Accurate Education, Pain Medications – Oxymorphone (Opana)

Oxymorphone (Opana)

Oxymorphone is an opioid medication used for the management of moderate to severe pain. It is similar to oxycodone but different in  ways that may offer advantages to some individuals.

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It is recommended to first read the following sections to become familiarized with some of the terms and concepts related here:


Neurobiology of Pain

Neuropathic Pain


Opioid Tolerance

Opioid Induced Hyperalgesia


Also see:

Buprenorphine for Pain


Methadone for Pain


Opioids – Individual

Opioids – Buprenorphine

                  (Butrans, Belbuca, Suboxone, Subutex, Zubsolv, Bunavail)

Opioids – Fentanyl (Duragesic)

Opioids – Hydrocodone (Norco, Vicodin)

Opioids – Hydromorphone (Dilaudid, Exalgo)

Opioids – Levorphanol

Opioids – Methadone (Dolobid)

Opioids – Oxycodone (Percocet, Oxycontin, Xtampza ER)

Opioids – Oxymorphone (Opana, Oxycmorphone ER, Opana ER)

Opioids – Morphine (MSIR, MSER, MSContin)

Opioids – Tapentadol (Nucynta)

Opioids – Tramadol (Ultram, Ultracet)


Definitions and Terms Related to Pain


Key to Links:

Grey text – handout

Red text – another page on this website

Blue text – Journal publication

‘Who, except the gods, can live time through forever without any pain?”

– Aeschylus (BC 525-BC 456) Greek dramatist.

Opioids – Oxymorphone (Opana)

Oxymorphone is a semisynthetic opioid that is generally considered to be about twice as potent as oxycodone and three times as potent as morphine with respect to it’s pain benefits and effects on respiratory depression. It is similar to oxycodone in that when oxycodone is metabolized by the liver, a significant amount (10-30%) of the oxycodone is converted to oxymorphone before entering the blood stream and impacting the brain and nervous system. This means that anyone who has been taking oxycodone has also, indirectly, been taking oxymorphone so that it may not exactly represent a “new” drug to these people.

For full prescribing information, see: Opana – prescribing information


How is oxymorphone different from oxycodone and other opioids?


Pain Benefits

While oxymorphone, like all opioids, acts on the mu-opioid receptor which provides the usual benefits for pain as well as the usual side effects, it is considered more potent for most people than hydrocodone, oxycodone or morphine. Due to individual variation, some people may tolerate oxymorphone better than some other opioids while some people may not.


It is believed that oxymorphone develops tolerance more slowly than oxycodone and morphine. This offers a significant potential advantage since it may provide a better opportunity to avoid the gradual escalation of opioid dosing necessary to maintain adequate pain control over long periods of time. Although studies are not conclusive, oxymorphone may cause less respiratory depression compared with the same doses of oxycodone.


Oxymorphone’s mechanism of relieving pain (analgesia) is thought to be solely based on its activity on mu-opiod receptors in the brain and nervous system. When analgesia comes solely from activity on the mu-opioid receptor, the analgesia is linited for nerve pain, which includes burning, electric, sharp or stabbing pain, or pain that starts in one location and shoots to another location (such as sciatica). Therefore the use of oxymorphone for nerve pain may lead to the need for higher doses to control the pain and for this reason, oxymorphone may not be the best choice for treating a pain condition that has a significant component of nerve pain.


Opioids whose pain benefits are believed to be limited to action on the mu-opioid receptor include hydrocodone (Norco, Lortab, Vicodin), hydromorphone (Dilaudid), oxycodone, oxymorphone and morphine. There are some other opioids that offer additional mechanisms of action for analgesia and they are likely to work better with nerve pain. These other opioids tramadol (Ultram), tapentadol (Nucynta), methadone and levorphanol.

See: Opioids and Nerve Pain


Oxymorphone Metabolism and Drug interactions

Compared with other opioids like morphine or oxycodone, oxymorphone is more lipid soluble which results in a more rapid transfer across the blood – brain barrier into the brain and potentially a shorter time to achieving maximum pain relief.


