Oxymorphone

Oxymorphone (Opana, Numorphan, Numorphone) or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany in 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time. It (along with hydromorphone) was designed to have less incidence of side effects than morphine and heroin. It was a success as it differs from morphine and heroin in its effects in that it generates less euphoria, sedation, itching and other histamine effects at equianalgesic doses. This also means a lower dependence liability.

The brand name Numorphan is derived by analogy to the Nucodan name for an oxycodone product (or vice versa) as well as Paramorphan/Paramorfan for dihydromorphine and Paracodin (dihydrocodeine). The only commercially available salt of oxymorphone in most of the world at this time is the hydrochloride, which has a free base conversion ratio of 0.891.

In some countries, hydromorphinol is distributed under the trade names Numorphan and Numorphan Oral. This is a relatively rare exception and the two drugs, whilst both being strong opioid analgesics, are notably different from one another.

Oxymorphone is administered as its hydrochloride salt via injection, or suppository; typically in dosages of 1 mg (injected) to 5 mg (suppository). Endo has been the major distributor of oxymorphone throughout the world and currently markets oxymorphone in the United States and elsewhere as Opana and Opana ER.

Opana is available as 5 mg and 10 mg tablets; Opana ER, an extended-release form of oxymorphone, is available as tablets in strengths of 5 mg,10 mg, 20 mg, 30 mg, and 40 mg. As of July 21, 2011 generic strengths equivalent to Opana ER 7½ mg and 15 mg are available. Some resources assert that 2, 12 and/or 15 mg IR tablets and 25, 36 and 50 mg extended release tablets will be introduced although apparently the timeline on that is not known to the public at this time. Opana Extended-Release tablets are based on the TIMERx system developed by a consortium led by Endo and Penwest. Some of these strengths (notably not the 7.5 mg) are available in an Opana IR–immediate release–form for breakthrough pain to be used by patients already on 24/7 opioid care such as fentanyl patches and sustained-relief morphine drugs like Avinza.

In addition to the sustained-release version for Opana, other versions of TIMERx are available and being developed for other protocols such as increasing, decreasing, stepwise increasing, and stepwise decreasing dose delivery over time, single and multiple bursts of medication, and combinations of the above.

Specifically, the apparent extension of the duration of effect of the IR tablets (all other things being equal, oxymorphone has a duration of action of 5 to 8 hours in most patients) versus similar drugs in commonly used immediate-release forms—for example Dilaudid (hydromorphone), morphine, Vilan (nicomorphine), Paramorfan (dihydromorphine) as well as prodrugs for this group such as hydrocodone, nicocodeine, codeine, dihydrocodeine and others—is often attributed to a marginal extended-release effect from various excipients, particularly those that are hydrophilic and form a gel-like substance at the pH levels in the stomach and duodenum.

Both as the result of this and the pharmacokinetics of oxymorphone, the IR tablets have a de facto duration of action of 5 to 13 hours (the mean would seem to be around 7 hours with a moderately small standard deviation and a left-skewed and leptokurtic frequency distribution) in patients with normal kidney and liver function. As a result, patients rotated on to extended release oxymorphone preparations from other opioids may very well need the Opana IR tablets, Numorphan ampoules or phials with hypodermic needles and/or a PCA pump, or immediate-release formulations of hydromorphone, dihydromorphine, high dose oxycodone, hydromorphinol, nicomorphine, diamorphine, or morphine for breakthrough pain incidents already in progress. An oxymorphone nasal spray is reportedly in development, along with a possible hydromorphone nasal spray and implantable osmotic pumps for both drugs.

The duration of action and metabolic half-life of oxymorphone mean that immediate-release tablets are more similar to analgesic preparations of methadone, levorphanol, piritramide, and existing extended-release forms of morphine, oxycodone, ketobemidone and so on. The extended-release Opana tablets can provide detectable analgesia for anywhere from 6 to 36+ hours (the mean appears to be very close to the lower end of the continuum), largely contingent on things that can alter the drug's liberation, absorption, distribution, metabolism, and elimination profile. One cause is unusual conditions in the upper and middle GI tract, such as created by misoprostol and Arthrotec (misoprostol plus diclofenac). Among other things, misoprostol is a smooth muscle agent with both a contact and systemic mucousagogue that coats the stomach and adjacent areas with increasing amounts of mucus. This can result in everything from even slower onset of action to intact tablets being passed with stool.

Oxymorphone is also produced within the human body when the liver metabolises oxycodone by means of O demethylation catalysed by the CYP2D6 enzyme. Approximately 10% of the dose is processed by the endocrine system in this respect; this can vary widely from person to person. The codeine-hydrocodone group and morphinans exhibit the same characteristics.

Consuming alcohol with Opana extended-release tablets can be an extremely dangerous situation. The absorption of oxymorphone can vary wildly in the presence of alcohol. Plasma concentrations were found to be as low as -50% of expected to as much as 270% more than expected. Elevated plasma levels could result in overdose. Opana ER does not cause "dose dumping", which creates a blast of drug release that plagues other long acting opioids.