Opana

Before taking oxymorphone,

• tell your doctor and pharmacist if you are allergic to oxymorphone, oxycodone (OxyContin, in Percocet, in Roxicet, others), codeine (in many pain relievers and cough medications), hydrocodone (Zohydro, in Anexsia, in Norco, in Reprexain, in Rezira, in Vicoprofen, in Vituz, others), dihydrocodeine (in Synalgos-DC), hydromorphone (Dilaudid, Exalgo), any other medications, or any of the ingredients in oxymorphone tablets or extended-release tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: antihistamines; buprenorphine (Buprenex, Butrans, Zubsolv, in Suboxone); butorphanol (Stadol); ipratropium (Atrovent, in Combivent); medications for irritable bowel disease, mental illness, motion sickness, Parkinson's disease, ulcers, or urinary problems; nalbuphine; and pentazocine (Talwin). Also tell your doctor or pharmacist if you are taking any of the following medications or have stopped taking them within the past two weeks: monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Emsam, Eldepryl, Zelapar), and tranylcypromine (Parnate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section, liver disease, or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take oxymorphone.
• tell your doctor if you have or have ever a blockage in your stomach or intestine, low blood pressure; Addison's disease (condition in which the adrenal gland does not produce enough hormone); seizures; urethral stricture (blockage of the tube that allows urine to leave the body); enlarged prostate (a male reproductive gland); or heart, kidney, pancreas, thyroid, or gall bladder disease.
• tell your doctor if you are breastfeeding.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking oxymorphone.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking oxymorphone.
• you should know that oxymorphone may make you drowsy, dizzy, or lightheaded. Do not drive a car or operate machinery until you know how this medication affects you.
• you should know that oxymorphone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that oxymorphone may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are using oxymorphone.

Opana comes as a tablet or an extended-release tablet to take by mouth. Your doctor will determine a dose that works for you.

You should take the drug on an empty stomach, at least one hour before or two hours after meals.

The regular tablet is typically taken every four to six hours.

The extended-release tablets are usually taken every 12 hours.

Follow the instructions on your prescription label carefully. Don't take more of the drug than is prescribed.

Swallow each extended-release tablet whole right after putting it in your mouth. Don't break, chew, dissolve, or crush the tablet.

If you do this, you could receive too much of the medicine at once, which could cause serious problems including overdose and death.

Some forms of this medicine are made with ingredients that the body doesn't absorb. You may notice part of the tablet in your stool. This is a normal side effect.

Opana Overdose

Symptoms of an overdose may include:

• Extreme drowsiness
• Muscle weakness
• Cold and clammy skin
• Confusion
• Pinpoint pupils
• Shallow breathing
• Slow heart rate
• Fainting
• Coma

If you suspect an overdose, you should contact a poison control center or emergency room immediately.

You can get in touch with a poison control center at (800) 222-1222.

Missed Dose of Opana

If you miss a dose of Opana, take it as soon as you remember.

However, if it's almost time for your next dose, skip the missed dose and continue on your regular dosing schedule.

Don't double up on doses to make up for a missed one.

• Endo Pharmaceuticals, Inc.

Contraindications

• Known hypersensitivity to oxymorphone, morphine analogs such as codeine, or any ingredient in the formulation.500 501 502

• Respiratory depression in the absence of resuscitative equipment.500 501 502

• Acute or severe asthma or hypercarbia.500 501 502

• Known or suspected paralytic ileus.500 501 502

• Moderate or severe hepatic impairment.500 501 502

• Extended-release preparation contraindicated in the management of immediate postoperative pain (first 12–24 hours following surgery), in patients with mild pain, and in those who are expected to require analgesia for a short period of time.501

• Parenteral use contraindicated in the treatment of pulmonary edema resulting from a chemical respiratory irritant.502

Warnings/Precautions

Warnings

Possible tolerance, psychologic dependence, and physical dependence following prolonged administration.500 501 Use only with careful surveillance in patients with a history of drug or alcohol dependence or abuse.500 501 Clinicians should consider abuse potential when prescribing or dispensing oxymorphone in situations where they are concerned about an increased risk of misuse, abuse, or diversion.502 However, concerns about abuse, addiction, and diversion should not prevent the proper management of pain.501 502

Oxymorphone tablets can be abused by crushing, chewing, “snorting” the powder, or dissolving the contents in water and injecting.501 502

Breaking, chewing, or crushing of extended-release tablets results in immediate release of the opiate and the risk of a potentially fatal overdose.501 (See Boxed Warning.)

