glycopyrrolate

Glycopyrrolate Oral Solution 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. Glycopyrrolate Oral Solution should be dosed at least one hour before or two hours after meals. The presence of high fat food reduces the oral bioavailability of Glycopyrrolate Oral Solution 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…

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 Glycopyrrolate Oral Solution are dry mouth, vomiting, constipation, flushing, and nasal congestion. The most common adverse reactions (incidence ≥30%) are dry mouth, vomiting, constipation, flushing, and nasal congestion. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Ajenat Pharmaceuticals LLC at 1-727-234-8872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 Glycopyrrolate Oral Solution 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 Glycopyrrolate Oral Solution in the placebo-controlled study and 131 new subjects).Table 2 presents adverse reactions reported by ≥ 15% of Glycopyrrolate Oral…

Glycopyrrolate Oral Solution 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 Glycopyrrolate Oral Solution. • Medical conditions that preclude anticholinergic therapy. ( 4 ) • Concomitant use of solid oral dosage forms of potassium chloride. ( 4 )

Because glycopyrrolate is a quaternary amine which does not easily cross the blood-brain barrier, symptoms of glycopyrrolate overdosage are generally more peripheral in nature rather than central compared to other anticholinergic agents. In case of accidental overdose, therapy may include: • Maintain an open airway, providing ventilation as necessary. • Managing any acute conditions such as hyperthermia, coma and or seizures as applicable, and managing any jerky myoclonic movements or choreoathetosis which may lead to rhabdomyolysis in some cases of anticholinergic overdosage. • Administering a quaternary ammonium anticholinesterase such as neostigmine to help alleviate-peripheral anticholinergic effects such as anticholinergic induced ileus. • Administering activated charcoal orally as appropriate.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Digoxin tablets: Use with glycopyrrolate can increase digoxin serum levels. Monitor patients and consider use of alternative dosage forms of digoxin. ( 7 ) • Amantadine: Effects of glycopyrrolate may be increased with concomitant administration of amantadine. Consider decreasing the dose of glycopyrrolate during concomitant use. ( 7 ) • Atenolol or metformin: Glycopyrrolate may increase serum levels of atenolol or metformin. Consider dose reduction when used with glycopyrrolate. ( 7 ) • Haloperidol or levodopa: Glycopyrrolate may decrease serum levels of haloperidol or levodopa. Consider a dose increase when used with glycopyrrolate. ( 7 ) Drugs Affected by Reduced GI Transit Time Glycopyrrolate reduces GI transit time, which may result in altered release of certain drugs when formulated in delayed- or controlled-release dosage forms. • The passage of potassium chloride tablets through the GI tract may be arrested or delayed with coadministration of glycopyrrolate. Solid dosage forms of potassium chloride are contraindicated [see Contraindications (4) ]. • Digoxin administered as slow dissolution oral tablets may have increased serum levels and enhanced action when administered with glycopyrrolate. Monitor patients receiving slow dissolution digoxin for increased action if glycopyrrolate is coadministered regularly. Consider the use of other oral dosage forms of digoxin (e.g., elixir or capsules). Amantadine The anticholinergic effects of glycopyrrolate may be increased with concomitant administration of amantadine. Consider decreasing the dose of glycopyrrolate during coadministration of amantadine. Drugs Whose Plasma Levels May be Increased by Glycopyrrolate Coadministration of glycopyrrolate may result in increased levels of certain drugs. • Atenolol's bioavailability may be increased with coadministration of glycopyrrolate. A reduction in the atenolol dose may be needed. • Metformin plasma levels may be elevated with coadministration of glycopyrrolate, increasing metformin's pharmacologic and toxic effects. Monitor clinical response to metformin with concomitant glycopyrrolate administration; consider a dose reduction of metformin if warranted. Drugs Whose Plasma Levels May be Decreased by Glycopyrrolate Coadministration of glycopyrrolate may result in decreased levels of certain drugs. • Haloperidol's serum level may be decreased when coadministered with glycopyrrolate, resulting in worsening of schizophrenic symptoms, and development of tardive dyskinesia. Closely monitor patients if coadministration cannot be avoided. • Levodopa's therapeutic effect may be reduced with glycopyrrolate administration. Consider increasing the dose of levodopa.