Data from FDA - Curated by EPG Health - Last updated 06 November 2017

Indication(s)

INDICATIONS AND USAGE Maintenance of Normal Sinus Rhythm (Delay in AF/AFl Recurrence) TIKOSYN is indicated for the maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter [AF/AFl]) in patients with atrial fibrillation/atrial flutter of greater than one week duration who have been converted to normal sinus rhythm. Because TIKOSYN can cause life threatening ventricular arrhythmias, it should be reserved for patients in whom atrial fibrillation/atrial flutter is highly symptomatic. In general, antiarrhythmic therapy for atrial fibrillation/atrial flutter aims to prolong the time in normal sinus rhythm. Recurrence is expected in some patients (see CLINICAL STUDIES ). Conversion of Atrial Fibrillation/Flutter TIKOSYN is indicated for the conversion of atrial fibrillation and atrial flutter to normal sinus rhythm. TIKOSYN has not been shown to be effective in patients with paroxysmal atrial fibrillation.

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Advisory information

contraindications
CONTRAINDICATIONS TIKOSYN is contraindicated in patients with congenital or acquired long QT syndromes. TIKOSYN should not be used in patients with a baseline QT interval or QTc >440 msec (500 msec in patients with ventricular conduction abnormalities). TIKOSYN is also contraindicated in patients with severe renal impairment (calculated creatinine clearance <20 mL/min). The concomitant use of verapamil or the cation transport system inhibitors cimetidine, trimethoprim (alone or in combination with sulfamethoxazole), or ketoconazole with TIKOSYN is contraindicated (see WARNINGS and PRECAUTIONS, Drug-Drug Interactions ), as each of these drugs cause a substantial increase in dofetilide plasma concentrations. In addition, other known inhibitors of the renal cation transport system such as prochlorperazine, dolutegravir and megestrol should not be used in patients on TIKOSYN. The concomitant use of hydrochlorothiazide (alone or in combinations such as with triamterene) with TIKOSYN is contraindicated (see PRECAUTIONS, Drug-Drug Interactions ) because this has been shown to significantly increase dofetilide plasma concentrations and QT interval prolongation. TIKOSYN is also contraindicated in patients with a known hypersensitivity to the drug.
Special warnings and precautions
PRECAUTIONS Renal Impairment The overall systemic clearance of dofetilide is decreased and plasma concentration increased with decreasing creatinine clearance. The dose of TIKOSYN must be adjusted based on creatinine clearance (see DOSAGE AND ADMINISTRATION ). Patients undergoing dialysis were not included in clinical studies, and appropriate dosing recommendations for these patients are unknown. There is no information about the effectiveness of hemodialysis in removing dofetilide from plasma. Hepatic Impairment After adjustment for creatinine clearance, no additional dose adjustment is required for patients with mild or moderate hepatic impairment. Patients with severe hepatic impairment have not been studied. TIKOSYN should be used with particular caution in these patients. Cardiac Conduction Disturbances Animal and human studies have not shown any adverse effects of dofetilide on conduction velocity. No effect on AV nodal conduction following TIKOSYN treatment was noted in normal volunteers and in patients with 1st degree heart block. Patients with sick sinus syndrome or with 2nd or 3rd degree heart block were not included in the Phase 3 clinical trials unless a functioning pacemaker was present. TIKOSYN has been used safely in conjunction with pacemakers (53 patients in DIAMOND studies, 136 in trials in patients with ventricular and supraventricular arrhythmias). Information for Patients Please refer patient to the Medication Guide. Prior to initiation of TIKOSYN therapy, the patient should be advised to read the Medication Guide and reread it each time therapy is renewed in case the patient's status has changed. The patient should be fully instructed on the need for compliance with the recommended dosing