70 ADVERSE DRUG REACTIONS
FURTHER READING AND WEB MATERIAL
Davies DM, Ferner RE de Glanville H. Textbook of adverse drug reac-
tions, 5th edn. Oxford: Oxford Medical Publications, 1998.
Dukes MNG, Aronson JA: 2000: Meylers’s side-effects of drugs, vol. 14.
Amsterdam: Elsevier (see also companion volumes Side-effects of
drugs annuals, 2003, published annually since 1977).
FDA Medwatch website. http://www.fda.gov/medwatch
Gruchalla RS, Pirmohamed M. Antibiotic allergy. New England Journal
of Medicine2006; 354 : 601–609 (practical clinical approach).
Howard RL, Avery AJ, Slavenburg S et al. Which drugs cause prevent-
able admissions to hospital? A systematic review. British Journal of
Clinical Pharmacology2006; 63 : 136–47.
MHRA and the Committee on Safety of Medicines and the Medicine
Control Agency. Current problems in pharmacovigilance. London:
Committee on Safety of Medicines and the Medicine Control
Agency. (Students are advised to monitor this publication for
ongoing and future adverse reactions.)
MHRA Current problems in pharmacovigilance website.
http://www.mhra.gov.uk/home/idcplg?IdcServiceSS_GET_PAGE&
nodeId368.
Pirmohamed M, James S, Meakin S et al. Adverse drug reactions as
cause of admission to hospital: prospective analysis of 18.820
patients.British Medical Journal2004; 329 : 15–19.
Rawlins MD, Thompson JW. Pathogenesis of adverse drug reactions,
2nd edn. Oxford: Oxford University Press, 1977.Case history
A 73-year-old man develops severe shoulder pain and is
diagnosed as having a frozen shoulder, for which he is pre-
scribed physiotherapy and given naproxen, 250 mg three
times a day, by his family practitioner. The practitioner knows
him well and checks that he has normal renal function for
his age. When he attends for review about two weeks later,
he is complaining of tiredness and reduced urine frequency.
Over the past few days he noted painful but non-swollen
joints and a maculopapular rash on his trunk and limbs. He
is afebrile and apart from the rash there are no other
abnormal physical signs. Laboratory studies show a normal
full blood count; an absolute eosinophil count raised at
490/mm^3. His serum creatinine was 110μmol/L at baseline
and is now 350μmol/L with a urea of 22.5 mmol/L; elec-
trolytes and liver function tests are normal. Urinalysis
shows 2protein, urine microscopy contains 100 leuko-
cytes/hpf with 24% eosinophils.
Question 1
If this is an adverse drug reaction, what type of reaction is
it and what is the diagnosis?
Question 2
What is the best management plan and should this patient
ever receive naproxen again?
Answer 1
The patient has developed an acute interstitial nephritis,
probably secondary to the recent introduction of naproxen
treatment. This is a well-recognized syndrome, with the
clinical features that the patient displays in this case. It can
be associated with many NSAIDs (both non selective NSAIDs
and COX-2 inhibitors), particularly in the elderly. This is a
type B adverse drug reaction whose pathophysiology is
probably a combination of type III and type IV hypersensi-
tivity reactions.
Answer 2
Discontinuation of the offending agent is vital and this
is sometimes sufficient to produce a return to baseline
values of renal function and the disappearance of systemic
symptoms of fever and the rash. Recovery may possibly be
accelerated and further renal toxicity minimized by a short
course (five to seven days) of high-dose oral corticosteroids,
while monitoring renal function. The offending agent
should not be used again in this patient unless the benefits
of using it vastly outweigh the risks associated with its use
in a serious illness.