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

How does Tikosyn act to convert atrial fibrillation or flutter to normal sinus rhythm?

Tikosyn demonstrates Vaughan Williams class III antiarrhythmic activity. The mechanism of action is blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current, IKr. Tikosyn is both highly potent and highly specific with no relevant blockade of other repolarizing potassium currents.

Tikosyn increases the monophasic action potential duration in a concentration-dependent manner because of delayed repolarization. This effect, and the related increase in effective refractory period, is observed in the atria and ventricles in both resting and paced electrophysiologic studies.

Can Tikosyn maintain NSR in patients requiring electrical cardioversion?

In 2 well-controlled clinical trials, Tikosyn was significantly (P≤0.001) more effective than placebo at maintaining patients in NSR for 1 year. In both studies, patients who did not convert to NSR pharmacologically were electrically cardioverted. There was no difference in maintenance of NSR among the patients cardioverted electrically versus those converted pharmacologically

What electrophysiologic effects should be monitored with Tikosyn?

Tikosyn causes an increase in QT interval on ECG as a result of it's effect in prolonging both the effective and functional refractory periods of the action potential. Tikosyn does not influence cardiac conduction velocity and sinus node function which is consistent with a lack of effect on the PR interval and QRS width in patients with pre-existing heart block and/or sick sinus syndrome.

To minimize the risk of induced proarrhythmia due to QT interval prolongation, patients initiated on Tikosyn should be placed a minimum of 3 days in a facility that can provide calculation of creatinine clearance, continuous electrocardiographic monitoring and cardiac resuscitation. Tikosyn is only available to hospitals and prescribers who have received appropriate Tikosyn dosing and treatment-initiation education.

Can I prescribe Tikosyn for patients with renal or hepatic dysfunction?

Tikosyn is CONTRAINDICATED for patients with a creatinine clearance <20 ml/min. Dose reduction is required for patients with a CLCr of 20-60 mL/min. (See Tikosyn (dofetilide) Dosing Algorithm).

No additional dose reduction is required for patients with mild to moderate hepatic impairment. Patients with severe hepatic dysfunction have not been studied and caution should be used in prescribing Tikosyn for these patients.

What are the potential adverse events?

Tikosyn can cause serious ventricular arrhythmias, primarily torsades de pointes which is associated with QT-interval prolongation. (see Warning in full prescribing information)

The most common adverse effects reported with Tikosyn are headache, chest pain and dizziness. (see full prescribing information for a complete list of adverse events)

Are adverse events dose-related?

Tikosyn induced ventricular arrhythmia (e.g. torsades de pointes) is associated with QT-interval prolongation and is directly related to the plasma concentration of Tikosyn. Reduced creatinine clearance or certain drug interactions (see drug-drug interactions) will increase Tikosyn plasma concentration and increase risk for development of serious ventricular arrhythmia.

Other adverse events are not observed to be dose-related.

What hemodynamic effects occur with Tikosyn?

Tikosyn has no negative inotropic effects and no effect on cardiac output, cardiac index, stroke volume index or systemic vascular resistance. In the overall clinical program for Tikosyn there was no effect on blood pressure and heart rate was decreased by 4 to 6 beats per minute.

Are there any potential drug-drug interactions?

Tikosyn use is contraindicated in combination with verapamil, cimetidine, trimethoprim (alone or in combination with sulfamethoxazole) or ketoconazole as each of these drugs causes a substantial increase in Tikosyn plasma concentrations. Other known inhibitors of renal cation transport such as prochlorperazine and megestrol should not be used in patients on tikosyn.

The concomitant use of hydrochlorothiazide with Tikosyn is also contraindicated because this has been shown to significantly increase Tikosyn plasma concentrations and QT interval prolongation.

How is TIKOSYN dosed?

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 3 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.

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. In clinical trials, potassium levels were generally maintained above 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.

What is the typical dosage for maintenance of NSR?

In 2, large, randomized clinical trials Tikosyn 500 mcg BID was significantly better than placebo at maintaining patients in NSR for 1 year. The recommended dosage of 500 mcg BID should be adjusted for CLCr and QTc response to therapy according the Tikosyn Dosing Algorithm.

Are there any dose adjustments for special populations?

Patients with heart disease (supraventricular and ventricular arrhythmias, ischemic heart disease, or congestive heart failure) have similar pharmacokinetics to healthy volunteers after adjusting for renal function. There is no additional dose adjustment required for elderly patients beyond the recommended adjustments for ClCr and QTc response to therapy. Women have approximately 12% to 18% lower clearance of oral Tikosyn than men after correction for weight and ClCr. Hormone replacement in female volunteers did not increase Tikosyn plasma concentrations. Dosing should be guided by the Tikosyn Dosing Algorithm.

What doses of TIKOSYN are available?

TIKOSYN is available in 3 dosages: 500 mcg, 250 mcg, and 125 mcg, and is available in bottles of 40 units in hospital pharmacies and 60 capsules in retail pharmacies.

What are contraindications for use of TIKOSYN?