of TIKOSYN and the potential for drug interactions, and the need for periodic monitoring of QTc and renal function to minimize the risk of serious abnormal rhythms. Medications and Supplements Assessment of patients' medication history should include all over-the-counter, prescription, and herbal/natural preparations with emphasis on preparations that may affect the pharmacokinetics of TIKOSYN such as cimetidine (see CONTRAINDICATIONS ), trimethoprim alone or in combination with sulfamethoxazole (see WARNINGS, CONTRAINDICATIONS ), prochlorperazine (see WARNINGS, CONTRAINDICATIONS ), megestrol (see WARNINGS, CONTRAINDICATIONS ), ketoconazole (see WARNINGS, CONTRAINDICATIONS ), dolutegravir (see CONTRAINDICATIONS ), hydrochlorothiazide (alone or in combinations such as with triamterene) (see CONTRAINDICATIONS ), other cardiovascular drugs (especially verapamil – see CONTRAINDICATIONS ), phenothiazines, and tricyclic antidepressants (see WARNINGS ). If a patient is taking TIKOSYN and requires anti-ulcer therapy, omeprazole, ranitidine, or antacids (aluminum and magnesium hydroxides) should be used as alternatives to cimetidine, as these agents have no effect on the pharmacokinetics of TIKOSYN. Patients should be instructed to notify their health care providers of any change in over-the-counter, prescription, or supplement use. If a patient is hospitalized or is prescribed a new medication for any condition, the patient must inform the health care provider of ongoing TIKOSYN therapy. Patients should also check with their health care provider and/or pharmacist prior to taking a new over-the-counter preparation. Electrolyte Imbalance If patients experience symptoms that may be associated with altered electrolyte balance, such as excessive or prolonged diarrhea, sweating, or vomiting or loss of appetite or thirst, these conditions should immediately be reported to their health care provider. Dosing Schedule Patients should be instructed NOT to double the next dose if a dose is missed. The next dose should be taken at the usual time. Drug/Laboratory Test Interactions None known. Drug-Drug Interactions Cimetidine (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with TIKOSYN (500 mcg BID) for 7 days has been shown to increase dofetilide plasma levels by 58%. Cimetidine at doses of 100 mg BID (OTC dose) resulted in a 13% increase in dofetilide plasma levels (500 mcg single dose). No studies have been conducted at intermediate doses of cimetidine. If a patient requires TIKOSYN and anti-ulcer therapy, it is suggested that omeprazole, ranitidine, or antacids (aluminum and magnesium hydroxides) be used as alternatives to cimetidine, as these agents have no effect on the pharmacokinetic profile of TIKOSYN. Verapamil (see CONTRAINDICATIONS ) Concomitant use of verapamil is contraindicated. Co-administration of TIKOSYN with verapamil resulted in increases in dofetilide peak plasma levels of 42%, although overall exposure to dofetilide was not significantly increased. In an analysis of the supraventricular arrhythmia and DIAMOND patient populations, the concomitant administration of verapamil with dofetilide was associated with a higher occurrence of Torsade de Pointes. Ketoconazole (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of ketoconazole is contraindicated. Ketoconazole at 400 mg daily (the maximum approved prescription dose) co-administered with TIKOSYN (500 mcg BID) for 7 days has been shown to increase dofetilide Cmax by 53% in males and 97% in females, and AUC by 41% in males and 69% in females. Trimethoprim Alone or in Combination with Sulfamethoxazole (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of trimethoprim alone or in combination with sulfamethoxazole is contraindicated. Trimethoprim 160 mg in combination with 800 mg sulfamethoxazole co-administered BID with TIKOSYN (500 mcg BID) for 4 days has been shown to increase dofetilide AUC by 103% and Cmax by 93%. Hydrochlorothiazide (HCTZ) Alone or in Combination with Triamterene (see CONTRAINDICATIONS ) Concomitant use of HCTZ alone or in combination with triamterene is contraindicated. HCTZ 