TIKOSYN TREATMENT GUIDELINES

TIKOSYN® (dofetilide) is indicated for the conversion and maintenance of normal sinus rhythm (delay in the time to recurrence of atrial fibrillation/atrial flutter) in highly symptomatic patients with atrial fibrillation/atrial flutter of greater than 1 week.

Below, you will find detailed treatment guidelines for TIKOSYN. Please call 1-877-TIKOSYN if you need additional information.

IIIa. Dosing Overview

Please review this overview of dosing for TIKOSYN.

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IIIb. Steps for Initiation and Dosing

The following are suggested guidelines for the initiation and dosing of TIKOSYN.

PREDOSE STEPS

1. Before initiating TIKOSYN therapy, previous antiarrhythmic therapy should be withdrawn for a minimum of 3 plasma half-lives. 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initiated following amiodarone therapy until amiodarone plasma levels are below 0.3 mcg/mL or until amiodarone has been withdrawn for at least 3 months.

2. Patients with atrial fibrillation should be anticoagulated according to usual medical practice.

3. Admit patient to the telemetry unit; choose a telemetry lead with a visible QT interval. All measurements of the QT interval should be from this lead.

4. Telemetry monitoring should continue for a minimum of 3 days or for 12 hours after conversion to normal sinus rhythm, whichever is longer.

5. The concomitant use of verapamil, hydrochlorothiazide (alone or in combination, such as with triamterene), or the cation transport system inhibitors cimetidine, trimethoprim (alone or in combination with sulfamethoxazole), and ketoconazole with TIKOSYN is contraindicated, as each drug causes a substantial increase in dofetilide plasma concentration. In addition, other known inhibitors of the renal cation transport system, such as prochlorperazine and megestrol, should not be used in patients on TIKOSYN. Click here for a list of contraindications for TIKOSYN.

6. CAUTION should be used when coadministering TIKOSYN with macrolide antibiotics, azole antifungals, protease inhibitors, and SRIs, as these agents may increase blood levels of TIKOSYN.

7.  Concomitant administration of TIKOSYN and digoxin is permitted. Carefully monitor patients for the signs and symptoms of digoxin toxicity. The concomitant administration of digoxin was associated with a higher occurrence of torsades de pointes. It is not clear whether this represents an interaction with TIKOSYN or the presence of more severe structural heart disease in patients taking digoxin.

8. If potassium (K+) is <4.0 mEq/L, replace K+ before administration of TIKOSYN.

9. Before administering the first dose of TIKOSYN on Day 1, measure the QTc interval (determine the QT if the heart rate is <60 bpm or >100 bpm).

10. Measure the QT interval (determine QTc) 2-3 hours after each dose of TIKOSYN until the patient is discharged.

11. Determine the patient’s actual body weight in kg.

12. Measure patient’s serum creatinine level as mg/dL.

13. Calculate patient’s creatinine clearance using the following formula:

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DOSING

14. The creatinine clearance results should be received by the pharmacy to dispense the first TIKOSYN dose.

15. If the calculated creatinine clearance is <20 mL/min, TIKOSYN is CONTRAINDICATED.

16. If the calculated creatinine clearance is >60 mL/min, the appropriate dose of TIKOSYN is 500 mcg BID.

17. If the calculated creatinine clearance is between 40 mL/min and 60 mL/min, the appropriate dose of TIKOSYN is 250 mcg BID.

18. If the calculated creatinine clearance is 20 mL/min to <40 mL/min, the appropriate dose of TIKOSYN is 125 mcg BID.

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POSTDOSE ADJUSTMENTS

19. The second dose of TIKOSYN should only be given after the QT has been determined. Only 1 down titration of TIKOSYN for QTc is suggested. If QTc is still excessively prolonged, DISCONTINUE TIKOSYN therapy.

20. During therapy initiation in the hospital, at 2-3 hours after each dose of TIKOSYN, determine the QTc to see if dose adjustment is necessary.

21. TIKOSYN should be given q12h (actual times may vary according to local hospital practice; the doses should be given at the same time each day, ie, 12 hours apart); QD TIKOSYN should be given at the same time every day. The risk of torsades de pointes is related to dose as well as to patient characteristics. Physicians may, therefore, in some cases, choose doses lower than determined by the algorithm. If at any time this lower dose is increased, the patient needs to be rehospitalized for 3 days. Previous toleration of higher doses does not eliminate the need for rehospitalization.

22. After the third TIKOSYN  dose, discuss with patient the option of filling Rx with patient's mail-order or retail pharmacy.  Both the mail-order and retail pharmacy must be enrolled in the T.I.P.S. program. The physician who orders a TIKOSYN prescription must be a confirmed participant of a TIKOSYN education program. You will need the patient’s final dose of TIKOSYN, patient’s full name (correct spelling), address, insurer, and physician’s name. If the TIKOSYN dose is changed or discontinued after the prescription has been faxed, please notify the mail-order or retail pharmacy immediately.

The T.I.P.S.™ Program is designed to allow retail pharmacies to stock and dispense TIKOSYN once they have been enrolled. Click here for T.I.P.S.™ enrollment information.

23. Contact your hospital pharmacy to order a TIKOSYN bottle with 14 capsules of the final dosage strength.* The patient should be discharged with this bottle to ensure a sufficient drug supply for uninterrupted dosing until the patient receives the first outpatient supply of medication. Patient will be directed to fill prescription as soon as possible, since pharmacy may not have TIKOSYN stocked and requires at least 24 hours to fill prescription.

*This bottle is supplied free of charge to hospitals.

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ACTIONS PRIOR TO PATIENT DISCHARGE

24. Ensure the patient received the TIKOSYN discharge bottle with 14 capsules.

25. Counsel your patient to use the tools in the TIKOSYN Patient Resource Kit.

26. Alert patients that blood work and ECG will be re-evaluated every 3 months by their doctor to check the renal function and the QTc.

27.  Inform the patient’s Healthcare Professional that the patient is now on TIKOSYN. Important points to
mention include:

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