(dofetilide)
DOSAGE AND ADMINISTRATION
DOSAGE AND ADMINISTRATION
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- 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.
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- 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.
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- 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.
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- 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).
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- 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 |
creatinine clearance (female) = | (140-age) × actual body weight in kg × 0.85 |
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 |
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 or QT (if heart rate is less than 60 beats per minute) (for in-hospital doses 2–5). No further down titration of Tikosyn based on QTc or QT is recommended.
NOTE: If at any time after the second dose of Tikosyn is given the QTc or QT 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:
Maintenance of TIKOSYN 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), TIKOSYN 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 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.
MEDICATION GUIDE
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:
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- feel faint
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- become dizzy, or
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- 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:
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- have an irregular heartbeat called long QT syndrome
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- have kidney problems or are on kidney dialysis
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- take any of these medicines:
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- cimetidine (TAGAMET, TAGAMET HB)1
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- verapamil (CALAN, CALAN SR, COVERA-HS, ISOPTIN, ISOPTIN SR, VERELAN, VERELAN PM, TARKA)1
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- ketoconazole (NIZORAL, XOLEGEL, EXTINA)1
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- trimethoprim alone (PROLOPRIM, TRIMPEX)1 or the combination of trimethoprim and sulfamethoxazole (BACTRIM, SEPTRA SULFATRIM)1
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- prochlorperazine (COMPAZINE, COMPO)1
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- megestrol (MEGACE)1
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- dolutegravir (TIVICAY)1
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- hydrochlorothiazide alone or in combination with other medicines (such as ESIDRIX, EZIDE, HYDRODIURIL, HYDRO-PAR, MICROZIDE, or ORETIC)1
- Ask your doctor if you are not sure if any of your medicines are the kind listed above.
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- 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:
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- have heart problems
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- have kidney or liver problems
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- are pregnant or plan to become pregnant. It is not known if TIKOSYN will harm your unborn baby.
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- 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:
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- heart problems
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- high blood pressure
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- depression or other mental problems
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- asthma
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- allergies, or hay fever
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- skin problems
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- 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?
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- Take TIKOSYN exactly as your doctor tells you.
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- Do not change your TIKOSYN dose unless your doctor tells you to.
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- Your doctor will do tests before you start and while you take TIKOSYN.
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- 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.
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- TIKOSYN can be taken with or without food.
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- 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 doctor.
What are the possible side effects of TIKOSYN?
TIKOSYN can cause serious side effects, including a type of abnormal heartbeat called Torsade de Pointes, which can lead to death. See "What is the most important information I should know about TIKOSYN?"
The most common side effects of TIKOSYN include:
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- headache
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- chest pain
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- dizziness
Call your doctor right away if you have signs of electrolyte imbalance:
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- severe diarrhea
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- unusual sweating
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- vomiting
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- not hungry (loss of appetite)
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- increased thirst (drinking more than normal)
Tell your doctor if you have any side effects that bother you or do not go away.
These are not all the possible side effects of TIKOSYN. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store TIKOSYN?
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- Store TIKOSYN between 59° to 86°F (15° to 30°C).
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- Keep TIKOSYN away from moisture and humidity.
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- Keep TIKOSYN in a tightly closed container.
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- Keep TIKOSYN and all medicines out of the reach of children.
General information about TIKOSYN
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TIKOSYN for a condition for which it was not prescribed. Do not give TIKOSYN to other people, even if they have the same symptoms you have. It may harm them.
This Medication Guide summarizes the most important information about TIKOSYN. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about TIKOSYN that is written for health professionals.
For more about TIKOSYN, go to www.tikosyn.com or call 1-877-TIKOSYN (1-877-845-6796).
What are the ingredients in TIKOSYN?
Active ingredient: dofetilide
Inactive ingredients:
- Capsule fill: microcrystalline cellulose, corn starch, colloidal silicon dioxide, and magnesium stearate
- Capsule shell: gelatin, titanium dioxide, and FD&C Yellow 6
- Imprinting ink: iron oxide black, shellac, n-butyl alcohol, isopropyl alcohol, propylene glycol, and ammonium hydroxide
- 1
- Listed trademarks are the property of their respective owners.
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