50 mg QD or HCTZ/triamterene 50/100 mg QD was co-administered with TIKOSYN (500 mcg BID) for 5 days (following 2 days of diuretic use at half dose). In patients receiving HCTZ alone, dofetilide AUC increased by 27% and Cmax by 21%. However, the pharmacodynamic effect increased by 197% (QTc increase over time) and by 95% (maximum QTc increase). In patients receiving HCTZ in combination with triamterene, dofetilide AUC increased by 30% and Cmax by 16%. However, the pharmacodynamic effect increased by 190% (QTc increase over time) and by 84% (maximum QTc increase). The pharmacodynamic effects can be explained by a combination of the increase in dofetilide exposure and the reductions in serum potassium. In the DIAMOND trials, 1252 patients were treated with TIKOSYN and diuretics concomitantly, of whom 493 died compared to 508 deaths among the 1248 patients receiving placebo and diuretics. Of the 229 patients who had potassium depleting diuretics added to their concomitant medications in the DIAMOND trials, the patients on TIKOSYN had a non-significantly reduced relative risk for death of 0.68 (95% CI: 0.376, 1.230). Potential Drug Interactions Dofetilide is eliminated in the kidney by cationic secretion. Inhibitors of renal cationic secretion are contraindicated with TIKOSYN. In addition, drugs that are actively secreted via this route (e.g., triamterene, metformin, and amiloride) should be co-administered with care as they might increase dofetilide levels. Dofetilide is metabolized to a small extent by the CYP3A4 isoenzyme of the cytochrome P450 system. Inhibitors of the CYP3A4 isoenzyme could increase systemic dofetilide exposure. Inhibitors of this isoenzyme (e.g., macrolide antibiotics, azole antifungal agents, protease inhibitors, serotonin reuptake inhibitors, amiodarone, cannabinoids, diltiazem, grapefruit juice, nefazadone, norfloxacin, quinine, zafirlukast) should be cautiously co-administered with TIKOSYN as they can potentially increase dofetilide levels. Dofetilide is not an inhibitor of CYP3A4 nor of other cytochrome P450 isoenzymes (e.g., CYP2C9, CYP2D6) and is not expected to increase levels of drugs metabolized by CYP3A4. Other Drug Interaction Information Digoxin Studies in healthy volunteers have shown that TIKOSYN does not affect the pharmacokinetics of digoxin. In patients, the concomitant administration of digoxin with dofetilide was associated with a higher occurrence of Torsade de Pointes. It is not clear whether this represents an interaction with TIKOSYN or the presence of more severe structural heart disease in patients on digoxin; structural heart disease is a known risk factor for arrhythmia. No increase in mortality was observed in patients taking digoxin as concomitant medication. Other Drugs In healthy volunteers, amlodipine, phenytoin, glyburide, ranitidine, omeprazole, hormone replacement therapy (a combination of conjugated estrogens and medroxyprogesterone), antacid (aluminum and magnesium hydroxides), and theophylline did not affect the pharmacokinetics of TIKOSYN. In addition, studies in healthy volunteers have shown that TIKOSYN does not affect the pharmacokinetics or pharmacodynamics of warfarin, or the pharmacokinetics of propranolol (40 mg twice daily), phenytoin, theophylline, or oral contraceptives. Population pharmacokinetic analyses were conducted on plasma concentration data from 1445 patients in clinical trials to examine the effects of concomitant medications on clearance or volume of distribution of dofetilide. Concomitant medications were grouped as ACE inhibitors, oral anticoagulants, calcium channel blockers, beta blockers, cardiac glycosides, inducers of CYP3A4, substrates and inhibitors of CYP3A4, substrates and inhibitors of P-glycoprotein, nitrates, sulphonylureas, loop diuretics, potassium sparing diuretics, thiazide diuretics, substrates and inhibitors of tubular organic cation transport, and QTc-prolonging drugs. Differences in clearance between patients on these medications (at any occasion in the study) and those off medications varied between -16% and +3%. The mean clearances of dofetilide