Prescription Drugs

CLINICAL PHARMACOLOGY Mechanism Of Action Scopolamine, a belladonna alkaloid, is an anticholinergic agent. 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. Pharmacokinetics The pharmacokinetics of scopolamine delivered via the system are due to the characteristics of both the drug and dosage form. The system is formulated to deliver in-vivo approximately 1 mg of scopolamine at an approximately constant rate to the systemic circulation over 3 days. Upon application to the postauricular skin, an initial priming dose of scopolamine is released from the adhesive layer to saturate skin-binding sites. The subsequent delivery of scopolamine to the blood is determined by the rate controlling membrane and is designed to produce stable plasma levels in a therapeutic range. Following removal of the used system, there is some degree of continued systemic absorption of scopolamine bound in the skin layers. Absorption Scopolamine is well absorbed percutaneously. Following application to the skin behind the ear, circulating plasma levels are detected within 4 hours with peak levels 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). 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. Metabolism and Excretion The exact elimination pattern of scopolamine has not been determined. Following patch removal, plasma levels 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.  Scopolamine is extensively metabolized and conjugated with less than 5% of the total dose appearing unchanged in the urine. The enzymes responsible for metabolizing scopolamine are unknown. Drug Interaction 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 mcM. Nonclinical Pharmacology 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. Clinical Studies 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. Post-Operative Nausea And Vomiting In two pivotal clinical efficacy studies in 391 adult female patients undergoing cesarean section or gynecological surgery with anesthesia and opiate analgesia, 66% of those treated with Transderm Scop® (compared to only 46% of those receiving placebo) reported no retching/vomiting within the 24-hour period following administration of anesthesia/opiate analgesia. When the need for additional antiemetic medication was assessed during the same period, there was no need for medication in 76% of patients treated with Transderm Scop as compared to 59% of placebo-treated patients.

CLINICAL PHARMACOLOGY This anticholinergic preparation blocks the responses of the sphincter muscle of the iris and the accommodative muscle of the ciliary body to cholinergic stimulation, producing pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia).

Transderm Scop® (scopolamine) Transdermal System DESCRIPTION The Transderm Scop® (scopolamine) transdermal system is a circular flat patch 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 α -(hydroxymethyl) benzeneacetic acid 9-methyl-3-oxa-9-azatricyclo [3.3.1.02,4 ] non-7-yl ester. The empirical formula is C17H21NO4 and its structural formula is: Scopolamine is a viscous liquid that has a molecular weight of 303.35 and a pKa of 7.55-7.81. The Transderm Scop system is a film 0.2 mm thick and 2.5 cm², with four layers. Proceeding from the visible surface towards the surface attached to the skin, these layers are: (1) a backing layer of tan-colored, aluminized, polyester film; (2) a drug reservoir 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) an adhesive formulation of mineral oil, polyisobutylene, and scopolamine. A protective peel strip of siliconized polyester, which covers the adhesive layer, is removed before the system is used. The inactive components, light mineral oil (12.4 mg) and polyisobutylene (11.4 mg), are not released from the system. Cross section of the system:

