Informed Consent Risk of Cheese Reaction

1
Informed ConsentRisk 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 tellyour
  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.

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2
Proposed Label for 30-40 mg Diet (excerpt)
4a - 8
3
Patient Information on Dietary Modifications

• A modified diet is not necessary when taking
  EMSAM 6mg/24 hours (20mg)
• 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
• 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)

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4
Patient Information on Dietary Modifications
(Continued)

• Dietary Modifications
• 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)
• All foods must be fresh or properly frozen
• Avoid foods when you are unaware of storage
  conditions

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5
Informed ConsentDescription 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.

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6
Transdermal SelegilinePivotal Trial II P0052
Acute MDD
HAMD-28
p lt 0.03 p lt0.04
Dosage
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7
Transdermal SelegilinePivotal Trial II P0052
Acute MDD
p lt 0.03 p lt0.04
HAMD-28
Dosage
2 - 18
8
Responder Rates for MDD Patients
inPlacebo-Controlled Studies
Improved
Defined as CGI-I score of 1 or 2
2 - 11
9
Tyramine Pressor Dose and TSF Values for
Individual Subjects Challenged in the Fasted and
Fed States
Fasted - lowest value obtained during 30-90 days
of EMSAM 40 mg treatment
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