Beyond the ‘purple drank’: Study of promethazine abuse according to the European Medicines Agency adverse drug reaction reports

Abstract

Background: Promethazine is a medicinal product, available on its own or in combination with other ingredients including dextromethorphan, paracetamol and/or expectorants. Anecdotal reports have however indicated that promethazine may have a misuse potential, especially in adolescents. Objective: We here aimed at studying how this phenomenon has been reported to the European Monitoring Agency Adverse Drug Reactions database. Methods: After a formal request to the European Monitoring Agency, the promethazine-specific dataset has been studied, performing a descriptive analysis of misuse/abuse/dependence-related adverse drug reaction reports. The study was approved by the University of Hertfordshire (LMS/PGR/UH/03234). Results: The analysis of promethazine data showed increasing levels of misuse/abuse/ dependence issues over time (2003–2019). Out of a total number of 1543 cases of adverse drug reactions, the abuse/misuse/dependence-related cases reported were 557, with ‘drug abuse’ (300/557: 53.8%) and ‘intentional product misuse’ (117/557: 21.0%). being the most represented adverse drug reactions. A high number of fatalities were described (310/557: 55.6%), mostly recorded as ‘drug toxicity/drug abuse’ cases, with opiates/opioids having been the most commonly reported concomitant drugs used. Conclusion: Anecdotal promethazine misuse/abuse reports have been confirmed by European Monitoring Agency data. Promethazine misuse/abuse appears to be an alarming issue, being associated with drug-related fatalities. Thus, healthcare professionals should be warned about a possible misuse of promethazine and be vigilant, as in some countries medicinal products containing promethazine can be purchased over the counter. Since promethazine is often available in association with opioids, its abuse may be considered a public health issue, with huge implications for clinical practice.

Focus on Over-the-Counter Drugs' Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants

“…Conversely, promethazine is used in cough syrups for its antihistaminic, antiemetic, and sedative effects, available with codeine in common cough suppressants (128); its abuse potential appears related to its calming and sedating effect and enhancement of other coingested substances (Table 1). A recreational use of promethazine mixed with a soft drink and/or alcohol ("purple drank") is currently popular among young people for its euphoric effects and easy accessibility (19,20,(129)(130)(131). Promethazine has been reported in SUD clients and is misused as a substitute for another drug or to increase the effects of inadequate dosing (i.e., to delay the onset of opioid withdrawal or to potentiate the sedating effect of benzodiazepines/Z-drugs) (13,19,20,103,129,130,132,133).…”

“…A recreational use of promethazine mixed with a soft drink and/or alcohol ("purple drank") is currently popular among young people for its euphoric effects and easy accessibility (19,20,(129)(130)(131). Promethazine has been reported in SUD clients and is misused as a substitute for another drug or to increase the effects of inadequate dosing (i.e., to delay the onset of opioid withdrawal or to potentiate the sedating effect of benzodiazepines/Z-drugs) (13,19,20,103,129,130,132,133). Overdose of promethazine is associated with an antimuscarinic delirium, agitation, and neuroleptic malignant syndrome (100, 102,104,133).…”

Side effects of the cough drug dextromethorphan, studied on ants as models

“…Being a first-generation antihistaminic, it easily penetrates the blood-brain barrier, causing adverse effects such as central nervous system (CNS) and respiratory depression 2 as well as dry mouth, constipation, blurred vision, sedation, urinary retention and dermatitis. 3,4 Moreover, cases of misuse and abuse have been reported for promethazine, 5 a fact also mentioned in a study on drugs abuse and dependence. 6 Another cough drug, codeine, belonging to the opioids, has been used since a long time and is still used as a central cough suppressant.…”

Editorial: Prescribing Psychotropics: Misuse, Abuse, Dependence, Withdrawal and Addiction

“…and over-the-counter (OTC) drugs (e.g., loperamide, dextromethorphan, promethazine, benzydamine etc.) (12)(13)(14)(15)(16)(17). Indeed, pharmacovigilance studies have helped in identifying signals of misuse associated with these molecules (18).…”