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HIGHLIGHTS OF PRESCRIBING INFORMATION --------------------------ADVERSE REACTIONS --------------------------- These highlights do not include all the information needed to use The most common adverse reactions (incidence ≥30%) are dry mouth, CUVPOSA® safely and effectively. See full prescribing information vomiting, constipation, flushing, and nasal congestion. (6) for CUVPOSA. To report SUSPECTED ADVERSE REACTIONS, contact Merz CUVPOSA (glycopyrrolate) oral solution Pharmaceuticals, LLC at 866-862-1211 or FDA at 1-800-FDA-1088 Initial U.S. Approval: 1961 or www.fda.gov/medwatch. --------------------------INDICATIONS AND USAGE---------------------- -------------------------DRUG INTERACTIONS----------------------------- CUVPOSA is an anticholinergic indicated to reduce chronic severe Digoxin tablets: Use with glycopyrrolate can increase digoxin drooling in patients aged 3-16 years with neurologic conditions serum levels. Monitor patients and consider use of alternative associated with problem drooling (e.g., cerebral palsy). (1) dosage forms of digoxin. (7) Amantadine: Effects of glycopyrrolate may be increased with concomitant administration of amantadine. Consider decreasing ---------------------DOSAGE AND ADMINISTRATION----------------- the dose of glycopyrrolate during concomitant use. (7) Initiate dosing at 0.02 mg/kg three times daily and titrate in Atenolol or metformin: Glycopyrrolate may increase serum levels increments of 0.02 mg/kg every 5-7 days, based on therapeutic of atenolol or metformin. Consider dose reduction when used with response and adverse reactions. (2) glycopyrrolate. (7) Maximum recommended dose is 0.1 mg/kg three times daily, not Haloperidol or levodopa: Glycopyrrolate may decrease serum to exceed 1.5-3 mg per dose based upon weight. (2) levels of haloperidol or levodopa. Consider a dose increase when Administer at least one hour before or two hours after meals. (2) used with glycopyrrolate. (7) -------------------DOSAGE FORMS AND STRENGTHS----------------- ------------------USE IN SPECIFIC POPULATIONS -------------------- 1 mg/5 mL, oral solution in 16 ounce bottles. (3) Pediatric use: The safety and effectiveness of glycopyrrolate has not been established in patients less than 3 years of age. (8.4) -------------------------CONTRAINDICATIONS --------------------------- Renal impairment: Use CUVPOSA with caution in patients with Medical conditions that preclude anticholinergic therapy. (4) renal impairment. (8.6) Concomitant use of solid oral dosage forms of potassium chloride. (4) ------------------WARNINGS AND PRECAUTIONS --------------------- Constipation or intestinal pseudo-obstruction: May present as See 17 for PATIENT COUNSELING INFORMATION and FDA- abdominal distention, pain, nausea, or vomiting. Assess patients approved patient labeling for constipation, particularly within 4-5 days of initial dosing or after a dose increase. (5.1) Incomplete mechanical intestinal obstruction: May present as diarrhea. If obstruction is suspected, discontinue CUVPOSA and Revised: 02/2018 evaluate. (5.2) High ambient temperature: To reduce the risk of heat prostration, avoid high temperatures. (5.3) Page 1 of 11 Reference ID: 4225923 FULL PRESCRIBING INFORMATION: CONTENTS * 1 INDICATIONS AND USAGE 13 NONCLINICAL TOXICOLOGY 2 DOSAGE AND ADMINISTRATION 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 3 DOSAGE FORMS AND STRENGTHS 14 CLINICAL STUDIES 4 CONTRAINDICATIONS 16 HOW SUPPLIED/STORAGE AND HANDLING 5 WARNINGS AND PRECAUTIONS 17 PATIENT COUNSELING INFORMATION 5.1 Constipation or Gastrointestinal Pseudo-obstruction 5.2 Diarrhea and Intestinal Obstruction 5.3 Hot Environmental Temperatures 5.4 Operating Machinery or an Automobile * Sections or subsections omitted from the full prescribing information 5.5 General Anticholinergic Effects are not listed. 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Postmarketing Experience 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal or Hepatic Impairment 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics ___________________________________________________________________________________________ Page 2 of 11 Reference ID: 4225923 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE CUVPOSA is indicated to reduce chronic severe drooling in patients aged 3 to 16 years with neurologic conditions associated with problem drooling (e.g., cerebral palsy). 