How Resistant to Tampering are Codeine Containing Analgesics on the Market? Assessing the Potential for Opioid Extraction

Abstract

IntroductionMisuse of opioid analgesics, in combination with diversion, dependence, and fatal overdoses, presents a serious problem for public health, which affects many countries worldwide. Within this context, tampering with opioids has been associated with serious harm. The aim of the present study was to assess the tampering potential of codeine combination analgesics on the market (containing codeine/non-opioid analgesics) by the extraction of codeine.MethodsCodeine was extracted from three combination formulations sold lawfully from licensed pharmacies without a medical prescription in Denmark and the UK. Extraction of codeine followed tampering procedures available on the Internet. The amounts of codeine and accompanying non-opioid analgesics in tampering products were analysed with liquid chromatography and tandem mass spectrometry (LC–MS/MS).ResultsLC–MS/MS showed recoveries of the total amounts of codeine in tampering products of 81–84% from Product 1 (codeine/acetylsalicylic acid); 61–67% from Product 2 (codeine/ibuprofen); and 42–71% from Product 3 (codeine/paracetamol). Recoveries of non-opioid analgesics ranged between: 57–73% acetylsalicylic acid; 5.5–8.5% ibuprofen, and 5.0–9.2% paracetamol.ConclusionWith the tampering procedures used, high amounts of codeine were separated from the accompanying analgesics in some, but not in all of the codeine containing formulations. Evidence-based medicine regulation, treatment for opioid dependence, and information to minimise risks to the public are essential components of an effective public health strategy to address the harms of tampering and misuse.FundingMarie Pedersen and Jensine Heiberg Foundation.

Tampering of opioid analgesics: a serious challenge for public health?

“…We recently extracted codeine from ‘over‐the‐counter’ preparations with simple household utensils such as coffee filters and recipes that we found on the internet. Our study showed that it was possible to separate codeine from the accompanying non‐opioid analgesics, thus allowing for consumption of large codeine doses without toxic doses of ibuprofen and paracetamol . The results also indicated that codeine extraction was ineffective in some formulations, and that the amounts of active substances, codeine and non‐opioid analgesics, varied in tampering products.…”

Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse

“…Thus, hepatotoxicity from paracetamol, or gastrointestinal damage (haemorrhages, ulcerations, hypokalaemia, metabolic acidosis) and nephrotoxicity caused by ibuprofen are common consequences of its misuse [ 27 , 39 , 40 , 41 ]. In effort to evade these harms, various homemade extraction methods are used to separate codeine from the abovementioned drugs—for example, the so-called cold water extraction that exploits solubility differences between ingredients [ 35 , 42 , 43 ]. Lately, some pharmaceutical companies begun to incorporate physical or chemical barriers to their products as a means to combat such practices [ 26 ].…”

“…Another alarming trend entails clandestine syntheses of more potent opioids with codeine used as a substrate. The “homebake” method results in the demethylation of codeine to morphine, while with a slightly more complex protocol [ 63 , 64 , 65 , 66 ] it is possible to obtain desomorphine—a drug with an 8–10 times stronger analgesic effect (up to 80–100 times stronger than the precursor codeine) and three times the toxicity of morphine [ 42 , 65 ]. Structural differences between these opioids are presented in Figure 2 .…”

The challenge of complex drug use: Associated use of codeine‐containing medicines and new psychoactive substances in a European cross‐sectional online population

“…Codeine extraction has been described amongst members of drug discussion forums (Cone, 2006;Foley, Breindahl, Hindersson, Deluca, & Kimergård, 2016). One study found that extracting codeine with the use of simple techniques and household appliances can yield different amounts of codeine and non-opioid analgesics in the extracted mixtures making it difficult to control the doses (Kimergård, Deluca, Hindersson, & Breindahl, 2016b). Understanding risk factors associated with medicine tampering may help implement harm reduction interventions and deliver treatment to specific populations of polysubstance users where the risk of harm is disproportionately great (Kapitány-Fövény et al, 2015;Kimergård et al, 2016a;Talu et al, 2010).…”