were 16% and 15% lower in patients on thiazide diuretics and inhibitors of tubular organic cation transport, respectively. Carcinogenesis, Mutagenesis, Impairment of Fertility Dofetilide had no genotoxic effects, with or without metabolic activation, based on the bacterial mutation assay and tests of cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes. Rats and mice treated with dofetilide in the diet for two years showed no evidence of an increased incidence of tumors compared to controls. The highest dofetilide dose administered for 24 months was 10 mg/kg/day to rats and 20 mg/kg/day to mice. Mean dofetilide AUCs(0–24hr) at these doses were about 26 and 10 times, respectively, the maximum likely human AUC. There was no effect on mating or fertility when dofetilide was administered to male and female rats at doses as high as 1.0 mg/kg/day, a dose that would be expected to provide a mean dofetilide AUC(0–24hr) about 3 times the maximum likely human AUC. Increased incidences of testicular atrophy and epididymal oligospermia and a reduction in testicular weight were, however, observed in other studies in rats. Reduced testicular weight and increased incidence of testicular atrophy were also consistent findings in dogs and mice. The no effect doses for these findings in chronic administration studies in these 3 species (3, 0.1, and 6 mg/kg/day) were associated with mean dofetilide AUCs that were about 4, 1.3, and 3 times the maximum likely human AUC, respectively. Pregnancy Dofetilide has been shown to adversely affect in utero growth and survival of rats and mice when orally administered during organogenesis at doses of 2 or more mg/kg/day. Other than an increased incidence of non-ossified 5th metacarpal, and the occurrence of hydroureter and hydronephroses at doses as low as 1 mg/kg/day in the rat, structural anomalies associated with drug treatment were not observed in either species at doses below 2 mg/kg/day. The clearest drug-effect associations were for sternebral and vertebral anomalies in both species; cleft palate, adactyly, levocardia, dilation of cerebral ventricles, hydroureter, hydronephroses, and unossified metacarpal in the rat; and increased incidence of unossified calcaneum in the mouse. The "no observed adverse effect dose" in both species was 0.5 mg/kg/day. The mean dofetilide AUCs(0–24hr) at this dose in the rat and mouse are estimated to be about equal to the maximum likely human AUC and about half the likely human AUC, respectively. There are no adequate and well controlled studies in pregnant women. Therefore, dofetilide should only be administered to pregnant women where the benefit to the patient justifies the potential risk to the fetus. Nursing Mothers There is no information on the presence of dofetilide in breast milk. Patients should be advised not to breast-feed an infant if they are taking TIKOSYN. Geriatric Use Of the total number of patients in clinical studies of TIKOSYN, 46% were 65 to 89 years old. No overall differences in safety, effect on QTc, or effectiveness were observed between elderly and younger patients. Because elderly patients are more likely to have decreased renal function with a reduced creatinine clearance, care must be taken in dose selection (see DOSAGE AND ADMINISTRATION ). Use in Women Female patients constituted 32% of the patients in the placebo-controlled trials of TIKOSYN. As with other drugs that cause Torsade de Pointes, TIKOSYN was associated with a greater risk of Torsade de Pointes in female patients than in male patients. During the TIKOSYN clinical development program, the risk of Torsade de Pointes in females was approximately 3 times the risk in males. Unlike Torsade de Pointes, the incidence of other ventricular arrhythmias was similar in female patients receiving TIKOSYN and patients receiving placebo. Although no study specifically investigated this risk, in post-hoc analyses, no increased mortality was observed in females on TIKOSYN compared to females on placebo. Pediatric Use The safety and effectiveness of TIKOSYN in children (<18 years old) has not been established.
