Loss of taste with 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 diagnosed in 2000 by gastroscopy, which demonstrated Barrett epithelium. He had been treated with a proton pump inhibitor since diagnosis and had surveillance 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 A_1c 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 emergency room with a 2-hour episode of marked positional vertigo. Results of cranial nerve and cerebellar examinations 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 clopidogrel 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 diminished taste, followed by 2 weeks of complete loss of taste. He had not lost his sense of smell but had suffered a subsequent 10-lb weight loss. Onset of complete taste loss occurred approximately 3 weeks after starting clopidogrel. Mr S.C. took several other medications, 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 nitrazepam once daily at bedtime.

Because there had been no other changes in medications, 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 indicated 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 concentrations. Ticlopidine, another antiplatelet agent, inhibits adenosine diphosphate–stimulated platelet aggregation and has severe effects on blood cells; it has not, however, been reported to cause ageusia.