ANNE ARUNDEL MEDICAL CENTER
CRITICAL CARE MEDICATION MANUAL
DEPARTMENT OF NURSING AND PHARMACY
Guidelines for Initiation of Oral Dofetilide (Tikosyn®)
Use Limited to Progressive and Critical Care Units
Indication
For pharmacologic conversion and maintenance of atrial fibrillation/flutter in highly
symptomatic patients with atrial fibrillation/flutter greater than 1 week..
Note: Dofetilide doses may only be ordered by physicians who are registered with the
manufacturer as having completed Tikosyn prescribing education. Orders by non-approved
physicians are not valid. The pharmacy has a list of currently-approved physicians.
Pre-printed orders, available in Tikosyn information packets on the units, are mandatory
for initiating Tikosyn at AAMC.
Mechanism of Action
Dofetilide is an antiarrhythmic drug with predominantly class III properties. Dofetilide prolongs
atrial and ventricular monophasic action potential duration due to delayed repolarization. The
dose-related increase in QT/QTc interval is due to prolonged effective and functional
refractoriness in the His-Purkinje system and the ventricles.
Special Administration and Monitoring Techniques
·
Use of dofetilide on the PCU AND Critical Care Unit requires strict adherence to the
manufacturer’s initiation, dosing, and monitoring guidelines. The steps required to
initiate therapy are outlined below, however details of the process and forms are in
information packets available on the PCU and Critical Care units
1. Patients who have Tikosyn initiated must remain hospitalized for 3 days or for 12 hours
following conversion to NSR, whichever is longer.
2. If patients will be obtaining Tikosyn through the mail-order syatem, patients should be
registered via ProCare Pharmacy Pharmacy Services Enrollment Form as soon as it is
decided that Tikosyn will be initiated, preferably from the physicians’ offices prior to
admission. The enrollment form may be found in the information packet on the units.
3. Contraindications - Tikosyn should not be used in patients with:
baseline QTc > 440 msec (or > 500 msec if pre-existing ventricular
conduction defect exists)
Creatinine Clearance < 20 ml/min
pre-existing congenital or acquired QT prolongation
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(contraindications cont.)
-
-
recent antiarrhythmics if:
< 3 half-lives since D/C the previous antiarrhythmic
< 3 months since D/C amiodarone (or Tikosyn OK if documented
amiodarone level is < 0.3 mg/L)
current use of: cimetidine (Tagamet), trimethoprim (Bactrim, Septra,
SMZ-TMP), ketoconazole (Nizoral), verapamil (Calan, Isoptin), megestrol
(Megace), prochlorperazine (Compazine), hydrochlorothiazide (HCTZ,
HCTZ combination products) or medications that can prolong QT interval
(phenothiazines, cisapride, bepridil, tricyclic antidepressants, and certain
macrolide (erythromycin-type) antibiotics.
4. Baseline EKG, creatinine (to calculate creatinine clearance), and electrolytes must be
determined on admission. Hypokalemia (K < 4.0) and hypomagnesemia (Mg < 2.0) must
be corrected prior to administration of Tikosyn.
5. Creatinine clearance must be calculated to allow determination of the starting dose (see
information packet or Dosing below).
6. Continuous EKG monitoring is required during the 3 day initiation process.
7. A 12-lead EKG must be obtained 2-3 hours after EACH dose of Tikosyn, and evaluated
for QTc prolongation by a cardiologist, prior to administration of the following dose.
Evaluation of the EKG is essential in determining whether it is safe to continue with the
medication or, in the case of the first dose only, a dose adjustment is needed. If QTc
exceeds > 15% of baseline or > 500 msec any time following the second or subsequent
doses, Tikosyn must be discontinued! For these reasons, only orders for single doses will
be accepted by the pharmacy (standing “Tikosyn __mg BID” orders are invalid).
8. Patients must receive the Tikosyn Patient Education box containing literature for patients,
other health professionals, and a video.
9. If a patient is going to use the mail-order pharmacy, a prescription must be faxed to the
ProCare Pharmacy prior to discharge. If the patient has access to an approved retail
pharmacy (TIPS program), a standard prescription may be written for the Tikosyn.
10. Prior to discharge home, patients must be given a 7 day supply of Tikosyn. The
prescribing physician should write prescription information on an inpatient order form;
the pharmacy will fill the 7 day prescription and send it to the unit to give to the patient
before leaving.
·
Use of pre-printed orders, available in packet, facilitates following these initiation steps.
·
Dofetilide may be pro-arrhythmic and can cause fatal arrhythmias, in particular torsades
de pointes (see Adverse Effects).
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Dosage and Administration
1. Dofetilide should be dosed as close to every 12 hours as possible (as opposed to BID).
2. The initial dose is based upon estimated creatinine clearance:
Creatinine Clearance Starting Tikosyn Dose
> 60 ml/min
500 mcg q 12 hrs
40-60 ml/min
250 mcg q 12 hrs
20-<40 ml/min
125 mcg q 12 hrs
< 20 ml/min
Contraindicated
3. The dose of Tikosyn may be reduced one time only: following the first dose if the 2-3 hour
QTc is > 500 msec (or > 15% baseline). For all further hospital doses, the drug is to be
discontinued if QTc exceeds these limits.
4. Therapy should not be interrupted for any reason unless the drug is to be discontinued. If
therapy is interrupted, the patient must begin the entire process, including the 3 day
hospitalization, over!
Precautions
Numerous potential serious drug interactions exist (see Contraindications) and must be addressed
before and during therapy with Tikosyn.
Tikosyn is eliminated to a small extent by the CYP 3A4 isoenzyme of the cytochrome P450
system. Drugs which are known to interfere with this system may decrease Tikosyn elimination.
Adverse Effects
Dofetilide can cause potentially fatal arrhythmias, particularly sustained polymorphic ventricular
tachycardia, usually in association with QT prolongation (torsades de pointes), but sometimes
without documented QT prolongation. It is essential that dofetilide be administered in the setting
of continuous EKG monitoring and by personnel trained in the identification and treatment of
acute ventricular arrhythmias, particularly polymorphic VT. Most cases of polymorphic VT
respond to overdrive pacing and intravenous magnesium infusion, however degeneration to VF
requiring defibrillation may occur.
Other common side effects include: headache, dizziness, insomnia, chest pain, dyspnea, nausea,
diarrhea, abdominal pain, flu-like symptoms, back pain, rash.
Comments
Patients with atrial fibrillation should be anticoagulated according to usual medical practice prior
to electrical or pharmacologic cardioversion.
Patients must be educated concerning potential drug interactions, side effects, and the importance
of not stopping therapy unless advised by their physician.
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