INDICATIONS Motion Sickness Transderm Scop® is indicated in adults for prevention of nausea and vomiting associated with motion sickness. [see Clinical Studies] Post Operative Nausea And Vomiting (PONV) Transderm Scop® is indicated in adults for prevention of nausea and vomiting associated with recovery from anesthesia and/or opiate analgesia and surgery. [see Clinical Studies] DOSAGE AND ADMINISTRATION Each Transderm Scop® patch is formulated to deliver in-vivo approximately 1mg of scopolamine over 3 days. Only one patch should be worn at any time. Do not cut the patch. The patch should be applied only to the skin in the postauricular (hairless area behind one ear) area. Handling After the patch is applied on the dry skin behind the ear, the hands should be washed thoroughly with soap and water and dried. Upon removal, the patch should be discarded. To prevent any traces of scopolamine from coming into direct contact with the eyes, after administration of the patch, the hands and the application site should be washed thoroughly with soap and water and dried. [see HOW SUPPLIED/Storage and Handling and PATIENT INFORMATION] Initiation Of Therapy Motion Sickness To prevent the nausea and vomiting associated with motion sickness, one Transderm Scop® patch (formulated to deliver approximately 1mg of scopolamine over 3 days) should be applied to the hairless area behind one ear at least 4 hours before the antiemetic effect is required. Post Operative Nausea and Vomiting To prevent post operative nausea and vomiting, one Transderm Scop® patch should be applied the evening before scheduled surgery, except for caesarian section. For caesarian section surgery, to minimize exposure of the newborn baby to the drug, apply the patch one hour prior to caesarian section Sections or subsections omitted from the full prescribing information are not listed. Continuation Of Therapy Should the patch become displaced, it should be discarded, and a fresh one placed on the hairless area behind the other ear. Motion Sickness If therapy is required for longer than 3 days, the first patch should be removed and a fresh one placed on the hairless area behind the other ear. Post Operative Nausea and Vomiting For perioperative use, the patch should be kept in place for 24 hours following surgery at which time it should be removed and discarded. HOW SUPPLIED Dosage Forms And Strengths The Transderm Scop® system is a tan-colored circular flat patch which contains 1.5 mg of scopolamine base and is formulated to deliver in-vivo approximately 1mg of scopolamine over 3 days. Storage And Handling The Transderm Scop® system is a tan-colored circular patch, 2.5 cm², on a clear, oversized, hexagonal peel strip, which is removed prior to use. Each Transderm Scop system contains 1.5 mg of scopolamine and is formulated to deliver in-vivo approximately 1 mg of scopolamine over 3 days. Transderm Scop® is available in packages of four patches. Each patch is foil wrapped. Patient instructions are included. [see PATIENT INFORMATION] 1 Package (4 patches) NDC 0067-4345-04 Storage The system should be stored at controlled room temperature between 20°C-25°C (68°F-77°F). Handling Since scopolamine can cause temporary dilation of the pupils and blurred vision if it comes in contact with the eyes, patients should be strongly advised to wash their hands thoroughly with soap and water immediately after handling the patch. In addition, it is important that used patches be disposed of properly to avoid contact with children or pets. [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and PATIENT INFORMATION] Manufactured by: ALZA Corporation, Vacaville, CA 95688. Distributed by: Novartis Cons umer Health, Inc., Parsippany, NJ 07054-0622. Revised: Dec 2014

INDICATIONS For mydriasis and cycloplegia in diagnostic procedures. For some pre- and postoperative states when a mydriatic and cycloplegic is needed in treatment of iridocyclitis. DOSAGE AND ADMINISTRATION For refraction, administer one or two drops topically in the eye(s) one hour before refracting. For uveitis, administer one or two drops topically in the eye(s) up to four times daily. HOW SUPPLIED In 5 mL and 15 mL plastic DROP-TAINER® dispensers. 5 mL NDC 0998-0331-05 15 mL NDC -15 STORAGE: Store at 46° to 80°F. Protect from light.

