accredited [60:<60 bpm. 1 2 Use is contraindicated if the QT c interval> 440 msec (500 msec in patients with ventricular conduction abnormalities). 1 2 (See Contraindications under Cautions.) Within 2 3 hours after administering the first dose, determine the QT c interval again. 1 2 Adjust subsequent dosage based on the QT c interval. 1 2 (See Table 2.) Within 2 3 hours after each subsequent dose (for in-hospital doses 2 5), determine the QT c interval. 1 2 12 No further downward titration of dosage based on QT c interval is recommended. 1 2 However, if at any time after the second dose is given the QT c >500 msec (550 msec in patients with ventricular conduction abnormalities), discontinue use. 1 2 Perform continuous ECG monitoring for a minimum of 3 days or for a minimum of 12 hours after electrical or pharmacologic conversion to normal sinus rhythm, whichever is greater. 1 2 Reevaluate QT c interval every 3 months or as medically warranted. 1 If QT c >500 msec (550 msec in patients with ventricular conduction abnormalities), discontinue use and carefully monitor the patient until the QT c interval returns to baseline values. 1 2 Drug Transfer A transition period is recommended prior to initiating therapy in patients receiving other antiarrhythmic agents. 1 2 Withhold class I and class III antiarrhythmic agents for 3 half-lives prior to initiating dofetilide. 1 Withhold amiodarone for 3 months or until serum amiodarone concentrations are <0.3 mcg/mL prior to administering dofetilide. 1 (See Drugs that Prolong QT Interval under Interactions.) Administration Administer orally twice daily without regard to meals. 1 2 Dosage Adults Supraventricular Tachyarrhythmias Oral Initially, 500 mcg twice daily; modify dosage according to Cl cr and QT c interval. 1 2 12 (See Table 1 and Table 2.) Table 1. Initial Dosage in Adults Based on Renal Function Calculated Cl cr (mL/minute) Dosage> 60 500 mcg twice daily 40 60 250 mcg twice daily 20 to <40 125 mcg twice daily> <20 Dofetilide is contraindicated Within 2 3 hours after administration of the first dose, determine the QT c interval. 1 2 If QT c interval has increased by> 15% or >500 msec (550 msec in patients with ventricular conduction abnormalities), adjust subsequent dosages as follows: 1 2 Table 2. Dosage Modification for QTc Prolongation Initial Dosage (Based on Cl cr ) Adjusted Dosage (for QT c Prolongation) 500 mcg twice daily 250 mcg twice daily 250 mcg twice daily 125 mcg twice daily 125 mcg twice daily 125 mcg once daily For subsequent monitoring of the QT interval, see QT Interval Determination under Dosage and Administration. Therapy may be initiated at lower dosages due to the risk of torsades de pointes. 1 2 Prescribing Limits Adults Supraventricular Tachyarrhythmias Oral Dosages >500 mcg twice daily have been associated with an increased incidence of torsades de pointes. 1 2 (See Arrhythmogenic Effects under Cautions.) Special Populations Hepatic Impairment No dosage adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh class A or B). 1 2 Use with particular caution in patients with severe hepatic insufficiency (Child-Pugh class C). 1 2 Renal Impairment Modify dosage according to the degree of renal impairment. 1 2 (See Table 1.) For calculation of the patient s Cl cr , see Renal Function Assessment under Dosage and Administration. Not studied in those undergoing dialysis; dosage recommendations are not known. 1 Geriatric Patients Select dosage with caution because of age-related decreases in renal function. 1 2 12 (See Table 1.) Cautions for Dofetilide Contraindications Congenital or acquired long QT syndromes; baseline QT or QT c interval >440 msec (500 msec in patients with ventricular conduction abnormalities). 1 2 Severe renal impairment (calculated Cl cr <20 mL/minute). 1 2 Concomitant use of verapamil or cation transport system inhibitors (e.g., cimetidine, ketoconazole, megestrol, prochlorperazine, or trimethoprim [alone or in combination with sulfamethoxazole]). 