March 2025 Newsletter

Strategies for Mitigating Dofetilide-Induced Ventricular Arrhythmias

By Myungsun Ro, PharmD, MS

In recent years, the Patient Safety Authority has received several reports of QT prolongation in patients receiving dofetilide. Approximately half of these reports were associated with serious adverse events, including torsades de pointes and other types of ventricular arrhythmias and cardiac arrest, some requiring a transfer to a higher level of care and at least one resulting in death. Some of these reports described a failure to adequately monitor electrocardiograms (EKGs) and adjust therapy in a timely manner. Others indicated concomitant use of medications contraindicated with dofetilide¹ and/or those known to prolong the QT interval,² such as azithromycin, fluconazole, hydrochlorothiazide, indapamide, levofloxacin, ondansetron, promethazine, and sulfamethoxazole/trimethoprim.

Dofetilide, also marketed under the brand name Tikosyn, is a class III antiarrhythmic agent used to treat irregular heartbeat in certain patients with atrial fibrillation or atrial flutter.¹ Due to the linear relationship between QTc interval and serum dofetilide concentrations, and its potential to induce life-threatening ventricular arrhythmias, the black box warning recommends starting or restarting dofetilide therapy in a facility that provides continuous EKG monitoring, serum creatinine monitoring, and access to cardiac resuscitation for a minimum of three days.¹ Contraindications include preexisting prolonged QTc interval, renal impairment, and concomitant medications or disease states that may further prolong the QTc interval or elevate serum dofetilide levels.¹

Until 2016, the U.S. Food and Drug Administration’s Risk Evaluation and Mitigation Strategy (REMS)^* program mandated certification of prescribers, pharmacies, and healthcare facilities in a national registry to ensure safe prescribing and dispensing of dofetilide.⁴ Although the dofetilide REMS program no longer exists, we strongly encourage healthcare facilities and providers to reevaluate their current protocols for dofetilide and ensure that they align with the information provided in the package insert¹ and documented in literature,^5,6 including dosage calculations, documented and potential drug interactions, patient-specific risk factors, and instructions for monitoring EKG and lab values, to ensure its safe and effective use.

To enhance the safety of dofetilide administration and mitigate the risk of ventricular arrhythmias, healthcare facilities are advised to consider implementing the action items below.

- Accurate medication reconciliation

• Conduct a thorough medication reconciliation process to verify the correct dofetilide dose for newly admitted patients who are continuing their chronic therapy from home.

- Engagement of specialized practitioners

• Restrict the prescribing of dofetilide (re)initiation therapy to cardiology.
• Engage the clinical pharmacists (e.g., in pharmacy-driven protocol) to monitor, evaluate, and adjust therapy based on risk factors and patient response to dose.⁷

- Optimization of electronic health records (EHR) and computerized provider order entry (CPOE)

• Incorporate clear and specific ordering instructions and monitoring parameters for EKG. If applicable, preselect within CPOE order panel by default to ensure timely EKG acquisition. For (re)initiation of therapy, EKG should be obtained at baseline and two to three hours after administration of each of the first five doses.¹
• Include instructions for dose modifications per package insert: dose should be decreased if increase in QTc or QT is >15% or >500 milliseconds after the first dose, and the therapy should be discontinued if at any time after the second dose QTc or QT increases >500 msec.¹ Refer to the package insert for detailed instructions on dose modifications and therapy adjustments.
• Activate interaction alerts for dofetilide within CPOE and EHR to notify healthcare providers of potential risks when dofetilide is ordered concurrently with medications known to prolong the QT interval or alter potassium levels. Employ a risk stratification strategy for these alerts to minimize alert fatigue and prioritize interactions with the greatest potential for adverse effects. Ensure that these alerts are prominently displayed for the prescribing and verifying providers.
• Integrate prompts and reminders for nurses to alert prescribers if magnesium, potassium, and serum creatinine levels deviate from their normal range.^1,5-7

- Additional instructions for monitoring

• Emphasize the importance of communicating the need for EKG monitoring, changes in lab values, and vigilance for potential arrhythmias during hand-offs.

- Competency training

• Provide competency training to all healthcare providers involved in the medication-use process, encompassing prescribing, verification, dispensing, administration, and monitoring of dofetilide.

- Patient education

• Empower patients to actively participate in their care by advising them to thoroughly review the dofetilide Medication Guide.¹ Emphasize the importance of correct administration, adherence to the dosing schedule, and recognition of potential adverse effects. Stress the need to maintain an accurate and accessible medication list. Furthermore, educate the patients on the requirement for readmission if they miss more than two consecutive doses of dofetilide.⁸

*REMS is a national program designed to prevent, monitor, and/or manage a specific serious risk associated with certain medications that have significant safety concerns. A primary goal of REMS is to ensure that the benefits of the medication outweigh its potential risks.³

