What are the effects of oxycodone

Oxycodone (Oxygesic®): Abuse, addiction and fatal consequences from injection of crushed prolonged-release tablets (announcement)

Oxycodone has been known since 1917, has been used therapeutically as an opioid analgesic since 1919 and has been subject to the narcotics prescription regulation since 1929. The old, strongly effective analgesic Eukodal® (oxycodone HCI), which has not been on the market since 1990, was dosed at 5 mg per tablet and 10 mg or 20 mg per ampoule. Oxycodone HCI has been on the market again since 1998 as Oxygesic® 10/20/40 mg prolonged-release tablets, and since 2001 also as 80-mg prolonged-release tablets, but not as ampoules. This pharmaceutical preparation leads to a more stable resorption rate and thus somewhat greater bioavailability with less variance. Indication areas are severe to very severe pain. According to several clinical studies, 1 mg is equi-effective with around 1.5 mg of morphine. An international, independent drug bulletin, of course, rated the therapeutic benefit of retarded oxycodone as limited, since rapid dose adjustment is not possible and the indivisible tablets that can be swallowed as a whole could cause additional difficulties in patients with swallowing disorders; it does not offer any advantages compared to morphine and should not be regarded as the first-line drug in this indication (1).

Eukodal® is represented in the systematized random sample of addicts of the German "early warning system for addiction (FWS)" in the 25 years of its term (2) with 137 case reports among 14,702 examined persons with addiction problems. 93 percent of the abusers were drug addicts; 94 percent of the subjects with regular abuse were dependent. 89 percent had experience with IV administration of oxycodone. The mean abuse dose was 343 mg oxycodone / day (the highest dose achieved and maintained for at least one week). In terms of "popularity", Eukodal® stood between heroin on the one hand and street morphine and Dicodid® on the other. Further details of abuse can be found in the FWS report (3). According to literature data and the overall pattern of the substance in the FWS, there is no doubt that oxycodone has a high potential for abuse (opiate type).

There has not been a break in the availability of oxycodone in the USA as in the Federal Republic of Germany. A few years ago the news came from there that mixed analgesic preparations with oxycodone were increasingly being abused orally and nasally as part of "recreational abuse" (5). There, several mixed preparations oxycodone (like codeine in Germany) are added. At the moment, only OxyContin®, which was introduced in 1996, appears to be available in the USA as an oxycodone monopreparation. Its regulation increased 18-fold by the year 2000, based on the year of availability on the market (7). OxyContin® is said to have the name "hillbilly heroin" in the drug scene (8). A survey by the US Drug Enforcement Administration (DEA) of forensic medicine institutes found 110 deaths reported in 30 US states (out of a total of 51) in which OxyContin® was the direct cause of death or a contributing cause. The agency described 172 further deaths in a preliminary notification as "possibly" caused by oxycodone (7).

The tablets are crushed by the abuser, whereby the retardation (AcroContin® system) becomes ineffective and the entire content of the tablets becomes effective immediately, so that a fatal overdose can result. At the instigation of the US Food and Drug Administration (FDA), the US manufacturer of OxyContin® added the strongest possible warning ("black box warning") to the product information in July 2001. The medical profession was informed that OxyContin® should only be used in patients with severe chronic pain and was not prescribable with the note "Use when required". The manufacturer's information now stated that the preparation, like other opioids, has a high potential for addiction. Abusers have found that when injected or snorted, crushed tablets immediately release very high doses of the product that can be fatal (4, 6).

The manufacturer has promised the production of an "abuse-resistant" form of the drug (7). According to the manufacturer, a fixed combination with an opioid antagonist, for example naloxone, is being considered, the usefulness of which would of course have to be proven first. The addiction experts at AkdÄ point out that such a combination is quite critical with regard to the occasional abuse by "leisure users", because naloxone does not trigger a withdrawal syndrome in an organism that has not been opiate-free and therefore cannot have an aversive effect. For road users, the situation would be completely different: Here, intravenous administration would trigger severe withdrawal symptoms, starting with severe nausea.