Medications are broken down (metabolized) in the liver via glucuronidation by UGT enzymes or via oxidation by the cytochrome P450 (Cyp450) enzymes. Oxymorphone is primarily metabolized in the liver by glucuronidation which offers some advantages.


The Cyp450 system of enzymes is very susceptible to genetic variation as well as susceptible to being enhanced or suppressed by other medications. This makes medications that are metabolized primarily by Cyp450 enzymes prone to individual variability in responsiveness, including effectiveness and side effects. Cyp450 enzymes are more susceptible to compromise with liver disease compared with UGT enzymes and therefore medications metabolized by Cyp450 enzymes may be more unpredictable in their effects and safety in liver disease.


Glucuronidation by the UGT enzymes is not known to be significantly influenced by genetic variants or other drug interactions, therefore oxymorphone may be less susceptible to drug interactions compared with opioids metabolized by the Cyp450 enzymes (hydrocodone, oxycodone, methadone, fentanyl).


Oxymorphone’s Clinical Effectiveness for Pain Conditions


Chronic Arthritis and Back Pain

Oxymorphone is effective for most moderate to severe pain, including pain related to chronic osteoarthritis such as joint and spine pain. Because oxymorphone may not be as effective as some other opioids for treating nerve pain (see above), it may not be the best choice for sciatica and other “shooting” pains, nor the best for the hand and foot pain associated with diabetic neuropathy.




Oxymorphone should be used with caution in people with epilepsy or who are otherwise prone to seizures. It raises intracranial pressure so should not be used in people with head injuries, brain tumors, or other conditions which increase intracranial pressure. Like all opioids and other sedatives, at higher doses it increases the risk of respiratory depression so it should be used with caution in people with asthma or severe COPD/emphysema and those at risk for sleep apnea.


For those individuals at risk for addiction, the use of oxymorphone and any opioid should be directed by a physician with expertise in addiction assessment and management. To understand the risks for addiction and means of reducing risk, see: Addiction Prevention.


Oxymorphone with Liver or Kidney Disease

Use of oxymorphone in moderate to severe liver disease can result in higher blood levels and therefore should be used with caution in patients with moderate-severe liver impairment. While oxymorphone primarily metabolized in the liver, oxymorphone and its metabolites are also excreted by the kidney and the risk of adverse reactions to this drug may be greater in patients with impaired kidney 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.


Oxymorphone Dosing

Oxymorphone (Immediate Release)

Oxymorphone is available in 5 mg and 10 mg tablets and is generally recommended to be taken every 4–6 hours on the basis of pain intensity. Oxymorphone is intended for acute pain relief and for “break through” pain when prescribed along with a long-acting or extended-release opioid for chronic pain. Because food enhances absorption of oxymorphone by as much as 50% which can lead to greater side effects, it should be taken on an empty stomach, at least one hour prior to, or two hours after eating. As with all opioids, please follow your prescribing clinician’s instructions.


Oxymorphone ER (Extended Release)

Oxymorphone ER is available in tablets of  5mg, 10mg, 15mg, 20mg, 30mg and 40 mg. Oxymorphone ER is generally advised to be taken every 12 hours.


Oxymorphone ER is intended only for the management of chronic pain. If patients need to be converted from oxymorphone IR to oxymorphone ER, the conversion between the two forms can be achieved quite simply under the guidance of the prescribing physician. Oxymorphone ER should be taken on an empty stomach, at least one hour prior to, or two hours after eating. As with all opioids, please follow your prescribing clinician’s instructions.


Oxymorphone (Immediate-Release) vs Oxymorphone ER (Extended-Release)

Clinical trials comparing immediate-release (IR) with comparable extended-release (ER) opioids generally show little difference with quality of pain relief or frequency of side effects. Some patients respond more favorably to either form, or a combination of the two.


