relaxants) may potentiate the effects of scopolamine transdermal system [see warnings and precautions ( 5.2 )] . either scopolamine transdermal system or the interacting drug should be chosen, depending on the importance of the drug to the patient. if the interacting drug cannot be avoided, monitor patients for cns adverse reactions. 7.2 anticholinergic drugs concomitant use of scopolamine with other drugs having anticholinergic properties may increase the risk of cns adverse reactions [see drug interactions ( 7.1 )], intestinal obstruction and/or urinary retention. consider more frequent monitoring during treatment with scopolamine transdermal system in patients receiving anticholinergic drugs [see warnings and precautions ( 5.2 , 5.4 )] . 7.3 oral drugs absorbed in the stomach scopolamine transdermal system, as an anticholinergic, may delay gastric and upper gastrointestinal motility and, therefore, the rate of absorption of other orally administered drugs. monitor patients for modified therapeutic effect of concomitant orally administered drugs with a narrow therapeutic index. 7.4 interaction with gastric secretion test scopolamine will interfere with the gastric secretion test. discontinue scopolamine transdermal system 10 days prior to testing.

s difficulty in urination. ( 5.4 , 7.2 ) • drug withdrawal/post-removal symptoms : anticholinergic symptoms may occur 24 hours or more after removal of the transdermal system. ( 5.5 ) • blurred vision : avoid contact with the eyes. ( 2.1 , 5.6 ) • magnetic resonance imaging (mri) skin burns : remove scopolamine transdermal system prior to mri scan. ( 5.7 ) 5.1 acute angle closure glaucoma the mydriatic effect of scopolamine may cause an increase in intraocular pressure resulting in acute angle closure glaucoma. monitor intraocular pressure in patients with open angle glaucoma and adjust glaucoma therapy during scopolamine transdermal system use, as needed. advise patients to immediately remove the transdermal system and contact their healthcare provider if they experience symptoms of acute angle closure glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). 5.2 neuropsychiatric adverse reactions psychiatric adverse reactions scopolamine has been reported to exacerbate psychosis. other psychiatric reactions have also been reported, including acute toxic psychosis, agitation, speech disorder, hallucinations, paranoia, and delusions [see adverse reactions ( 6.2 )] . monitor patients for new or worsening psychiatric symptoms during treatment with scopolamine transdermal system. also, monitor patients for new or worsening psychiatric symptoms during concomitant treatment with other drugs that are associated with similar psychiatric effects [see drug interactions ( 7.1 )] . seizures seizures and seizure-like activity have been reported in patients receiving scopolamine. weigh this potential risk against the benefits before prescribing scopolamine transdermal system to patients with a history of seizures, including those receiving anti-epileptic medication or who have risk factors that can lower the seizure threshold. cognitive adverse reactions scopolamine can cause drowsiness, disorientation, and confusion. discontinue scopolamine transdermal system if signs or symptoms of cognitive impairment develop. elderly and pediatric patients may be more sensitive to the neurological and psychiatric effects of scopolamine transdermal system. consider more frequent monitoring during treatment with scopolamine transdermal system in elderly patients [see use in specific populations ( 8.5 )] . scopolamine transdermal system is not approved for use in pediatric patients [see use in specific populations ( 8.4 )] . hazardous activities scopolamine transdermal system may impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor vehicle, operating machinery or participating in underwater sports. concomitant use of other drugs that cause central nervous system (cns) adverse reactions (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics) or have anticholinergic properties (e.g., other belladonna alkaloids, sedating antihistamines, meclizine, tricyclic antidepressants, and muscle relaxants) may increase this effect [see drug interactions ( 7.1 )] . inform patients not to operate motor vehicles or other dangerous machinery or participate in underwater sports until they are reasonably certain that scopolamine transdermal system does not affect them adversely. 5.3 eclamptic seizures in pregnant women eclamptic seizures have been reported in pregnant women with severe preeclampsia soon after injection of intravenous and intramuscular scopolamine [see use in specific populations ( 8.1 )]. avoid use of scopolamine transdermal system in patients with severe preeclampsia. 5.4 gastrointestinal and urinary disorders scopolamine, due to its anticholinergic properties, can decrease gastrointestinal motility and cause urinary retention. consider more frequent monitoring during treatment with scopolamine transdermal system in patients suspected of having intestinal obstruction, patients with pyloric obstruction or urinary bladder neck obstruction and patients receiving other anticholinergic drugs [see drug interactions ( 7.2 )] . discontinue scopolamine transdermal system in patients who develop difficulty in urination. 5.5 drug withdrawal/post-removal symptoms discontinuation of scopolamine transdermal system, usually after several days of use, may result in withdrawal symptoms, such as disturbances of equilibrium, dizziness, nausea, vomiting, abdominal cramps, sweating, headache, mental confusion, muscle weakness, bradycardia and hypotension. the onset of these symptoms is generally 24 hours or more after the transdermal system has been removed. instruct patients to seek medical attention if they experience severe symptoms. 5.6 blurred vision scopolamine can cause temporary dilation of the pupils resulting in blurred vision if it comes in contact with the eyes. advise patients to wash their hands thoroughly with soap and water and dry their hands immediately after handling the transdermal system [see dosage and administration ( 2.1 )] . 5.7 magnetic resonance imaging (mri) skin burns scopolamine transdermal system contains an aluminized membrane. skin burns have been reported at the application site in patients wearing an aluminized transdermal system during an mri scan. remove scopolamine transdermal system before undergoing an mri.

