Handbook of Drug Interactions

224 Auer
1.2.6. Flecainide (Class IC)
Proarrhythmic effects are one of the most important adverse effects of flecainide.
Its marked slowing of conduction precludes its use in patients with second-degree AV
block without a pacemaker and warrants cautious administration in patients with intraventricular
conduction disorders. Aggravation of existing ventricular arrhythmias or
onset of new ventricular arrhythmias can occur in 5–30% of patients, the increased percentage
in patients with preexisting sustained ventricular tachycardia, cardiac decompensation,
and higher doses of the drug. Failure of the flecainide-related arrhythmia
to respond to therapy, including electrical cardioversiondefibrillation, may result in a
mortality as high as 10% in patients who develop proarrhythmic events. Negative inotropic
effects can cause or worsen heart failure. Patients with sinus node dysfunction
may experience sinus arrest, and those with pacemakers may develop an increase in
pacing threshold. In the CAST, patients treated with flecainide had 5.1% mortality or
nonfatal cardiac arrest compared with 2.3% in the placebo group over 10 mo. Mortality
was highest in those with non-Q-wave infarction, frequent premature ventricular complexes,
and faster heart rates, raising the possibility of drug interaction with ischemia
and electrical instability. Exercise can amplify the conduction slowing in the ventricle
produced by flecainide and in some cases can precipitate a proarrhythmic response.
Therefore, exercise testing has been recommended to screen for proarrhythmia. CNS
complaints, including confusion and irritability, represent the most frequent noncardiac
adverse effect.
1.2.7. Propafenone (Class IC)
Minor noncardiac effects occur in about 15% of patients, with dizziness, disturbances
in taste, and blurred vision the most common and gastrointestinal side effects
next. Exacerbation of bronchospastic lung disease can occur. Cardiovascular side effects
occur in 10–15% of patients, including conduction abnormalities such as AV block,
sinus node depression, and worsening of heart failure. Proarrhythmic responses, more
often in patients with a history of sustained ventricular tachycardia and decreased ejection
fractions, appear less commonly than with flecainide and may be in the range of
5%. The applicability of data from the CAST about flecainide to propafenone is not
clear, but limiting propafenone’s application in a manner similar to other IC drugs seems
prudent at present until more information is available. Its beta-blocking actions may
make it different, however.
1.2.8. Moricizine (Class IC)
Usually the drug is well tolerated. Noncardiac adverse effects primarily involve the
nervous system and include tremor, mood changes, headache, vertigo, nystagmus, and
dizziness. GI side effects include nausea, vomiting, and diarrhea. Worsening of congestive
heart failure is uncommon but can happen. Proarrhythmic effects have been reported
in about 3–15% of patients and appear to be more common in patients with severe ventricular
arrhythmias. Advancing age increases the susceptibility to adverse effects.
1.2.9. -Blockers (Class II)
Adverse cardiovascular effects from propranolol include unacceptable hypotension,
bradycardia, and congestive heart failure. The bradycardia may be due to sinus