Abrupt cessation of therapy or sudden reduction in dosage after prolonged use may result in withdrawal symptoms.500 501 502 After prolonged exposure to opiate analgesics, if withdrawal is necessary, it must be undertaken gradually.500 501 502

Health-care professionals should contact the professional licensing board or controlled substance authority in their states for information about prevention and detection of abuse or diversion.501 502

The major toxicity associated with oxymorphone.501 502 e

Occurs most frequently in geriatric or debilitated patients and in those with conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic opiate dosages may dangerously decrease pulmonary ventilation.501 502 e

Use with extreme caution in patients with hypoxia, hypercapnia, or substantially decreased respiratory reserve (e.g., asthma, COPD, cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression, coma).501 502 e In such patients, even therapeutic oxymorphone doses may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.501 502 e Consider use of non-opiate analgesics.501 502 e Use oxymorphone only with careful medical supervision and at lowest effective dosage.501 502 e

Additive depressant effects may occur with concomitant use of other CNS depressants including other opiates, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, illicit drugs associated with CNS depression, and alcohol.501 502 e (See Specific Drugs under Interactions.)

Hypoventilation, hypotension, and profound sedation or coma may occur.501 502 e

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.400 Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.400

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.400 If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.400 In some patients, switching to a different opiate improved symptoms.400

Respiratory depressant effects of oxymorphone (with CO2 retention and secondary elevation of CSF pressure) may be markedly exaggerated in the presence of head injury, other intracranial lesions, or preexisting increase in intracranial pressure.501 502 e

Opiates produce effects (e.g., pupillary changes) that may obscure neurologic signs of further increase in pressure in patients with head injuries.501 502 e

Possible severe hypotension in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant drugs that compromise vasculature tone (e.g., phenothiazines, general anesthetics).500 501 502 e

Use with caution in patients in circulatory shock, because vasodilation produced by the drug may further reduce cardiac output and BP.500 501 502

General Precautions

Administration may complicate assessment of patients with acute abdominal conditions.500 501 502 (See GI Effects under Cautions.)

May aggravate preexisting seizures in patients with seizure disorders.501 502 e May induce seizures.500 501 502

Use with caution in debilitated patients, those sensitive to CNS depressants, patients with Addison's disease, CNS depression or coma, kyphoscoliosis, myxedema or hypothyroidism, prostatic hypertrophy, urethral stricture, severe impairment of pulmonary function, toxic psychosis, acute alcoholism, delirium tremens, or following GI surgery.500 501 502

May cause spasm of the sphincter of Oddi.500 501 502 Use with caution in patients with biliary tract disease, including acute pancreatitis, and patients undergoing biliary tract surgery.500 501 502

Monitor for decreased bowel motility in post-operative patients.500 501 502 (See Acute Abdominal Conditions under Cautions.)

Contraindicated in patients with known or suspected paralytic ileus.500 501 502

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;400 401 402 403 404 causality not established.400 Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.400 Perform appropriate laboratory testing in patients with manifestations of hypogonadism.400

Specific Populations

Category C.500 501 502

Use parenteral preparation with caution during labor.502 Administration during labor may cause neonatal respiratory depression.502 An opiate antagonist and resuscitative equipment for reversal of opiate-induced respiratory depression should be readily available when opiates are administered during labor and delivery.502

Use of oxymorphone tablets and extended-release tablets not recommended during or immediately prior to labor.501

Infants born to women regularly taking opiates during pregnancy may be physically dependent.500 501 502

Not known whether oxymorphone is distributed into human milk.500 501 502 Women receiving oxymorphone generally should not nurse.500 501 502

Safety and efficacy not established in pediatric patients <18 years of age.500 501 502

No substantial difference in efficacy of oral preparations in geriatric patients relative to younger adults.500 501 Dizziness, somnolence, confusion, nausea reported more frequently in geriatric adults than in younger adults.500 501

Following oral administration, plasma concentrations of oxymorphone are higher in geriatric patients ≥65 years of age than in younger patients.500 501 502 (See Special Populations under Pharmacokinetics.)

Parenteral preparation not systematically evaluated in geriatric adults.502

Select dose with caution, starting at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.500 501 502

Use with caution in patients with mild hepatic impairment.500 501 502 (See Hepatic Impairment under Dosage and Administration.)

Contraindicated in patients with moderate or severe hepatic impairment.500 501 502

Use with caution in patients with moderate or severe renal impairment.500 501 502 Dosage adjustment needed in these patients.500 501 502 (See Renal Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Nausea, constipation, pyrexia, somnolence, vomiting, pruritus, headache, dizziness, confusion.500 501 502

Absorption

Bioavailability

Absolute oral bioavailability is 10%.500 501

Onset

5–10 minutes following IV administration.502 a

10–15 minutes following sub-Q or IM administration.a

Duration

3–6 hours following parenteral administration.502 a

Food

Conventional tablets with high-fat meal: Peak plasma concentration and AUC increase 38%.500

Extended-release tablets with food: Peak plasma concentrations increase 50%; time to peak plasma concentrations delayed; no change in AUC or small increase.501