opolamine transdermal system is formulated to deliver in vivo approximately 1 mg of scopolamine over 3 days. • only wear one transdermal system at any time. • do not cut the transdermal system. • apply the transdermal system to the skin in the postauricular area (hairless area behind one ear). • after the transdermal system is applied on the dry skin behind the ear, wash hands thoroughly with soap and water and dry hands [see warnings and precautions ( 5.6 )] . • if the transdermal system becomes displaced, discard the transdermal system, and apply a new transdermal system on the hairless area behind the other ear. • upon removal, fold the used transdermal system in half with the sticky side together, and discard in household trash in a manner that prevents accidental contact or ingestion by children, pets or others. 2.2 recommended adult dosage motion sickness apply one scopolamine transdermal system to the hairless area behind one ear at least 4 hours before the antiemetic effect is required – for use up to 3 days. if therapy is required for longer than 3 days, remove the first transdermal system and apply a new scopolamine transdermal system behind the other ear. ponv for surgeries other than cesarean section : apply one scopolamine transdermal system the evening before scheduled surgery. remove the transdermal system 24 hours following surgery.

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. motion sickness the most common adverse reaction (approximately two thirds) was dry mouth. less common adverse reactions, included drowsiness (less than one sixth), blurred vision and dilation of the pupils. ponv common adverse reactions, occurring in at least 3% of patients in ponv clinical trials are shown in table 1. scopolamine transdermal system % (n = 461) placebo % (n = 457) dry mouth 29 16 dizziness 12 7 somnolence 8 4 agitation 6 4 visual impairment 5 3 confusion 4 3 mydriasis 4 0 pharyngitis 3 2 *occurring in at least 3% of patients and at a rate higher than placebo 6.2 postmarketing experience the following adverse reactions have been identified during post-approval use of scopolamine transdermal system. 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. 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 pruritus, 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

relaxants) may potentiate the effects of scopolamine transdermal system [see warnings and precautions ( 5.2 )] . either scopolamine transdermal system or the interacting drug should be chosen, depending on the importance of the drug to the patient. if the interacting drug cannot be avoided, monitor patients for cns adverse reactions. 7.2 anticholinergic drugs concomitant use of scopolamine with other drugs having anticholinergic properties may increase the risk of cns adverse reactions [see drug interactions ( 7.1 )], intestinal obstruction and/or urinary retention. consider more frequent monitoring during treatment with scopolamine transdermal system in patients receiving anticholinergic drugs [see warnings and precautions ( 5.2 , 5.4 )] . 7.3 oral drugs absorbed in the stomach scopolamine transdermal system, as an anticholinergic, may delay gastric and upper gastrointestinal motility and, therefore, the rate of absorption of other orally administered drugs. monitor patients for modified therapeutic effect of concomitant orally administered drugs with a narrow therapeutic index. 7.4 interaction with gastric secretion test scopolamine will interfere with the gastric secretion test. discontinue scopolamine transdermal system 10 days prior to testing.