1 2 b (See Specific Drugs under Interactions.) Concomitant use of hydrochlorothiazide alone or in combination with triamterene. 1 Known hypersensitivity to dofetilide. 1 2 12 Warnings/Precautions Warnings Arrhythmogenic Effects May cause serious ventricular arrhythmias, principally polymorphic ventricular tachycardia associated with QT interval prolongation (i.e., torsades de pointes). 1 2 3 4 5 6 7 8 11 Generally occurs within the first 3 days of initiation of therapy. 1 2 The risk is threefold greater in women than in men. 1 2 (See Boxed Warnings.) Reduce risk of torsades de pointes by controlling the plasma concentration (e.g., adjustment of initial dofetilide dosage according to Cl cr , avoiding certain drug interactions) and monitoring the ECG for excessive increases in the QT interval. 1 2 Mortality Limited evidence suggests a possible excess mortality as a result of dofetilide use. 1 General Precautions Cardiovascular Conduction No apparent adverse effects on conduction velocity. 1 2 AV nodal conduction unaffected in normal volunteers or in patients with first degree heart block. 1 2 Used safely in conjunction with pacemakers. 1 2 Metabolic Effects Hypokalemia or hypomagnesemia may increase the risk of torsades de pointes. 1 2 Closely monitor patients experiencing prolonged or excessive diarrhea, sweating, vomiting, loss of appetite, or thirst. 1 2 Closely monitor patients receiving concomitant therapy with drugs that may increase the risk of such electrolyte imbalance (e.g., diuretics). 1 2 (See Specific Drugs under Interactions.) Specific Populations Pregnancy Category C. 1 2 Lactation Not known whether dofetilide is distributed into milk. 1 2 Use not recommended. 1 2 Pediatric Use Safety and efficacy not established. 1 2 Geriatric Use No substantial differences in safety and efficacy relative to younger adults. 1 2 Select dosage with caution because of age-related decreases in renal function. 1 2 12 Renal Impairment If clearance is decreased, dosage adjustments are necessary depending on degree of renal impairment. 1 b Safety and efficacy not established in patients with Cl cr> <20 mL/minute. 1 2 (See Table 1 under Dosage and Administration for dosage adjustment based on Cl cr .) Hepatic Impairment Not studied in patients with severe hepatic impairment; use with particular caution in these patients. 1 2 (See Hepatic Impairment under Dosage and Administration.) Common Adverse Effects Headache, chest pain, dizziness. 1 Interactions for Dofetilide Metabolized by CYP3A4, 1 a but has a low affinity for this isoenzyme. 1 Does not inhibit CYP isoenzymes. b Carefully screen patient s medication history, including all OTC, prescription, and herbal/natural preparations with emphasis on those that may affect dofetilide pharmacokinetics. 1 b If discontinuance of dofetilide is necessary to permit administration of potentially interacting drug(s), allow a washout period of at least 2 days. 1 b Drugs Inhibiting Renal Tubular Cationic Transport Pharmacokinetic interaction (decreased dofetilide elimination). 1 2 12 May increase the risk of torsades de pointes 1 2 12 (See Elimination under Pharmacokinetics, and see Contraindications under Cautions.) Use concurrent therapy with care. 1 Drugs Secreted by Renal Tubular Cationic Transport Potential pharmacokinetic interaction (decreased dofetilide elimination and increased plasma concentration). 1 2 12 May increase risk of torsades de pointes. 1 2 12 Use concurrent therapy with care. 1 Substances Affecting Hepatic Microsomal Enzymes Inhibitors of CYP3A4: Potential pharmacokinetic interaction (decreased dofetilide metabolism and possible increased systemic exposure). 1 2 12 Concomitant use not recommended. 1 12 b Drugs that Prolong QT Interval Potential pharmacodynamic interaction (increased risk of ventricular arrhythmias). 1 2 Concomitant use not recommended. 