SCOPOLAMINE- scopolamine_patch, extended release

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. 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. 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 in vitro in vivo.

INDICATIONS AND USAGE
Scopolamine transdermal system 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. Scopolamine transdermal system 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.
SPL PATIENT PACKAGE INSERT
PATIENT INFORMATION Scopolamine (skoe pol'' a meen) Transdermal System Read this Patient Information before you start using scopolamine transdermal system 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 scopolamine transdermal system? nausea and vomiting from motion sickness nausea and vomiting from anesthesia or taking opioid pain medicines after surgery Who should not use scopolamine transdermal system? Do not use scopolamine transdermal system if you: have an eye problem called angle closure glaucoma. are allergic to scopolamine, belladonna alkaloids or any of the ingredients in scopolamine transdermal system. See the end of this leaflet for a list of the ingredients in scopolamine transdermal system. Ask your doctor if you are not sure. What should I tell my doctor before using scopolamine transdermal system? have glaucoma (increased pressure in the eye). have a history of seizures or psychosis. have problems with your stomach or intestines. have trouble urinating. are scheduled to have a gastric secretion test. have liver or kidney problems. are pregnant or plan to become pregnant. It is not known if scopolamine can harm your unborn baby. are breastfeeding or plan to breastfeed. Scopolamine 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 scopolamine transdermal system. Tell your doctor about all the medicines you take, a sedative, hypnotic, opioid or anxiolytic (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 How should I use scopolamine transdermal system? See the detailed Instructions for Use It is important that you apply scopolamine transdermal system exactly as your doctor tells you to. Your doctor may change your scopolamine transdermal system dose. Do not Wear only one scopolamine transdermal system at any time. If you use too many scopolamine transdermal system, call your doctor or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away. What should I avoid while using scopolamine transdermal system? You should not drink alcohol while using scopolamine transdermal system. 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 scopolamine transdermal system affects you. You should be careful if you use scopolamine transdermal system while you participate in watersports because you may feel lost or confused (disoriented). Limit contact with water while swimming and bathing because scopolamine transdermal system may fall off. If scopolamine transdermal system 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 scopolamine transdermal system? Scopolamine transdermal system may cause serious side effects, including: angle closure glaucoma. worsening of seizures. an unusual reaction called acute psychosis. confusion agitation rambling speech hallucinations (seeing or hearing things that are not there) paranoid behaviors and delusions (false belief in something) worsening of your preeclampsia during pregnancy. difficulty urinating. difficulties in food passing from the stomach to the small intestines, which may cause abdominal pain, nausea or vomiting. increased body temperature (hyperthermia) and a decrease in sweating. withdrawal symptoms after removing scopolamine transdermal system after using it for several days. temporary increase in the size of your pupil and blurry vision, The most common side effects of using scopolamine transdermal system include: dry mouth blurred vision or eye problems feeling sleepy or drowsy disorientation (confusion) dizziness feeling agitated or irritable pharyngitis (sore throat) 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 scopolamine transdermal system. General information about the safe and effective use of scopolamine transdermal system. What are the ingredients in scopolamine transdermal system? Active ingredient: Inactive ingredients: Manufactured by: Zydus Lifesciences Ltd. Distributed by: Zydus Pharmaceuticals (USA) Inc. Rev.: 06/25

Application and Removal 2. 1 Each Scopolamine 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 with soap and water after application. Avoid touching or applying pressure to the transdermal system once applied. Upon removal, fold used transdermal system in half with sticky side together, discard to prevent accidental contact or ingestion and wash the hands and application site with soap and water. Recommended Dosage Motion Sickness 2. 2 Each scopolamine transdermal system is formulated to deliver in vivo Only wear one transdermal system at any time. 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. 7 If the transdermal system becomes displaced, discard the transdermal system and apply a new transdermal system on the hairless area behind the other ear. Once the transdermal system has been affixed, avoid touching or applying pressure to the transdermal system while it is being worn, since pressure exerted on it may cause scopolamine to ooze out at the edge. 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. Wash the hands and application site with soap and water after transdermal system removal [see Warnings and Precautions ( 5. 7 Motion Sickness Apply one scopolamine transdermal system to the hairless area behind one ear at least 4 hours before the antiemetic effect is required en dash 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.

