ECTRIMS 2012 (Lyon, France)
Poster 529: Thursday, October 11, 2012, 15:30 - 17:00
Click on poster (below) to download:
Background:
Recent safety concerns regarding the risk for bradyarrhythmia with
fingolimod has resulted in U.S. Food and Drug Administration (FDA)
changes to the package insert (PI) for the only oral MS disease
modifying drug. Previously the PI listed no contraindications, while the
04/2012 version lists treatment with Class Ia anti-arrhythmic drugs
among the new contraindications. Fixed dose dextromethorphan/quinidine
(DM/Q) is FDA approved for the treatment of pseudobulbar affect (PBA),
which is increasingly recognized as a common MS symptom. Quinidine at
very low doses (10 mg twice a day) blocks CYP2D6 metabolism of DM, thus
allowing this NMDA receptor antagonist and sigma-1 agonist to enter the
central nervous system and exert its therapeutic effect. Qunidine causes
dose-dependant QTc (corrected Q-T interval) prolongation, but the doses
of Q used in the combination treatment for PBA is over 10-fold lower
than the doses used for cardiac arrhythmias.
Rationale:
Despite the unlikelihood of any interaction between fingolimod and fixed
dose DM/Q for PBA, fingolimod’s PI change, no longer allows concomitant
treatment with these medications. Since no patients in the pivotal
phase III trials for either medication were treated with the other, the
current study is aimed at exploring the experience of a single MS Center
with concomitant use of these medications, prior to the PI update in
April 2012.
Methods:
Retrospective case series of six MS patients at a single MS
Center treated with concomitant fingolimod and fixed dose DM/Q.
Results:
The mean length of time between starting fingolimod and starting DM/Q
was 5 months (range: 1 – 8). There were no symptomatic bradycardias
during either the first dose administration of fingolimod or subsequent
to the initiation of DM/Q. Two weeks after initiation of DM/Q, the
median decrease in heart rate and increase in QTc was 7 bpm and 14.5
msec (and QTc was never greater than 427 msec). Aside from improvement
in their PBA, the following other improvements were reported with
initiation of DM/Q: improved cognition, concentration, energy and
initiation/completion of tasks, with reduction in spasticity, fatigue
and feeling of being overwhelmed from pain.
Conclusion:
Initiating DM/Q in fingolimod-treated patients may be safe and
effective. PBA is a potentially disabling MS symptom and there is a need
to clarify whether the recent change to fingolimod’s PI should exclude
concomitant treatment with DM/Q. Further controlled safety trials of
concomitant fingolimod and DM/Q is needed.
- Dr. Daniel Kantor, MD
Medical Director
Neurologique
info@neurologique.org
www.neurologique.org
Posts
