Case Report of Ivabradine Intoxication

Abstract

Ivabradine is a drug used for the treatment of angina and chronic heart failure in cases of intolerance or insufficiency of response to beta-blocker treatment. A 47-year-old man was admitted to the emergency department of the hospital for a voluntary intoxication with 280 mg of ivabradine: he presented drowsiness and a mild sinusal bradycardia (50 bpm) associated with a well-tolerated low blood pressure at 100/50 mmHg. No complication was noted and he was discharged from the hospital on Day 3. A method for ivabradine assay in serum was obtained using liquid chromatography coupled with a mass spectrometry detection method. After a deproteinization step using QuECHERS salts and acetonitrile, a chromatographic separation was performed using a 5-µm 50 × 2.1 mm Xterra® column (Waters, France). Detection was performed using an LTQ linear ion-trap mass spectrometer equipped with an electrospray ionization source used in a positive ionization mode (ThermoFisher Scientific, San Jose CA, USA) and a detection in full MS(2) scan. The limit of quantification of ivabradine was 10 µg/L, and the method was linear up to 1000 µg/L. The ivabradine concentration in the patient's serum was 375 µg/L. This concentration value was >30 times those measured after therapeutic doses intakes. Nevertheless, the bradycardia was no more severe than the one observed with therapeutic dosage. In conclusion, this case tends to show an absence of correlation between blood concentration and severity of the troubles in cases of overdosage.

Acute on Chronic Ivabradine Overdose: a Case Report

“…Since it recently became available in the USA in April 2015, there are few case reports of overdose [2,3]. As ivabradine slows the sinoatrial (SA) node, one commonly reported adverse effect is bradycardia [4,5].…”

“…The patient's ivabradine concentration 3 h post-admission was 130, 120, and 110 ng/mL, using EDTA, serum separator, and plasma separator tubes, respectively. For comparison, one prior overdose case reported a concentration of 375 ng/ml after gastric lavage but did not provide any subsequent concentrations [2]. In a trial of ivabradine at therapeutic doses, patients were noted to have a mean concentration of 9.7 ng/mL 13 h postingestion, with a maximum concentration of 25 ng/mL [2,11].…”

“…In the limited number of reported human overdose cases to date, the opposite has been noted. Two cases (including this case report) exist describing successful reversal with atropine [2]. In another case isoproterenol was ineffective [3].…”

“…Therapeutically, it antagonizes the I f or Bfunny^current, resulting in a reduced heart rate. While it has been extensively studied in heart failure, myocardial ischemia, and postural orthostatic tachycardia syndrome (POTS), there are few reported cases of overdose [2,3]. We report a case of acute on chronic intentional ivabradine overdose in a 26-year-old female on ivabradine for POTS.…”

Cardiovascular Toxicity of Cardiovascular Drugs

“…Ivabradine causes direct inhibition of spontaneous depolarization of sinus node without interfering with the conduction of auricular and ventricular activities. 206 However, ivabradine has been found to be safer and more effective for angina and chronic heart failure. 204 Nonetheless, owing to pharmacodynamic properties, some adverse events were noted observed both before-and after-marketing authorization such as AV block and syncope.…”