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 Hyperthermia [see Warnings and Precautions ( 5. 5 )] Drug Withdrawal/Post-Removal Symptoms [see Warnings and Precautions ( 5. 6 Blurred Vision [see Warnings and Precautions ( 5. 7 Most common adverse reactions are: Motion Sickness (> 15%): 6. 1 PONV (>= 3%): 6. 1 To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www. gov/Safety/MedWatch. 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 * * Scopolamine Transdermal System Placebo % (N = 461) % (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 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 : Nervous system disorders: General disorders and administration site conditions: Eye disorders: Skin and subcutaneous tissue disorders : Renal and urinary disorders: Ear and labyrinth disorders :.

Scopolamine transdermal system 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 11 Angle closure glaucoma. 2 Hypersensitivity to scopolamine or other belladonna alkaloids or to any ingredient or component of the formulation or delivery system.

Geriatric Patients: 5. 5 Renal or Hepatic Impairment: 5. 6 Risk Summary Eclamptic seizures have been reported in pregnant women with severe preeclampsia soon after injection of intravenous or intramuscular scopolamine. Avoid use of scopolamine transdermal system in patients with severe preeclampsia [see Warnings and Precautions (5. 3) and 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 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. 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 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. 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. 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 or from the underlying maternal condition. The safety and effectiveness of scopolamine transdermal system have not been established in pediatric patients. Pediatric patients are particularly susceptible to the anticholinergic adverse reactions of scopolamine, including neurologic and psychiatric adverse reactions and drug withdrawal syndrome. Serious adverse reactions of acute psychosis (e. , disorientation, hallucinations), , amblyopia hyperthermia (including a fatal case), and mydriasis have also been reported in pediatric patients [see Warnings and Precautions ( 5. 5 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 [ Precautions ( 5. 5 [see Warnings and Precautions ( 5. 2 Serious adverse reactions of hyperthermia have been reported postmarketing in geriatric patients receiving transdermal scopolamine, including a fatal case. Geriatric patients may be more susceptible to the anticholinergic effects of disruption in thermoregulation. Advise patients if body temperature increases, or they are not sweating in warm environmental conditions, to remove the transdermal system and contact their healthcare provider [see Warnings and Precautions ( 5. 5 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.

RECENT MAJOR CHANGES
Warnings and Precautions, Hyperthermia ( 5.5 4/2025
DRUG INTERACTIONS
Drugs Causing Central Nervous System (CNS) Adverse Reactions: 7. 1 Anticholinergic Drugs: 7. 2 Oral Drugs Absorbed in the Stomach: 7. 3 Interaction with Gastric Secretion Test: 7. 4 The concurrent use of scopolamine transdermal system with other drugs that cause CNS adverse reactions of drowsiness, dizziness or disorientation (e. , sedatives, hypnotics, opiates, anxiolytics and alcohol) or have anticholinergic properties (e. , other belladonna alkaloids, sedating antihistamines, meclizine, tricyclic antidepressants and muscle relaxants) may potentiate the effects of scopolamine transdermal system [see Warnings and Precautions ( 5. 2 Concomitant use of scopolamine with other drugs having anticholinergic properties may increase the risk of CNS adverse reactions [see Drug Interactions ( 7. 1 [see Warnings and Precautions ( 5. 4 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. Scopolamine will interfere with the gastric secretion test. Discontinue scopolamine transdermal system 10 days prior to testing.

OVERDOSAGE
Anticholinergic toxicity includes, both central and peripheral signs and symptoms: agitation, central nervous system effects (e.g., coma, confusion, hallucinations, lethargy, seizures, somnolence), decreased bowel sounds, dry flushed skin, dry mouth, hyperthermia, hypertension supraventricular arrhythmias, tachycardia, urinary retention, visual disturbances (e.g., amblyopia, mydriasis). These symptoms can be severe and may require medical intervention. In cases of toxicity remove the scopolamine 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 ( 5.6 If over-exposure occurs, call the Poison Help line at 1-800-222-1222 for current information on the management of poisoning or overdosage.
NONCLINICAL TOXICOLOGY
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
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. Scopolamine transdermal system was applied from 4 to 16 hours prior to the onset of motion in these studies. A clinical efficacy study evaluated 168 adult female patients undergoing gynecological surgery with anesthesia and opiate analgesia. Patients received scopolamine transdermal system 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 scopolamine transdermal system 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 scopolamine transdermal system as compared to 72% of placebo-treated patients.

Zydus Pharmaceuticals USA Inc.

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