JamesEckburg and Multiple Sclerosis Fingolimod
The information in this medication sheet has been adapted from the FDA-approved prescribing information for Gilenya.
Description
Gilenya™ is a new class of medication called a sphingosine 1-phosphate receptor modulator, which is thought to act by retaining certain white blood cells (lymphocytes) in the lymph nodes, thereby preventing those cells from crossing the blood-brain barrier into the central nervous system (CNS). Preventing the entry of these cells into the CNS reduces inflammatory damage to nerve cells.
Gilenya was evaluated in two large-scale, phase III clinical trials involving people with relapsing-remitting MS:
In a two-year study (FREEDOMS) comparing two doses of Gilenya to placebo, Gilenya (at the lower, 0.5mg dose) reduced relapses by 54% and reduced the risk of disability progression by 30% compared to placebo. Gilenya also reduced brain lesion activity as measured by MRI.
In a one-year study (TRANSFORMS) comparing two doses of Gilenya to interferon beta-1a (Avonex), Gilenya (at the lower, 0.5mg dose) reduced relapses by 52% compared with Avonex; reduced disease activity as measured by the number of new and newly enlarged T2 lesions on MRI scans compared with Avonex (1.6 vs 2.6, respectively at one year); reduced brain lesion activity as measured by MRI.
In August 2011, the FDA approved an update in the prescribing information for Gilenya to include the MRI findings from both the TRANSFORMS and FREEDOMS studies. In both clinical trials, Gilenya showed a reduction in gadolinium-enhancing lesions, which indicate new MS activity. The data from the TRANSFORMS study indicated that at 12 months, the mean number of gadolinium-enhancing T1 lesions was significantly lower for patients treated with Gilenya at the 0.5 mg dose than for patients taking interferon beta-1a (Avonex), 0.2 vs 0.5 respectively. In the FREEDOMS trial, the mean number of gadolinium-enhancing T1 lesions was significantly lower at 24 months for the group treated with Gilenya (0.5 mg dose) than for the placebo group, 0.2 vs 1.1.
Gilenya has not been studied in people under the age of 18.
Approval by the U.S. Food and Drug Administration (FDA)
Gilenya was approved by the U.S. Food and Drug Administration (FDA) in 2010 for adults with relapsing forms of MS to reduce the frequency of clinical relapses and to delay the accumulation of physical disability.
http://www.youtube.com/watch?v=JSJaDWheyGk&feature=colike
In April, 2012, the FDA (along with the European Medicines Agency — EMA) revised the prescribing information for Gilenya based on independent safety reviews initiated by the agencies after deaths had been reported among patients taking Gilenya. The revised prescribing information defines who should avoid using this MS therapy based on pre-existing medical conditions, and alters the recommended testing and heart monitoring that occurs when the first dose is given:
All those starting treatment with Gilenya should have an electrocardiogram prior to dosing and after the 6-hour observation period. During the observation period, blood pressure and heart rate should be measured hourly.
People whose first-dose monitoring indicates potentially unsafe heart events may require longer monitoring, and any who require treatment for low heart rate during the first-dose monitoring will need to be monitored overnight.
Gilenya is not advisable for people who have had a history or presence of specific heart and vascular conditions, including heart attack, stroke, and heartbeat irregularities, and people taking heart rate-lowering medication.
If anyone with a pre-existing heart condition is started on Gilenya, after the first dose the patient should be monitored overnight with continuous electrocardiogram in a medical facility.
The heart function monitoring applies only to people initiating their first dose, and not to people who are already taking daily doses of Gilenya. There are also revised recommendations for people who re-initiate treatment after discontinuing Gilenya. People should not make changes to their Gilenya therapy without consulting their prescriber.
http://www.youtube.com/watch?v=lUS5Tiq5O28&feature=colike
Macular Edema:
Oral MS Drug May Increase Risk for Macular Edema
A report from the North American Neuro-Ophthalmology Society (NANOS) and the AAO
ONE Neuro-Ophthalmology Committee
*ONE Neuro-ophthalmology chair: Andrew G. Lee, MD for the ONE Committee
Data from recent multinational Phase 2 and 3 clinical trials of fingolimod (Gilenya, Novartis) suggest an association of the agent to a low risk of cystoid macular edema (CME). Fingolimod is the first oral medication approved by the U.S. FDA for relapsing forms of MS and is an immunomodulator that regulates lymphocyte distribution, reducing lymphocyte recirculation from lymphoid tissue to blood and peripheral tissues. A two-year FDA clinical trial compared fingolimod with placebo and another one-year trial compared fingolimod with interferon beta-1a.
Although several clinical trials to date have shown fingolimod to be well tolerated, side effects have included bradycardia, headache, upper respiratory tract infection, shortness of breath, diarrhea and nausea. In the two-year trial, macular edema occurred in 0.4 percent of patients treated with fingolimod and 0.1 percent who received the placebo.
Study patients were monitored with medical histories, visual acuity, contrast sensitivity, dilated ophthalmoscopy, optical coherence tomography (OCT), and had ophthalmic examinations at 1, 3, 6, 12 and 18 months.
Compared to placebo, Fingolimod reduced the MS relapse rate and increased the percentage of patients without a MS relapse in both studies. The differences were statistically significant.
http://www.youtube.com/watch?v=i7hG_YS1WiE&feature=colike
Transient bradycardia, HTN
Because of the risk of transient bradycardias and heart block after the first dose, the recommended level of cardiovascular monitoring of all patients after their first dose of fingolimod has now increased as outlined here
Fingolimod (Gilenya▼) is authorised to treat relapsing-remitting multiple sclerosis in patients whose disease has failed to respond to beta-interferon or is severe and getting worse rapidly. It is a sphingosine-1 phosphate receptor modulator.
Fingolimod is known to cause transient bradycardias and might be associated with atrioventricular block after the first dose; these are reflected in existing recommendations to observe patients for signs and symptoms of bradycardia in the 6 hours post administration.
The European Medicines Agency (EMA) has started a review of the benefits and risks of fingolimod after becoming aware of new post-marketing evidence about its possible cardiovascular effects after taking the first dose. This includes a 59-year-old patient from the USA with multiple sclerosis who died within 24 hours of taking the first dose of Gilenya. This patient was being treated with metoprolol and amlodipine for hypertension.
The exact cause of death is currently unknown. In addition to the unexplained death in the USA, six other unexplained deaths (including three cases of sudden death) after starting treatment with fingolimod have also been reported. As at Feb 6, 2012, we have received four UK reports of suspected adverse reactions with fingolimod, including one case of bradycardia and hypotension occurring 4 hours after the first dose with a drop in heart rate experienced again the following day.
While the review of fingolimod is ongoing, the EMA’s Committee for Medicinal Products for Human Use now recommends that the level of cardiovascular monitoring of all patients is increased after their first dose of fingolimod:
Patients that are taking this drug have to be watched and check on redularly with their Doctors. Their care has to be writen down and saved for research.
http://www.youtube.com/watch?v=L7UvhwORTd4&feature=colike
This is just some of the side effects of Fingloimod in the treatment of Multiple Sclerosis.
James Eckburg
Senior Health and Wellness Strategist
www.Jamescornershop.com,
www.eckburgjoe.veretekk.com
114 E. Franklin St.
Lanark, Illinois 61046
skype: jamesoeck1
joeckburg@gmail.com