The minimum effective plasma concentration of oxymorphone for analgesia varies widely among patients, especially among patients who have been previously treated with agonist opioids. As a result, patients need to be individually titrated to achieve a balance between therapeutic and adverse effects. There is a general relationship between increasing opioid plasma concentration and increasing frequency of adverse experiences such as nausea, vomiting, CNS effects, and respiratory depression. The effective analgesic dose for some patients will be too high to be tolerated by other patients.
Steady-state levels are achieved after three days of multiple dose administration. Under both single-dose and steady-state conditions, dose proportionality has been established for the 5 mg, 10 mg, 20 mg, and 40 mg tablet strengths for both peak plasma levels C max and extent of absorption AUC Table 1.
A similar increase in Cmax was also observed with oxymorphone solution. Examination of the AUC suggests that most of the difference between fed and fasting conditions occurs in the first four hours after dose administration.
After oral dosing with a single dose of 40 mg, a peak oxymorphone plasma level of 2. After oral dosing with a single dose of 40 mg in fasted subjects, the mean peak oxymorphone plasma level is 2. Oxymorphone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, and profound sedation, coma, or death may result.
Formal studies on the distribution of oxymorphone in various tissues have not been conducted. Oxymorphone is highly metabolized principally in the liver and undergoes reduction or conjugation with glucuronic acid to form both active and inactive metabolites. The two major metabolites of oxymorphone are oxymorphoneglucuronide and 6-OH-oxymorphone. The mean plasma AUC for oxymorphoneglucuronide is approximately fold higher than the parent compound.
The pharmacologic activity of the glucuronide metabolite has not been evaluated. The majority of oxymorphone-derived radioactivity was found in the urine and feces. On average, age greater than 65 years was associated with a 1. There was a consistent tendency for female subjects to have slightly higher AUC ss and C max values than male subjects; however, gender differences were not observed when AUC ss and C max were adjusted by body weight. The liver plays an important role in the pre-systemic clearance of orally administered oxymorphone.
Accordingly, the bioavailability of orally administered oxymorphone may be markedly increased in patients with moderate to severe liver disease. The disposition of oxymorphone was compared in 6 patients with mild, 5 patients with moderate, and one patient with severe hepatic impairment and 12 subjects with normal hepatic function.
The bioavailability of oxymorphone was increased by 1. In one patient with severe hepatic impairment, the bioavailability was increased by In vitro studies revealed little to no biotransformation of oxymorphone to 6-OH-oxymorphone by any of the major cytochrome P CYP P isoforms at therapeutically relevant oxymorphone plasma concentrations. Therefore, it is not expected that oxymorphone, or its metabolites will act as inhibitors of any of the major CYP P enzymes in vivo.
Patients with chronic low back pain who were suboptimally responsive to their current non-opioid therapy entered a 4-week, open-label dose titration phase. Thereafter, patients were titrated to a stabilized dose, at increments of mg every 12 hours every days. Sixty three percent of the patients enrolled were able to titrate to a tolerable dose and were randomized into a week double-blind treatment phase with placebo or their stabilized dose of OPANA ER.
During the first 4 days of double-blind treatment patients were allowed an unlimited number of OPANA, an immediate-release IR formulation of oxymorphone, 5 mg tablets, every hours as supplemental analgesia; thereafter the number of OPANA was limited to two tablets per day.
This served as a tapering method to minimize opioid withdrawal symptoms in placebo patients. Sixty-eight percent of patients treated with OPANA ER completed the week treatment compared to forty seven percent of patients treated with placebo. The proportion of patients with various degrees of improvement from screening to study endpoint is shown in Figure 1.
Patients currently on chronic opioid therapy entered a 4-week, open-label titration phase with OPANA ER dosed every 12 hours at an approximated equianalgesic dose of their pre-study opioid medication. During the first 4 days of double-blind treatment, patients were allowed an unlimited number of OPANA 5 mg tablets, every hours as supplemental analgesia; thereafter the number of OPANA was limited to two tablets per day.
Proportion of patients with various degrees of improvement from screening to study endpoint is shown in Figure 2. OPANA ER is indicated for the relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for an extended period of time. OPANA ER is not indicated for pain in the immediate post-operative period hours following surgery for patients not previously taking opioids because of the risk of oversedation and respiratory depression requiring reversal with opioid antagonists.
OPANA ER is not indicated for pain in the post-operative period if the pain is mild or not expected to persist for an extended period of time. OPANA ER is not indicated for pain in the immediate post-operative period the first hours following surgery , or if the pain is mild, or not expected to persist for an extended period of time.
OPANA ER is only indicated for post-operative use if the patient is already receiving the drug prior to surgery or if the post-operative pain is expected to be moderate or severe and persist for an extended period of time.
Physicians should individualize treatment, moving from parenteral to oral analgesics as appropriate. See American Pain Society guidelines. OPANA ER is contraindicated in any situation where opioids are contraindicated such as: patients with respiratory depression in the absence of resuscitative equipment or in unmonitored settings , and in patients with acute or severe bronchial asthma or hypercarbia.
Opioid agonists have the potential for being abused and are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Concerns about abuse, addiction, and diversion should not prevent the proper management of pain. Healthcare professionals should contact their State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product. Oxymorphone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, and profound sedation or coma may result.