1 12 b Specific Drugs and Foods Drug or Food Interaction Comments Amiloride Potential decreased dofetilide elimination and increased plasma dofetilide concentrations; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 Amiodarone Potential increased plasma dofetilide concentrations; 1 possible increased risk of ventricular arrhythmias 1 Withhold amiodarone for at least 3 months or until serum amiodarone concentrations are> <0.3 mcg/mL prior to administering dofetilide 1 Amlodipine Pharmacokinetic interaction unlikely 1 b Antacids (aluminum or magnesium hydroxides) Pharmacokinetic interaction unlikely 1 b Consider as alternative therapy for cimetidine 1 b Antiarrhythmic agents Possible increased risk of ventricular arrhythmias 1 2 Concomitant use not recommended. 1 b 12 Withhold class I and class III antiarrhythmic agents for at least 3 half-lives prior to initiating dofetilide 1 Antidepressants, tricyclic Possible increased risk of ventricular arrhythmias 1 2 Concomitant use not recommended 1 b 12 Antifungal agents, azole Potential decreased dofetilide metabolism and possible increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use certain azoles concomitantly with caution 1 b Concomitant use of ketoconazole is contraindicated 1 2 Antiretroviral agents, HIV protease inhibitors Potential decreased dofetilide metabolism and possible increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 2 12 Use concomitantly with caution 1 b Bepridil Possible increased risk of ventricular arrhythmias 1 2 Concomitant use not recommended 1 b 12 Cannabinoids Potential decreased dofetilide metabolism and possible increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Cimetidine Decreased dofetilide elimination; possible increased risk of torsades de pointes 1 2 12 Concomitant use contraindicated 1 2 Cisapride Possible increased risk of ventricular arrhythmias 1 2 Concomitant use not recommended 1 b 12 Digoxin Pharmacokinetic interaction unlikely. 1 2 Uncertain potential pharmacodynamic interaction (increased risk of torsades de pointes). 1 Diltiazem Potential decreased dofetilide metabolism and possible increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Diuretics, potassium-depleting Possible increased risk of electrolyte imbalance (i.e., hypokalemia or hypomagnesemia) and increased risk of torsades de pointes 1 2 Close monitoring recommended during concomitant therapy 1 2 Concomitant use of hydrochlorothiazide or in combination with triamterene is contraindicated 1 2 Glyburide Pharmacokinetic interaction with dofetilide unlikely 1 Grapefruit juice Potential decreased dofetilide metabolism and possible increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Hormone replacement therapy Pharmacokinetic interaction unlikely 1 b Hydrochlorothiazide (with or without triamterene) Increased dofetilide AUC and peak plasma concentrations; 1 possible increased risk of QT interval prolongation 1 Concomitant use contraindicated 1 Ketoconazole Decreased dofetilide elimination; 1 2 possible increased risk of torsades de pointes 1 2 12 Concomitant use contraindicated 1 2 Macrolides, oral Possible increased risk of ventricular arrhythmias 1 2 Concomitant use not recommended 1 b 12 Megestrol Decreased dofetilide elimination; 1 2 possible increased risk of torsades de pointes 1 2 12 Concomitant use contraindicated 1 2 Metformin Decreased dofetilide elimination and increased plasma dofetilide concentration; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Nefazodone Potential decreased dofetilide metabolism and increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Norfloxacin Potential decreased dofetilide metabolism and increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Omeprazole Pharmacokinetic interaction unlikely 1 2 Consider as alternative therapy for cimetidine 1 b Oral contraceptives Pharmacokinetic interaction unlikely 1 b Phenothiazines Possible increased risk of ventricular arrhythmias 1 2 Concomitant