neffy

5 WARNINGS AND PRECAUTIONS Absorption of neffy may be affected by underlying structural and anatomical nasal conditions. ( 5.1 ) Administer with caution in patients with heart disease; may aggravate angina pectoris or produce ventricular arrhythmias. ( 5.2 ) May aggravate certain coexisting conditions. ( 5.2 ) The presence of a sulfite in this product should not deter use. ( 5.3 ) 5.1 Potential Altered Absorption of Neffy in Patients with Underlying Structural or Anatomical Nasal Conditions Clinical pharmacology studies with neffy included subjects with history of allergic rhinitis, but did not include subjects with underlying structural and anatomical nasal conditions (e.g., polyps, history of nasal fractures or injuries, or history of nasal surgery). Absorption of neffy may be affected by underlying structural and anatomical nasal conditions. Consider use of other epinephrine products given by other routes of administration for patients with underlying structural or anatomical nasal conditions. 5.2 Risks Associated with Use of Epinephrine in Certain Coexisting Conditions Some patients may be at greater risk for developing adverse reactions after epinephrine administration. Despite these concerns, it should be recognized that the presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation. Therefore, patients with these conditions, and/or any other person who might be in a position to administer neffy to a patient experiencing anaphylaxis should be carefully instructed in regard to the circumstances under which epinephrine should be used. Epinephrine should be administered with caution to patients who have heart disease, including patients with cardiac arrhythmias, coronary artery disease, or hypertension. In such patients, or in patients who are on drugs that may sensitize the heart to arrhythmias, epinephrine may precipitate or aggravate angina pectoris, as well as produce ventricular arrhythmias [see Drug Interactions (7) and Adverse Reactions (6) ] . Epinephrine can temporarily exacerbate the underlying condition or increase symptoms in patients with the following: hyperthyroidism, Parkinson's disease, diabetes, renal impairment. Epinephrine should be administered with caution in patients with these conditions, including elderly patients and pregnant women. 5.3 Allergic Reactions Associated with Sulfite Epinephrine is the preferred treatment for serious allergic or other emergency situations even though neffy contains sodium metabisulfite, a sulfite that may in other products cause allergic-type reactions including anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons. The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulfite(s) in neffy should not deter administration of the drug for treatment of serious allergic or other emergency situations.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Risks Associated with Use of Epinephrine in Certain Coexisting Conditions [see Warnings and Precautions (5.2) ] Allergic Reactions Associated with Sulfite [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥2%) are throat irritation, intranasal paresthesia, headache, nasal discomfort, feeling jittery, paresthesia, fatigue, tremor, rhinorrhea, nasal pruritus, sneezing, abdominal pain, gingival pain, hypoesthesia oral, nasal congestion, dizziness, nausea, and vomiting. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact ARS Pharmaceuticals Operations Inc. at 1-877-MY-NEFFY (877-696-3339) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Adverse Reactions in Four Clinical Pharmacology Studies with Neffy for Adult Subjects Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of neffy 2 mg is based on four clinical pharmacology studies in 175 healthy adults and adults with type I allergy without anaphylaxis, who did not have structural or anatomical nasal conditions [see Clinical Pharmacology (12.2 , 12.3) ] . The four clinical pharmacology studies were designed to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of one dose of neffy 2 mg sprayed into one nostril or two doses of neffy 2 mg sprayed into either the same or opposite nostril, administered 10 minutes apart, with PK and PD profiles of one or two dose(s) of epinephrine injection administered intramuscularly. The common adverse reactions that occurred with neffy 2 mg after one and two dose(s) are listed in Table 1. Table 1: Adverse Reactions with One or Two Dose(s) of Neffy with Incidence Greater than or Equal to 2% in Adults [Studies 1, 2, 3, and 4] Adverse Reaction Data include subjects with nasal allergen challenge induced rhinitis Neffy 2 mg One Dose Neffy 2 mg Two Doses Two nasal doses of neffy 2 mg were administered 10 minutes apart N = 134 The trials used a crossover design and therefore the total number of subjects do not match the number of unique subjects (n = 175) N = 85 Throat irritation 2 (2%) 16 (19%) Headache 8 (6%) 15 (18%) Nasal discomfort 13 (10%) 11 (13%) Feeling jittery 1 (1%) 9 (11%) Tremor 0 (0%) 7 (8%) Rhinorrhea 4 (3%) 6 (7%) Nasal pruritus 0 (0%) 3 (4%) Sneezing 0 (0%) 3 (4%) Abdominal pain 1 (1%) 3 (4%) Gingival pain 0 (0%) 3 (4%) Hypoesthesia oral 0 (0%) 3 (4%) Nasal Congestion 0 (0%) 2 (2%) Dizziness 4 (3%) 2 (2%) Nausea 4 (3%) 2 (2%) Vomiting 3 (2%) 2 (2%) Adverse Reactions in a Clinical Pharmacology Study with Neffy for Pediatric Subjects A single-arm PK/PD study (Study 5) in pediatric subjects 