References

1. National Library of Medicine. Label: TIKOSYN - Dofetilide Capsule. Dailymed. [https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=02438044-d6a3-49e9-a1ac-3aad21ef2c8c] Updated October 21, 2024. Accessed January 2025.
2. Woosley RL, Heise CW, Gallo T, Woosley RD, et al. QTdrugs List. In: Crediblemeds. AZCERT, Inc. Accessed January 2025.
3. U.S. Food and Drug Administration. Risk Evaluation and Mitigation Strategies (REMS). FDA. https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems. Updated May 16, 2023. Accessed January 15, 2025.
4. U.S. Food and Drug Administration. Information for Tikosyn (dofetilide) https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-tikosyn-dofetilide. FDA. Published March 9, 2016. Accessed January 2025.
5. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation. 2020;142(15):e214-e33. doi: doi:10.1161/CIR.0000000000000905
6. Tagle-Cornell MC, Ayoub C, Bird C, et al. Safety of Dofetilide in Stable Patients and Investigating Traits of Susceptibility to Torsade de Pointes. IJC Heart Vasc. 2024;54:101475. doi: 10.1016/j.ijcha.2024.101475
7. Tisdale JE. Drug-Induced QT Interval Prolongation and Torsades de Pointes: Role of the Pharmacist in Risk Assessment, Prevention and Management. Can Pharm J (Ott). 2016;149(3):139-52. Epub 2016/05/24 doi: 10.1177/1715163516641136 PubMed PMID: 27212965; PubMed Central PMCID: PMCPMC4860751
8. Cho JH, Youn SJ, Moore JC, et al. Safety of Oral Dofetilide Reloading for Treatment of Atrial Arrhythmias. Circ Arrhythm Electrophysiol. 2017;10(10). Epub 2017/10/19 doi: 10.1161/circep.117.005333 PubMed PMID: 29038104; PubMed Central PMCID: PMCPMC5685174

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Risk Assessment Basics for the Infection Preventionist

Wednesday, March 12, 2025

1 to 2 p.m.

The Centers for Medicare & Medicaid Services (CMS) and the Pennsylvania Department of Health require long-term care facilities to have an infection prevention risk assessment as part of their infection prevention program. With an increase in the number of new infection preventionists joining the field, the Patient Safety Authority (PSA) has recognized a challenge to compliance and facilitation while conducting an annual risk assessment.

Join PSA infection prevention advisor Amanda Bennett, MPH, MLS, for a webinar on “Risk Assessment Basics for the Infection Preventionist.” She will go over the components of an infection prevention risk assessment, how to perform it, and how to create actionable goals based on the gaps identified.

1.0 continuing education hours will be awarded for completion of this course. Continuing education credits apply to Pennsylvania registered nurses only.

Are you a new patient safety officer (PSO)? Or maybe you just want to brush up on Pennsylvania event reporting requirements?

After completing this series, broken into four easy-to-digest modules, you’ll understand your responsibilities as a PSO, how to apply reporting guidelines to various scenarios, and the key elements of the Medical Care Availability and Reduction of Error (MCARE) Act (i.e., Act 13 of 2002) and why it was enacted.

1.0 continuing education hours will be awarded for the completion of each individual module listed above. Continuing education credits apply to Pennsylvania registered nurses only.

Please note that this course is a repeat of the educational programs that we offered in 2021, 2022, 2023, and 2024, and is being offered again as 90-minute sessions for those patient safety professionals who were unable to attend all the modules.

*While anyone is still welcome to attend, please come aware that the information being presented in these sessions is specific to Pennsylvania acute care facilities. If your facility is not both located in Pennsylvania and an acute care facility, this information will not apply to you.

Module I: MCARE Overview

Tuesday, April 1, 2025

10:30 a.m. to 12 p.m. EDT

Registration Link:

https://papsa.webex.com/weblink/register/r262ba3d80bd48fd554d4d2d6e4f087cc

Module II: The Role of the PSO Thursday, April 3, 2025

10:30 a.m. to 12 p.m. EDT

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Module III: Reporting

Tuesday, April 8, 2025

10:30 a.m. to 12 p.m. EDT

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Module IV: Reporting Specific Types of Events

Thursday, April 10, 2025

10:30 a.m. to 12 p.m. EDT

Registration Link:

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Artificial Intelligence and Human Factors in Healthcare Quality and Safety

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This conference will focus on the emerging need for optimization of the human-AI interaction in healthcare and the issues at the intersection of human factors engineering, patient safety, quality and value enhancement, and AI. Recognized academic, clinical, and industry experts will attempt to define future directions in this field and propose an agenda for research over the next five to seven years.

When: April 10–11, 2025

Who should attend: Healthcare professionals, administrators, and policymakers involved in healthcare quality and safety, and anyone who is interested in learning more about the future of healthcare quality and safety in the era of AI. The conference will highlight the approach of human factors in AI, with the goal of optimizing the “human-AI dyad” to enhance the quality, value, effectiveness, and safety of care. Attendees will learn from a diverse range of academic and industry leaders in the fields of human factors engineering, artificial intelligence, and healthcare quality and safety. Discussions will address critical topics such as error prevention, detection, recovery, health system resilience, and alleviating provider burnout—all of which are more pertinent than ever as AI tools continue to reshape the healthcare landscape.

Registration fee: In-person attendance is $150. Virtual attendance is $100. Students and trainees attendance is $50.