PATIENT INFORMATION Transderm Scop® pronounced tran(t)s-derm skop (scopolamine) transdermal system patch Read this Patient Information before you start using Transderm Scop® and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. What is Transderm Scop®? The Transderm Scop® patch is a prescription medicine used for adults to: help prevent nausea and vomiting from motion sickness help prevent nausea and vomiting from anesthesia or taking opioid pain medicines after surgery It is not known if Transderm Scop® is safe or effective in children. Who should not use Transderm Scop®? Do not use Transderm Scop® if you: have an eye problem called angle closure glaucoma if you are allergic to any of the ingredients in Transderm Scop® or other medicines called belladonna alkaloids. See the end of this leaflet for a list of the ingredients in Transderm Scop®. Ask your doctor if you are not sure. What should I tell my doctor before using Trans derm Scop®? Before you use Transderm Scop®, tell your doctor if you: are scheduled to have a gastric secretion test have glaucoma (increased pressure in the eye) have liver or kidney problems have problems with your stomach or intestines have trouble urinating have a history of seizures or psychosis have any other medical conditions are pregnant or plan to become pregnant. It is not known if Transderm Scop® can harm your unborn baby. are breast-feeding or plan to breast-feed. Transderm Scop® can pass into your breast milk and may harm your baby. Talk to your doctor about the best way to feed your baby if you use Transderm Scop®. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Transderm Scop® may affect the way other medicines work, and other medicines may affect how Transderm Scop® works. Medicines that you take by mouth may not be absorbed well while you use Transderm Scop®. Especially tell your doctor if you take: a sedative or tranquilizer (medicines that make you sleepy) an antidepressant medicine an anticholinergic medicine, such as an allergy or cold medicine, a medicine to treat bladder or bowel spasms, certain asthma medicines, or other medicines for motion sickness. Ask your doctor if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of them and show it to your doctor or pharmacist when you get a new medicine. How should I use Transderm Scop®? Use Transderm Scop® exactly as your doctor tells you to use it. Transderm Scop® is a tan-colored circle shaped patch. Wear only one patch at any time. Do not cut the patch. To help prevent nausea and vomiting from motion sickness: Apply one Transderm Scop® patch to your skin on a hairless area behind one ear at least 4 hours before the activity to prevent nausea and vomiting. If the treatment is needed for longer than 3 days, remove the patch from the hairless area behind your ear. Get a new Transderm Scop® patch and place it on the hairless area behind your other ear. To help prevent nausea and vomiting after surgery: Follow your doctor's instructions about when to apply Transderm Scop® before your scheduled surgery. The Transderm Scop® patch should be left in place for 24 hours after surgery. After 24 hours the patch should be removed and thrown away. Apply Transderm Scop® as follows: Inside the Transderm Scop® package, you will find one Transderm Scop® patch. A tan colored patch with a metallic (silver) sticky surface is adhered to a clear disposable backing (See Figure 1). Figure 1 1. Select a hairless area of skin behind one of your ears. Avoid areas on your skin that may have cuts, pain or tenderness. Wipe the area of your skin with a clean, dry tissue. 2. Cut along dotted line on the Transderm Scop® package to open (See Figure 2). Figure 2 3. Remove the clear plastic backing from the tan-colored round patch (See Figure 3). Figure 3 4. Avoid touching the metallic adhesive (sticky) surface on the patch with your hands (See Figure 4). Figure 4 5. Apply the metallic adhesive surface of the patch firmly to the dry area of skin behind your ear. The tan-colored side of the patch should be facing up and showing (See Figure 5). Wash your hands with soap and water right away after applying the patch, so that any medicine from the patch that gets on your hands will not get into your eyes. Figure 5 After removing the patch, be sure to wash your hands andtransscop the area behind your ear thoroughly with soap and water. Note that the used patch will still contain some of the active ingredient after use. To avoid accidental contact or ingestion by children or pets, fold the used patch in half with the sticky side together. Dispose in the trash out of the reach of children and pets. If you use too much Transderm Scop®, call your doctor or local poison control center, or go to the nearest hospital emergency room right away. What should I avoid while using Transderm Scop®? You should not drink alcohol while using Transderm Scop®. It can increase your chances of having serious side effects. You should not drive, operate heavy machinery, or do other dangerous activities until you know how Transderm Scop® affects you. You should not use Transderm Scop® during a Magnetic Resonance Imaging scan (MRI). Remove Transderm Scop® patch before undergoing an MRI; it can cause your skin to burn. You should be careful if you use Transderm Scop® while you participate in watersports because you may feel lost or confused (disoriented). Limit contact with water while swimming and bathing because the Transderm Scop® patch may fall off. If the patch falls off, throw it away and apply a new one on the hairless area behind your other ear. What are the possible side effects of Transderm Scop®? Transderm Scop® may cause serious side effects, including: angle closure glaucoma. If you have open angle glaucoma and use Transderm Scop®, remove the patch and call a doctor right away if you get pain and reddening of your eyes with an increase in the size of your pupil (the small dark circle in the eye). temporary increase in the size of your pupil and blurry vision, especially if Transderm Scop® comes in contact with your eyes difficulties in urinating difficulties in food passing from the stomach to the small intestines , which may cause abdominal pain, nausea or vomiting. worsening of seizures. Tell your doctor about any worsening of seizures while using Transderm Scop®. an unusual reaction called acute psychosis : Tell your doctor if you have any of these symptoms: confusion agitation rambling speech hallucinations (seeing or hearing things that are not there) paranoid behaviors and delusions (false belief in something) skin burns at the site of the patch. This can happen during a medical test called a Magnetic Resonance Imaging scan (MRI). Transderm Scop® contains aluminum and should be removed from your skin before you have an MRI. The most common side effects of using Transderm Scop® include: dry mouth drowsiness disorientation (confusion) blurred vision pharyngitis memory trouble dizziness restlessness agitation problems urinating skin rashes or redness, application site burning dry itchy, or reddened whites of the eyes, and eye pain Symptoms when removing Transderm Scop®. Some people may have certain symptoms 24 hours or more after removing Transderm Scop®. These symptoms may include: dizziness nausea vomiting headache problems with balance and walking decrease in blood pressure muscle weakness decrease in heart rate Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Transderm Scop®. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may reports side effects to FDA at 1-800- FDA-1088. How should I store Transderm Scop®? Store Transderm Scop® at room temperature between 68°F and 77°F (20°C and 25°C) until you are ready to use it. Keep Transderm Scop® and all medicines out of reach of children. General Information about Trans derm Scop® Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use Transderm Scop® for a condition for which it was not prescribed. Do not give Transderm Scop® to other people, even if they have the same symptoms you have. It may harm them. This patient information leaflet summarizes the most important information about Transderm Scop®. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor forinformation about Transderm Scop® that is written for the health professionals. For more information, go to www. transdermscop.com or call 1-800-452-0051. What are the ingredients in the Transderm Scop® patch? Active ingredient: Scopolamine Inactive ingredients : light mineral oil and polyisobutylene and aluminized polyester film