2 DOSAGE AND ADMINISTRATION CUVPOSA must be measured and administered with an accurate measuring device [see Patient Counseling Information (17)]. Initiate dosing at 0.02 mg/kg orally three times daily and titrate in increments of 0.02 mg/kg every 5-7 days based on therapeutic response and adverse reactions. The maximum recommended dosage is 0.1 mg/kg three times daily not to exceed 1.5-3 mg per dose based upon weight. For greater detail, see Table 1. During the four-week titration period, dosing can be increased with the recommended dose titration schedule while ensuring that the anticholinergic adverse events are tolerable. Prior to each increase in dose, review the tolerability of the current dose level with the patient’s caregiver. CUVPOSA should be dosed at least one hour before or two hours after meals. The presence of high fat food reduces the oral bioavailability of CUVPOSA if taken shortly after a meal [see Clinical Pharmacology (12.3)]. Table 1: Recommended Dose Titration Schedule (each dose to be given three times daily) Weight Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Dose Level 5 kg lbs (~0.02 mg/kg) (~0.04 mg/kg) (~0.06 mg/kg) (~0.08 mg/kg) (~0.1 mg/kg) 13-17 27-38 0.3 mg 1.5 mL 0.6 mg 3 mL 0.9 mg 4.5 mL 1.2 mg 6 mL 1.5 mg 7.5 mL 18-22 39-49 0.4 mg 2 mL 0.8 mL 4 mL 1.2 mg 6 mL 1.6 mg 8 mL 2.0 mg 10 mL 23-27 50-60 0.5 mg 2.5 mL 1.0 mg 5 mL 1.5 mg 7.5 mL 2.0 mg 10 mL 2.5 mg 12.5 mL 28-32 61-71 0.6 mg 3 mL 1.2 mg 6 mL 1.8 mg 9 mL 2.4 mg 12 mL 3.0 mg 15 mL 33-37 72-82 0.7 mg 3.5 mL 1.4 mg 7 mL 2.1 mg 10.5 mL 2.8 mg 14 mL 3.0 mg 15 mL 38-42 83-93 0.8 mg 4 mL 1.6 mg 8 mL 2.4 mg 12 mL 3.0 mg 15 mL 3.0 mg 15 mL 43-47 94-104 0.9 mg 4.5 mL 1.8 mg 9 mL 2.7 mg 13.5 mL 3.0 mg 15 mL 3.0 mg 15 mL ≥48 ≥105 1.0 mg 5 mL 2.0 mg 10 mL 3.0 mg 15 mL 3.0 mg 15 mL 3.0 mg 15 mL 3 DOSAGE FORMS AND STRENGTHS CUVPOSA is available as a 1mg/5 mL clear, cherry-flavored solution for oral administration in 16 ounce bottles. 4 CONTRAINDICATIONS CUVPOSA is contraindicated in: Patients with medical conditions that preclude anticholinergic therapy (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis). Patients taking solid oral dosage forms of potassium chloride. The passage of potassium chloride tablets through the gastrointestinal (GI) tract may be arrested or delayed with coadministration of CUVPOSA. Page 3 of 11 Reference ID: 4225923 5 WARNINGS AND PRECAUTIONS 5.1 Constipation or Intestinal Pseudo-obstruction Constipation is a common dose-limiting adverse reaction which sometimes leads to glycopyrrolate discontinuation [see Adverse Reactions (6.1)]. Assess patients for constipation, particularly within 4-5 days of initial dosing or after a dose increase. Intestinal pseudo-obstruction has been reported and may present as abdominal distention, pain, nausea or vomiting. 5.2 Incomplete Mechanical Intestinal Obstruction Diarrhea may be an early symptom of incomplete mechanical intestinal obstruction, especially in patients with ileostomy or colostomy. If incomplete mechanical intestinal obstruction is suspected, discontinue treatment with CUVPOSA and evaluate for intestinal obstruction. 5.3 High Ambient Temperatures In the presence of high ambient temperature, heat prostration (fever and heat stroke due to decreased sweating) can occur with the use of anticholinergic drugs such as CUVPOSA. Advise patients/caregivers to avoid exposure of the patient to hot or very warm environmental temperatures. 5.4 Operating Machinery or an Automobile CUVPOSA may produce drowsiness or blurred vision. As appropriate for a given age, warn the patient not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, or performing hazardous work while taking CUVPOSA. 5.5 Anticholinergic Drug Effects Use CUVPOSA with caution in patients with conditions that are exacerbated by anticholinergic drug effects including: Autonomic neuropathy Renal disease Ulcerative colitis – Large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason may precipitate or aggravate “toxic megacolon”, a serious complication of the disease Hyperthyroidism Coronary heart disease, congestive heart failure, cardiac tachyarrhythmias, tachycardia, and hypertension Hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Constipation or intestinal pseudo-obstruction [see Warnings and Precautions (5.1)] Incomplete mechanical intestinal obstruction [see Warnings and Precautions (5.2)] The most common adverse reactions reported with CUVPOSA are dry mouth, vomiting, constipation, flushing, and nasal congestion. 6.1 Clinical Trials Experience 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 data described below reflect exposure to CUVPOSA in 151 subjects, including 20 subjects who participated in an 8-week placebo-controlled study (Study 1) and 137 subjects who participated in a 24-week open-label study (six subjects who received CUVPOSA in the placebo-controlled study and 131 new subjects). Table 2 presents adverse reactions reported by ≥ 15% of CUVPOSA-treated subjects from the placebo-controlled clinical trial.

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