Special Populations

Oxymorphone extended-release tablets: Bioavailability increased 26, 57, or 65% in patients with mild (Clcr 51–80 mL/minute), moderate (Clcr 30–50 mL/minute), or severe renal impairment (Clcr <30 mL/minute), respectively.501

Oxymorphone extended-release tablets: Based on information from a few individuals with hepatic impairment, bioavailability increased 1.6-, 3.7-, or 12.2-fold in patients with mild, moderate, or severe hepatic impairment, respectively.501

Oxymorphone extended-release tablets: Plasma concentrations increased 40% in geriatric individuals.501

Distribution

Plasma Protein Binding

10–12%.500 501

Elimination

Metabolism

Extensively metabolized in the liver; undergoes reduction or conjugation with glucuronic acid to form oxymorphone-3-glucuronide and 6-OH-oxymorphone.500 501 502

Elimination Route

33–38% excreted in the urine as oxymorphone-3-glucuronide, <1% excreted in urine as 6-OH-oxymorphone, <1% excreted unchanged in the urine.500 501 502

Half-life

Extended-release tablets: 9.4–11.3 hours.501

• A potent analgesic; shares the actions of the opiate agonists.500 501 502

• Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.e

• Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).e

• Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.e

• Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.e

• Agonist activity at the opiate μ- or κ-receptor can result in analgesia, miosis, and/or decreased body temperature.e

• Agonist activity at the μ-receptor can also result in suppression of opiate withdrawal (and antagonist activity can result in precipitation of withdrawal).e

• Respiratory depression may be mediated by μ-receptors, possibly μ2-receptors (which may be distinct from μ1-receptors involved in analgesia); κ- and δ-receptors may also be involved in respiratory depression.e

In the U.S.

• Opana
• Opana ER

Available Dosage Forms:

• Tablet, Extended Release
• Tablet

Therapeutic Class: Analgesic

Chemical Class: Opioid

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 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 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 Renal Impairment

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 with Central 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 Titration and 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)].

8.1 Pregnancy

Risk Summary

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome.  Available data with Opana in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, reduced postnatal survival of pups and an increased incidence of stillborn pups were observed following oral treatment of pregnant rats with oxymorphone during gestation and through lactation at doses 2.4 and 12 times the human daily dose of 20 mg/day (HDD), respectively.  Reduced fetal weights were observed with oral administration of oxymorphone to pregnant rats and rabbits during organogenesis at exposures up to 4.9 and 48.8 times the HDD, respectively [see Data].  Based on animal data, advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.  All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.  In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.3)].

Labor or Delivery

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.  An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate.  Opana is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate.  Opioid analgesics, including Opana, can 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 dilation, which tends to shorten labor.  Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Data

Animal Data

Pregnant rats were treated with oxymorphone hydrochloride from Gestation Day 6 to 17 via oral gavage doses of 5, 10, or 25 mg/kg/day (2.4, 4.9, or 12.2 times the HDD based on body surface area, respectively).  Reduced mean fetal weights were observed at 4.9 times the HDD.  Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups and mortality in the high dose group).

Pregnant rabbits were treated with oxymorphone hydrochloride from Gestation Day 7 to 20 via oral gavage doses of 10, 25, or 50 mg/kg/day (9.8, 24.4, or 48.8 times the HDD based on body surface area, respectively).  Decreased mean fetal weights were noted at 48.8 times the HDD.  Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights).

Pregnant rats were treated with oxymorphone hydrochloride from Gestation Day 6 to Lactation Day 20 via oral gavage doses of 1, 5, 10, or 25 mg/kg/day (0.5, 2.4, 4.9, or 12.2 times the HDD based on body surface area, respectively).  Increased neonatal death (postnatal day 0-1) was noted at 2.4 times the HDD.  Decreased pup survival over the first week of life, reduced pup birth weight, and reduced postnatal weight gain were noted at 4.9 times the HDD.  Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups and mortality in the 10 and 25 mg/kg/day groups).

In a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of 153 mg/kg oxymorphone hydrochloride (62.2 times the HDD) on Gestation Day 8 to pregnant hamsters.  This dose also produced significant maternal toxicity (20% maternal deaths).

8.2 Lactation

Risk Summary

There is no information regarding the presence of oxymorphone in human milk, the effects on the breastfed infant, or the effects on milk production.  The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Opana and any potential adverse effects on the breastfed child from Opana or from the underlying maternal condition.

Clinical Considerations

Monitor infants exposed to Opana through breast milk 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.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Opana and any potential adverse effects on the breastfed infant from Opana or from the underlying maternal condition.

8.3 Females and Males of Reproductive Potential

Infertility

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Clinical Pharmacology (12.2), Nonclinical Toxicology (13.1)].