levels achieved in humans using a transdermal system. 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 background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data human data eclamptic seizures in published case reports, two pregnant patients with severe preeclampsia were administered intravenous and intramuscular scopolamine, respectively, and developed eclamptic seizures soon after scopolamine administration [see warnings and precautions ( 5.3 )] . animal data in animal reproduction studies, when pregnant rats and rabbits received scopolamine hydrobromide by daily intravenous injection, no adverse effects were observed in rats. an embryotoxic effect was observed in rabbits at doses producing plasma levels approximately 100 times the levels achieved in humans using a transdermal system. scopolamine administered parenterally to rats and rabbits at doses higher than the dose delivered by scopolamine transdermal system did not affect uterine contractions or increase the duration of labor. 8.2 lactation risk summary scopolamine is present in human milk. there are no available data on the effects of scopolamine on the breastfed infant or the effects on milk production. because there have been no consistent reports of adverse events in breastfed infants over decades of use, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for scopolamine transdermal system and any potential adverse effects on the breastfed child from scopolamine transdermal system or from the underlying maternal condition. 8.4 pediatric use safety and effectiveness in pediatric patients have not been established. pediatric patients are particularly susceptible to the adverse reactions of scopolamine; including mydriasis, hallucinations, amblyopia and drug withdrawal syndrome. neurologic and psychiatric adverse reactions, such as hallucinations, amblyopia and mydriasis have also been reported. 8.5 geriatric use clinical trials of scopolamine transdermal system did not include sufficient number of subjects aged 65 years and older to determine if they respond differently from younger subjects. in other clinical experience, elderly patients had an increased risk of neurologic and psychiatric adverse reactions, such as hallucinations, confusion, dizziness and drug withdrawal syndrome [see warnings and precautions ( 5.2 , 5.5 )]. consider more frequent monitoring for cns adverse reactions during treatment with scopolamine transdermal system in elderly patients [see warnings and precautions ( 5.2 )] . 8.6 renal or hepatic impairment scopolamine transdermal system has not been studied in patients with renal or hepatic impairment. consider more frequent monitoring during treatment with scopolamine transdermal system in patients with renal or hepatic impairment because of the increased risk of cns adverse reactions [see warnings and precautions ( 5.2 )].

defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data human data eclamptic seizures in published case reports, two pregnant patients with severe preeclampsia were administered intravenous and intramuscular scopolamine, respectively, and developed eclamptic seizures soon after scopolamine administration [see warnings and precautions ( 5.3 )] . animal data in animal reproduction studies, when pregnant rats and rabbits received scopolamine hydrobromide by daily intravenous injection, no adverse effects were observed in rats. an embryotoxic effect was observed in rabbits at doses producing plasma levels approximately 100 times the levels achieved in humans using a transdermal system. scopolamine administered parenterally to rats and rabbits at doses higher than the dose delivered by scopolamine transdermal system did not affect uterine contractions or increase the duration of labor.

