Vol 54: february • féVrier 2008 Canadian Family Physician•Le Médecin de famille canadien
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Current Practice
•Pratique courante
Case Report Case Report
Loss of taste with clopidogrel
Andrew J. Cave
MB ChB MClSc FCFP FRCGPDiane W. Cox
PhD FCCMG FRSCOzair Vicaruddin
S
ide effects of new medications often do not reveal themselves in the course of initial clinical trials but are discovered when their use becomes a standard of care and, therefore, widespread (eg, cyclooxygenase-2 inhibitors, hormone replacement therapy, thalidomide).This is particularly true for rare side effects. Family physicians are in an excellent position to observe these late-onset side effects, as they are most likely aware of all the medications their patients are taking and can recognize potential interactions. We present the case of a man with a serious but reversible side effect of clopidogrel.
Case description
Mr S.C. was a physically active 71-year-old man with type 2 diabetes and coronary artery disease. In 2000 he had a 3-vessel coronary artery bypass. He also had spinal stenosis, migraine headaches, and sleep apnea. Gastroesophageal reflux disease was diag- nosed in 2000 by gastroscopy, which demonstrated Barrett epithelium. He had been treated with a pro- ton pump inhibitor since diagnosis and had surveil- lance gastroscopies in 2002, 2003, and 2005, each of which showed benign epithelium without dysplasia.
Helicobacter pylori was not seen in biopsy specimens.
In August 2004 he experienced an episode of atrial fibrillation, but an investigational stress test and a 24-hour ambulatory electrocardiogram were normal.
His hemoglobin A1c levels in 2004 and 2005 were 6.9%
and 6.8%, respectively (normal 4.3% to 6.1%).
In October 2005 Mr S.C. presented to the emergen- cy room with a 2-hour episode of marked positional vertigo. Results of cranial nerve and cerebellar exami- nations were normal, as was a computed tomography scan of his head. His symptoms were observed on arrival in emergency but resolved spontaneously. On December 7 he was started on 75 mg/d of clopido- grel bisulfate in addition to continuing his 325-mg dose of enteric-coated acetylsalicylic acid (ASA). He presented to the physician on January 11, 2006, with a 4-week history of taste disturbance: 2 weeks of dimin- ished taste, followed by 2 weeks of complete loss of taste. He had not lost his sense of smell but had suf- fered a subsequent 10-lb weight loss. Onset of com- plete taste loss occurred approximately 3 weeks after starting clopidogrel. Mr S.C. took several other medi- cations, all of which were of long-term use: 500 mg of metformin twice daily; 2.5 mg of ramipril once daily;
40 mg of esomeprazole once daily; 325 mg of ASA
once daily; and occasional use of 2.5 mg of nitraz- epam once daily at bedtime.
Because there had been no other changes in medi- cations, the patient discontinued the clopidogrel.
All his other medications were continued as before.
Three weeks after discontinuation of clopidogrel, symptoms began to abate. But the almost complete return of taste took 4 months. The patient remained off this medication and was symptom free.
Adverse reaction
Reversible ageusia (loss of taste) has previously been reported as a side effect of clopidogrel bisulfate in 4 patients (2 cases reported in detail, 1 case referenced from the Drug Commission of the German Medical Association,1 and 1 case referenced from India2).
Clopidogrel is indicated for secondary prevention in patients with widespread atherosclerosis, coronary artery disease, and a history of a coronary or cerebral event such as transient ischemic attack. It is also indi- cated for short-term use after coronary artery stenting.3 The CAPRIE study demonstrated a relative risk reduction of 8.7% in favour of clopidogrel for thrombotic events (eg, stroke, myocardial infarction, or vascular death) over ASA.4 The use of clopidogrel with ASA slightly reduces vascular events in patients with unstable angina but has a potential for increased risk of hemorrhage.5,6 The product monograph lists taste disorders as a “very rarely” occurring adverse reaction of clopidogrel.3 This information is not provided in the patient brochure.
The mechanism for this side effect of clopidogrel is not yet understood. Clopidogrel, like ticlopidine, is a thienopyridine derivative and is metabolized through opening of the thiophene ring. In vitro, it inhibits an enzyme in the P450 system when in high concentra- tions. Ticlopidine, another antiplatelet agent, inhibits adenosine diphosphate–stimulated platelet aggregation and has severe effects on blood cells; it has not, how- ever, been reported to cause ageusia.
Conclusion
As the anticipated use of clopidogrel has been expanded for primary prevention of cardiovascular events in patients with peripheral vascular disease7,8 and as a generic form is now available, it is likely that more patients will have clopidogrel initiated and managed in primary care. In addition to the factors of an increased cost for only modest advantage and increased risk of hemorrhage, the prescriber needs to consider the
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Canadian Family Physician•Le Médecin de famille canadien Vol 54: february • féVrier 2008Case Report
possible loss-of-taste side effect. Although not a life- threatening side effect, loss of taste is distressing for the patient and can lead to loss of appetite and weight loss in already compromised patients. Physicians need to be aware of this side effect, as its onset is delayed and, therefore, might not be associated with the medication.
More important, the reported events in the literature to date have all been reversible upon discontinuation of the drug, so the association should not be missed.
Dr Cave is a Professor in the Department of Family Medicine, Dr Cox is a Professor in the Department of Medical Genetics, and Mr Vicaruddin is a summer student research assistant in the Department of Family Medicine at the University of Alberta in Edmonton.
Competing interests None declared
Correspondence to: Dr Andrew J. Cave, Department of Family Medicine, 901 College Plaza, University of Alberta, Edmonton, AB T6G 2C8; telephone 780 492-2593;
fax 780 492-8191; e-mail [email protected] references
1. Golka K, Roth E, Huber J, Schmitt K. Reversible ageusia as an effect of clopi- dogrel treatment. Lancet 2000;355(9202):465-6.
2. Koc F, Ozeren A. Reversible ageusia associated with clopidogrel treatment.
Neurol India 2006;54:218-9.
3. Product Monograph. Plavix. In: Repchinsky C, Editor-in-Chief. Compendium of pharmaceuticals and specialties. The Canadian drug reference for health pro- fessionals. Ottawa, ON: Canadian Pharmacists Association; 2006. p. 1680-3.
4. CAPRIE Steering Committee. A randomised, blinded trial of clopi- dogrel versus aspirin in patients at risk of ischaemic events. Lancet 1996;348(9038):1329-39.
5. Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004;364(9431):331-7.
6. Schleinitz MD, Heidenreich PA. A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone. Ann Intern Med 2005;142(4):251-9.
7. Abramson BL, Huckell V, Gupta A, Verma S, Teo KK, Lindsay T, et al. 2005 Canadian Cardiovascular Consensus Conference, peripheral arterial disease.
Ottawa, ON: Canadian Cardiovascular Society; 2005. Available from: http://
www.ccs.ca/download/consensus_conference/consensus_conference_
archives/CCFinalPre_CJC_Pub.pdf. Accessed 2007 December 10.
8. American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care 2003;26(12):3333-41.
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EDITOR’S KEY POINTS
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Rarely, clopidogrel bisulfate can cause ageusia (loss of taste). The loss of taste can be complete and can contribute to decreased appetite and weight loss.
The onset can be delayed.
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This side effect is reversible upon discontinuation of the medication.
POINTS DE REPèRE Du RéDACTEuR
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Le bisulfate de clopidogrel cause parfois une agueusie (perte du goût). Cette perte peut être complète et contribuer à une diminution de l’ap- pétit et à une perte de poids. Un délai d’apparition est possible.
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