Transderm Scop

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in labeling: • Acute Angle Closure Glaucoma [see Warnings and Precautions ( 5.1 )] • Neuropsychiatric Adverse Reactions [see Warnings and Precautions ( 5.2 )] • Eclamptic Seizures in Pregnant Women [see Warnings and Precautions ( 5.3 )] • Gastrointestinal and Urinary Disorders [see Warnings and Precautions ( 5.4 )] • Drug Withdrawal/Post-Removal Symptoms [see Warnings and Precautions ( 5.5 )] • Blurred Vision [see Warnings and Precautions ( 5.6 )] • MRI Skin Burns [see Warnings and Precautions ( 5.7 )] Most common adverse reactions are: • Motion Sickness (>15%): dry mouth, drowsiness, blurred vision and dilation of the pupils. ( 6.1 ) • PONV (≥ 3%): dry mouth, dizziness, somnolence, agitation, visual impairment, confusion, mydriasis and pharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline Consumer Healthcare at 1-800-398-5876 or FDA at 1-800-FDA-1088 or www.fda.gov/Safety/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 . Table 1 Common Adverse Reactions* in Surgical Patients for the Prevention of PONV *occurring in at least 3% of patients and at a rate higher than placebo Transderm Scōp % (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 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

4 CONTRAINDICATIONS Transderm Scōp is contraindicated in patients with: • angle closure glaucoma [see Warnings and Precautions ( 5.1 )] . • hypersensitivity to scopolamine or other belladonna alkaloids or to any ingredient or component in the formulation or delivery system. Reactions have included rash generalized and erythema [see Adverse Reactions ( 6.2 ), Description ( 11 )] . • Angle closure glaucoma. ( 4 , 6.2 ) • Hypersensitivity to scopolamine or other belladonna alkaloids or to any ingredient or component of the formulation or delivery system. ( 4 , 7 )

11 DESCRIPTION Transderm Scōp (scopolamine transdermal system) is designed for continuous release of scopolamine following application to an area of intact skin on the head, behind the ear. Each system contains 1.5 mg of scopolamine base. Scopolamine is (9-methyl-3-oxa-9-azatricyclo[3.3.1.0 2,4 ]nonan-7-yl) 3-hydroxy-2-phenylpropanoate. The empirical formula is C 17 H 21 NO 4 and its structural formula is: Scopolamine has a molecular weight of 303.35 and a pKa of 7.55-7.81. The Transderm Scōp transdermal system is a circular, 0.2 mm thick, 2.5 cm 2 film with four layers. Proceeding from the visible surface towards the surface attached to the skin, these layers are: (1) a backing membrane of tan-colored, aluminized, polyester film; (2) a drug layer of scopolamine, light mineral oil, and polyisobutylene; (3) a microporous polypropylene membrane that controls the rate of delivery of scopolamine from the system to the skin surface; and (4) a contact layer formulation of mineral oil, polyisobutylene, and scopolamine. A release liner of siliconized polyester, which covers the adhesive layer, is removed before the system is used. Cross section of the system: Scopolamine structural formula Cross section of transdermal system

2 DOSAGE AND ADMINISTRATION Application and Removal ( 2.1 ): • Each Transderm Scōp transdermal system delivers 1 mg of scopolamine over 3 days. • Only wear one transdermal system at a time. • Do not cut the transdermal system. • Wash hands thoroughly after application. • Upon removal, fold used transdermal system in half with sticky side together, and discard to prevent accidental contact or ingestion. Recommended Dosage : • Motion Sickness : Apply one transdermal system to the hairless area behind one ear at least 4 hours before antiemetic effect is required for use up to 3 days. If therapy for more than 3 days is required, remove the first transdermal system and apply a new transdermal system behind the other ear. ( 2.2 ) • PONV : For surgeries other than cesarean section, apply one transdermal system behind the ear the evening before surgery and remove 24 hours following surgery. ( 2.2 ) 2.1 Important Application and Removal Instructions • Each Transderm Scōp 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 Transderm Scōp 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 Transderm Scōp transdermal system behind the other ear. PONV For surgeries other than cesarean section : Apply one Transderm Scōp transdermal system the evening before scheduled surgery. Remove the transdermal system 24 hours following surgery.