Adverse reactions
ADVERSE REACTIONS The TIKOSYN clinical program involved approximately 8,600 patients in 130 clinical studies of normal volunteers and patients with supraventricular and ventricular arrhythmias. TIKOSYN was administered to 5,194 patients, including two large, placebo-controlled mortality trials (DIAMOND CHF and DIAMOND MI) in which 1,511 patients received TIKOSYN for up to three years. In the following section, adverse reaction data for cardiac arrhythmias and non-cardiac adverse reactions are presented separately for patients included in the supraventricular arrhythmia development program and for patients included in the DIAMOND CHF and MI mortality trials (see CLINICAL STUDIES, Safety in Patients with Structural Heart Disease, DIAMOND Studies , for a description of these trials). In studies of patients with supraventricular arrhythmias, a total of 1,346 and 677 patients were exposed to TIKOSYN and placebo for 551 and 207 patient years, respectively. A total of 8.7% of patients in the dofetilide groups were discontinued from clinical trials due to adverse events compared to 8.0% in the placebo groups. The most frequent reason for discontinuation (>1%) was ventricular tachycardia (2.0% on dofetilide vs. 1.3% on placebo). The most frequent adverse events were headache, chest pain, and dizziness. Serious Arrhythmias and Conduction Disturbances Torsade de Pointes is the only arrhythmia that showed a dose-response relationship to TIKOSYN treatment. It did not occur in placebo treated patients. The incidence of Torsade de Pointes in patients with supraventricular arrhythmias was 0.8% (11/1346) (see WARNINGS ). The incidence of Torsade de Pointes in patients who were dosed according to the recommended dosing regimen (see DOSAGE AND ADMINISTRATION ) was 0.8% (4/525). Table 6 shows the frequency by randomized dose of serious arrhythmias and conduction disturbances reported as adverse events in patients with supraventricular arrhythmias. Table 6: Incidence of Serious Arrhythmias and Conduction Disturbances in Patients with Supraventricular Arrhythmias TIKOSYN Dose Placebo Arrhythmia event: <250 mcg BID N=217 250 mcg BID N=388 >250–500 mcg BID N=703 >500 mcg BID N=38 N=677 Ventricular arrhythmiasPatients with more than one arrhythmia are counted only once in this category. Ventricular arrhythmias and ventricular tachycardia include all cases of Torsade de Pointes. 3.7% 2.6% 3.4% 15.8% 2.7% Ventricular fibrillation 0 0.3% 0.4% 2.6% 0.1% Ventricular tachycardia 3.7% 2.6% 3.3% 13.2% 2.5% Torsade de Pointes 0 0.3% 0.9% 10.5% 0 Various forms of block AV block 0.9% 1.5% 0.4% 0 0.3% Bundle branch block 0 0.5% 0.1% 0 0.1% Heart block 0 0.5% 0.1% 0 0.1% In the DIAMOND trials, a total of 1,511 patients were exposed to TIKOSYN for 1757 patient years. The incidence of Torsade de Pointes was 3.3% in CHF patients and 0.9% in patients with a recent MI. Table 7 shows the incidence of serious arrhythmias and conduction disturbances reported as adverse events in the DIAMOND subpopulation that had AF at entry to these trials. Table 7: Incidence of Serious Arrhythmias and Conduction Disturbances in Patients with AF at Entry to the DIAMOND Studies TIKOSYN Placebo N=249 N=257 Ventricular arrhythmiasPatients with more than one arrhythmia are counted only once in this category. Ventricular arrhythmias and ventricular tachycardia include all cases of Torsade de Pointes. 14.5% 13.6% Ventricular fibrillation 4.8% 3.1% Ventricular tachycardia 12.4% 11.3% Torsade de Pointes 1.6% 0 Various forms of block AV block 0.8% 2.7% (Left) bundle branch block 0 0.4% Heart block 1.2% 0.8% Other Adverse Reactions Table 8 presents other adverse events reported with a frequency of >2% on TIKOSYN and reported numerically more frequently on TIKOSYN than on placebo in the studies of patients with supraventricular arrhythmias. Table 8: Frequency of Adverse Events Occurring at >2% on TIKOSYN, and Numerically More Frequently on TIKOSYN than Placebo in Patients with Supraventricular Arrhythmias TIKOSYN Placebo Adverse Event % % headache 11 9 chest pain 10 7 dizziness 8 6 respiratory tract infection 7 5 dyspnea 6 5 nausea 5 4 flu syndrome 4 2 insomnia 4 3 accidental injury 3 1 back pain 3 2 procedure (medical/surgical/health service) 3 2 diarrhea 3 2 rash 3 2 abdominal pain 3 2 Adverse events reported at a rate >2% but no more frequently on TIKOSYN than on placebo were: angina pectoris, anxiety, arthralgia, asthenia, atrial fibrillation, complications (application, injection, incision, insertion, or device), hypertension, pain, palpitation, peripheral edema, supraventricular tachycardia, sweating, urinary