TIKOSYN is contraindicated with verapamil, hydrochlorothiazide (alone or in combination, such as with triamterene), and cation transport inhibitors such as cimetidine, ketoconazole, trimethoprim (alone or in combination with sulfamethoxazole), prochlorperazine, and megestrol.

TIKOSYN is also contraindicated in patients with congenital or acquired QT syndromes, severe renal impairment, or known hypersensitivity to TIKOSYN. Click here to see a list of contraindications for use of TIKOSYN.

How does Tikosyn affect mortality in patients with heart failure?

Survival data from large, double-blind trials (DIAMOND-CHF and DIAMOND-MI) showed that 1-year mortality rates were 36% (541 of 1511 patients) with Tikosyn and 37% (560 of 1517 patients) with placebo. In an analysis of 506 high-risk patients with significant heart failure (LVEF<35%) and atrial fibrillation/flutter at baseline the 1-year mortality on Tikosyn was 31% versus 32% on placebo.

Does allowing retail pharmacies to provide/dispense TIKOSYN eliminate the need to hospitalize the patient upon initiation?

No. According to the TIKOSYN boxed warning, to minimize the risk of induced arrhythmia, TIKOSYN should be reserved for patients who are highly symptomatic, and patients initiated or re-initiated on TIKOSYN should be placed for a minimum of 3 days in a hospital or other facility that can calculate creatinine clearance, and provide continuous electrocardiographic monitoring and cardiac resuscitation. TIKOSYN is still available only to hospitals and prescribers who have received appropriate TIKOSYN dosing and treatment initiation education.

Do I still need to fill out pharmacy patient enrollment forms if the patient will be receiving the drug from a retail pharmacy?

No. However, we encourage physicians to inform their patients, prior to hospitalization, to let their local pharmacies know that they will be started on TIKOSYN. This will allow the pharmacies adequate time to enroll in the program and to order the product when the patient is discharged. Cards providing T.I.P.S. program information are available for patients to give to their local pharmacies and are included in the Patient Resource Kit.

Are materials available for patients to use to inform their retail pharmacies about this program?

Yes. Please call 1-877-TIKOSYN (845-6796) to request materials, or visit our website at www.Tikosyn.com.

How can I obtain TIKOSYN patient-education or physician-related materials?

To obtain patient-education or physician-related materials, please call 1-877-TIKOSYN (845-6796) or visit our website at www.Tikosyn.com for immediate access to Tikosyn materials.

What is the T.I.P.S. program?

T.I.P.S.™ stands for TIKOSYN In Pharmacy System. The T.I.P.S. program is designed to allow retail pharmacies to stock and dispense TIKOSYN once they have been enrolled. Enrollment consists of signing an enrollment form that states the following:

The pharmacy acknowledges receipt of the T.I.P.S. program materials and that the appropriate staff in the pharmacy are aware that for each outpatient prescription for TIKOSYN:

The pharmacist will verify that a prescriber has participated in the TIKOSYN Education Distribution Program and is confirmed in the TIKOSYN database before dispensing by checking the database via the Interactive Voice Response (IVR) telephone number, 1-800-788-7353, or the Web site, http://www.tikosynlist.com/.

The pharmacist will stamp each prescription for distribution with the T.I.P.S.™ stamp, verifying that the prescriber is a confirmed participant in the TIKOSYN Education Distribution Program. The pharmacist will then initial and date the stamped prescription in the appropriate areas.

A copy of the above information is posted or otherwise made available to pharmacy staff to ensure that the staff understands these special conditions for use of TIKOSYN.

Please note that the T.I.P.S.™ Program Administrator has implemented a process whereby a sample of prescriptions for TIKOSYN is retroactively matched against the TIKOSYN Confirmed Participant Database to assure compliance with these conditions.

How can a retail pharmacy enroll in the T.I.P.S. program?

Complete and submit the online T.I.P.S. Enrollment Form and order a T.I.P.S. Information Kit from this website.

Call 1-877-TIKOSYN (845-6796) to request a T.I.P.S. Enrollment and Information Kit.

What steps do I need to follow to dispense TIKOSYN?

The first step is enrollment. Access the retail pharmacy link on this website; complete and submit the T.I.P.S. Program Enrollment Form. Additionally, for your convenience, the T.I.P.S. Program Kit can also be ordered through this website.

Contact our Customer Service Representative at 1-877-TIKOSYN (845-6796) and request a T.I.P.S. Enrollment and Program Kit. This kit includes everything you need to participate in the T.I.P.S. program:

Fax-back enrollment form
Easy-to-follow instructions for ordering and dispensing TIKOSYN
T.I.P.S.™ information to post in the pharmacy for your staff
T.I.P.S.™ Prescription Stamp

You can confirm enrollment after 1 or 2 business days by calling 1-877-TIKOSYN (845-6796) or checking online at: http://www.tikosynlist.com/. Pharmacists will need to enter their DEA or NABP number.

How can I find out which retail pharmacies are enrolled in the program and can stock and dispense TIKOSYN?

