Sunday, September 02, 2012

MS notes AAN meeting Gilenya 2012

Jeffrey Cohen on Gilenya
1. O.5 mg daily is only approved dose, lower doses are being tested
2. May take a month or more to completely clear out of system
3. Caution in patients with severe liver disease
4.  Drug interactions occur with inhibitors of liver metabolism, esp ketoconazole; drugs that lower heart rate (beta blockers and calcium channel blockers), drugs that affect QT interval esp amiodarone, other antiarryhtmics which could cause Q onT phenomenon and tachyarrythmias. 
5.  In their center they weight at least three months to switch onto gilenya from natalizumab, etanercept and other antiimmunosuppressants
6.  Freedoms, about 50 % decrease in relapses, slowing brain atrophy, disability v. avonex and placebo
7.  Musculoskeletal side effects including back pain and others is common.
8.  Lymphocyte counts come back within 1-2 months after stopping drugs, although it is longer in some patients.
9.  Relationship between lymphocyte count in blood and infections is tenuous or nonexistant, tend to ignore .
10.  Case of PML reported : details dx ms in 2007, treated with interferon, then natalizumab in 2008, found to be seropositive to JCV antibody in 2011 and changed to Gilenya.  MRI at that time showed one new lesion, which actually was likely first PML episode.  Later treated with steroids for a relapse, no benefit, visual changes led to stopping gilenya after fourteen weeks, PML found, but was there before starting drug.
11.  HR stays abnormal for up to a month and gradually returns to normal.
12.  Holter before hand is useless
13.  Patient death 23 hours after first dose in November 2011: details:  EMA (Europe) and FDA reviewed.  Recommendations are similar.  CHMP recommendations: stronger language for patients with contraindications, including prior cardiac and CVD which require overnight monitoring, not just overnight;caution in patients on certain drugs, liberal use of cardiology consultation.  First dose monitoring should now include VS and EKG prior to dosing, continuous monitoring during dosing.  Extend monitoring until HR has increased at least two consecutive hours, and if concern, monitor overnight. In USA, less tringent changes for first dose monitoring: EKG prior to dosing and prior to discharge; monitor at least six hours, do hourly VS during dosing.  D/C criteria similar to Europe.  Overnight monitoring for those with symptomatic bradycardia, QTc pronlongation or conditions that would predispose to QTc prolongation.
14.  In first two weeks, repeat induction if they skip one day; in second two weeks, if they skip a week; subsequently if they miss two weeks of therapy.
15.  HTN during gilenya beware of.
16.  Macular edema:  half time is symptomatic (blurring), half time asymptomatic.  Usually unilateral, may b bilateral.  Increased in diabetics, (excluded in ph 3 trial), higher dose, and those with uveitis and ? ON.  Reverses within several months if drug is discontinued.
17.  Cases exist of MI, CVA, PRES, others.  HA's seen in trials and is the most frequent reason to discontinue medication:  exacerbation of preexisting migraine.
18.  Sense of SOB or cough
Summary-- his opinion-- used in 800 patients.  Check  LFT's no CBCs, OCT repeated after 3 months
Using in RRMS Approved as first line therapy but actually use less often.

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