OVERDOSE No information provided. CONTRAINDICATIONS Contraindicated in persons with primary glaucoma or a tendency toward glaucoma, e.g., narrow anterior chamber angle; and in those showing hypersensitivity to any component of this preparation.

SIDE EFFECTS 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 Scop, 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 Scop 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 Scop 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 Scop (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 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 Scop, 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. 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 Scop. Similar symptoms, including disturbances of equilibrium, have been reported in some patients following discontinuation of use of the Transderm Scop 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. These symptoms can be severe and may require medical intervention. DRUG INTERACTIONS The absorption of oral medications may be decreased during the concurrent use of scopolamine because of decreased gastric motility and delayed gastric emptying. [see WARNINGS AND PRECAUTIONS] Scopolamine should be used with caution in patients taking other drugs that are capable of causing CNS effects such as sedatives, tranquilizers, or alcohol. Special attention should be paid to potential interactions with drugs having anticholinergic properties; e.g., other belladonna alkaloids, antihistamines (including meclizine), tricyclic antidepressants, and muscle relaxants. In vitro studies indicated that the potential for scopolamine to alter the pharmacokinetics of other concomitant medications through inhibition of CYP 1A2, 2C8, 2C9, 2C19, 2D6 and 3A4 or induction of CYP 1A2 and 3A4 is low; however, in vivo studies have not been conducted. [see CLINICAL PHARMACOLOGY] Laboratory Test Interactions Scopolamine will interfere with the gastric secretion test. Drug Abuse And Dependence Controlled Substance Class Scopolamine is not a controlled substance. Abuse Scopolamine is an antagonist at muscarinic receptors in the cholinergic system. Drugs in this class are not known to have significant abuse potential in humans. Dependence Abrupt termination of Transderm Scop may result in withdrawal symptoms such as dizziness, nausea, vomiting, abdominal cramps, sweating, headache, mental confusion, muscle weakness, bradycardia and hypotension. [see ADVERSE REACTIONS and OVERDOSAGE] These withdrawal symptoms indicate that anticholinergic drugs, like scopolamine may produce physical dependence. These symptoms can be severe and may require medical intervention.