1 INDICATIONS AND USAGE Transderm Scōp is indicated in adults for the prevention of: • nausea and vomiting associated with motion sickness. • post-operative nausea and vomiting (PONV) associated with recovery from anesthesia and/or opiate analgesia and surgery. Transderm Scōp is an anticholinergic indicated in adults for the prevention of: • nausea and vomiting associated with motion sickness. ( 1 ) • post-operative nausea and vomiting (PONV) associated with recovery from anesthesia and/or opiate analgesia and surgery. ( 1 )

9.1 Controlled Substance Transderm Scōp contains scopolamine, which is not a controlled substance.

9.3 Dependence Termination of Transderm Scōp, 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 . These withdrawal symptoms indicate that scopolamine, like other anticholinergic drugs, may produce physical dependence. The onset of these symptoms, generally 24 hours or more after the transdermal system has been removed, can be severe and may require medical intervention [see Warnings and Precautions ( 5.5 )] .

9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance Transderm Scōp contains scopolamine, which is not a controlled substance. 9.3 Dependence Termination of Transderm Scōp, 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 . These withdrawal symptoms indicate that scopolamine, like other anticholinergic drugs, may produce physical dependence. The onset of these symptoms, generally 24 hours or more after the transdermal system has been removed, can be severe and may require medical intervention [see Warnings and Precautions ( 5.5 )] .

10 OVERDOSAGE The signs and symptoms of anticholinergic toxicity include: lethargy, somnolence, coma, confusion, agitation, hallucinations, convulsion, visual disturbance, dry flushed skin, dry mouth, decreased bowel sounds, urinary retention, tachycardia, hypertension, and supraventricular arrhythmias. These symptoms can be severe and may require medical intervention. In cases of toxicity remove the Transderm Scōp transdermal system. Serious symptomatic cases of overdosage involving multiple transdermal system applications and/or ingestion may be managed by initially ensuring the patient has an adequate airway and supporting respiration and circulation. This should be rapidly followed by removal of all transdermal systems from the skin and the mouth. If there is evidence of transdermal system ingestion, endoscopic removal of swallowed transdermal systems, or administration of activated charcoal should be considered, as indicated by the clinical situation. In any case where there is serious overdosage or signs of evolving acute toxicity, continuous monitoring of vital signs and ECG, establishment of intravenous access, and administration of oxygen are all recommended. The signs and symptoms of overdose/toxicity due to scopolamine should be carefully distinguished from the occasionally observed syndrome of withdrawal [see Warnings and Precautions ( 5.5 )]. Although mental confusion and dizziness may be observed with both acute toxicity and withdrawal, other characteristic findings differ: tachyarrhythmias, dry skin, and decreased bowel sounds suggest anticholinergic toxicity, while bradycardia, headache, nausea and abdominal cramps, and sweating suggest post-removal withdrawal. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

7 DRUG INTERACTIONS • Drugs Causing Central Nervous System (CNS) Adverse Reactions : Monitor patients for CNS adverse reactions (drowsiness, dizziness or disorientations). ( 7.1 ) • Anticholinergic Drugs : Consider more frequent monitoring during treatment in patients receiving other anticholinergic drugs. ( 7.2 ) • Oral Drugs Absorbed in the Stomach : Monitor for increased or decreased therapeutic effect of the oral drug. ( 7.3 ) • Interaction with Gastric Secretion Test : Discontinue use of Transderm Scōp 10 days prior to testing. ( 7.4 ) 7.1 Drugs Causing Central Nervous System (CNS) Adverse Reactions The concurrent use of Transderm Scōp with other drugs that cause CNS adverse reactions of drowsiness, dizziness or disorientation (e.g., sedatives, hypnotics, opiates, anxiolytics and alcohol) or have anticholinergic properties (e.g., other belladonna alkaloids, sedating antihistamines, meclizine, tricyclic antidepressants, and muscle relaxants) may potentiate the effects of Transderm Scōp [see Warnings and Precautions ( 5.2 )] . Either Transderm Scōp 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 Transderm Scōp in patients receiving anticholinergic drugs [see Warnings and Precautions ( 5.2 , 5.4 )] . 7.3 Oral Drugs Absorbed in the Stomach Transderm Scōp, 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 Transderm Scōp 10 days prior to testing.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Scopolamine, a belladonna alkaloid, is an anticholinergic. Scopolamine acts: i) as a competitive inhibitor at postganglionic muscarinic receptor sites of the parasympathetic nervous system, and ii) on smooth muscles that respond to acetylcholine but lack cholinergic innervation. It has been suggested that scopolamine acts in the central nervous system (CNS) by blocking cholinergic transmission from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center. Scopolamine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate, and depress motor function. 12.3 Pharmacokinetics The system is formulated to deliver approximately 1 mg of scopolamine to the systemic circulation over 3 days. Absorption Following application to the skin behind the ear, circulating plasma concentrations are detected within 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.

