Scopolamine Transdermal System

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. ( 1 )

Transdermal system: a circular, flat, tan-colored transdermal system imprinted with “SCOP 1 mg/3 days” in a repeating pattern. Transdermal system: 1 mg/3 days ( 3 )

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 ), 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 )

• Acute Angle Closure Glaucoma : Monitor for increased intraocular pressure in patients with open-angle glaucoma and adjust glaucoma therapy as needed. Discontinue if signs or symptoms of acute angle closure glaucoma develop. ( 5.1 )
• Neuropsychiatric Adverse Reactions : May cause psychiatric and cognitive effects, seizures and impair mental and/or physical abilities. Monitor patients for new or worsening psychiatric symptoms during treatment and during concomitant treatment with other drugs that are associated with similar psychiatric effects. ( 5.2 , 7.1 )
• Eclamptic Seizures in Pregnant Women : Avoid use in patients with severe preeclampsia. ( 5.3 )
• Gastrointestinal and Urinary Disorders : Consider more frequent monitoring during treatment in patients suspected of having intestinal obstruction; patients with pyloric obstruction, patients with impeded urine flow or receiving other anticholinergic drugs. Discontinue if patient develops difficulty in urination. ( 5.4 , 7.2 )
• Hyperthermia : Serious adverse reactions have been reported postmarketing in adult and pediatric patients, including fatal cases. If symptoms occur, remove the transdermal system, and contact a healthcare provider. ( 5.5 )
• Drug Withdrawal/Post-Removal Symptoms : Anticholinergic symptoms may occur 24 hours or more after removal of the transdermal system. ( 5.6 )
• Blurred Vision : Avoid contact with the eyes. ( 2.1 , 5.7 )
• Magnetic Resonance Imaging (MRI) Skin Burns : Remove scopolamine transdermal system prior to MRI scan. ( 5.8 )

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 )]. In cases of psychiatric reactions occurring scopolamine transdermal system should be removed at once. If, despite this, the symptoms persist in a severe form, instruct patients to seek medical attention. 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. If, despite this, the symptoms persist in a severe form, instruct patients to seek medical attention. 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 patients with impeded flow of urine (e.g., in diseases of the prostate 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 Hyperthermia Serious adverse reactions of hyperthermia have been reported postmarketing in adult and pediatric patients receiving transdermal scopolamine, including fatal cases. Anticholinergic agents, including scopolamine, can increase core body temperature and reduce sweating, which may cause further increases in body temperature. Hyperthermia may be exacerbated by exposure to external heat sources or high environmental temperature. Pediatric and geriatric patients may be more susceptible to these anticholinergic effects on 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. Symptoms may persist following removal of the used transdermal system as there may be continued systemic absorption of scopolamine through the skin. Scopolamine transdermal system is not approved for use in pediatric patients [see Use in Specific Populations ( 8.4 , 8.5 )] .

5.6 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.

5.7 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, do not touch the system while wearing it, and wash hands and the application site with soap and water after transdermal system removal [see Dosage and Administration ( 2.1 )] .

5.8 Magnetic Resonance Imaging (MRI) Skin Burns Scopolamine transdermal system contains an aluminized membrane. […]

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 )]
• MRI Skin Burns [see Warnings and Precautions ( 5.8 )] 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 Padagis ® at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in 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 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: disorientation, hallucinations, and paranoia Nervous system disorders : amnesia, coordination abnormalities, disturbance in attention, headache, restlessness, speech disorder General disorders and administration site conditions : application site reactions (including blistering, burning, pruritus, and rash) and hyperthermia Eye disorders : amblyopia, angle closure glaucoma, dry eyes, eyelid irritation, eye pruritus Skin and subcutaneous tissue disorders : erythema, rash generalized, skin irritation Renal and urinary disorders : dysuria Ear and labyrinth disorders : vertigo

• 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 scopolamine transdermal system 10 days prior to testing. ( 7.4 )

7.1 Drugs Causing Central Nervous System (CNS) Adverse Reactions The concurrent use of scopolamine transdermal system 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 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.

• 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 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] . 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. 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. 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 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. 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 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.g., disorientation, hallucinations), amblyopia, hyperthermia (including a fatal case), and mydriasis have also been reported in pediatric patients [see Warnings and Precautions ( 5.2 , 5.5 )] .

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 , 5.6 )]. Consider more frequent monitoring for CNS adverse reactions during treatment with scopolamine transdermal system in geriatric patients [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 )] .

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 )].

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.