SIDE EFFECTS Prolonged use may produce local irritation, characterized by follicular conjunctivitis, vascular congestion, edema, exudate, and an eczematoid dermatitis. Somnolence, dryness of the mouth, or visual hallucinations may occur. DRUG INTERACTIONS No Information Provided

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Open Angle Glaucoma Patients Currently Being Treated for Open Angle Glaucoma Glaucoma therapy in patients with open angle glaucoma should be monitored and may need to be adjusted during Transderm Scop use, as the mydriatic effect of scopolamine may cause an increase in intraocular pressure. Patients should be advised to remove the patch immediately and promptly contact a physician in the event that they experience symptoms of acute angle closure glaucoma (pain and reddening of the eyes, accompanied by dilated pupils). Temporary Dilation Of The Pupil Scopolamine can cause temporary dilation of the pupils and blurred vision if it comes in contact with the eyes. Patients should be strongly advised to wash their hands thoroughly with soap and water immediately after handling the patch. [see ADVERSE REACTIONS] In addition, it is important that used patches be disposed of properly to avoid contact with children or pets. [see HOW SUPPLIED/ Storage and Handling] Preexisting Gastrointestinal Or Urinary Bladder Obstructions Transderm Scop should be used with caution in patients with pyloric obstruction or urinary bladder neck obstruction. Caution should be exercised when administering an antiemetic or anticholinergic drug, including Transderm Scop, to patients suspected of having intestinal obstruction. Patients should be instructed to remove the patch if they develop any difficulties in urinating. [see ADVERSE REACTIONS] History Of Seizures Or Psychosis Transderm Scop should be used with caution in patients with a history of seizures or psychosis since scopolamine can potentially aggravate both disorders. Idiosyncratic Reactions Idiosyncratic reactions may occur with ordinary therapeutic doses of scopolamine. The most serious of these that have been reported are: acute toxic psychosis, including confusion, agitation, speech disorder, hallucinations, paranoia, and delusions. [see ADVERSE REACTIONS] Specific Populations Pediatric A safe and effective dose has not been established in the pediatric population [see Use in Specific Populations]. Children are particularly susceptible to the side effects of belladonna alkaloids; including mydriasis, hallucinations, amyblyopia, and drug withdrawal syndrome. Neurologic and psychiatric adverse reactions, such as hallucinations, amblyopia and mydriasis have also been reported when one half or one quarter of a patch has been applied. Elderly Transderm Scop should be used with caution in the elderly because of the increased likelihood of CNS effects, such as hallucinations, confusion, dizziness and drug withdrawal syndrome. Clinical trials of Transderm Scop did not include sufficient number of subjects aged 65 years and older to determine if they respond differently from younger subjects. [see Use in Specific Populations] Renal and Hepatic Impaired Transderm Scop should be used with caution in individuals with impaired renal or hepatic functions because of the increased likelihood of CNS effects. Transderm Scop has not been studied in these populations. [see Use in Specific Populations] Safety Hazards Drowsiness Since drowsiness, disorientation, and confusion may occur with the use of scopolamine, patients should be warned of the possibility and cautioned against engaging in activities that require mental alertness, such as driving a motor vehicle or operating dangerous machinery. Disorienting Effects Patients who expect to participate in underwater sports should be cautioned regarding the potentially disorienting effects of scopolamine. [see PATIENT INFORMATION] MRI Skin Burns Skin burns have been reported at the patch site in several patients wearing an aluminized transdermal system during a Magnetic Resonance Imaging scan (MRI). Because Transderm Scop contains aluminum, it is recommended to remove the system before undergoing an MRI. Patient Counseling Information See FDA-approved patient labeling (PATIENT INFORMATION) Please read this instruction sheet carefully before opening the system package. Transderm Scop® Transdermal System Generic Name: scopolamine, pronounced skoe-POL-a-meen Elderly patients should be informed that Transderm Scop may cause a greater likelihood of CNS effects, such as hallucinations, confusion, dizziness and drug withdrawal syndrome and to seek immediate medical care if they become confused, disoriented or dizzy while wearing the patch or after removing. Patients should be informed that since Transderm Scop may cause drowsiness, disorientation and confusion they should avoid engaging in activities that require mental alertness such as driving a motor vehicle or operating dangerous machinery. Patients who expect to participate in underwater sports should be cautioned regarding the potentially disorienting effects of Transderm Scop. Because of the possibility of drowsiness, disorientation and confusion, patients should be informed that they should avoid drinking