6 ADVERSE REACTIONS Most common adverse reactions during motion sickness clinical trials are dry mouth, drowsiness and blurred vision. (6.1) Most common adverse reactions during PONV trials (≥ than 3%) are dry mouth, dizziness, somnolence, urinary retention, agitation, visual impairment, confusion, mydriasis and pharyngitis. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-398-5876 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 clinical practice. Motion Sickness In motion sickness clinical studies of Transderm Scōp®, the most frequent adverse reaction was dry mouth. This occurred in about two thirds of patients on drug. A less frequent adverse drug reaction was drowsiness, which occurred in less than one sixth of patients on drug. Transient impairment of eye accommodation, including blurred vision and dilation of the pupils, was also observed. Post-Operative Nausea and Vomiting In a total of five clinical studies in which Transderm Scōp® was administered perioperatively to a total of 461 patients where safety was assessed, dry mouth was the most frequently reported adverse drug reaction, which occurred in approximately 29% of patients on drug. Dizziness was reported by approximately 12% of patients on drug. Other adverse drug reactions reported from these studies, with a frequency of ≥3% of patients treated with Transderm Scōp® and with a frequency higher than placebo were, in descending order: somnolence, urinary retention, agitation/restlessness, visual impairment, confusion, mydriasis and pharyngitis (see Table 6.1). Table 6.1 PONV: Adverse Drug Reactions in ≥3% of Patients Transderm Scōp® (N=461) Placebo (N=457) n % n % Adverse Drug Reactions 303 65.7 259 56.7 Dry mouth 133 28.9 72 15.8 Dizziness 57 12.4 33 7.2 Somnolence 36 7.8 16 3.5 Urinary Retention 33 7.2 30 6.6 Agitation 28 6.1 20 4.4 Visual Impairment 23 5.0 12 2.6 Confusion 18 3.9 14 3.1 Mydriasis 16 3.5 2 0.4 Pharyngitis 15 3.3 10 2.2 6.2 Postmarketing Experience The following adverse drug reactions, further to those reported from clinical trials, have been identified during postapproval use of Transderm Scop®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to confirm a definite causal relationship. In worldwide marketing with Transderm Scōp®, the following adverse drug reactions were reported by body system. Psychiatric disorders: acute psychosis including: hallucinations disorientation, and paranoia. Nervous system disorders: headache, amnesia, coordination abnormalities, speech disorder, disturbance in attention, restlessness. General disorders and administration site conditions: application site burning. Eye disorders: dry eyes, eye pruritis, angle closure glaucoma, amblyopia, eyelid irritation. Skin and subcutaneous tissue disorders: rash generalized, skin irritation, erythema. Renal and urinary disorders: dysuria. Ear and Labyrinth Disorders: vertigo. 6.3 Drug Withdrawal/Post-Removal Symptoms Symptoms such as dizziness, nausea, vomiting, abdominal cramps, sweating, headache mental confusion, muscle weakness, bradycardia and hypotension may occur following abrupt discontinuation of anticholinergic drugs such as Transderm Scōp®. Similar symptoms, including disturbances of equilibrium, have been reported in some patients following discontinuation of use of the Transderm Scōp® system. These symptoms usually do not appear until 24 hours or more after the patch has been removed. These symptoms can be severe and may require medical intervention. Some symptoms may be related to adaptation from a motion environment to a motion-free environment.