(dofetilide)
The TIKOSYN clinical program involved approximately 8,600 patients in 130 clinical studies of normal volunteers and patients with supraventricular and ventricular arrhythmias. TIKOSYN was administered to 5,194 patients, including two large, placebo-controlled mortality trials (DIAMOND CHF and DIAMOND MI) in which 1,511 patients received TIKOSYN for up to three years.
In the following section, adverse reaction data for cardiac arrhythmias and non-cardiac adverse reactions are presented separately for patients included in the supraventricular arrhythmia development program and for patients included in the DIAMOND CHF and MI mortality trials (see CLINICAL STUDIES, Safety in Patients with Structural Heart Disease, DIAMOND Studies, for a description of these trials).
In studies of patients with supraventricular arrhythmias, a total of 1,346 and 677 patients were exposed to TIKOSYN and placebo for 551 and 207 patient years, respectively. A total of 8.7% of patients in the dofetilide groups were discontinued from clinical trials due to adverse events compared to 8.0% in the placebo groups. The most frequent reason for discontinuation (>1%) was ventricular tachycardia (2.0% on dofetilide vs. 1.3% on placebo). The most frequent adverse events were headache, chest pain, and dizziness.
Torsade de Pointes is the only arrhythmia that showed a dose-response relationship to TIKOSYN treatment. It did not occur in placebo treated patients. The incidence of Torsade de Pointes in patients with supraventricular arrhythmias was 0.8% (11/1346) (see WARNINGS). The incidence of Torsade de Pointes in patients who were dosed according to the recommended dosing regimen (see DOSAGE AND ADMINISTRATION) was 0.8% (4/525). Table 6 shows the frequency by randomized dose of serious arrhythmias and conduction disturbances reported as adverse events in patients with supraventricular arrhythmias.
| TIKOSYN Dose | Placebo | ||||
|---|---|---|---|---|---|
| Arrhythmia event: | <250 mcg BID N=217 | 250 mcg BID N=388 | >250–500 mcg BID N=703 | >500 mcg BID N=38 | N=677 |
3.7% | 2.6% | 3.4% | 15.8% | 2.7% | |
Ventricular fibrillation | 0 | 0.3% | 0.4% | 2.6% | 0.1% |
Ventricular tachycardia† | 3.7% | 2.6% | 3.3% | 13.2% | 2.5% |
Torsade de Pointes | 0 | 0.3% | 0.9% | 10.5% | 0 |
Various forms of block | |||||
AV block | 0.9% | 1.5% | 0.4% | 0 | 0.3% |
Bundle branch block | 0 | 0.5% | 0.1% | 0 | 0.1% |
Heart block | 0 | 0.5% | 0.1% | 0 | 0.1% |
In the DIAMOND trials, a total of 1,511 patients were exposed to TIKOSYN for 1757 patient years. The incidence of Torsade de Pointes was 3.3% in CHF patients and 0.9% in patients with a recent MI.
Table 7 shows the incidence of serious arrhythmias and conduction disturbances reported as adverse events in the DIAMOND subpopulation that had AF at entry to these trials.
| TIKOSYN | Placebo | |
|---|---|---|
| N=249 | N=257 | |
14.5% | 13.6% | |
Ventricular fibrillation | 4.8% | 3.1% |
Ventricular tachycardia† | 12.4% | 11.3% |
Torsade de Pointes | 1.6% | 0 |
Various forms of block | ||
AV block | 0.8% | 2.7% |
(Left) bundle branch block | 0 | 0.4% |
Heart block | 1.2% | 0.8% |
Table 8 presents other adverse events reported with a frequency of >2% on TIKOSYN and reported numerically more frequently on TIKOSYN than on placebo in the studies of patients with supraventricular arrhythmias.
| TIKOSYN | Placebo | |
|---|---|---|
| Adverse Event | % | % |
|
|
|
headache | 11 | 9 |
chest pain | 10 | 7 |
dizziness | 8 | 6 |
respiratory tract infection | 7 | 5 |
dyspnea | 6 | 5 |
nausea | 5 | 4 |
flu syndrome | 4 | 2 |
insomnia | 4 | 3 |
accidental injury | 3 | 1 |
back pain | 3 | 2 |
procedure (medical/surgical/health service) | 3 | 2 |
diarrhea | 3 | 2 |
rash | 3 | 2 |
abdominal pain | 3 | 2 |
Adverse events reported at a rate >2% but no more frequently on TIKOSYN than on placebo were: angina pectoris, anxiety, arthralgia, asthenia, atrial fibrillation, complications (application, injection, incision, insertion, or device), hypertension, pain, palpitation, peripheral edema, supraventricular tachycardia, sweating, urinary tract infection, ventricular tachycardia.
The following adverse events have been reported with a frequency of ≤2% and numerically more frequently with TIKOSYN than placebo in patients with supraventricular arrhythmias: angioedema, bradycardia, cerebral ischemia, cerebrovascular accident, edema, facial paralysis, flaccid paralysis, heart arrest, increased cough, liver damage, migraine, myocardial infarct, paralysis, paresthesia, sudden death, and syncope.
The incidences of clinically significant laboratory test abnormalities in patients with supraventricular arrhythmias were similar for patients on TIKOSYN and those on placebo. No clinically relevant effects were noted in serum alkaline phosphatase, serum GGT, LDH, AST, ALT, total bilirubin, total protein, blood urea nitrogen, creatinine, serum electrolytes (calcium, chloride, glucose, magnesium, potassium, sodium), or creatine kinase. Similarly, no clinically relevant effects were observed in hematologic parameters.
In the DIAMOND population, adverse events other than those related to the post-infarction and heart failure patient population were generally similar to those seen in the supraventricular arrhythmia groups.
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:
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:
What should I tell my doctor before taking TIKOSYN?
Before taking TIKOSYN, tell your doctor about all of your medical conditions including if you:
Especially tell your doctor if you take medicines to treat:
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?
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:
Call your doctor right away if you have signs of electrolyte imbalance:
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?
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:
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