Patients and physicians can call 1-877-TIKOSYN and speak to a Customer Service Representative (CSR) to find out if a pharmacy is enrolled in T.I.P.S. The CSR can provide this information when given the name, address, or ZIP code for the pharmacy. If a pharmacy is not enrolled in the T.I.P.S. program, the pharmacist can call 1-877-TIKOSYN to learn how to enroll and order TIKOSYN.

To find out if a pharmacy stocks TIKOSYN, the patient or physician must call the pharmacy directly. The CSR at 1-877-TIKOSYN can provide the name/number of the enrolled pharmacy.

Can TIKOSYN be ordered from my wholesaler?

TIKOSYN is not stocked by your wholesaler, but must be ordered through your wholesaler. See ordering steps below:

Order TIKOSYN through your wholesaler
TIKOSYN orders faxed by your wholesaler are processed during normal Pfizer Customer Service business hours—Monday through Friday 7:00AM to 6:00PM Central Time
Pfizer will verify pharmacy enrollment and drop-ship TIKOSYN to pharmacy

For further information on how to order TIKOSYN, please call a Customer Service Representative at 1-877-TIKOSYN (845-6796)

Will the current mail-order program still be available for my TIKOSYN patients who prefer to receive their drug from PharmaCare Specialty Pharmacy?

Yes. The PharmaCare Specialty Pharmacy mail-order program will continue to be available to patients who prefer to receive their medication through PharmaCare. Upon patient discharge, PharmaCare requires the pharmacy enrollment form be completed and faxed along with the prescription, to PharmaCare Specialty Pharmacy.

Do physicians still need to participate in the TIKOSYN program before they can prescribe the drug?

Yes. To comply with the TIKOSYN boxed warning, only confirmed participants in the TIKOSYN program will be able to prescribe TIKOSYN. The retail pharmacist will be responsible for checking the TIKOSYN Confirmed Prescriber Database.

How can I check if a prescriber has been confirmed in the TIKOSYN program?

Before dispensing a TIKOSYN prescription, pharmacists must confirm that the prescriber is a Healthcare professional who has participated in the TIKOSYN Education Distribution Program and is listed in the TIKOSYN confirmed database.

To verify that a prescriber is a participant in the program, pharmacists will need to access the program database by phone at 1-800-788-7353 or online at www.tikosynlist.com and enter their pharmacy DEA number.
At the prompt, pharmacists will need to enter the prescriber’s DEA or medical license number.
The message will state whether the DEA number belongs to a prescriber who is a confirmed participant in the TIKOSYN Education Distribution Program.
After verification, pharmacists will stamp the back of the prescription with the stamp and put their initials and the date in the spaces provided.
Pharmacists should dispense TIKOSYN as prescribed in accordance with standard pharmacy practice.
Pharmacists should not dispense TIKOSYN if prescriber participation in the TIKOSYN Education Distribution Program cannot be verified.
Pharmacists should ask these prescribers to call 1-877-TIKOSYN to speak to a TIKOSYN Customer Service Representative.

I lost the stamp. How can I get another one?

If you have lost your stamp, you can simply contact 1-877-TIKOSYN to request a new one.

I have 2 pharmacies. Do I have to enroll both of them?

If each pharmacy has a different DEA number, and is going to stock and dispense TIKOSYN, you will need to enroll both pharmacies.

I cannot work this IVR system, and I have no access to a Web site. What should I do?

When you call the IVR line, you must first press the "*" button before pressing the button corresponding to the FIRST letter of the DEA number. You will be given a choice of which letter is the FIRST letter of the DEA number (eg, A=1, B=2). After you make the choice for the FIRST letter of the DEA number, press the "*" button again before pressing the button corresponding to the SECOND letter of the DEA number. You will then be given a choice again of which letter is the SECOND letter of the DEA number, as in the above example. Enter the rest of the DEA numbers and end by pressing the "#" button.

For example: AB 246813

Press the “*” button.

You will hear: Press “1” for letter “A” and press “2” for letter “B.”

• Then press “1.”

• Then press the “*” button.

• You will hear: Press “1” for letter “A” and press “2” for letter “B.”

• Then press “2.”

• Then enter 246813.

• Finally, press the “#” button. At that point you will hear the confirmation of the pharmacy. To confirm a prescriber, the DEA number has to be entered following the same sequence. There is a choice to enter a medical license number in place of a DEA number.

Whom can I call for additional information?

For additional information and Tikosyn materials, please call 1-877-TIKOSYN (845-6796) or visit our website at www.Tikosyn.com.

TIKOSYN is indicated for the maintenance of normal sinus rhythm in patients with atrial fibrillation/atrial flutter of greater than one week duration who have been converted to normal sinus rhythm.

TIKOSYN is indicated for the conversion of atrial fibrillation/atrial flutter to normal sinus rhythm.

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). TIKOSYN is available only to hospitals and prescribers who have received appropriate TIKOSYN dosing and treatment initiation education (see DOSAGE AND ADMINISTRATION). For full Prescribing information, please click here.

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