Variability in the quality of overdose advice in Summary of Product Characteristics (SPC) documents: gut decontamination recommendations for CNS drugs

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The Summary of Product Characteristics (SPC) is a legal document that gives healthcare providers information concerning each specific drug, including advice on the management of overdose. • Clinical outcomes after drug overdose may be influenced by the appropriate use of gut decontamination procedures. • The extent to which poisoning management advice in the SPC agrees with Poisons Centres recommendations is uncertain. WHAT THIS STUDY ADDS • Significant discrepancies exist between poisoning management advice contained in SPC documents and TOXBASE recommendations. • SPC documents may include inappropriate recommendations for induced emesis and gastric lavage, or omission of oral activated charcoal as a potentially effective therapy. • The SPC document cannot be relied on as a primary reference source for advice concerning drug overdose. AIMS Deliberate self‐poisoning is a major cause of morbidity and mortality. The Summary of Product Characteristics (SPC) document is a legal requirement for all drugs, and Section 4.9 addresses the features of toxicity and clinical advice on management of overdose. The quality and appropriateness of this advice have received comparatively little attention. METHODS Section 4.9 of the SPC was examined for all drugs in the central nervous system (CNS) category of the British National Formulary. Advice concerning gut decontamination was examined with respect to specific interventions: induced vomiting, oral activated charcoal, gastric lavage, and other interventions. Data were compared with standard reference sources for clinical management advice in poisoning. These were graded ‘A’ if no important differences existed, ‘B’ if differences were noted but not thought clinically important, and ‘C’ if differences were thought to be clinically significant. RESULTS SPC documents were examined for 258 medications from 67 manufacturers. The overall agreement was ‘A’ in 23 (8.9%), ‘B’ in 28 (10.9%) and ‘C’ in 207 (80.2%). Discrepancies were due to inappropriate recommendation of induced emesis in 21.7% (95% confidence interval 17.1, 27.1), gastric lavage in 38.4% (32.7, 44.4), other gut decontamination in 5.8% (3.6, 9.4) and failure to recommend oral activated charcoal in 57.4% (51.1, 63.4). CONCLUSIONS Gut decontamination advice in SPC documents with respect to CNS drugs was inadequate. Possible reasons for the observed discrepancies and ways of improving the consistency of advice are proposed.

Comparative Drug Dose and Drug Combinations in Patients that Present to Hospital Due to Self‐Poisoning

“…Few data exist concerning the combinations of drugs that might be involved in acute overdose, and the toxicity of each agent is normally addressed separately. For example, the clinical management advice offered in the Summary of Product Characteristics for licensed medications and that of specialised poisons centres normally concerns only a specific agent [22][23][24]. Despite this, it is recognised that drug toxicity is enhanced when particular combinations of drugs are co-ingested.…”

The role of Periodic Safety Update Reports in the safety management of biopharmaceuticals

“…Data on this is usually lacking at the time of authorization and is added to the label through post authorization SPC updates [25]. In addition, unlike the case for biopharmaceuticals, safety events of small molecules are included in a considerable number of post-approval regulatory actions related to toxicity as a result of overdose, data which are often lacking at the time of authorization and which may be included in post-authorization SPC updates [26]. Therefore, it could be that for small molecules the outcome of pharmacovigilance activities differ, and future research could compare our results with those for small molecules.…”

Physicians' reported needs of drug information at point of care in Sweden

“…Drug–drug interaction alerts though are currently difficult to extract from SmPC texts since information about interactions is typically not classified regarding their clinical relevance. Alongside this, often the current text contains unspecific information with no clinical recommendation about how to handle the interaction [12]. Additionally, drug–drug interaction information has to be extracted from two different SmPCs (the two interacting drugs) which often are currently not consistent [21].…”

“…In addition, certain information can be included in different sections, for example, information about drug interactions might be found in the section for contraindications or drug interactions, all of which potentially reduces their utility in practice. Although the SmPC holds important information that supports rational drug prescribing, the present structure, the inconsistency of the content and the absence of classification systems prevents integration into CDSSs in their current format and the generation of alerts [12].…”