What dofetilide does
Dofetilide is what we call a pure Class III antiarrhythmic. Unlike sotalol, it has no beta-blocker effect; unlike amiodarone, it doesn’t act on multiple channels. It does one thing — it blocks the IKr potassium channel in heart cells, which lengthens the time it takes for the cells to reset after each beat. That lengthening makes it harder for atrial fibrillation and flutter to sustain.
The narrowness of its action is both its strength (no thyroid, lung, or liver toxicity to worry about long-term) and its risk (the same lengthening shows up on the ECG as a longer QT interval, and a QT that becomes too long can trigger torsades de pointes, a dangerous ventricular arrhythmia). All of the rules around dofetilide exist to keep the QT in a safe range.
Dofetilide is sold in the United States as Tikosyn (dofetilide) by Pfizer.
Who we prescribe it for
We use dofetilide for one main purpose:
- Atrial fibrillation and atrial flutter — both to convert episodes back to normal rhythm and to maintain normal rhythm afterward.
It is particularly useful in patients who have structural heart disease (where flecainide and propafenone are off the table) and want to avoid amiodarone’s organ side effects. It is also a reasonable option in patients with heart failure with reduced ejection fraction, where many other rhythm drugs are not safe.
We do not use dofetilide in patients with significant kidney dysfunction (creatinine clearance under about 20), baseline QT prolongation, or a history of torsades.
Hospital initiation — the three-day admission
Dofetilide must be started in a hospital on a continuous cardiac monitor. This is required by the FDA-mandated program governing the drug — there is no outpatient version of this. Centers that prescribe it have specific training and protocols.
A typical admission looks like this:
- Baseline labs: kidney function, potassium, magnesium. Electrolytes must be normal.
- Baseline ECG to measure starting QT.
- First dose chosen by kidney function (usually 500 mcg twice daily for normal function, lower for reduced kidney function).
- ECG checked two to three hours after each of the first five doses.
- If the QT goes up too much after the first dose, we lower the dose; if it gets too long after a later dose, we stop the drug.
- Discharge on day three once five doses have been delivered and the QT has stayed in a safe range.
This may seem cumbersome but it is the only way to start dofetilide safely. Every restart after a long break uses the same protocol.
Dosing by kidney function
Dofetilide is cleared almost entirely by the kidneys. Dosing is tied tightly to creatinine clearance:
- CrCl above 60: 500 mcg twice daily.
- CrCl 40–60: 250 mcg twice daily.
- CrCl 20–39: 125 mcg twice daily.
- CrCl under 20: do not use.
If kidney function changes — from dehydration, a new medication, contrast for a scan, or progression of kidney disease — the dofetilide level can climb. We check kidney function at every follow-up and any time something has changed.
Drug interactions — the absolute “no” list
A few medications cause such dramatic increases in dofetilide levels that they are contraindicated — meaning we will not start dofetilide if you take them, and you must not take them while on dofetilide:
- Cimetidine (a common over-the-counter heartburn medication).
- Ketoconazole and itraconazole.
- Verapamil.
- Trimethoprim (often combined with sulfamethoxazole as Bactrim or Septra).
- Hydrochlorothiazide (in combination products).
- Prochlorperazine.
- Megestrol.
Beyond this list, anything else that prolongs the QT — certain antibiotics (azithromycin, levofloxacin), antifungals, antidepressants, antipsychotics, ondansetron, methadone — needs careful review. Always tell new prescribers you are on dofetilide. Tell pharmacy too — many pharmacies flag these combinations automatically.
Side effects to watch for
Dofetilide is well-tolerated in most patients. Side effects we hear about:
- Headache (most common).
- Chest pain or palpitations.
- Dizziness.
- Mild nausea or GI upset.
- Insomnia.
The serious concern is torsades de pointes — fainting, near-fainting, or a rhythm that feels different and faster than your usual AF should prompt urgent attention.
A meaningful advantage over amiodarone: dofetilide does not cause thyroid, lung, liver, eye, or skin toxicity, and the long-term monitoring burden is much lighter.
Monitoring
After discharge, we check an ECG at follow-up and any time a new interacting medication is started. Kidney function and electrolytes are checked at routine intervals — at least every six months, more often if circumstances change.
When to call us
Call urgently for fainting, near-fainting, palpitations that feel different from your usual rhythm, or any new medication starting that may interact. Always check with us first before adding antibiotics, antifungals, or new heart medications.
Manufacturer reference
For official prescribing information, indications, and the latest information on Tikosyn (dofetilide) from Pfizer, see the manufacturer’s medical information site: Tikosyn on pfizermedicalinformation.com. (External link — content there is the manufacturer’s and may be technical.)