12.1 Mechanism of Action Scopolamine, a belladonna alkaloid, is an anticholinergic. Scopolamine acts: i) as a competitive inhibitor at postganglionic muscarinic receptor sites of the parasympathetic nervous system, and ii) on smooth muscles that respond to acetylcholine but lack cholinergic innervation. It has been suggested that scopolamine acts in the central nervous system (CNS) by blocking cholinergic transmission from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center. Scopolamine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate, and depress motor function.

12.3 Pharmacokinetics The system is formulated to deliver approximately 1 mg of scopolamine to the systemic circulation over 3 days. Absorption Following application to the skin behind the ear, circulating plasma concentrations are detected within 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.

20190301

10

3 DOSAGE FORMS AND STRENGTHS Transdermal system: a circular, flat, tan-colored transdermal system imprinted with “Scopolamine 1 mg/3 days” Transdermal system: 1 mg/3 days ( 3 )

Transderm Scop Scopalamine SCOPOLAMINE SCOPOLAMINE POLYISOBUTYLENE (1100000 MW) POLYISOBUTYLENE (35000 MW) LIGHT MINERAL OIL

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term studies in animals have been conducted to evaluate the carcinogenic potential of scopolamine. The mutagenic potential of scopolamine has not been evaluated. Fertility studies were performed in female rats and revealed no evidence of impaired fertility or harm to the fetus due to scopolamine hydrobromide administered by daily subcutaneous injection. Maternal body weights were reduced in the highest-dose group (plasma level approximately 500 times the level achieved in humans using a transdermal system). However, fertility studies in male animals were not performed.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term studies in animals have been conducted to evaluate the carcinogenic potential of scopolamine. The mutagenic potential of scopolamine has not been evaluated. Fertility studies were performed in female rats and revealed no evidence of impaired fertility or harm to the fetus due to scopolamine hydrobromide administered by daily subcutaneous injection. Maternal body weights were reduced in the highest-dose group (plasma level approximately 500 times the level achieved in humans using a transdermal system). However, fertility studies in male animals were not performed.

NDA017874

Transderm Scop

Scopalamine

10019-553

HUMAN PRESCRIPTION DRUG

TRANSDERMAL

PRINCIPAL DISPLAY PANEL NDC 10019-553-03 Transderm Scop (scopolamine) TRANSDERMAL SYSTEM, 1 mg/3 days Formulated delivery of approximately 1 mg over three days Rx ONLY 10 Transdermal Systems Multipack ©20YY GSK or licensor. Rev. MM/20YY 07-03-00-0059 883366-10C TransDerm Scop Representative Carton 10019-553-03

Warnings and Precautions ( 5.3 ) 03/2019

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Administration Instructions Counsel patients on how to apply and remove the transdermal system [see Dosage and Administration ( 2.1 )] : • Only wear one transdermal system at any time. • Do not cut the transdermal system. • Apply the transdermal system to the skin in the postauricular (hairless area behind one ear) area. • After the transdermal system is applied on the dry skin behind the ear, wash hands thoroughly with soap and water and dry hands. • 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. Patients with Open-Angle Glaucoma Advise patients with open-angle glaucoma to remove the Transderm Scōp 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 Transderm Scōp and contact a healthcare provider immediately if they experience a seizure. • Advise patients, especially elderly patients, that cognitive impairment may occur during treatment with Transderm Scōp,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 Transderm Scōp 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 Transderm Scōp transdermal system before treatment is complete, withdrawal symptoms may occur and to seek immediate medical care if they develop severe symptoms after removing Transderm Scōp [see Warnings and Precautions ( 5.5 )] . Blurred Vision Inform patients that temporary dilation of the pupils and blurred vision may occur if Transderm Scōp 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 Transderm Scōp transdermal system before undergoing an MRI [see Warnings and Precautions ( 5.7 )]. Marketed by: Baxter Healthcare Corporation Deerfield, IL 60015 USA Manufactured by: ALZA Corporation, Vacaville, CA 95688 for GSK Consumer Healthcare, Warren, NJ 07059 For Product Inquiry 1 800 ANA DRUG (1-800-262-3784) Trademarks are owned by or licensed to the GSK group of companies. ©2019 GSK group of companies or its licensor

