A Case of Hypotension and Bradycardia Precipitated by Drug Interaction of Clarithromycin and Calcium-Channel Blocker.

Abstract

To the Editor: The Hispanic population has a high incidence of Helicobacter pylori infection, and macrolide antibiotics are the mainstay of the treatment protocols. Macrolide antibiotics may potentiate effects of calcium-channel blockers (CCBs), which is widely underappreciated. We present a case of hypotension requiring hospitalization after the simultaneous use of CCBs and macrolide antibiotics. A 75-year-old Hispanic woman with a history of hypertension, diabetes mellitus type 2, hepatitis C, and recently diagnosed H. pylori gastritis presented to the emergency department with diaphoresis, weakness, and blurring of vision. She had a BP of 75/30 mmHg and a heart rate of 48 beats per minute. Her antihypertensive medications included felodipine 10 mg, losartan 100 mg, and atenolol 100 mg daily. Three days before admission, her primary physician had started her on clarithromycin. Her basic metabolic profile was unremarkable except a serum creatinine of 1.6 mg/dL, up from 0.8 mg/dL at admission. Electrocardiogram showed junctional rhythm. She was given intravenous glucagon, calcium gluconate, and normal saline and transferred to the coronary care unit. Upon improvement, she was discharged on metronidazole, amoxicillin, and omeprazole with a follow-up appointment with her physician in a week. She did not require any hypertensive medications. Macrolides (erythromycin, clarithromycin, azithromycin) are the most widely prescribed antibiotics, with more than 66 million prescriptions dispensed in 2008 in the United States alone.1 Although well tolerated, they can provoke drug interactions by inhibition of the cytochrome P450 isoenzyme 3A4 involved in drug metabolism, potentially leading to toxicity.2, 3 Clarithromycin and erythromycin, but not azithromycin, strongly inhibit cytochrome P450 isoenzyme 3A4.4, 5 Potentially significant hypotension and shock, with Q-T prolongation, may occur when macrolide antibiotics are administered concomitantly with CCBs.6 The likelihood of hypotension appears to be low, but the risk of adverse effects and the severity of the effects appear to be greater for individuals who are older and those with multiple comorbidities. The kidney is especially prone to injury from poor perfusion, so hospitalization with acute kidney injury is a clinically important consequence.7 The mechanism of kidney injury is hemodynamically mediated. Moreover, in this case, bradycardia was more pronounced because the woman was taking atenolol, which is primarily renally excreted, leading to further hemodynamic compromise and poor kidney perfusion and kidney injury.8 The Naranja score for the probability of this reaction being due to clarithromycin was 9, indicating a definitive adverse drug reaction. Hispanic individuals have a higher incidence of H. pylori infection than the non-Hispanic U.S. population.9 Clarithromycin is one of the treatment drugs in H. pylori eradication protocols.10 Older adults taking CCBs were at greater risk of admission to the hospital for the treatment of hypotension or shock after the use of clarithromycin or erythromycin. The current case highlights the consequences of an underappreciated yet avoidable drug interaction involving medications that millions of people use every year. Clinicians should be aware of the potential interaction between these drugs. When a macrolide is required, preferential use of azithromycin should be considered in individuals receiving a CCB. Temporary cessation of the CCB for the duration of clarithromycin therapy or selection of a non–CYP3A4-inhibiting antibiotic when clinically appropriate is another possible approach. In older adults taking CCBs, concurrent use of clarithromycin was associated with a significantly greater 30-day risk of hospitalization with acute kidney injury and hypotension than use of azithromycin.7 Conflict of Interest: The corresponding author affirms that she has listed everyone who contributed significantly to the work. Also, there are no financial, personal, or other conflicts associated with the case report. Author Contributions: Vibha Agrawal: data acquisition and interpretation, concept and design, manuscript analysis and preparation of manuscript; Dr Shobhna Chaudhari, Dr Alexander Sy and Dr Lolo Delatre : revision of the manuscript for important intellectual contents. Sponsor's Role: Not applicable.