Adverse reactions: Introduction

Last updated: Sunday, July 05, 2015

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Amoxicillin-induced rash  
Courtesy of Skoch3, Wikimedia Commons
Wherever you work in pharmacy, you will be asked about adverse drug reactions (ADRs), as well as a large number of related patient safety issues (e.g. contra-indications). Statistics from pharmacy patient helplines in hospitals show that a high proportion of their calls are also concerned with side effects. ADRs occur in 10-20% of hospitalised inpatients and may be responsible for 1 in 1000 deaths on medical wards. Studies suggest about 5% of all hospital admissions are due to ADRs. Although it has been studied less well, as many as 2% of GP consultations may be due to suspected ADRs.

ADRs are great mimickers of disease, causing diagnostic confusion and resulting in unnecessary referral and investigation. Certain disorders are commonly drug-induced and a thorough assessment of drug exposure is particularly important in these cases. Examples include rashes, electrolyte disturbances, postural hypotension, confusion, constipation, renal or liver dysfunction, and gastrointestinal haemorrhage. Less common examples include blood dyscrasias.

Some patients have an increased susceptibility to ADRs including the elderly, neonates and children, patients with multiple disease states (e.g. ICU patients, HIV patients), those with impaired kidney or liver function, and patients receiving polypharmacy. Ignoring manufacturers’ contra-indications or failing to monitor the patient adequately are also common methods of increasing the likelihood of known ADRs.

What is an ADR?

What are the essential features of an ADR?

  • There is some evidence that at least one medicine is responsible.
  • The effect is unintended.
  • It is harmful, or potentially harmful.
  • The reaction is seen at normal doses used clinically (to distinguish ADRs from ‘toxicity’ which is used to describe the symptoms of overdose or poisoning).

Expressing incidence

The EU has a classification system which is used in SPCs and patient information leaflets:

  • Very common ≥ 1 in 10 (e.g. cough with ramipril). 
  • Common ≤ 1 in 10 but ≥ 1 in 100 (e.g. epistaxis with dabigatran). 
  • Uncommon ≤ 1 in 100 but ≥ 1 in 1000 (e.g. pathological gambling with pramipexole). 
  • Rare ≤ 1 in 1000 but ≥ 1 in 10,000 (e.g. rhabdomyolysis with simvastatin). 
  • Very rare ≤ 1 in 10,000 (e.g. Stevens-Johnson syndrome with ciprofloxacin).


Clinical problems involving ADRs 

Pharmacists encounter many clinical problems concerning adverse reactions, such as:

  • Can drug X cause symptom Y? How common is this side effect? Is it reversible?
  • Which of drugs A, B or C is the most likely cause of symptom Y?
  • How should I manage a suspected ADR in this patient?
  • This patient has experienced a suspected reaction to drug X. Is it safe to use another drug from the same or related therapeutic class?
  • What are the long-term risks of drug X?
  • An SPC or patient information leaflet mentions side effect Y. Why is this listed? More information required.
  • More information on the incidence or characteristics of a specific side effect (e.g. pulmonary reactions to amiodarone, methotrexate-induced liver disease etc.).