Tikosyn dofetilide .25 mg Capsule, 60-count

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.

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 or QT must be checked using an average of 5–10 beats.

If the QTc or QT 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. Proceed to Step 2 if the QTc or QT is 440 msec.

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 to 60 mL/min 250 mcg twice daily 20 to <40 mL/min 125 mcg twice daily <20 mL/min Tikosyn 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 or QT (if heart rate is less than 60 beats per minute). If the QTc or QT has increased by greater than 15% compared to the baseline established in Step 1 OR if the QTc or QT 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 or QT 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…

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.

MEDICATION GUIDE TIKOSYN ® (Tee' ko sin) (dofetilide) Capsules Read the Medication Guide before you start taking TIKOSYN and each time you get a refill. This information does not take the place of talking with your doctor about your condition or treatment. What is the most important information I should know about TIKOSYN?

TIKOSYN can cause serious side effects, including a type of abnormal heartbeat called Torsade de Pointes, which can lead to death. To establish the right dose of TIKOSYN, treatment with TIKOSYN must be started in a hospital where your heart rate and kidney function will be checked for the first 3 days of treatment. It is important that when you go home, you take the exact dose of TIKOSYN that your doctor prescribed for you.

While you take TIKOSYN, always watch for signs of abnormal heartbeat. Call your doctor and go to the hospital right away if you: • feel faint • become dizzy, or • have a fast heartbeat What is TIKOSYN? TIKOSYN is a prescription medicine that is used to treat an irregular heartbeat (atrial fibrillation or atrial flutter).

It is not known if TIKOSYN is safe and effective in children under 18 years of age. Who should not take TIKOSYN? Do not take TIKOSYN if you: • have an irregular heartbeat called long QT syndrome • have kidney problems or are on kidney dialysis • take any of these medicines: • cimetidine (TAGAMET, TAGAMET HB) Listed trademarks are the property of their respective owners. • verapamil (CALAN, CALAN SR, COVERA-HS, ISOPTIN, ISOPTIN SR, VERELAN, VERELAN PM, TARKA) • ketoconazole (NIZORAL, XOLEGEL, EXTINA) • trimethoprim alone (PROLOPRIM, TRIMPEX) or the combination of trimethoprim and sulfamethoxazole (BACTRIM, SEPTRA SULFATRIM) • prochlorperazine (COMPAZINE, COMPO) • megestrol (MEGACE) • dolutegravir (TIVICAY) • hydrochlorothiazide alone or in combination with other medicines (such as ESIDRIX, EZIDE, HYDRODIURIL, HYDRO-PAR, MICROZIDE, or ORETIC) Ask your doctor if you are not sure if any of your medicines are the kind listed above. • are allergic to dofetilide in TIKOSYN.

See the end of this leaflet for a complete list of ingredients in TIKOSYN. What should I tell my doctor before taking TIKOSYN? Before taking TIKOSYN, tell your doctor about all of your medical conditions including if you: • have heart problems • have kidney or liver problems • are pregnant or plan to become pregnant.

It is not known if TIKOSYN will harm your unborn baby. • are breast-feeding or plan to breast-feed. It is not known if TIKOSYN passes into your breast milk. You and your doctor should decide if you will take TIKOSYN or breast-feed.

You should not do both. Especially tell your doctor if you take medicines to treat: • heart problems • high blood pressure • depression or other mental problems • asthma • allergies, or hay fever • skin problems • infections Ask your doctor if you are not sure about the medicines you take. Tell your doctor about all prescription and non-prescription medicines, vitamins, dietary supplements, and any natural or herbal remedies.

TIKOSYN and other medicines may affect each other, causing serious side effects. If you take TIKOSYN with certain medicines, you will be more likely to have a different type of abnormal heartbeat. See "Who should not take TIKOSYN?" Know the medicines you take.

Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine. How should I take TIKOSYN? • Take TIKOSYN exactly as your doctor tells you. • Do not change your TIKOSYN dose unless your doctor tells you to. • Your doctor will do tests before you start and while you take TIKOSYN. • Do not stop taking TIKOSYN until your doctor tells you to stop. If you miss a dose, just take the next dose at your regular time.

Do not take 2 doses of TIKOSYN at the same time. • TIKOSYN can be taken with or without food. • If you take too much TIKOSYN, call your doctor or go to the nearest hospital emergency room right away. Take your TIKOSYN capsules with you to show to the…