A Danish Survey of Antihistamine Use and Poisoning Patterns

Abstract

The first-generation antihistamine, promethazine, became a prescription-only drug in Denmark as of December 2014. First-generation antihistamines are known to have a higher toxic potential than second-generation antihistamines. The aim of this study was to provide a nationwide description of the antihistamine use and poisoning pattern from 2007 to 2013 in Denmark based on two independent databases. There were 1049 antihistamine exposures in the national, advisory telephone service specialized in poisonings, the Danish Poison and Information Centre (DPIC), and 456 exposures in the three registers used within the State Serum Institute of Denmark (SSI), a department under the Danish Ministry of Health dealing with research-based health surveillance in Denmark. First-generation antihistamines constitute 61% and 73% of antihistamine registrations in DPIC and SSI, respectively. Antihistamine exposures increased by 7 exposures/10,000 enquiries per year in DPIC and six admissions per year in SSI -this increase is not significant due to a sudden decrease in 2012. Intentional exposures constituted 65% in DPIC of which 82% was due to suicide attempts, and 78% of the involved antihistamines were first-generation antihistamines. Accidental exposures constituted 33% of which 61% were due to play and 29% involved first-generation antihistamines. Single antihistamine exposures constituted 65% of DPIC exposures of which 98% involved only one brand of antihistamine. Multidrug exposures constituted 35% of DPIC exposures with equally distributed coingestants. Hospitalization was recommended in 78% of DPIC exposures. Admissions required only 1-day of treatment in 91% of the SSI exposures. One of the 14 identified deaths in the SSI study population was directly related to antihistamine poisoning. Results support the limited disclosure of promethazine in Denmark and illustrate a generation-specific pattern indicating a suspected replacement of promethazine with other firstgeneration antihistamines.

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

“…The current study provides a large amount of descriptive data highlighting that promethazine can be taken at high dosages, through nonapproved administration routes, and in a setting of polydrug use (Hughes et al, 2016;Novak et al, 2016). Promethazine misuse has been increasingly recorded since the early 2000s, consistently with data from US poison centres reporting antihistamine exposures rising in the period 2007-2013 (Jensen et al, 2017). This is not surprising, since the pharmacodynamic properties of promethazine underpins its sought-after central effects.…”

“…Alcohol (Burns and Boyer, 2013;Jensen et al, 2017) CNS depressant effects 'Lean', 'sizzurp', 'purple drank' and other street concoctions containing promethazine, codeine and alcohol, along with other potential sedatives Euphoria, relaxation, 'slight giddiness and disorienting' and 'nice hallucination'.…”

Misuse of prescription and over-the-counter drugs to obtain illicit highs: how pharmacists can prevent abuse

“…As a histamine (H)1 receptor antagonist, promethazine is commonly used for symptomatic relief from nausea and vomiting, for allergic conditions, motion sickness, and the common cold. Often available with codeine in common cough suppressants, its abuse potential appears related to its calming and sedating effect, and enhancement of other co-ingested substances, such as benzodiazepines and opioids [34,48,117]. The abuse of promethazine mixed with a soft drink and candy with some variants including purple coloured alcohol ("purple drank") has become popular in young people for its euphoric effects and easy accessibility [12,28,37].…”

Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse

“…Surprisingly, supratherapeutic doses may cause paradoxical CNS stimulation (euphory, hallucinations), mainly due to anticholinergic poisoning [ 59 ]. Promethazine misuse is either related to its calming effect or ability to induce paradoxical euphoria and occasional hallucinations (auditory and visual), when administered in larger amounts [ 60 ]. Such effects are further enhanced by the simultaneous consumption of alcohol.…”