14 CLINICAL STUDIES 14.1 Prevention of Motion Sickness In 195 adult subjects of different racial origins who participated in clinical efficacy studies at sea or in a controlled motion environment, there was a 75% reduction in the incidence of motion-induced nausea and vomiting. Transderm Scōp was applied from 4 to 16 hours prior to the onset of motion in these studies. 14.2 Prevention of Post-Operative Nausea and Vomiting A clinical efficacy study evaluated 168 adult female patients undergoing gynecological surgery with anesthesia and opiate analgesia. Patients received Transderm Scōp or placebo applied approximately 11 hours before anesthesia/opiate analgesia. No retching/vomiting during the 24-hour post-operative period was reported in 79% of those treated with Transderm Scōp compared to 72% of those receiving placebo. When the need for additional antiemetic medication was assessed during the same period, there was no need for medication in 89% of patients treated with Transderm Scōp as compared to 72% of placebo-treated patients.

8.5 Geriatric Use Clinical trials of Transderm Scōp 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 Transderm Scōp in elderly patients [see Warnings and Precautions ( 5.2 )] .

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.

8.1 Pregnancy Risk Summary Available data from observational studies and postmarketing reports with scopolamine use in pregnant women have not identified a drug associated risk of major birth defects, miscarriage, or adverse fetal outcomes. Avoid use of Transderm Scōp in pregnant women with severe preeclampsia because eclamptic seizures have been reported after exposure to scopolamine (see Data). In animal studies, there was no evidence of adverse developmental effects with intravenous administration of scopolamine hydrobromide revealed in rats. Embryotoxicity was observed in rabbits at intravenous doses producing plasma levels approximately 100 times the 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 Transderm Scōp did not affect uterine contractions or increase the duration of labor.

8 USE IN SPECIFIC POPULATIONS • Geriatric Patients : Consider more frequent monitoring during treatment due to increased risk of CNS adverse reactions. ( 5.2 , 8.5 ) • Renal or Hepatic Impairment : Consider more frequent monitoring during treatment due to increased risk of CNS adverse reactions. ( 5.2 , 8.6 ) 8.1 Pregnancy Risk Summary Available data from observational studies and postmarketing reports with scopolamine use in pregnant women have not identified a drug associated risk of major birth defects, miscarriage, or adverse fetal outcomes. Avoid use of Transderm Scōp in pregnant women with severe preeclampsia because eclamptic seizures have been reported after exposure to scopolamine (see Data). In animal studies, there was no evidence of adverse developmental effects with intravenous administration of scopolamine hydrobromide revealed in rats. Embryotoxicity was observed in rabbits at intravenous doses producing plasma levels approximately 100 times the 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 Transderm Scōp 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 Transderm Scōp and any potential adverse effects on the breastfed child from Transderm Scōp 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 Transderm Scōp 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 Transderm Scōp in elderly patients [see Warnings and Precautions ( 5.2 )] . 8.6 Renal or Hepatic Impairment Transderm Scōp has not been studied in patients with renal or hepatic impairment. Consider more frequent monitoring during treatment with Transderm Scōp in patients with renal or hepatic impairment because of the increased risk of CNS adverse reactions [see Warnings and Precautions ( 5.2 )].

16 HOW SUPPLIED/STORAGE AND HANDLING Transderm Scōp (scopolamine transdermal system) 1 mg/3 days is available as the following: Cartons of 10 and 24 transdermal systems, packaged into individual foil pouches. • Carton of 10 transdermal systems. NDC 10019-553-03 • Carton of 24 transdermal systems. NDC 10019-553-04 Store at controlled room temperature between 68°F to 77°F (20°C to 25°C). Store pouch(es) in an upright position. Do not bend or roll pouch(es). Wash hands thoroughly with soap and water immediately after handling the transdermal system. 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 [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.6 )] .