9/17/2019
`
`Important Safety Info
`
`Start Tecfidera® (dimethyl fumarate)
`Prescribing Info
`
`Patient Site
`
`Help Your Patients Get Started on TECFIDERA
`Routine monitoring helps ensure patient safety
`
`1
`
`Obtain Prior to Initiation
`
`After Initiation
`
`Complete blood count (CBC) with lymphocyte
`count
`
` At 6 months
`
`Liver tests
`(serum aminotransferase, alkaline phosphatase, and
`total bilirubin)
`
` Every 6-12 months thereafter, and
`as clinically indicated
`
` Repeat as clinically indicated
`
`Learn more
`
`One pill, twice daily
`
`1
`
`Start
`7 days with 120 mg twice daily
`
`AM
`
`PM
`
` 120 mg
`
` 120 mg
`
`Continue
`with 240 mg twice daily
`
`AM
`
`PM
`
` 240 mg
`
` 240 mg
`
`One pill, twice a day
`Can be taken with or without food
`Should be swallowed whole and intact, not crushed or chewed, and the capsule contents should not be sprinkled on food
`Temporary dose reductions to 120 mg twice a day may be considered for individuals who do not tolerate the maintenance dose.
`Within 4 weeks, the recommended dose of 240 mg twice a day should be resumed
`Discontinuation of TECFIDERA should be considered for patients unable to tolerate return to the maintenance dose
`
`IMPORTANT SAFETY INFORMATION AND INDICATION
`
`https://www.tecfiderahcp.com/en_us/home/start-tecfidera/getting-started.html
`
`EXPAND
`
`1/4
`
`MYLAN PHARMS. INC. EXHIBIT 1103 PAGE 1
`
`

`

`9/17/2019
`
`Start Tecfidera® (dimethyl fumarate)
`
`See how to manage dosing tolerability issues
`
`Supporting your patients from the start
`
`Patient Website
`At TECFIDERA.com, patients will nd videos and interactive information about TECFIDERA, as well as discussion
`guides to help facilitate a productive patient-physician dialogue. Patients can also search and register for local events
`where they can connect with other people living with relapsing forms of MS.
`
`Patient Information Brochure
`An easy-to-read review of what to expect on TECFIDERA. It includes information on:
`
`
`
`Taking TECFIDERA
`Adverse events
`Patient support
`Request a brochure from your TECFIDERA sales representative or download the brochure now to familiarize yourself
`with the content.
`
`Welcome Kit
`Delivered to patients once you’ve prescribed TECFIDERA. Each kit includes a welcome brochure with tips to help your
`patients start and stay on TECFIDERA and get the most out of treatment.
`
`TecTrack™ App
`The TecTrack™ app helps patients remember to take their medication and is available for download on the App Store
`or Google Play.
`
`
`
`The Above MS™ program from Biogen supports you and your patients with tips, tools, and more:
`Personalized support from people who are here to help
`One-on-one RMS support by phone
`Nurse Educators are available by phone 24/7
`A variety of nancial and insurance support services for eligible patients
`
`Learn more about Above MS™
`
`Fill out a Start Form to help your patients get the support they need.
`
`Download Start Form
`
`QuickStart can help eligible patients with free 7-day samples of 120 mg TECFIDERA
`IMPORTANT SAFETY INFORMATION AND INDICATION
`Download Start Form
`
`https://www.tecfiderahcp.com/en_us/home/start-tecfidera/getting-started.html
`
`EXPAND
`
`2/4
`
`MYLAN PHARMS. INC. EXHIBIT 1103 PAGE 2
`
`