Drug addiction is characterized by a preoccupation with the procurement, hoarding, and abuse of drugs for non-medicinal purposes. Drug addiction is treatable, utilizing a multi-disciplinary approach, but relapse is common.
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. 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.
Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised. In addition, parenteral drug abuse is commonly associated with transmission of infectious disease 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. Respiratory depression is a particular potential problem 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.
OPANA ER should be administered 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. Alternative non-opioid analgesics should be considered, and oxymorphone should be employed only under careful medical supervision at the lowest effective dose in such patients. In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the possible respiratory depressant effects of opioid analgesics and their potential to elevate cerebrospinal fluid pressure resulting from vasodilation following CO 2 retention may be markedly exaggerated.
Furthermore, opioid analgesics can produce effects on pupillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries. OPANA ER, like all opioid analgesics, may cause severe hypotension in an individual 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 which compromise vasomotor tone.
OPANA ER, like all opioid analgesics, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. These patients should be started with the lowest dose and titrated slowly while carefully monitoring for side effects.
Opioid analgesics should be used with caution especially when combined with other drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known potential risks of respiratory depression, altered mental state and postural hypotension.
OPANA ER should be used with caution in elderly and debilitated patients and in patients who are known to be sensitive to central nervous system depressants, such as those with cardiovascular, pulmonary, renal, or hepatic disease. The administration of oxymorphone may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Oxymorphone may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings.
OPANA ER is intended for use in patients who require more than several days continuous treatment with an opioid analgesic. OPANA ER is not indicated for pre-emptive analgesia administration pre-operatively for the management of post-operative pain. OPANA ER is only indicated for postoperative use in the patient if the patient is already receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time.
Physicians should individualize treatment, moving from parenteral to oral analgesics as appropriate see American Pain Society guidelines. Ileus is a common post-operative complication, especially after intra-abdominal surgery with opioid analgesia. Caution should be taken to monitor for decreased bowel motility in post-operative patients receiving opioids.
Standard supportive therapy should be implemented. OPANA ER, 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.
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 tolerance is not unusual during chronic opioid therapy. 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. However, the history of an addictive disorder does not necessarily preclude the use of this medication for the treatment of chronic pain.
These patients will require intensive monitoring for signs of misuse, abuse, or addiction. Oxymorphone is highly metabolized principally in the liver and undergoes reduction or conjugation with glucuronic acid to form both active and inactive metabolites see Pharmacokinetics: Metabolism. The concomitant use of other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol may produce additive CNS depressant effects.
Additive effects resulting in respiratory depression, hypotension, profound sedation or coma may result if these drugs are taken in combination with the usual doses of OPANA ER.
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. In addition, CNS side effects have been reported confusion, disorientation, respiratory depression, apnea, seizures following coadministration of cimetidine with opioid analgesics; no clear-cut cause and effect relationship was established.
Carcinogenesis: Long-term studies have been completed to evaluate the carcinogenic potential of oxymorphone in both Sprague-Dawley rats and CD-1 mice. Oxymorphone HCl was administered to Sprague-Dawley rats 2. No evidence of carcinogenic potential was observed in rats.
No evidence of carcinogenic potential was observed in mice. Even more frustrating is having severe pain and turning to medications for relief, only to have the drugs not work. If this happens, take heart. There are stronger medications available that may ease your pain even after other drugs failed to work. These include the prescription drugs Opana and Roxicodone. Opana and Roxicodone are both in a class of drugs called opiate analgesics or narcotics.
Both medications work on the opioid receptors in your brain. By acting on these receptors, these drugs change the way you think about pain. This helps to dull your feeling of pain. The following table gives you a side-by-side comparison of some of the features of these two drugs.
Opana is the brand-name version of the generic drug oxymorphone. Roxicodone is a brand name for the generic drug oxycodone. These medications are also available as generic drugs, and both come in immediate-release versions. However, only Opana is also available in an extended-release form, and only Opana comes in an injectable form. The length of your treatment with either drug depends on your type of pain. However, long-term use is not recommended to avoid addiction. Both medications are controlled substances.
Taking either medication not as prescribed can lead to overdose or death. Your doctor may monitor you for signs of addiction during your treatment with Opana or Roxicodone. Ask your doctor about the safest way to take these medications. At the same time, you should also never stop taking Opana or Roxicodone without talking to your doctor.
Stopping either drug suddenly can cause withdrawal symptoms, such as:. When you need to stop taking Opana or Roxicodone, your doctor will slowly lower your dosage over time to decrease your risk of withdrawal. Opana and Roxicodone are both available as generic drugs. The generic version of Opana is called oxymorphone. For general information, Learn About Clinical Studies. Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information.
Search for terms. Save this study. Warning You have reached the maximum number of saved studies Bioavailability of Oxymorphone Hydrochloride 40 mg Extended Release Tablets Under Fasted Conditions The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
Listing a study does not mean it has been evaluated by the U. Federal Government. Read our disclaimer for details. Last Update Posted : March 29, Study Description. The purpose of this study is to demonstrate the relative bioequivalence of oxymorphone hydrochloride extended-release tablets Sandoz with Opana extended release oxymorphone hydrochloride tablets.
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