use not recommended 1 Phenytoin Pharmacokinetic interaction unlikely 1 b Prochlorperazine Decreased dofetilide elimination; 1 2 possible increased risk of torsades de pointes 1 2 12 Concomitant use contraindicated 1 2 Propranolol Pharmacokinetic interaction unlikely 1 b Quinine Potential decreased dofetilide metabolism and increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Ranitidine Pharmacokinetic interaction unlikely 1 2 Consider ranitidine as alternative therapy for cimetidine 1 b SSRIs Potential decreased dofetilide metabolism and increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Theophylline Pharmacokinetic interaction unlikely 1 2 Triamterene Potential decreased dofetilide elimination and increased plasma concentrations 1 2 12 Use concomitantly with caution 1 b Concomitant use of hydrochlorothiazide in combination with triamterene is contraindicated 1 2 Trimethoprim (with or without sulfamethoxazole) Decreased dofetilide elimination; 2 possible increased risk of torsades de pointes 1 2 12 Concomitant use contraindicated 1 2 Verapamil Increased plasma dofetilide concentrations; 1 2 possible increased risk of torsades de pointes 1 2 12 Concomitant use contraindicated 1 2 Warfarin Pharmacodynamic or pharmacokinetic interaction unlikely 1 2 Zafirlukast Potential decreased dofetilide metabolism and possible increased systemic exposure; 1 2 12 possible increased risk of torsades de pointes 1 2 12 Use concomitantly with caution 1 b Dofetilide Pharmacokinetics Absorption Bioavailability Absolute bioavailability is> 90%. 1 a Peak plasma concentrations are attained within 2 3 hours. a Steady-state plasma concentrations are attained within 2 3 days. 1 Food Food delays absorption but does not affect total bioavailability. 2 Distribution Extent Apparent volume of distribution is 3 L/kg. 1 In animal studies, in utero growth and survival is affected adversely. 1 Not known whether dofetilide is distributed into human milk. 1 Plasma Protein Binding 60 70%. 1 a Elimination Metabolism Metabolized by CYP3A4, 1 a but the drug has a low affinity for this isoenzyme. 1 Elimination Route Excreted principally in urine (80%); urinary excretion is mainly as unchanged drug (80%) and inactive or minimally active metabolites (20%). 1 Eliminated via glomerular filtration and active tubular secretion. 1 Half-life Terminal half-life is approximately 10 hours. 1 2 Special Populations With decreasing Cl cr (renal impairment), the overall drug systemic clearance is decreased and plasma concentration increased. 1 Not known whether hemodialysis removes dofetilide from plasma. 1 Pharmacokinetics not altered in patients with mild to moderate hepatic insufficiency (Child-Pugh class C). 1 Pharmacokinetics not studied in patients with severe hepatic insufficiency (Child-Pugh class C). 1 2 Stability Storage Oral Capsules and Tablets 15 30 C in tight, well closed containers. 1 Protect from moisture and humidity. 1 Actions More selective in its cellular actions than some other class III antiarrhythmic agents (e.g., amiodarone, sotalol). 4 5 7 11 Prolongs the action potential duration and effective refractory period in both atrial and ventricular cardiac tissue, principally due to delayed repolarization. 1 2 4 5 11 Selectively inhibits the rapidly activating component of the potassium channel (delayed rectifier potassium current I Kr ) involved in repolarization of cardiac cells. 1 2 3 4 5 8 11 Does not affect cardiac conduction velocity and sinus node function. 1 2 4 5 7 11 Has no effect on sodium channels (associated with class I antiarrhythmic agents) or β- or α-adrenergic receptors at clinically relevant concentrations. 1 2 4 11 Negligible effects on heart rate or BP. 2 4 5 11 12 May improve slightly cardiac contractility. 2 4 5 11 12 Advice to Patients Importance of reading the manufacturer s patient information prior to beginning therapy and rereading it each time the prescription is refilled in case patient status has changed. 