Medicare Advantage

Medical Policy

Medical Policy Bulletin

Title:

Dofetilide (Tikosyn®) Use in the Inpatient Setting

Policy #:

MA08.021c

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.

MEDICALLY NECESSARY

An inpatient admission for the initiation, dose escalation or reinitiation of dofetilide (Tikosyn) is considered medically necessary and, therefore, covered for either of the following indications:

For conversion of atrial fibrillation (AF) and atrial flutter (AFL) (AF/AFL) to normal sinus rhythm (NSR)
For the maintenance of NSR (delay in time recurrence of AF/AFL) in individuals with AF/AFL of greater than 1 week's duration who have been converted to NSR

Dofetilide (Tikosyn) should be reserved for individuals in whom AF/AFL is highly symptomatic because the drug can cause life-threatening ventricular arrhythmias.

Therapy with dofetilide (Tikosyn) for initiation, dose escalation, and, if necessary, reinitiation, must be done according to the product labeling, for a minimum of 3 days in an inpatient setting that provides continuous electrocardiographic (ECG) monitoring in the presence of personnel trained in the management of serious ventricular arrhythmias. Additionally, individuals should not be discharged within 12 hours of electrical or pharmacologic conversion to NSR.

For information on maintenance therapy with dofetilide (Tikosyn), refer to the Guidelines section of this policy.

NOT MEDICALLY NECESSARY

Dofetilide (Tikosyn) has not been shown to be effective in individuals with paroxysmal atrial fibrillation; therefore, it is considered not medically necessary and is not covered for this condition.

EXPERIMENTAL/INVESTIGATIONAL

All other uses of dofetilide (Tikosyn) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

There is no Medicare coverage determination addressing dofetilide (Tikosyn) in the inpatient setting; therefore, the Company policy is applicable.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

Dofetilide (Tikosyn) has arrhythmogenic potential and may cause serious ventricular arrhythmias, principally polymorphic ventricular tachycardia associated with QT-interval prolongation (i.e., Torsades de pointes). Because an increased QT interval and the risk of ventricular arrhythmias are directly related to plasma dofetilide (Tikosyn) concentrations, electrocardiographic (ECG) monitoring for excessive increases in the QT interval, dosage adjustment based on calculated creatinine clearance, and the avoidance of certain medications with known drug interactions are essential.

According to the manufacturer, initiation of therapy with dofetilide (Tikosyn) and any subsequent increase in dosage should be performed in a hospital setting where cardiac resuscitation can be performed and where the individual can be monitored by personnel trained in the management of serious ventricular arrhythmias. Continuous ECG monitoring should be performed for a minimum of 3 days (until steady-state plasma concentrations are obtained), or for a minimum of 12 hours after electrical or pharmacologic conversion to normal sinus rhythm, whichever is greater. A previously successful increase in the dosage of dofetilide (Tikosyn) does not eliminate the need for rehospitalization for a subsequent dosage increase.

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, an inpatient admission for the initiation or reinitiation of dofetilide (Tikosyn) is covered under the medical benefits of the Company's Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

However, drugs that are identified in this policy as not medically necessary are not eligible for coverage or reimbursement by the Company.

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when dofetilide (Tikosyn) is covered under a member's medical benefit (Part B benefit). It does not address instances when dofetilide (Tikosyn) is covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The FDA approved the use of dofetilide (Tikosyn) for the labeled indications in October 1999.

PEDIATRIC USE
The safety and effectiveness of dofetilide (Tikosyn) in pediatric individuals have not been established.

Description

Dofetilide (Tikosyn) is an oral antiarrhythmic drug with Class III properties, which can cause cardiac action potential prolongation. The mechanism of action is the blockade of the cardiac ion channel that carries the rapid component of the delayed rectifier potassium current, IKr. At concentrations covering several orders of magnitude, dofetilide (Tikosyn) blocks only IKr, with no relevant block of the other repolarizing potassium currents (e.g., IKs, IK1). At clinically relevant concentrations, dofetilide (Tikosyn) has no effect on sodium channels (associated with Class I effect), adrenergic alpha-receptors, or adrenergic beta-receptors (associated with Class II effect). This causes the refractory period of atrial tissue to increase, hence its effectiveness in the treatment of atrial fibrillation and atrial flutter.

Dofetilide (Tikosyn) can also cause serious ventricular arrhythmias, primarily Torsade de pointes, a type of ventricular tachycardia associated with QT prolongation.

ATRIAL FIBRILLATION/ATRIAL FLUTTER

Dofetilide (Tikosyn) is indicated for highly symptomatic atrial fibrillation or atrial flutter (irregular heartbeats). Dofetilide (Tikosyn) has also been shown to be effective in converting the irregular heartbeats to normal rhythm. In addition, dofetilide (Tikosyn) may help maintain the normal rhythm for a longer period of time.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Hospital Formulary Service (AHFS). Dofetilide (Tikosyn®). Drug Information 2023. [Lexi-comp Web site]. 12/12/2023. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed January 9, 2024.