alcohol. In addition, patients should be informed that the following medications should be used with caution when taking Transderm Scop: sedatives or tranquilizers drugs with anticholinergic properties (e.g., other belladonna alkaloids), antihistamines (including meclizine) tricyclic antidepressants muscle relaxants Patients with the following conditions should be informed about the chance of developing serious reactions with Transderm Scop®: patients with open angle glaucoma (may cause an increase in intraocular pressure) patients with impaired kidney or liver function (increased likelihood of CNS effects) patients with a history of seizures or psychosis (can potentially worsen both disorders) patients with obstruction at the level of the pylorus, which is the outlet of the stomach, or urinary bladder neck obstruction (may cause difficulties in urinating) patients suspected of having intestinal obstruction pregnant or nursing mothers Patients should be informed that if they remove the Transderm Scop patch suddenly before treatment is complete, the following withdrawal symptoms may occur: dizziness, nausea, vomiting, abdominal cramps, sweating, headache, mental confusion, muscle weakness, slow heart rate and low blood pressure. Patients should be instructed to seek immediate medical care if they develop any of these symptoms after removing Transderm Scop. Patients should be informed that Transderm Scop can cause temporary dilation of the pupils and blurred vision if it comes in contact with the eyes. Patients should be informed to wash their hands thoroughly with soap and water immediately after handling the patch. In addition, patients should be informed that used patches must be disposed of properly to avoid contact with children or pets. Patients should be informed that skin burns have been reported at the patch site in several patients wearing an aluminized transdermal system during a Magnetic Resonance Imaging scan (MRI). Because Transderm Scop contains aluminum, patients should be advised to remove the system before undergoing an MRI. Patients should be advised to use only one patch at a time. Patients should be advised not to cut the patch. Use In Specific Populations Pregnancy Pregnancy Category C Based on data from one prospective study of Transderm Scop in cesarean delivery, the rate of newborn adverse events in both the Transderm Scop and placebo groups were the same. The rates were 10.5% (12 events in 114 newborns) in both treatment groups. None of these events were considered life threatening or drug related. Jaundice was the only adverse event occurring more frequently with Transderm Scop than placebo: 9 events (7.9%) versus 2 events (1.8%) (p=0.031). Jaundice, a common occurrence in newborns, resolved with ultraviolet light and did not prolong the hospital stay. There are no adequate and well-controlled studies of Transderm Scop use during pregnancy. 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. Transderm Scop should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus and the mother. Labor And Delivery During a clinical study among women undergoing cesarean section treated with Transderm Scop in conjunction with epidural anesthesia and opiate analgesia, no evidence of CNS depression was found in newborns. [see Clinical Studies] Scopolamine administered parenterally to rats and rabbits at doses higher than the dose delivered by Transderm Scop did not affect uterine contractions or increase the duration of labor. Scopolamine does cross the placenta. Nursing Mothers Scopolamine is excreted in human milk. Caution should be exercised when Transderm Scop is administered to a nursing woman. Pediatric Use A safe and effective dose has not been established in the pediatric population. [see WARNINGS AND PRECAUTIONS] Geriatric Use Transderm Scop should be used with caution in the elderly because of the increased likelihood of CNS effects, such as hallucinations, confusion and dizziness. Clinical trials of Transderm Scop did not include sufficient number of subjects aged 65 years and older to determine if they respond differently from younger subjects. [see WARNINGS AND PRECAUTIONS] Renal Or Hepatic Impairment Transderm Scop should be used with caution in individuals with impaired renal or hepatic functions because of the increased likelihood of CNS effects. [see WARNINGS AND PRECAUTIONS]

WARNINGS Do not touch dropper tip to any surface, as this may contaminate the solution. For topical use only-not for injection. In infants and small children, use with extreme caution. PRECAUTIONS To avoid excessive absorption, the lacrimal sac should be compressed by digital pressure for two to three minutes after instillation. To avoid inducing angle closure glaucoma, an estimation of the depth of the angle of the anterior chamber should be made. PATIENT WARNING: Patient should be advised not to drive or engage in other hazardous activities when drowsy or while pupils are dilated. Patient may experience sensitivity to light and should protect eyes in bright illumination during dilation. Parents should be warned not, to get this preparation in their child†s mouth and to wash their own hands and the child†s hands following administration.