Adverse Drug Reactions related to mortality and morbidity

#Adverse Drug Reactions related to mortality and morbidity

Adverse Event Reaction related Mortality and Morbidity: Drug-Drug interactions and Overdoses


Adverse Drug Reactions (ADRs) are a major contributing factor to morbidity and mortality resulting in 6.5-10.9% of hospital admissions and mortality rates of 0.15-2.9%. A considerable number of ADRs are preventable particularly those caused by drug-drug interactions and overdoses. Preventive measures such as adhering to Risk Management Plans (RMPs), ongoing Pharmacovigilance (PV) awareness training for healthcare professionals and patients could help reduce the prevalence rates of ADRs.


Adverse drug reactions are an acknowledged factor contributing to morbidity and mortality universally and have caused the withdrawal of 28 drugs from the US market between 1976 and 2007. The World Health Organization defined an ADR as any noxious, unintended or undesired effect of a drug that occurs at doses normally used in humans for the prophylaxis, diagnosis, or therapy. ADRs are classified into two major groups:

  • type A are predictable reactions from the known pharmacological action of the drug, and usually dose-dependent
  • type B (idiosyncratic) are unpredictable and independent of the dose e.g. allergic reactions.

Other minor categories include:

  • type C which are chronic and are dependent on dose and time
  • type D which are delayed reactions
  • type E which covers withdrawal
  • type F for unexpected failure of therapy (Hinson et al., 2010).

This paper discusses ADR rates of morbidity and mortality and ADR prevalence factors with a particular interest in Drug-Drug Interactions (and overdoses. Preventability of the ADRs is also discussed.


  • Hospital admissions due to ADRs vary in literature, with estimates of 3% in the Netherlands and Germany, 6.5-8.8% in the UK, 5.8% in Italy, and 12.8% in Greece.
  • Mortality rates due to ADRs are estimated from 0.1-2.9%. A retrospective eight-year (1999-2006) study conducted in the US of >2 million deaths revealed that 2341 deaths (0.1 per 100,000) were ADR-related deaths. In 2005, drugs were the leading cause of death estimated at 739, 936 per year.
  • The socio-economic healthcare costs associated with ADRs are very high, £466m/year in the UK annually, and A$946 200 in Australia are related to ADR hospital admissions.
  • A significant percentage of ADRs are considered preventable with varying estimates of 40-77% in literature. Overdoses contributed to average 30% of ADRs while drug-drug reactions 4-32%.
  • Factors contributing to ADR prevalence and/or susceptibility include: increase in the number marketed drugs, type of drug, increase in aging population, pregnancy, gender, disease state, genetics, ethnicity, polypharmacy, and urbanization.
  • Type A are commonly reported, as such are preventable by either dose adjustment or avoiding drug interactions.
  • Medications errors, off-label use, misuse and abuse are potential causes of ADRs that are usually excluded from ADR studies. However, Iatrogenic deaths in the US cause up to 7.8 million deaths per 10years, and medication errors were estimated at 14% fatality rate.


ADRs remain a significant contributing factor to morbidity and mortality worldwide despite increased awareness, past mistakes or experiences, and stricter regulations. The figures are likely to increase if preventive measures are not exercised. Most reported ADRs are Type A (predictable and dose dependent) and as such could be prevented. Drug-drug interactions and overdose contribute to a significant portion of preventable ADRs. The most promising prevention approach by far is precision medicine which combines genetic analysis with factors such as behavioural, functional, environmental and lifestyle information.

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This publication was written by:

Angella Angiji - Associate Consultant 

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