Contraindications
4 CONTRAINDICATIONS PREVDUO ® is contraindicated in patients with: • known hypersensitivity to neostigmine methylsulfate (known hypersensitivity reactions have included urticaria, angioedema, erythema multiforme, generalized rash, facial swelling, peripheral edema, pyrexia, flushing, hypotension, bronchospasm, bradycardia and anaphylaxis) and glycopyrrolate or any inactive ingredients [ see Warnings and Precautions ( 5.3 ) ]. • peritonitis or mechanical obstruction of the intestinal or urinary tract. • Glaucoma; obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as in achalasia, pyloroduodenal stenosis, etc.); paralytic ileus, intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis. • Hypersensitivity to neostigmine, glycopyrrolate, or nonactive ingredients ( 4 ) • Peritonitis or mechanical obstruction of the intestinal or urinary tract ( 4 ) • Patients with glaucoma; obstructive uropathy; obstructive disease of the gastrointestinal tract; paralytic ileus, intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis ( 4 ).
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Neostigmine Methylsulfate There are no adequate or well-controlled studies of neostigmine in pregnant women. It is not known whether neostigmine can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. The incidence of malformations in human pregnancies has not been established for neostigmine as the data are limited. All pregnancies, regardless of drug exposure, have a background risk of 2 to 4% for major birth defects, and 15 to 20% for pregnancy loss. No adverse effects were noted in rats or rabbits treated with human equivalent doses of neostigmine methylsulfate doses up to 8.1 and 13 mcg/kg/day, respectively, during organogenesis (0.1 to 0.2-times the maximum recommended human dose of 5 mg/60 kg person/day based on body surface area comparisons). Anticholinesterase drugs, including neostigmine may cause uterine irritability and induce premature labor when administered to pregnant women near term. Glycopyrrolate Limited data available with glycopyrrolate use during pregnancy have not identified a drug-associated risk of birth defects and miscarriage, however, most of the reported exposures occurred after the first trimester. Most of the available data are based on studies with exposures that occurred at the time of Cesarean-section delivery, and these studies have not identified an adverse effect on maternal outcomes or infant Apgar scores (see Data). In animal reproduction studies in pregnant rats and rabbits administered glycopyrrolate orally (rats) and intramuscularly (rabbits) during the period of organogenesis, no teratogenic effects were seen at 640-times and 10-times the maximum recommended human dose (MRHD) of 1 mg (on a mg/m 2 basis), respectively (see Data). The estimated background risk for 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, t