Informed Consent Risk of Cheese Reaction A possible risk of using selegiline is uncontrolled hypertension (high blood pressure), the so-called “cheese reaction”, which can occur if you eat foods containing tyramine, e.g., aged cheese, liquor, dry sausage, yogurt, raisins, liver, pickled herring, Fava beans, sauerkraut, and over-the-counter cough/cold medications. Therefore, it is important that you tell your doctor immediately if you have any of the following symptoms: headache, heart palpitations, a sense of constriction in the throat or chest, sweating, dizziness, neck stiffness, nausea, or vomiting. 1b - 83

Proposed Label for mg Diet (excerpt) Class Tyramine Foods to Avoid Safe, No or Low Tyramine Meat, Poultry, Fish Aged & Spoiled Fresh & Fresh processed Vegetables Fava bean pods All others Dairy Aged cheeses Processed cheeses, yogurt Beverages Tap beers Unpasteurized beers Alcohol not recommended Bottled & canned beer Miscellaneous Marmite, sauerkraut, soy products Brewer’s & Baker’s yeast Commercial chain restaurant pizza 4a - 8

Patient Information on Dietary Modifications u A modified diet is not necessary when taking EMSAM 6mg/24 hours (20mg) u The consumption of certain foods and beverages during treatment with EMSAM 9mg/24 hours (30mg) or 12mg/24 hours (40mg) dose may lead to a sudden, large increase in blood pressure, called a ‘‘hypertensive crisis’’ (a potentially life-threatening situation). (See What are the possible side effects of EMSAM?) Dietary Modifications: u To prevent a hypertensive crisis, the following foods and beverages should be avoided beginning on the first day of EMSAM 9mg/24 hours (30mg) or 12mg/24 hours (40mg) treatment and continue until 2 weeks after a dose reduction to EMSAM 6mg/24 hours (20mg) or stopping EMSAM 9mg/24 hours (30mg) or 12mg/24 hours (40mg): 4b - 8

Patient Information on Dietary Modifications (Continued) Dietary Modifications: u 12mg/24 hours (40mg): –Air dried, aged and fermented meats, sausages and salamis (including cacciatore, hard salami and mortadella); pickled herring; and any spoiled or improperly stored meat, poultry and fish (e.g., foods that have undergone changes in coloration, odor, or become moldy) –Broad bean pods (fava bean pods) –Aged cheeses –All varieties of tap beer, and beers that have not been pasteurized so as to allow for ongoing fermentation should be avoided during EMSAM treatment –Concentrated yeast extract (e.g., Marmite), sauerkraut, all soybean products (including soy sauce and tofu) u All foods must be fresh or properly frozen u Avoid foods when you are unaware of storage conditions 4b - 9

Informed Consent Description of Symptoms of Hypertensive Crisis Severe headache, flushing, sudden elevation of blood pressure, awareness of rapid or pounding heart, nausea, vomitting, sweating, fever, and chest pain. Although rare, hypertensive crisis may be a life-threatening reaction that requires immediate medical attention. 1b - 84

Transdermal Selegiline Pivotal Trial II: P0052 Acute MDD HAMD-28:p < 0.03 p <0.04 Dosage

Transdermal Selegiline Pivotal Trial II: P0052 Acute MDD HAMD-28 p < 0.03 p <0.04 Dosage

Responder Rates* for MDD Patients in Placebo-Controlled Studies StudyEMSAMPlacebo E P P * Defined as CGI-I score of 1 or 2 % Improved

Tyramine Pressor Dose and TSF Values for Individual Subjects Challenged in the Fasted and Fed States Tyramine Pressor Dose (mg) SubjectFasted*FedFed/Fasted *Fasted - lowest value obtained during days of EMSAM 40 mg treatment 3a - 20