Dofetilide (Page 8 of 9)

Instructions for Individualized Dose Initiation

Initiation of Dofetilide Therapy

Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QTc or QT must be checked using an average of 5 beats to 10 beats. If the QTc or QT is greater than 440 msec (500 msec in patients with ventricular conduction abnormalities), dofetilide 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 dofetilide is determined as follows:

Calculated Creatinine ClearanceDofetilide Dose
> 60 mL/min 500 mcg twice daily
40 mL/min to 60 mL/min 250 mcg twice daily
20 mL/min to < 40 mL/min 125 mcg twice daily
< 20 mL/min Dofetilide is contraindicated
in these patients

Step 4. Administer the adjusted dofetilide dose and begin continuous ECG monitoring.

Step 5. At 2 hours to 3 hours after administering the first dose of dofetilide, 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 daily250 mcg twice daily
250 mcg twice daily125 mcg twice daily
125 mcg twice daily125 mcg once a day

Step 6. At 2 hours to 3 hours after each subsequent dose of dofetilide, determine the QTc or QT (if heart rate is less than 60 beats per minute) (for in-hospital doses 2 to 5). No further down titration of dofetilide based on QTc or QT is recommended.

NOTE: If at any time after the second dose of dofetilide is given the QTc or QT is greater than 500 msec (550 msec in patients with ventricular conduction abnormalities), dofetilide 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:

Diagram
(click image for full-size original)

Maintenance of Dofetilide Therapy

Renal function and QTc or QT (if heart rate is less than 60 beats per minute) should be re‑evaluated every three months or as medically warranted. If QTc or QT exceeds 500 milliseconds (550 msec in patients with ventricular conduction abnormalities), dofetilide therapy should be discontinued and patients should be carefully monitored until QTc or QT returns to baseline levels. If renal function deteriorates, adjust dose as described in Initiation of dofetilide 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 dofetilide. In clinical trials (see CLINICAL STUDIES), the highest dose of 500 mcg BID of dofetilide 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 dofetilide therapy, electrical conversion should be considered. Patients continuing on dofetilide 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 dofetilide therapy, whichever is greater.

Switch to Dofetilide from Class I or other Class III Antiarrhythmic Therapy

Before initiating dofetilide 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, dofetilide 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 Dofetilide Prior to Administration of Potentially Interacting Drugs

If dofetilide 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).

HOW SUPPLIED

Dofetilide 125 mcg (0.125 mg) capsules are supplied as No. 4 capsules with opaque light orange cap and opaque white body, printed with ‘125 mcg’ in black ink on body and “710” in black ink on cap and are available in:

Dofetilide 250 mcg (0.25 mg) capsules are supplied as No. 4 capsules with opaque peach cap and opaque peach body, printed with ‘250 mcg’ in black ink on body and “711” in black ink on cap and are available in:

Dofetilide 500 mcg (0.5 mg) capsules are supplied as No. 2 capsules with opaque peach cap and opaque white body, printed with ‘500 mcg’ in black ink on body and “712” in black ink on cap and are available in:

125 mcg (0.125mg) 250 mcg (0.25 mg) 500 mcg (0.5 mg)
Obverse ‘125 mcg’ ‘250 mcg’ ‘500 mcg’
Reverse “710” “711” “712”
Bottle of 60 69452-131-17 69452-132-17 69452-133-17

Store at controlled room temperature, 15° to 30°C (59° to 86°F).

PROTECT FROM MOISTURE AND HUMIDITY.

Dispense in tight containers (USP).

Rx Only

Distributed by: Bionpharma, Inc.
Princeton, NJ 08540

Made in India

948026787
Revised: 1/2023

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