1 2 (See REMS.) Importance of informing a clinician immediately if new rapid heartbeats, lightheadedness, or fainting occur. 1 2 If a clinician cannot be contacted, proceed to the nearest hospital emergency room. 1 2 Importance of informing a clinician immediately if excessive or prolonged diarrhea, sweating, vomiting, or loss of appetite or thirst occurs. 1 Importance of adherence to dosage and medical appointment schedule. 1 2 Take drug at same time each day and omit any missed doses. 1 2 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses. 1 2 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 2 Importance of informing patients of other important precautionary information. (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Distribution of dofetilide is restricted. (See Restricted Distribution Program under Dosage and Administration.) Dofetilide Routes Dosage Forms Strengths Brand Names Manufacturer Oral Capsules 0.125 mg Tikosyn Pfizer 0.25 mg Tikosyn Pfizer 0.5 mg Tikosyn Pfizer AHFS DI Essentials. Copyright 2017, Selected Revisions June 2, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Pfizer. Tikosyn (dofetilide) capsules prescribing information. New York, NY; 2004 Mar. 2. Pfizer. Tikosyn (dofetilide) product monograph and confirmation of education. New York, NY. From Tikosyn web site (). 2000 March. 3. Anon. Dofetilide for atrial fibrillation. Med Lett Drugs Ther . 2000; 42:41-2. 4. Kalus JS, Mauro VF. Dofetilide: a class III-specific antiarrhythmic agent. Ann Pharmacother . 2000; 34:44-56. [PubMed 10669186] 5. Lenz TL, Hilleman DE. Dofetilide, a new class III antiarrhythmic agent. Pharmacotherapy . 2000; 20:776-86. [PubMed 10907968] 6. Greenbaum RA, Campbell TJ, Channer KS et al. Conversion of atrial fibrillation and maintenance of sinus rhythm by dofetilide: the EMERALD (European and Australian Multicenter Evaluative Research on Atrial Fibrillation Dofetilide) study. Circulation . 1998; 98(Suppl I):I-633. Abstract No. 3326. 7. Torp-Pedersen C, Moller M, Bloch-Thomsen PE et al for the Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. N Engl J Med. 1999; 341:857-65. 8. Stevenson WG, Stevenson LW. Atrial fibrillation in heart failure. N Engl J Med. 1999; 341:910-1. Editorial. [PubMed 10486424] 9. Pfizer. Become a confirmed TIKOSYN prescriber. From web site. Accessed October 11, 2000. 10. Pfizer. Become a confirmed TIKOSYN institution. From web site. Accessed October 11, 2000. 11. McClellan KJ, Markham A. Dofetilide: a review of its use in atrial fibrillation and atrial flutter. Drugs . 1999; 58:1043-59. [PubMed 10651390] 12. Pfizer, New York, NY: Personal communication. a. Mounsey JP, DiMarco JP. Dofetilide Circulation . 2000; 102:2665-70. b. Pfizer. Tikosyn (dofetilide) product monograph and confirmation of education. New York, NY. From Tikosyn web site. 2002 March. Next Interactions Print this page Add to My Med List More about dofetilide Side Effects During Pregnancy Dosage Information Drug Images Drug Interactions Support Group Pricing & Coupons En Español 41 Reviews Add your own review/rating Drug class: group III antiarrhythmics Consumer resources Dofetilide Dofetilide (Advanced Reading) Professional resources Dofetilide (FDA) Dofetilide (Wolters Kluwer) Other brands: Tikosyn Related treatment guides Arrhythmia ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturer Greenstone LLC Drug Class Group III antiarrhythmics Related Drugs Arrhythmia propranolol , amiodarone , verapamil , lidocaine , Inderal , Tikosyn , Pacerone , mexiletine , Calan , Cordarone , quinidine , Mexitil , Calan SR , procainamide , Verelan , disopyramide , Norpace , Nexterone , Isoptin SR , Ethmozine , Norpace CR , Pronestyl , More... Dofetilide Rating 41 User Reviews 7.9 /10 41 User Reviews 7.9 Rate it! Dofetilide Images Dofetilide systemic 125 mcg (ML 125) View all images} } immediately
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