`

`9/17/2019
`
`Start Tecfidera® (dimethyl fumarate)
`
`TECFIDERA Nurse Educators are available by phone 24/7 to help patients manage common side effects
`
`Explore Above MS™
`
`Learn how MS experts set expectations with patients
`
`Watch video
`
`Reference: 1. TECFIDERA Prescribing Information, Biogen, Cambridge, MA.
`
`IMPORTANT SAFETY INFORMATION
`TECFIDERA (dimethyl fumarate) is contraindicated in patients with known hypersensitivity to dimethyl fumarate or any of the excipients of
`®
`TECFIDERA. TECFIDERA can cause anaphylaxis and angioedema after the rst dose or at any time during treatment. Patients experiencing
`signs and symptoms of anaphylaxis and angioedema (which have included difculty breathing, urticaria, and swelling of the throat and tongue)
`should discontinue TECFIDERA and seek immediate medical care.
`
`Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with TECFIDERA. PML is an opportunistic viral
`infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to
`death or severe disability. A fatal case of PML occurred in a patient who received TECFIDERA in a clinical trial. PML has also occurred in the
`postmarketing setting in the presence of lymphopenia (<0.8x10 /L) persisting for more than 6 months. While the role of lymphopenia in these
`9
`cases is uncertain, the majority of cases occurred in patients with lymphocyte counts <0.5x10 /L. The symptoms associated with PML are
`9
`diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision,
`and changes in thinking, memory, and orientation leading to confusion and personality changes. At the rst sign or symptom suggestive of
`PML, withhold TECFIDERA and perform an appropriate diagnostic evaluation. MRI ndings may be apparent before clinical signs or symptoms.
`
`TECFIDERA may decrease lymphocyte counts; in clinical trials there was a mean decrease of ~30% in lymphocyte counts during the rst year
`which then remained stable. Four weeks after stopping TECFIDERA, mean lymphocyte counts increased but not to baseline. Six percent of
`TECFIDERA patients and <1% of placebo patients had lymphocyte counts <0.5x10 /L. TECFIDERA has not been studied in patients with pre-
`9
`existing low lymphocyte counts.
`
`There was no increased incidence of serious infections observed in patients with lymphocyte counts <0.8x10 /L or ≤0.5x10 /L in controlled
`9
`9
`trials, although one patient in an extension study developed PML in the setting of prolonged lymphopenia (lymphocyte counts predominantly
`<0.5x10 /L for 3.5 years). In controlled and uncontrolled clinical trials, 2% of patients experienced lymphocyte counts <0.5x10 /L for at least six
`9
`9
`months. In these patients, the majority of lymphocyte counts remained <0.5x10 /L with continued therapy. A complete blood count including
`9
`lymphocyte count should be obtained before initiating treatment, 6 months after starting, every 6 to 12 months thereafter and as clinically
`indicated. Consider treatment interruption if lymphocyte counts <0.5x10 /L persist for more than six months and follow lymphocyte counts
`9
`until lymphopenia is resolved. Consider withholding treatment in patients with serious infections until resolved. Decisions about whether or not
`to restart TECFIDERA should be based on clinical circumstances.
`
`Clinically signicant cases of liver injury have been reported in patients treated with TECFIDERA in the postmarketing setting. The onset has
`ranged from a few days to several months after initiation of treatment. Signs and symptoms of liver injury, including elevation of serum
`aminotransferases to greater than 5-fold the upper limit of normal and elevation of total bilirubin to greater than 2-fold the upper limit of normal
`have been observed. These abnormalities resolved upon treatment discontinuation. Some cases required hospitalization. None of the reported
`cases resulted in liver failure, liver transplant, or death. However, the combination of new serum aminotransferase elevations with increased
`levels of bilirubin caused by drug-induced hepatocellular injury is an important predictor of serious liver injury that may lead to acute liver
`failure, liver transplant, or death in some patients.
`
`Elevations of hepatic transaminases (most no greater than 3 times the upper limit of normal) were observed during controlled trials.
`
`Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels before initiating TECFIDERA and during treatment, as clinically
`indicated. Discontinue TECFIDERA if clinically signicant liver injury induced by TECFIDERA is suspected.
`
`TECFIDERA may cause ushing (e.g. warmth, redness, itching, and/or burning sensation). 40% of patients taking TECFIDERA reported ushing,
`which was mostly mild to moderate in severity. Three percent of patients discontinued TECFIDERA for ushing and <1% had serious ushing
`events that led to hospitalization. Taking TECFIDERA with food may reduce ushing. Alternatively, administration of non-enteric coated aspirin
`prior to dosing may reduce the incidence or severity of ushing.
`
`IMPORTANT SAFETY INFORMATION AND INDICATION
`
`https://www.tecfiderahcp.com/en_us/home/start-tecfidera/getting-started.html
`
`EXPAND
`
`3/4
`
`MYLAN PHARMS. INC. EXHIBIT 1103 PAGE 3
`
`

`

`Start Tecfidera® (dimethyl fumarate)
`9/17/2019
`TECFIDERA may cause gastrointestinal (GI) events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). Four percent of
`TECFIDERA patients and <1% of placebo patients discontinued due to GI events. The incidence of serious GI events was 1%. The most common
`adverse reactions associated with TECFIDERA versus placebo are ushing (40% vs 6%) and GI events: abdominal pain (18% vs 10%), diarrhea
`(14% vs 11%), nausea (12% vs 9%).
`
`A transient increase in mean eosinophil counts was seen during the rst two months.
`
`TECFIDERA should be used during pregnancy only if the potential benet justies the potential risk to the fetus. Encourage patients who
`become pregnant while taking TECFIDERA to enroll in the TECFIDERA pregnancy registry by calling 1-866-810-1462 or visiting
`www.TECFIDERApregnancyregistry.com.
`
`INDICATION
`TECFIDERA (dimethyl fumarate) is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated
`®
`syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
`
`Please see full Prescribing Information.
`
`Start TECFIDERA
`Getting Started
`Dosing
`Support Program
`Demonstrated Efcacy
`Pivotal Trial Designs
`Proven in Pivotal Trials
`Extension Study
`Newly Diagnosed 2- and 6-Year Analyses
`Well-Known Safety
`Safety
`Adverse Events
`Managing Common Side Effects
`Access and Reimbursement
`Coverage and $0 Copay
`Sample Program and QuickStart
`Real-World Experience
`Global Experience
`MS Expert Video Library
`FAQs
`Register/
`Sign In
`
`Terms of Use
`
`Privacy Policy
`
`Contact Us
`
`Unsubscribe
`
`© 2019 Biogen. All rights reserved. 08/19
`All trademarks are the property of their respective owners.
`For US Healthcare Professionals Only.
`
`IMPORTANT SAFETY INFORMATION AND INDICATION
`
`https://www.tecfiderahcp.com/en_us/home/start-tecfidera/getting-started.html
`
`EXPAND
`
`4/4
`
`MYLAN PHARMS. INC. EXHIBIT 1103 PAGE 4
`
`