects. There were several adverse events that were more frequently observed in subjects 65 and over compared to younger subjects. These adverse events included dizziness, somnolence, confusion, and nausea. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Impairment

In a study of extended -release oxymorphone tablets, patients with mild hepatic impairment were shown to have an increase in bioavailability of 1.6 fold. OPANA should be used with caution in patients with mild impairment. These patients should be started with the lowest dose and titrated slowly while carefully monitoring for side effects. OPANA is contraindicated for patients with moderate and severe hepatic impairment [see Contraindications, Warnings and Precautions, and Dosage and Administration].

Renal Impairment

In a study of extended-release oxymorphone tablets, patients with moderate to severe renal impairment were shown to have an increase in bioavailability ranging from 57-65%. Such patients should be started cautiously with lower doses of OPANA and titrated slowly while monitoring for side effects [see Dosage and Administration].

Drug Abuse and Dependence

Controlled Substance

OPANA contains oxymorphone, a mu opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine and other opioids. Oxymorphone can be abused and is subject to criminal diversion [see Warnings and Precautions].

Abuse

All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. Addiction is characterized by one or more of the following: impaired control over drug use, compulsive use, use for non-medical purposes, and continued use despite harm. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.

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

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

OPANA is intended for oral use only. Abuse of OPANA poses a risk of overdose and death. This risk is increased with concurrent abuse of OPANA with alcohol and other substances. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

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

Dependence

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

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

OPANA should not be abruptly discontinued [see Dosage and Administration]. If OPANA is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

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

Overdosage

Symptoms

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

OPANA may cause miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Treatment

In the treatment of OPANA overdosage, primary attention should be given to the re-establishment of a patent airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.

The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression that may result from overdosage or unusual sensitivity to opioids including OPANA. Nalmefene is an alternative pure opioid antagonist, which may be administered as a specific antidote to respiratory depression resulting from opioid overdose. Since the duration of action of OPANA may exceed that of the antagonist, keep the patient under continued surveillance and administer repeated doses of the antagonist according to the antagonist labeling as needed to maintain adequate respiration.

In patients receiving OPANA, opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression. Administer opioid antagonists cautiously to persons who are known, or suspected to be, physically dependent on any opioid agonist including OPANA. In such cases, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome. In an individual physically dependent on opioids, administration of the usual dose of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the antagonist administered. If respiratory depression is associated with muscular rigidity, administration of a neuromuscular blocking agent may be necessary to facilitate assisted or controlled ventilation. Muscular rigidity may also respond to opioid antagonist therapy.

How Supplied/Storage and Handling

OPANA tablets are supplied as follows:

5 mg Tablet:

Blue, round, convex tablets debossed with E612 over 5 on one side and plain on the other.

Bottles of 100 tablets with child-resistant closure NDC 63481-612-70

Unit-Dose package of 100 tablets (5 blister cards of 20
tablets, not child-resistant, for hospital use only) NDC 63481-612-75

10 mg Tablet:

Red, round, convex tablets debossed with E613 over 10 on one side and plain on the other.

Bottles of 100 tablets with child-resistant closure NDC 63481-613-70

Unit-Dose package of 100 tablets (5 blister cards of 20
tablets, not child-resistant, for hospital use only) NDC 63481-613-75

OPANA may be targeted for theft and diversion. Healthcare professionals should contact their State Medical Board, State Board of Pharmacy, or State Control Board for information on how to detect or prevent diversion of this product, and security requirements for storing and handling of OPANA.

Healthcare professionals should advise patients to store OPANA in a secure place, preferably locked and out of the reach of children and other non-caregivers.

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

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

Advise patients to dispose of any unused tablets from a prescription by flushing them down the toilet as soon as they are no longer needed.

Patient Counseling Information

  • Advise patients that OPANA contains oxymorphone, which is a morphine-like pain reliever, and should be taken only as directed.
  • Advise patients that OPANA is a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
  • Advise patients to keep OPANA in a secure place out of the reach of children and pets. Accidental consumption especially in children may result in overdose or death. When OPANA is no longer needed, the unused tablets should be destroyed by flushing down the toilet.
  • Advise patients to report episodes of breakthrough pain and adverse experiences occurring during therapy to their doctor. Individualization of dosage is essential to make optimal use of this medication.
  • Advise patients not to adjust the dose of OPANA without consulting the prescriber.
  • Advise patients that OPANA may cause drowsiness, dizziness, or lightheadedness and may impair mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car, operating machinery, etc.
  • Advise patients that OPANA will add to the effect of alcohol and other CNS depressants (such as antihistamines, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and monoamine oxidase [MAO] inhibitors).
  • Advise patients not to combine OPANA with alcohol or other central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, because dangerous additive effects may occur, resulting in serious injury or death.
  • Advise patients of the potential for severe constipation. Appropriate laxatives and/or stool softeners and other therapeutic approaches should be considered for use with the initiation of OPANA therapy.
  • Advise women of childbearing potential who become or are planning to become pregnant to consult their physician regarding the effects of opioid analgesics and other drug use during pregnancy on themselves and their unborn child.
  • Advise women of childbearing potential who become or are planning to become pregnant that safe use in pregnancy has not been established. Prolonged use of opioid analgesics during pregnancy may cause fetal-neonatal physical dependence, and neonatal withdrawal may occur.
  • Advise patients that if they have been receiving treatment with OPANA for more than a few weeks and cessation of therapy is indicated, it may be appropriate to taper the OPANA dose, rather than abruptly discontinue it, due to the risk of precipitating withdrawal symptoms. Their physician can provide a dose schedule to accomplish a gradual discontinuation of the medication.

Manufactured for:
Endo Pharmaceuticals Inc.
Malvern, PA 19355