On the other hand, the US manufacturer doubts the validity of the DEA data (letter from Purdue to Mundipharma dated March 19, 2003). In an analysis, initiated and sponsored by the manufacturer, of 1,419 deaths that became known to the manufacturer in connection with the use of oxycodone and of which 1,249 were evaluated, 1,137 (91 percent) related to the misuse of oxycodone; In three percent (N = 34) of the latter, it was the sole abuse of oxycodone, with OxyContin® being clearly identifiable as the abused agent in only 12 cases (9). (From the AkdÄ's point of view, this result is not surprising, because most drug deaths involve more than one substance. The value of each individual substance, for example a benzodiazepine, has to be assessed critically with regard to its cause of death).

According to the manufacturer, the same retardation system is used for the Oxygesic® tablets sold in Germany as in the USA. Up until the end of 2000, when the EWS ended, the EWS contained one documented case of Oxygesic® abuse and six anecdotal reports from the EWS environment. Even if the danger of a repetition of the US situation in the Federal Republic is limited by the German narcotics legislation, oxycodone has its own history of abuse here as well, as described at the beginning. Some abusers may still remember the earlier Eukodal® tablets and are therefore in particular danger; One Oxygesic® 80 mg tablet now contains 8-16 times the dose of the old Eukodal® tablets. This dose can be fatal to a non-tolerant adult. Therefore, the German technical information also points out that the 80 mg prolonged-release tablet "should not be taken by patients who have not previously received opioids". The abuse patterns in the drug scene on this side of the Atlantic are not significantly different from those in the USA. Here, too, tablets are crushed by addicts and administered intravenously. The relevant experience with Rohypnol® (Flunitrazepam) urges caution and critical handling of oxycodone. The concern for optimal care of pain patients in the Federal Republic must not suppress concern for the lives of drug addicts. From the AkdÄ's point of view, therefore, the question arises as to whether the indication of the Oxygesic® 80 mg tablet should not be restricted even more, despite its advantages in palliative medicine, which are also emphasized by members of the AkdÄ, or whether another delay mechanism should be used. A naloxone admixture cannot be predicted with regard to its success. The AkdÄ would like to see the German technical information adapted to the US for OxyContin insofar as the indication should expressly only be the "long-term treatment" of severe and very severe pain. The medical profession recommends the AkdÄ not to use Oxygesic® prolonged-release tablets as the drug of choice for analgesia of street addicts and otherwise only to prescribe Oxygesic® strictly according to the indications in view of the warnings from the American regulatory authority cited above. For pain therapy in drug addicts, the following can be considered: increasing the previous methadone dose, non-steroidal anti-inflammatory drugs and local anesthetics. Please inform the AkdÄ of all observed side effects (including suspected cases). You can use the report form printed at regular intervals on the penultimate cover page of the Deutsches Ärzteblatt or call it up on the AkdÄ website at www.akdae.de.

literature
1. Anonymous: Oral oxycodon no better than oral morphine. Prescrire International 2003; 12: 83-84.
2. Keup W: Abuse pattern in addiction to alcohol, medication and drugs. Early warning system data for the Federal Republic of Germany 1976-1990. Lambertus publishing house, Freiburg i. Br., 1993: p. 874.
3. Keup W: Abuse of oxycodone (Eukodal®-Oxygesic®). Dates and thoughts on reintroduction in the pharmaceutical market. Early Warning System Report No. 138, May 5, 2002.
4. McLellan F: US FDA improves warning on abused drug. Lancet 2002; 358: 568.
5. Sannerud CA, Gauvin DV, Sapienza FL: Recent trends in patterns of street drug abuse in the United States. Soc Neurosc Abstracts 2000; 26 (1-2): para. 870.
6. SCRIP: US boxed warning for OxyContin. SCRIP No. 2665 (August 1, 2001a): p. 21.
7. SCRIP: US debates OxyContin use and abuse. SCRIP No. 2698 (November 23, 2001b): p.16.
8. SCRIP: Time to reformulate OxyContin. SCRIP No. 2669 (August 15, 2001 c): p. 20th
9. Cone EJ, Fant RV, Rohay JM et al .: Oxycodone Involvement in Drug Abuse Deaths: A DAWN-Based Classification Scheme Applied to an Oxycodone Postmortem Database Containing Over 1000 Cases. Journal of Analytical Toxicology 2003; 27: 57-67.


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