tract infection, ventricular tachycardia. The following adverse events have been reported with a frequency of ≤2% and numerically more frequently with TIKOSYN than placebo in patients with supraventricular arrhythmias: angioedema, bradycardia, cerebral ischemia, cerebrovascular accident, edema, facial paralysis, flaccid paralysis, heart arrest, increased cough, liver damage, migraine, myocardial infarct, paralysis, paresthesia, sudden death, and syncope. The incidences of clinically significant laboratory test abnormalities in patients with supraventricular arrhythmias were similar for patients on TIKOSYN and those on placebo. No clinically relevant effects were noted in serum alkaline phosphatase, serum GGT, LDH, AST, ALT, total bilirubin, total protein, blood urea nitrogen, creatinine, serum electrolytes (calcium, chloride, glucose, magnesium, potassium, sodium), or creatine kinase. Similarly, no clinically relevant effects were observed in hematologic parameters. In the DIAMOND population, adverse events other than those related to the post-infarction and heart failure patient population were generally similar to those seen in the supraventricular arrhythmia groups.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION Therapy with TIKOSYN must be initiated (and, if necessary, re-initiated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Patients should continue to be monitored in this way for a minimum of three days. Additionally, patients should not be discharged within 12 hours of electrical or pharmacological conversion to normal sinus rhythm. The dose of TIKOSYN must be individualized according to calculated creatinine clearance and QTc. (QT interval should be used if the heart rate is <60 beats per minute. There are no data on use of TIKOSYN when the heart rate is <50 beats per minute.) The usual recommended dose of TIKOSYN is 500 mcg BID, as modified by the dosing algorithm described below. For consideration of a lower dose, see Special Considerations below. Serum potassium should be maintained within the normal range before TIKOSYN treatment is initiated and should be maintained within the normal range while the patient remains on TIKOSYN therapy. (See WARNINGS, Hypokalemia and Potassium-Depleting Diuretics ). In clinical trials, potassium levels were generally maintained above 3.6–4.0 mEq/L. Patients with atrial fibrillation should be anticoagulated according to usual medical practice prior to electrical or pharmacological cardioversion. Anticoagulant therapy may be continued after cardioversion according to usual medical practice for the treatment of people with AF. Hypokalemia should be corrected before initiation of TIKOSYN therapy (see WARNINGS, Ventricular Arrhythmia ). Patients to be discharged on TIKOSYN therapy from an inpatient setting as described above must have an adequate supply of TIKOSYN, at the patient's individualized dose, to allow uninterrupted dosing until the patient can fill a TIKOSYN prescription. Instructions for Individualized Dose Initiation Initiation of TIKOSYN Therapy Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QTc must be determined using an average of 5–10 beats. If the QTc is greater than 440 msec (500 msec in patients with ventricular conduction abnormalities), TIKOSYN is contraindicated. If heart rate is less than 60 beats per minute, QT interval should be used. Patients with heart rates <50 beats per minute have not been studied. Step 2. Calculation of creatinine clearance: Prior to the administration of the first dose, the patient's creatinine clearance must be calculated using the following formula: creatinine clearance (male) = (140-age) × actual body weight in kg 72 × serum creatinine (mg/dL) creatinine clearance (female) = (140-age) × actual body weight in kg × 0.85 72 × serum creatinine (mg/dL) When serum creatinine is given in µmol/L, divide the value by 88.4 (1 mg/dL = 88.4 µmol/L). Step 3. Starting Dose: The starting dose of TIKOSYN is determined as follows: Calculated Creatinine Clearance TIKOSYN Dose >60 mL/min 500 mcg twice daily 40 – 60 mL/min 250 mcg twice daily 20 – <40 mL/min 125 mcg twice daily <20 mL/min Dofetilide is contraindicated in these patients Step 4. Administer the adjusted TIKOSYN dose and begin continuous ECG monitoring. Step 5. At 2–3 hours after administering the first dose of TIKOSYN, determine the QTc. If the QTc has increased by greater than 15% compared to the baseline established in Step 1 OR if the QTc is greater than 500 msec (550 msec in patients with ventricular conduction abnormalities), subsequent dosing should be adjusted as follows: If the Starting Dose