Indication:
Ventricular tachycardia
Summary-
Indecainide is an effective class IC antiarrhythmic agent that may offer an alternative for
patients who cannot tolerate the GI side effects of quinidine or the CNS effects of other
class IC agents. Lily is recommending a dosage of 100mg to 200mg a day, and they plan
to market only the twice a day formulation( an immediate release form for 4 times daily
administratiion was also tested in clinical trials.
Because of recent findings of the Cardiac Arrhythmias Suppression Trials (CAST)
which reduced the indications for encainde and flecainide to treatment of life-threatening
arrhythmias only, Lily is reviewing their CAST study data to determine if there is any potential
relevance to indecainde
In November 1988, the FDAs Cardiac-Renal Drugs Advisory Committee unanimously
recommended approval of indecainide for sustained ventricular tachycardia,
ventricular fibrillation, nonsustained ventricular and chronic benign PVCs.Indecainde
was approved by FDA in December 1989. However, Lily has made a decision not to market
the drug at this time.
Adverse Reaction:
Side effects-
In clinical trials the following side effects were noticed-
Dizziness (18% with 200mg dose) 12% with 150mg ) proarrhythmias(14.8% )
congestive heart failure (3.9%) . Each affect appeared to be dose related
Other adverse reactions reported in the similar patient population studies included -
Headache, blurry vision, impotence, lightheadeness, confusion, thought disorders,
nausea and constipation. Most reactions mild and respond to dosage adjustment.
Pharmacology/ Pharmacokinetics:
Pharmacology-
Indecainde is a Class IC antiarrhythmic agent that is structurally similar to the investigational
agent aprindine. Other available Class IC antiarrhythmics are encainde (Enkaid) and
Flecainide( Tambocor). This class of drug markedly suppresses premature ventricular
complexes (PVCs) and depresses intramyocardial conduction.
Indecainde prolong the PR and QRS intervals, significantly increasing the intraventricular
conduction time without significantly affecting artial or ventricular refracoriness. There
appears to be no significant hemodynamic effects.
Pharmackinetics-
Indecainde is completely absorbed following oral administration. In animals the half-life
is 3 to 5 hours, however, the half-life in patients is considerably longer (9 to 10 hours)
suggesting that twice- daily dosing may be effective in some patients .
Indecainde is metabolised in the liver to desisopropyl indecainde. This metabolite
appears to have a longer half-life than the patent drug, althogh the plasma levels
of the metabolite are approximately 10% to those of indecainde. it is not known whether
desisopropyl indecaindepossess any antiarrhythmic effects.
Approximately 63% of indecainde is recovered in the urine with <10% recovered as
ventricular ectopic deploarizations and plasma levels or half-life of either indecainde
or the metabolite
Clinical trials-
Clinical information regarding the efficacy of indecainde is available only through
several studies using small patient populations. Antiarrhythmic efecicacy appear to be
similar to encainde and flecainde.
Efficacy was mainained in some patients for upto 2 years. Indecainde orally or
IV markedly suppresses the frequency of PVCs particularly repetitive forms.
In one study, 60% to 82% had more than 95% elimination of couplets and 56% to 74%
had complete elimination of ventricular tachycardia.
The average suppression of PVCs with most available antiarrhythmics ranges from
50% to 75%. The degree of supression was comparable to encainde and flecainde.
Other studies have reported a 90% reduction in PVCs in approximately 85% of the
patientsand elimination of ventricular tachcardia in 85% of the patients.
In a study involving 231 of the patients indecainide reduced PVC by 93% while
disopyramide reduced PVCs by 80%, the suppression of runs of ventricular tachycardia
were equivalent for both the drugs.
In a study of 11 patients, indecainde suppressed ventricular premature beats in 90% of
the patients, but suppresion of ventricular tachycardia was acheived only in 45% of patients
In data from five clinical trials through the manufacturer invloving 792 patients,70%
receiving indecainde responed to <200mg/day and 90% responded to 300mg/day
Manufacturer Details