hin 4 hours with peak concentrations being obtained, on average, within 24 hours. the average plasma concentration produced is 87 pg/ml (0.28 nm) for free scopolamine and 354 pg/ml for total scopolamine (free + conjugates). following removal of the used transdermal system, there is some degree of continued systemic absorption of scopolamine bound in the skin layers. distribution the distribution of scopolamine is not well characterized. it crosses the placenta and the blood brain barrier and may be reversibly bound to plasma proteins. elimination metabolism and excretion scopolamine is metabolized and conjugated with less than 5% of the total dose appearing unchanged in the urine. the enzymes responsible for metabolizing scopolamine are unknown. the exact elimination pattern of scopolamine has not been determined. following transdermal system removal, plasma concentrations of scopolamine decline in a log linear fashion with an observed half-life of 9.5 hours. less than 10% of the total dose is excreted in the urine as the parent drug and metabolites over 108 hours. drug interaction studies an in vitro study using human hepatocytes examined the induction of cyp1a2 and cyp3a4 by scopolamine. scopolamine did not induce cyp1a2 and cyp3a4 isoenzymes at the concentrations up to 10 nm. in an in vitro study using human liver microsomes which evaluated the inhibition of cyp1a2, 2c8, 2c9, 2c19, 2d6 and 3a4, scopolamine did not inhibit these cytochrome p450 isoenzymes at the concentrations up to 1 micromolar. no in vivo drug-drug interaction studies have been conducted.

the exact elimination pattern of scopolamine has not been determined. following transdermal system removal, plasma concentrations of scopolamine decline in a log linear fashion with an observed half-life of 9.5 hours. less than 10% of the total dose is excreted in the urine as the parent drug and metabolites over 108 hours. drug interaction studies an in vitro study using human hepatocytes examined the induction of cyp1a2 and cyp3a4 by scopolamine. scopolamine did not induce cyp1a2 and cyp3a4 isoenzymes at the concentrations up to 10 nm. in an in vitro study using human liver microsomes which evaluated the inhibition of cyp1a2, 2c8, 2c9, 2c19, 2d6 and 3a4, scopolamine did not inhibit these cytochrome p450 isoenzymes at the concentrations up to 1 micromolar. no in vivo drug-drug interaction studies have been conducted.

n in 89% of patients treated with scopolamine transdermal system as compared to 72% of placebo-treated patients.

ith open-angle glaucoma advise patients with open-angle glaucoma to remove the scopolamine transdermal system immediately and contact their healthcare provider if they experience symptoms of acute angle closure glaucoma, including pain and reddening of the eyes, accompanied by dilated pupils, blurred vision and/or seeing halos around lights [see warnings and precautions ( 5.1 )] . neuropsychiatric adverse reactions • advise patients that psychiatric adverse reactions may occur, especially in patients with a past psychiatric history or in those receiving other drugs also associated with psychiatric effects, and to report to their healthcare provider any new or worsening psychiatric symptoms. • advise patients to discontinue scopolamine transdermal system and contact a healthcare provider immediately if they experience a seizure. • advise patients, especially elderly patients, that cognitive impairment may occur during treatment with scopolamine transdermal system, especially in those receiving other drugs also associated with cns effects, and to report to their healthcare provider if they develop signs or symptoms of cognitive impairment such as hallucinations, confusion or dizziness. • inform patients not to operate motor vehicles or other dangerous machinery or participate in underwater sports until they are reasonably certain that scopolamine transdermal system does not affect them adversely [see warnings and precautions ( 5.2 )] . decreased gastrointestinal motility and urinary retention instruct patients to remove the transdermal system if they develop symptoms of intestinal obstruction (abdominal pain, nausea or vomiting) or any difficulties in urinating [see warnings and precautions ( 5.4 )] . drug withdrawal/post-removal symptoms inform patients that if they remove the scopolamine transdermal system before treatment is complete, withdrawal symptoms may occur and to seek immediate medical care if they develop severe symptoms after removing scopolamine transdermal system [see warnings and precautions ( 5.5 )] . blurred vision inform patients that temporary dilation of the pupils and blurred vision may occur if scopolamine transdermal system comes in contact with the eyes. instruct patients to wash their hands thoroughly with soap and water immediately after handling the transdermal system [see dosage and administration ( 2.1 ), warnings and precautions ( 5.6 )] . mri skin burns instruct patients to remove the scopolamine transdermal system before undergoing an mri [see warnings and precautions ( 5.7 )]. manufactured by: aveva drug delivery systems an apotex company miramar, fl 33025 distributed by perrigo® allegan, mi 49010 · www.perrigo.com 5a800 rc br7