A Special Note: Opana ER (Extended Release)

Opana-ER, an extended release form of oxymorphone, was first introduced in 2006 and then reformulated and released in 2012 in an effort to reduce the ability for it’s abuse by intranasal (IN) by nasal snorting and intravenous (IV) injection. Research experience over the years showed that while the reformulation did deter IN abuse, it did not effectively reduce IV abuse. As a result of continued IV abuse, in 2017 the FDA called for the removal of Opana ER from the market and in September 2017 sales were discontinued.


Of note, the FDA did not call for the removal of the generic versions of oxymorphone ER which offered no abuse deterrence at all, not even intranasal. The generic versions are still available on the market.




If the generic versions remain on the market, what was the argument for removing the Opana ER version? Investigation of the FDA documentation is somewhat confusing in this regard. The focus of federal reporting of adverse events related to the use of Opana ER centered on intravenous abuse and the occurence of a condition called Thrombotic Microangiopathy (TMA), in which damage occurs to the walls of blood vessels that results in anemia, abnormal blood clotting and injury to body organs, especially the kidney.


From the time of release of reformulated Opana ER in December 2011 through June 2016, 59 cases of TMA were reported with injections of opioids, most of them associated with reformulated Opana ER. Research indicates the mechanism of injury in TMA is linked to the IV injection of one of the inert ingredients that is part of the abuse deterrent formulation. It remains unanswered as to why the occurence of TMA is higher with Opana ER than other opioids manufactured with the same abuse deterrent inert ingredients.


In one study (NAVIPPRO) when statistics from 2012-2016 were reviewed by the FDA, it appears that for every 50,000 Opana ER tablets dispensed by prescription, there were about 1 to 1-1/4 cases of IV abuse (not deaths). Similar injection abuse rates for generic oxymorphone ER in the same period were found while overall abuse prevalence highest for IR and ER oxycodone. Of note, IN abuse of Opana ER was reduced significantly but this IN reduction was associated with increased IV abuse and concerns were expressed that this was a driver behind the increase in IV abuse. The increase in IV abuse was statistically mostly driven by Tennessee and other Appalachian states and Indiana.


The final conclusions of the FDA included (see FDA – Regulatory History of Opana ER 2017):

  1. Opana ER and other oxymorphone products represent small fraction of overall opioid use and abuse
  2. Relative to prescribed availability, Opana ER and other oxymorphone products may be relatively likely to be abused or misused, but varies geographically
  3. Generic oxymorphone ER has high nasal abuse rates
  4. Reformulated Opana ER and generic oxymorphone ER both have high injection abuse rates, with only slightly lower rates for oxymorphone IR.


So it would appear that despite the fact that millions of prescriptions of Opana ER had been properly and effectively used by patients for chronic pain, the actions of a very small percentage of people using the medication in ways that it was not intended and instructed specifically against, drove the FDA to remove from the market a useful medication for the management of chronic pain.

See: the Politics of Pain





Oxymorphone (Opana) – Overviews

  1. Opana – prescribing information
  2. Pharmacodynamic effects of oral oxymorphone – Abuse liability, analgesic profile and direct physiological effects in humans – 2016
  3. Review of oral oxymorphone in the management of pain – 2008


Oxymorphone ER – Opana ER

  1. Opana ER – new formulation prescribing information
  2. Food Effect with Xtampza ER
  3. Efficacy and safety of OPANA ER (oxymorphone extended release) for relief of moderate to severe chronic low back pain in opioid-experienced patient… – PubMed – NCBI
  4. FDA Asks Endo Pharma to Take Opana ER Off the Market -Medscape 2017
  5. FDA Calls for Opana ER’s Removal Due to Abuse Concerns
  6. FDA – Regulatory History of Opana ER 2017
  7. Thrombotic Thrombocytopenic Purpura (TTP)–Like Illness Associated with Intravenous Opana ER Abuse — Tennessee, 2012
  8. Thrombotic Microangiopathy Secondary to Intravenous Abuse of Opana„ ER – 2017
  9. Opana-induced thrombotic microangiopathy masquerading as thrombotic thrombocytopenic purpura – 2017
  10. A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER. – 2017 PubMed – NCBI


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