Brendorp B, Elming H, Jun L, et al. QTc interval as a guide to select those patients with congestive heart failure and reduced left ventricular systolic function who will benefit from antiarrhythmic treatment with dofetilide. Circulation. 2001;103:1422-1427.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Dofetilide (Tikosyn®). [ClinicalKey Web site]. 08/13/2023. Available at: https://www.clinicalkey.com/#!/. [via subscription only]. Accessed January 9, 2024.

IBM Micromedex® DRUGDEX® (electronic version). Dofetilide(Tikosyn®). [Micromedex Web site]. IBM Watson Health, Greenwood Village, Colorado, USA. 01/04/2024. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 8, 2024.

Kaber L. Dofetilide, a new class III antiarrhythmic drug reduces hospital admissions for congestive heart failure - secondary endpoints of the DIAMOND-CHF study (abstract). J Am Coll Cardiol. 1998;31(suppl 2A):31.

Kober L, Bloch Thomsen PEB, Moller M, et al. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Lancet. 2000;356:2052-2058.

Lexi-Drugs Compendium. Dofetilide(Tikosyn®). [Lexicomp Online Web site]. 01/04/2024. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed January 9, 2024.

Pedersen OD, Bagger H, Keller N, et al. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function. A Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) substudy. Circulation. 2001;104:292-296.

Rousseau MF, Massart PE, Galanti L, et al. Contrasting effects of intravenous dofetilide and amiodarone on cardiac sympathetic drive in patients with congestive heart failure (abstract). J Am Coll Cardiol. 1998;31(suppl 2A):32.

Tikosyn® (dofetilide) [prescribing information]. New York, NY: Pfizer, Inc. 08/2023. Available at: https://labeling.pfizer.com/ShowLabeling.aspx?id=639. Accessed January 8, 2024.

Torp-Pedersen C. Dofetilide: a new class III antiarrhythmic drug which is safe in patients with congestive heart failure (abstract). J Am Coll Cardiol. 1998;31(suppl 2A):160.

Torp-Pedersen C, Moller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. N Engl J Med. 1999;341:857-865.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Dofetilide (Tikosyn®). Prescribing information. [FDA Web site]. 08/08/2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020931s017lbl.pdf. Accessed January 8, 2024.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

MEDICALLY NECESSARY

I48.11 Longstanding persistent atrial fibrillation

I48.19 Other persistent atrial fibrillation

I48.20 Chronic atrial fibrillation, unspecified

I48.3 Typical atrial flutter

I48.4 Atypical atrial flutter

NOT MEDICALLY NECESSARY

I48.0 Paroxysmal atrial fibrillation

HCPCS Level II Code Number(s)

N/A

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.021c:

03/05/2025	This policy has been reissued in accordance with the Company's annual review process to communicate the Company's coverage positions for dofetilide (Tikosyn®) use in the inpatient setting.
03/11/2024	This version of the policy will become effective 03/11/2024. This policy has been updated to communicate the Company's coverage positions for dofetilide (Tikosyn®) use in the inpatient setting. Therapy with dofetilide (Tikosyn®) indication has been expanded to include dose escalation and reinitiation per compendia.

Revisions From MA08.021b:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
06/02/2023	The policy has been reviewed and reissued to communicate the Company’s continuing position on dofetilide (Tikosyn®) use in the inpatient setting.
06/01/2022	The policy has been reviewed and reissued to communicate the Company’s continuing position on dofetilide (Tikosyn®) use in the inpatient setting.
05/24/2021	The policy has been reviewed and reissued to communicate the Company’s continuing position on dofetilide (Tikosyn®) use in the inpatient setting.
07/15/2020	This policy has been reissued in accordance with the Company's annual review process.
10/09/2019	The policy has been reviewed and reissued to communicate the Company’s continuing position on dofetilide (Tikosyn®) use in the inpatient setting.
10/01/2019	This version of the policy will become effective 10/01/2019. The following ICD-10 CM codes have been added to this policy: I48.11 Longstanding persistent atrial fibrillation I48.19 Other persistent atrial fibrillation I48.20 Chronic atrial fibrillation, unspecified The following ICD-10 CM codes have been termed from this policy: I48.1 Persistent atrial fibrillation I48.2 Chronic atrial fibrillation

Revisions From MA08.021a:

11/07/2018	This policy became effective 06/29/2016. It has been reviewed and reissued to communicate the Company’s continuing position on Dofetilide (Tikosyn®) Use in the Inpatient Setting.
06/21/2017	This policy has been reissued in accordance with the Company's annual review process.
06/29/2016	This version of the policy will become effective 06/29/2016. This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling. The following codes were removed from the policy: I48.91 I48.92.

Revision From MA08.021:

05/27/2015	The policy has been reviewed and reissued to communicate the Company’s continuing position on dofetilide (Tikosyn®) Use in the Inpatient Setting.
01/01/2015	This is a new policy.

Version Effective Date:

03/11/2024

Version Issued Date: