Karbinal ER

1 INDICATIONS AND USAGE Karbinal ER is indicated for adults and pediatric patients 2 years of age and older for the symptomatic treatment of: Seasonal and perennial allergic rhinitis Vasomotor rhinitis Allergic conjunctivitis due to inhalant allergens and foods Mild, uncomplicated allergic skin manifestations of urticaria and angioedema Dermatographism As therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled Amelioration of the severity of allergic reactions to blood or plasma Karbinal ER is indicated for adults and pediatric patients 2 years of age and older for the symptomatic treatment of: Seasonal and perennial allergic rhinitis ( 1 ) Vasomotor rhinitis ( 1 ) Allergic conjunctivitis due to inhalant allergens and foods ( 1 ) Mild, uncomplicated allergic skin manifestations of urticaria and angioedema ( 1 ) Dermatographism ( 1 ) As therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled ( 1 ) Amelioration of the severity of allergic reactions to blood or plasma ( 1 )

2 DOSAGE AND ADMINISTRATION Adults and Adolescents 12 years of age and older ( 2 .3): 7.5 mL to 20 mL (6 mg to 16 mg) orally every 12 hours Pediatric patients 2 years to 11 years of age (approximately 0.2 mg/kg/day to 0.4 mg/kg/day) ( 2 .4): 2 years to 3 years – 3.75 mL to 5 mL (3 mg to 4 mg) orally every 12 hours 4 years to 5 years – 3.75 mL to 10 mL (3 mg to 8 mg) orally every 12 hours 6 years to 11 years – 7.5 mL to 15 mL (6 mg to 12 mg) orally every 12 hours 2.1 General Administration Instructions The dosage of Karbinal ER should be individualized based on the severity of the condition and the response of the patient. Start with lower doses and increase as needed and tolerated. Administer Karbinal ER by the oral route only. Measure Karbinal ER with an accurate milliliter measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage. A pharmacist can provide an appropriate measuring device and can provide instructions for measuring correct dose. Shake Karbinal ER well before use. 2.2 Recommended Dosage for Adults and Adolescents 12 years of age and older: Administer 7.5 mL to 20 mL (6 mg to 16 mg) orally every 12 hours 2.3 Recommended Dosage for Pediatric Patients 2 years to 11 years of age (approximately 0.2 mg/kg/day to 0.4 mg/kg/day) 2 years to 3 years: Administer 3.75 mL to 5 mL (3 mg to 4 mg) orally every 12 hours administered orally 4 years to 5 years: Administer 3.75 mL to 10 mL (3 mg to 8 mg) orally every 12 hours administered orally 6 years to 11 years: Administer 7.5 mL to 15 mL (6 mg to 12 mg) orally every 12 hours administered orally 2.1 General Administration Instructions The dosage of Karbinal ER should be individualized based on the severity of the condition and the response of the patient. Start with lower doses and increase as needed and tolerated. Administer Karbinal ER by the oral route only. Measure Karbinal ER with an accurate milliliter measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage. A pharmacist can provide an appropriate measuring device and can provide instructions for measuring correct dose. Shake Karbinal ER well before use. 2.2 Recommended Dosage for Adults and Adolescents 12 years of age and older: Administer 7.5 mL to 20 mL (6 mg to 16 mg) orally every 12 hours 2.3 Recommended Dosage for Pediatric Patients 2 years to 11 years of age (approximately 0.2 mg/kg/day to 0.4 mg/kg/day) 2 years to 3 years: Administer 3.75 mL to 5 mL (3 mg to 4 mg) orally every 12 hours administered orally 4 years to 5 years: Administer 3.75 mL to 10 mL (3 mg to 8 mg) orally every 12 hours administered orally 6 years to 11 years: Administer 7.5 mL to 15 mL (6 mg to 12 mg) orally every 12 hours administered orally

4 CONTRAINDICATIONS Karbinal ER is contraindicated in: children younger than 2 years of age because deaths have been reported in this age group (see Warnings and Precautions (5.1)] patients who are hypersensitive to carbinoxamine maleate or any of the inactive ingredients in Karbinal ER [see Warnings and Precautions (5.1)] patients who are taking monoamine oxidase inhibitors (MAOI) [see Drug Interactions(7)]. Children younger than 2 years of age ( 4 ) Patients with known hypersensitivity to the drug or any of the inactive ingredients ( 4 ) Monoamine oxidase inhibitors (MAOI) ( 4 )

5 WARNINGS AND PRECAUTIONS Activities requiring mental alertness: Avoid engaging in hazardous tasks requiring complete mental alertness such as driving or operating machinery. ( 5.2 ) Anticholinergic actions: Use with caution in patients with increased intraocular pressure, narrow angle glaucoma, hyperthyroidism, cardiovascular disease, hypertension, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, pyloroduodenal obstruction. ( 5.3 ) Contains sodium metabisulfite, a sulfite that may cause anaphylaxis including life-threatening or less severe asthmatic episodes in susceptible individuals. ( 5.4 ) 5.1 Pediatric Mortality Deaths have been reported in children less than 2 years of age who were taking carbinoxamine-containing drug products; therefore, Karbinal ER is contraindicated in children younger than 2 years of age. 5.2 Somnolence and Impaired Mental Alertness Karbinal ER may produce marked drowsiness and impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of Karbinal ER. Avoid concurrent use of Karbinal ER with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur. 5.3 Concomitant Medical Conditions Karbinal ER has anticholinergic (atropine-like) properties and, therefore, should be used with caution in patients with: increased intraocular pressure, narrow angle glaucoma, hyperthyroidism, cardiovascular disease, hypertension, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, or pyloroduodenal obstruction. 5.4 Allergic Reactions due to Sulfites, including Anaphylaxis Karbinal ER contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic individuals.

7 DRUG INTERACTIONS Do not use of Karbinal ER in patients who are taking monoamine oxidase inhibitors (MAOIs), which prolong and intensify the anticholinergic (drying) effects of antihistamines. Avoid use of Karbinal ER with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc.) due to additive effects. Monoamine oxidase inhibitors (MAOIs): Prolong and intensify the anticholinergic (drying) effects. ( 4 and 7 ) Alcohol and CNS depressants (hypnotics, sedatives, tranquilizers, etc.): Avoid concomitant use due to additive adverse effects. ( 7 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are descrived elsewhere in the labeling: Somnolense and Impaired Mental Alertness [see Warnings and Precautions (5.2) ]. Allergic Reactions due to Sulfites, including Anaphylaxis [see Warnings and Precautions (5.4)]. The most frequent adverse reactions include: sedation, sleepiness, dizziness, disturbed coordination, epigastric distress, and thickening of bronchial secretions. In clinical use, younger children and older adults may be particularly sensitive to adverse reactions [see Pediatric Use (8.4) and Geriatric Use (8.5) ]. The following adverse reactions, listed by body system, have been identified in case reports and during the use of carbinoxamine in observational studies. 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. Body as a Whole : Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of mouth, nose and throat. Cardiovascular : Hypotension, headache, palpitations, tachycardia, extrasystoles. Central Nervous System : Fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesia, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, hysteria, neuritis, convulsions. Gastrointestinal : Anorexia, nausea, vomiting, diarrhea, constipation. Hematologic : Hemolytic anemia, thrombocytopenia, agranulocytosis. Laboratory : Increase in uric acid levels. Respiratory : Tightness of chest and wheezing, nasal stuffiness. Urogenital : Urinary frequency, difficult urination, urinary retention, early menses. Most common adverse reactions are: sedation, sleepiness, dizziness, disturbed coordination, epigastric distress, and thickening of bronchial secretions. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cerecor, Inc., at 1-866-416-9637 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary Published data over decades of use of antihistamines, including carbinoxamine, have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal out comes. However, published dat a specifically evaluating the risk of carbinoxamine were not found. Animal reproductive studies have not been conducted with carbinoxamine maleate. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.