Based on Creatinine Clearance is: Then the Adjusted Dose (for QTc Prolongation) is: 500 mcg twice daily 250 mcg twice daily 250 mcg twice daily 125 mcg twice daily 125 mcg twice daily 125 mcg once a day Step 6. At 2–3 hours after each subsequent dose of TIKOSYN, determine the QTc (for in-hospital doses 2–5). No further down titration of TIKOSYN based on QTc is recommended. NOTE: If at any time after the second dose of TIKOSYN is given the QTc is greater than 500 msec (550 msec in patients with ventricular conduction abnormalities), TIKOSYN should be discontinued. Step 7. Patients are to be continuously monitored by ECG for a minimum of three days, or for a minimum of 12 hours after electrical or pharmacological conversion to normal sinus rhythm, whichever is greater. The steps described above are summarized in the following diagram: flow chart Maintenance of TIKOSYN Therapy Renal function and QTc should be re-evaluated every three months or as medically warranted. If QTc exceeds 500 milliseconds (550 msec in patients with ventricular conduction abnormalities), TIKOSYN therapy should be discontinued and patients should be carefully monitored until QTc returns to baseline levels. If renal function deteriorates, adjust dose as described in Initiation of TIKOSYN Therapy, Step 3. Special Considerations Consideration of a Dose Lower than that Determined by the Algorithm The dosing algorithm shown above should be used to determine the individualized dose of TIKOSYN. In clinical trials (see CLINICAL STUDIES ), the highest dose of 500 mcg BID of TIKOSYN as modified by the dosing algorithm led to greater effectiveness than lower doses of 125 or 250 mcg BID as modified by the dosing algorithm. The risk of Torsade de Pointes, however, is related to dose as well as to patient characteristics (see WARNINGS ). Physicians, in consultation with their patients, may therefore in some cases choose doses lower than determined by the algorithm. It is critically important that if at any time this lower dose is increased, the patient needs to be rehospitalized for three days. Previous toleration of higher doses does not eliminate the need for rehospitalization. The maximum recommended dose in patients with a calculated creatinine clearance greater than 60 mL/min is 500 mcg BID; doses greater than 500 mcg BID have been associated with an increased incidence of Torsade de Pointes. A patient who misses a dose should NOT double the next dose. The next dose should be taken at the usual time. Cardioversion If patients do not convert to normal sinus rhythm within 24 hours of initiation of TIKOSYN therapy, electrical conversion should be considered. Patients continuing on TIKOSYN after successful electrical cardioversion should continue to be monitored by electrocardiography for 12 hours post cardioversion, or a minimum of 3 days after initiation of TIKOSYN therapy, whichever is greater. Switch to TIKOSYN from Class I or other Class III Antiarrhythmic Therapy Before initiating TIKOSYN therapy, previous antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of three (3) plasma half-lives. Because of the unpredictable pharmacokinetics of amiodarone, TIKOSYN should not be initiated following amiodarone therapy until amiodarone plasma levels are below 0.3 mcg/mL or until amiodarone has been withdrawn for at least three months. Stopping TIKOSYN Prior to Administration of Potentially Interacting Drugs If TIKOSYN needs to be discontinued to allow dosing of other potentially interacting drug(s), a washout period of at least two days should be followed before starting the other drug(s).
Pregnancy and lactation
Nursing Mothers There is no information on the presence of dofetilide in breast milk. Patients should be advised not to breast-feed an infant if they are taking TIKOSYN.

More information

Category Value
Authorisation number NDA020931
Agency product number R4Z9X1N2ND
Orphan designation No
Product NDC 0069-5820,0069-5810,0069-5800
Date Last Revised 25-10-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 310004
Storage and handling Store at controlled room temperature, 15° to 30°C (59° to 86°F). PROTECT FROM MOISTURE AND HUMIDITY. Dispense in tight containers (USP).
Marketing authorisation holder Pfizer Laboratories Div Pfizer Inc
Warnings To minimize the risk of induced arrhythmia, patients initiated or re-initiated on TIKOSYN should be placed for a minimum of 3 days in a facility that can provide calculations of creatinine clearance, continuous electrocardiographic monitoring, and cardiac resuscitation. For detailed instructions regarding dose selection, see DOSAGE AND ADMINISTRATION .