8.4 Pediatric Use

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

8.5 Geriatric Use

Opana should be used with caution in elderly patients [see Clinical Pharmacology (12.3)].

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.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Opana slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.5)].

Oxymorphone is known to be substantially excreted by the kidney and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because the elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Hepatic Impairment

In a study of extended-release oxymorphone tablets, patients with mild hepatic impairment were shown to have an increase in bioavailability compared to the subjects with normal hepatic function.  Opana should be used with caution in patients with mild impairment.  These patients should be started with the lowest dose (5 mg) and titrated slowly while carefully monitoring for signs of respiratory and central nervous system depression.  Opana is contraindicated for patients with moderate and severe hepatic impairment [see Dosage and Administration (2.3), Contraindications (4), Warnings and Precautions (5.14), and Clinical Pharmacology (12.3)].

8.7 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 compared to the subjects with normal renal function [see Clinical Pharmacology (12.3)]. Such patients should be started be started with the lowest dose (5 mg) and titrated slowly while monitoring for signs of respiratory and central nervous system depression [see Dosage and Administration (2.4) Clinical Pharmacology (12.3)].

Opana (oxymorphone hydrochloride) tablet is an opioid agonist available in 5 mg and 10 mg tablet strengths for oral administration. The chemical name for oxymorphone hydrochloride is 4, 5α-epoxy-3, 14-dihydroxy-17-methylmorphinan-6-one hydrochloride. The molecular weight is 337.80.  The molecular formula is C17H19NO4. HCl and it has the following chemical structure.

Oxymorphone hydrochloride is white to off white odorless powder, which is sparingly soluble in alcohol and ether, but freely soluble in water.

The inactive ingredients in Opana include:  lactose monohydrate, magnesium stearate, and pregelatinized starch.  In addition, the 5 mg tablets contain FD&C blue No. 2 aluminum lake.  The 10 mg tablets contain D&C red No. 30 aluminum lake. 

Opana (oxymorphone hydrochloride) 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

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).

Applies to oxymorphone: injectable solution, oral tablet, oral tablet extended release, rectal suppository

General

The most commonly reported adverse reactions included nausea, pyrexia, somnolence, vomiting, pruritus, headache, dizziness, constipation, and confusion. Additionally, the following adverse events were reported with the extended release tablet, diarrhea, insomnia, fatigue, decreased appetite and abdominal pain.[Ref]

Gastrointestinal

Very common (10% or more): Constipation (up to 26%), nausea (up to 33%), vomiting (up to 16%)
Common (1% to 10%): Dry mouth, abdominal distention, flatulence, abdominal pain, diarrhea, dyspepsia
Frequency not reported: Paralytic ileus, ileus
Postmarketing reports: Difficulty swallowing tablets[Ref]

Respiratory

Common (1% to 10%): Hypoxia, dyspnea
Frequency not reported: Respiratory depression, atelectasis, bronchospasm, decreased oxygen saturation, respiratory distress, respiratory rate decreased
laryngospasm, laryngeal edema, apnea[Ref]

Nervous system

Very common (10% or more): Somnolence (up to 19%), dizziness (excluding vertigo; up to 18%)
Common (1% to 10%): Headache, confusion
Frequency not reported: Sedation, CNS depression
Postmarketing reports: Amnesia, convulsion, memory impairment[Ref]

Hypersensitivity

Frequency not reported: Hypersensitivity including dermatitis allergic, urticaria, pruritus, face swelling[Ref]

Cardiovascular

Common (1% to 10%): Tachycardia, hypotension, edema, flushing, hypertension
Frequency not reported: Bradycardia, palpitations, orthostatic hypotension, syncope[Ref]

Psychiatric

Common (1% to 10%): Anxiety, insomnia, confusion, disorientation, restlessness, nervousness, depression
Frequency not reported: Mental impairment, dysphoria, euphoric mood, agitation, hallucination, drug dependence, drug abuse, feeling jittery[Ref]

Genitourinary

Frequency not reported: Ureteral spasm, urinary hesitation, urinary retention, oliguria, difficult micturition[Ref]

Dermatologic

Very common (10% or more): Pruritus (up to 15%)
Common (1% to 10%): Increased sweating
Frequency not reported: Dermatitis[Ref]

Metabolic

Common (1% to 10%): Decreased appetite, dehydration, decreased weight
Frequency not reported: Anorexia[Ref]

Hepatic

Frequency not reported: Biliary colic[Ref]

Other

Very common (10% or more): Pyrexia (14%)
Frequency not reported: Fatigue, asthenia, hot flashes, clamminess, weakness[Ref]

Ocular

Common (1% to 10%): Vision blurred
Frequency not reported: Miosis, diplopia, visual disturbances[Ref]

Local

Frequency not reported: Injection site reaction[Ref]

Some side effects of Opana may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.