Can pantoprazole cause tachycardia?

Comment by InpharmD Researcher

There is limited data directly linking pantoprazole use to tachycardia. While reports from the FDA Adverse Event Reporting System highlight instances of tachycardia among pantoprazole users, this data cannot establish causation. Furthermore, while chronic proton pump inhibitor (PPI) may lead to hypomagnesemia, potentially increasing the risk of arrhythmia, specific mentions of the risk of tachycardia are scarce in existing literature. Although an isolated case report (Table 1) suggests a possible connection between pantoprazole and ventricular tachycardia, an observational study on critically ill patients found no significant association between PPI exposure and cardiac arrhythmia.

Background

According to the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) public dashboard, a total of 79,252 cases of pantoprazole-associated adverse events have been reported from 1997 to 2024. The incidence of tachycardia has been reported in 417 cases (0.53%). It should be noted that FAERS data is not representative of the true occurrence of adverse effects in the U.S. population. The database is subject to unverified reports that may be duplicates or incomplete. Therefore, the existence of reports does not establish causation or demonstrate rates of occurrence. [1]

A 2019 review discusses the cardiovascular risks associated with proton pump inhibitors (PPIs). Although the risk of pantoprazole potentially causing tachycardia is not addressed, the authors highlight that chronic PPI use can lead to hypomagnesemia, which subsequently may promote cardiac arrhythmias. This increased risk of hypomagnesemia typically emerges around 3 months after starting PPI therapy and may worsen with prolonged use. Furthermore, it is suggested cardiac arrhythmias are increased in likelihood when heart failure patients are co-prescribed PPIs alongside thiazides or loop diuretics. [2]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Does Pantoprazole cause tachycardia?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-2 for your response.

Pantoprazole (Proton Pump Inhibitor) Contributing to Torsades de Pointes Storm
Design	Case report
Case presentation	A 53-year-old man, with a history of chronic alcohol abuse but no prior cardiac issues, was admitted after experiencing palpitations and dizziness for a day. His physical exam revealed an irregularly irregular rapid pulse and high blood pressure (157/104 mm Hg). An electrocardiogram (ECG) showed atrial fibrillation with a rapid ventricular response, averaging 190 beats per minute. Initial labs were mostly normal, except for electrolyte imbalances: sodium 136 mEq/L, potassium 4.6 mmol/L, chloride 100 mEq/L, bicarbonate 16 mEq/L, blood urea nitrogen 11 mg/dL, creatinine 0.68 mg/dL, calcium 9 mg/dL, and magnesium 1.5 mg/dL. He was treated with intravenous (IV) diltiazem for rate control, IV heparin for anticoagulation, and oral pantoprazole 40 mg once daily for peptic ulcer prophylaxis. Seven hours later, he developed sustained polymorphic ventricular tachycardia and became unresponsive. Treatment included 1 g of IV magnesium sulfate, IV lidocaine bolus of 100 mg, and maintenance of 1 mg/min infusion, followed by 3 successive cardioversions. Another 2 g of magnesium sulfate was administered intravenously, and the patient was intubated for airway protection. After successful cardioversion, his ECG showed sinus rhythm with T wave alternans and alternating QT intervals.
Study Author Conclusions	In summary, we conclude that the addition of a PPI, which is the standard of care in critically ill patients, should be used with caution in patients who have a previous tendency to hypomagnesemia, as in our patient. In these patients, PPIs can potentiate the hypomagnesemia-induced lethal arrhythmias, which can result in sudden cardiac death. PPI therapy can potentially be dangerous in critically ill patients who are prone to electrolyte and nutritional abnormalities.

References:

Bibawy JN, Parikh V, Wahba J, et al. Pantoprazole (proton pump inhibitor) contributing to Torsades de Pointes storm. Circ Arrhythm Electrophysiol. 2013;6(2):e17-e19. doi:10.1161/CIRCEP.112.000101

Proton Pump Inhibitor (PPI) Use Is not Associated with Cardiac Arrhythmia in Critically Ill Patients
Design	Single-center, retrospective study N= 8,046 patients
Objective	To determine whether premorbid use of PPI was associated with the risk of arrhythmia
Study Groups	PPI (n= 1,973) Histamine H2-receptor antagonists (H2RA; n= 483) No PPI/No H2RA (n= 5,590)
Inclusion Criteria	Patients admitted to the intensive care unit (ICU); pre-admission medication information available
Exclusion Criteria	Patients without documented electrocardiogram (ECG) rhythm; had paced rhythm; lacked clinical data
Methods	Medical records were retrospectively examined to find the medication section of discharge summaries, aiming to identify patients' prior medication exposure. PPI or H2RA exposure was defined as any instance of these medications being listed as pre-admission medication.
Duration	Between 2001 and 2008
Outcome Measures	Any arrhythmias
Baseline Characteristics		PPI exposure (n= 1,973)	H2RA (n= 483)	No PPI/No H2RA (n= 5,590)
	Age, years	68.14 ± 14.69	68.84 ± 14.23	64.49 ± 16.92
	Male	55.4%	57.9%	59.0%
	Race White Black Hispanic Asian Other	71.81% 7.97% 2.31% 1.65% 1.84%	68.60% 8.33% 2.71% 2.33% 1.55%	68.51% 7.10% 2.51% 2.11% 2.93%
	Comorbidities Congestive Heart Failure Renal disease Hypertension Diabetes Mellitus	24.98% 7.55% 34.47% 29.51%	22.09% 6.78% 34.11% 30.81%	16.87% 4.07% 33.35% 24.10%
Results	PPI use was associated with higher arrhythmia risk (odds ratio [OR]1.18; 95% confidence inerval [CI] 1.02 to 1.36; p=0.02), but adjustment for comorbidities made non-significant (OR 0.96; 95% CI; 0.83 to 1.12; p= 0.62). No increased risk of atrial or ventricular arrhythmias with PPI use was noted. 4.3% (1147/8046) of admission ECGs showed non-sinus cardiac origin. Among these, there were 73 instances of ventricular tachycardia. This finding was provided within a figure.
Adverse Events	N/A
Study Author Conclusions	PPI exposure is not associated with an increased risk of arrhythmias in critically ill patients.
InpharmD Researcher Critique	The study has inherent limitations due to its single-center retrospective design. Additionally, the study did not specify the particular PPIs used and assessed cardiac arrhythmias in general, thereby limiting the generalizability. Since PPIs can be purchased without a prescription, there is a likelihood of bias due to exposure that went unnoticed, and the duration of PPI use was not provided.

References:

Chen KP, Lee J, Mark RG, et al. Proton pump inhibitor use is not associated with cardiac arrhythmia in critically ill patients. J Clin Pharmacol. 2015;55(7):774-779. doi:10.1002/jcph.479