Scopolamine

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. post-operative nausea and vomiting (PONV) associated with recovery from anesthesia and/or opiate analgesia and surgery.

Application and Removal: 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: 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. PONV: For surgeries other than cesarean section, apply one transdermal system behind the ear the evening before surgery and remove 24 hours following surgery.

2.1Important Application and Removal Instructions Each

scopolamine 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 . 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 .

2.2Recommended Adult Dosage Motion Sickness

Apply one scopolamine transdermal system to the hairless area behind one ear at least 4 hours before the antiemetic effect is required – for use up to 3 days. If therapy is required for longer than 3 days, remove the first transdermal system and apply a new scopolamine transdermal system behind the other ear. PONV For surgeries other than cesarean section: Apply one scopolamine transdermal system the evening before scheduled surgery.

Remove the transdermal system 24 hours following surgery.

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. 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. 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. Drug Withdrawal/Post-Removal Symptoms: Anticholinergic symptoms may occur 24 hours or more after removal of the transdermal system. 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.

5.1Acute 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).

5.2Neuropsychiatric 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 . 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 . 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 . Scopolamine transdermal system is not approved for use in pediatric patients . 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 . 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.

5.3Eclamptic Seizures in Pregnant Women Eclamptic

seizures have been reported in pregnant women with severe preeclampsia soon after injection of intravenous and intramuscular scopolamine . Avoid use of scopolamine transdermal system in patients with severe preeclampsia.

5.4Gastrointestinal 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 . Discontinue scopolamine transdermal system in patients who develop difficulty in urination.

5.5Hyperthermia 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 .

5.6Drug 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.

5.7Blurred 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 .

5.8Magnetic Resonance Imaging

(MRI) Skin Burns Scopolamine transdermal system contains an aluminized membrane. Skin burns have been reported at the application site in patients wearing an aluminized transdermal system during an MRI scan. Remove scopolamine transdermal system before undergoing an MRI.

Scopolamine transdermal system is contraindicated in patients with: angle closure glaucoma . 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 . 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 )

8.1Pregnancy 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 . 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 . 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.

Most common adverse reactions are: Motion Sickness (>15%): dry mouth, drowsiness, blurred vision and dilation of the pupils. PONV (≥ 3%): dry mouth, dizziness, somnolence, agitation, visual impairment, confusion, mydriasis and pharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . The following serious adverse reactions are described elsewhere in labeling: Acute Angle Closure Glaucoma Neuropsychiatric Adverse Reactions Eclamptic Seizures in Pregnant Women Gastrointestinal and Urinary Disorders Hyperthermia Drug Withdrawal/Post-Removal Symptoms Blurred Vision MRI Skin Burns

6.1Clinical 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 occurring in at least 3% of patients and at a rate higher than placebo 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

6.2Postmarketing 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