8 to 17 years of age who weigh 30 kg or greater with type I allergy without anaphylaxis was conducted to assess the PK/PD of neffy 2 mg. A total of 42 pediatric subjects who weigh 30 kg or greater (body weight range: 31 kg to 95 kg; age range: 8 to 17 years) were enrolled, including 21 subjects who received one nasal dose of neffy 2 mg [see Clinical Pharmacology (12.3) ] . Common adverse reactions reported in these subjects who received one dose of neffy 2 mg include nasal discomfort (19%), intranasal paresthesia (19%), rhinorrhea (14%), sneezing (14%), paresthesia (10%), fatigue (10%), and feeling jittery (10%). Adverse Reactions from Postapproval Use of Epinephrine Products The following adverse reactions have been identified during postapproval use of epinephrine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular : angina, arrhythmias (including fatal ventricular fibrillation), cerebral hemorrhage, hypertension, pallor, palpitations, tachyarrhythmia, tachycardia, vasoconstriction, ventricular ectopy, and stress cardiomyopathy Metabolism and Nutrition Disorders : transient hyperglycemia, sweating Neurological : disorientation, impaired memory, panic, psychomotor agitation, sleepiness, tingling, weakness Psychiatric : anxiety, apprehensiveness, restlessness Respiratory : respiratory difficulties

<table width="75%"><caption>Table 1: Adverse Reactions with One or Two Dose(s) of Neffy with Incidence Greater than or Equal to 2% in Adults [Studies 1, 2, 3, and 4]</caption><col width="50%" align="left" valign="middle"/><col width="10%" align="right" valign="middle"/><col width="15%" align="left" valign="middle"/><col width="10%" align="right" valign="middle"/><col width="15%" align="left" valign="middle"/><thead><tr><th rowspan="3" styleCode="Lrule Rrule" valign="bottom">Adverse Reaction <footnote ID="K689">Data include subjects with nasal allergen challenge induced rhinitis</footnote></th><th colspan="2" align="center" styleCode="Botrule Rrule">Neffy 2 mg One Dose </th><th colspan="2" align="center" styleCode="Botrule Rrule">Neffy 2 mg Two Doses <footnote ID="K705">Two nasal doses of neffy 2 mg were administered 10 minutes apart</footnote></th></tr><tr styleCode="Botrule"><th colspan="2" align="center" styleCode="Rrule">N = 134 <footnote ID="ft1">The trials used a crossover design and therefore the total number of subjects do not match the number of unique subjects (n = 175)</footnote></th><th colspan="2" align="center" styleCode=" Rrule">N = 85 <footnoteRef IDREF="ft1"/></th></tr><tr><th styleCode="Rrule"> </th><th styleCode="Rrule"> </th><th styleCode="Rrule"> </th><th styleCode="Rrule"> </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Throat irritation</td><td styleCode="Rrule">2</td><td styleCode="Rrule">(2%)</td><td styleCode="Rrule">16</td><td styleCode="Rrule">(19%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Headache</td><td styleCode="Rrule">8</td><td styleCode="Rrule">(6%)</td><td styleCode="Rrule">15</td><td styleCode="Rrule">(18%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nasal discomfort</td><td styleCode="Rrule">13</td><td styleCode="Rrule">(10%)</td><td styleCode="Rrule">11</td><td styleCode="Rrule">(13%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Feeling jittery</td><td styleCode="Rrule">1</td><td styleCode="Rrule">(1%)</td><td styleCode="Rrule">9</td><td styleCode="Rrule">(11%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Tremor</td><td styleCode="Rrule">0</td><td styleCode="Rrule">(0%)</td><td styleCode="Rrule">7</td><td styleCode="Rrule">(8%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Rhinorrhea</td><td styleCode="Rrule">4</td><td styleCode="Rrule">(3%)</td><td styleCode="Rrule">6</td><td styleCode="Rrule">(7%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nasal pruritus</td><td styleCode="Rrule">0</td><td styleCode="Rrule">(0%)</td><td styleCode="Rrule">3</td><td styleCode="Rrule">(4%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Sneezing</td><td styleCode="Rrule">0</td><td styleCode="Rrule">(0%)</td><td styleCode="Rrule">3</td><td styleCode="Rrule">(4%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Abdominal pain</td><td styleCode="Rrule">1</td><td styleCode="Rrule">(1%)</td><td styleCode="Rrule">3</td><td styleCode="Rrule">(4%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Gingival pain</td><td styleCode="Rrule">0</td><td styleCode="Rrule">(0%)</td><td styleCode="Rrule">3</td><td styleCode="Rrule">(4%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypoesthesia oral</td><td styleCode="Rrule">0</td><td styleCode="Rrule">(0%)</td><td styleCode="Rrule">3</td><td styleCode="Rrule">(4%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nasal Congestion</td><td styleCode="Rrule">0</td><td styleCode="Rrule">(0%)</td><td styleCode="Rrule">2</td><td styleCode="Rrule">(2%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dizziness</td><td styleCode="Rrule">4</td><td styleCode="Rrule">(3%)</td><td styleCode="Rrule">2</td><td styleCode="Rrule">(2%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nausea</td><td styleCode="Rrule">4</td><td styleCode="Rrule">(3%)</td><td styleCode="Rrule">2</td><td styleCode="Rrule">(2%)</td></tr><tr><td styleCode="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">3</td><td styleCode="Rrule">(2%)</td><td styleCode="Rrule">2</td><td styleCode="Rrule">(2%)</td></tr></tbody></table>