Transderm Scop

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.

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.

Manufactured by: ALZA Corporation, Vacaville, CA 95688. Distributed by: Novartis Cons umer Health, Inc., Parsippany, NJ 07054-0622. Revised: Dec 2014

Motion Sickness

Transderm Scop® is indicated in adults for prevention of nausea and vomiting associated with motion sickness.

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.

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.

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.

Transderm Scop® is contraindicated in the following populations:

• Patients with angle closure glaucoma.
• Persons who are hypersensitive to the drug scopolamine or other belladonna alkaloids or to any ingredient or component in the formulation or delivery system.

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. In addition, it is important that used patches be disposed of properly to avoid contact with children or pets.

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.

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.

Specific Populations

Pediatric

A safe and effective dose has not been established in the pediatric population. 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.

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.

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.

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. 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.

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.

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.

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

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.

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.

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. These withdrawal symptoms indicate that anticholinergic drugs, like scopolamine may produce physical dependence. These symptoms can be severe and may require medical intervention.

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.

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

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.

Because strategies for the management of drug overdose continually evolve, it is strongly recommended that a poison control center be contacted to obtain up-to-date information regarding the management of Transderm Scop® patch overdose. The prescriber should be mindful that antidotes used routinely in the past may no longer be considered optimal treatment. For example, physostigmine, used more or less routinely in the past, is seldom recommended for the routine management of anticholinergic syndromes.

Until up-to-date authoritative advice is obtained, routine supportive measures should be directed to maintaining adequate respiratory and cardiac function. The signs and symptoms of anticholinergic toxicity include: lethargy, somnolence, coma, confusion, agitation, hallucinations, convulsion, visual disturbance, dry flushed skin, dry mouth, decreased bowel sounds,urinary retention, tachycardia, hypertension, and supraventricular arrhythmias. These symptoms can be severe and may require medical intervention.

In cases of toxicity remove the patch. Serious symptomatic cases of overdosage involving multiple patch 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 patches from the skin and the mouth. If there is evidence of patch ingestion, gastric lavage, endoscopic removal of swallowed patches, 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 symptoms of overdose/toxicity due to scopolamine should be carefully distinguished from the occasionally observed syndrome of withdrawal. Although mental confusion and dizziness may be observed with both acute toxicity and withdrawal, other characteristic findings differ: tachyarrhythmias, dry skin, and decreased bowel sounds suggest anticholinergic toxicity, while bradycardia, headache, nausea and abdominal cramps, and sweating suggest post-removal withdrawal. Obtaining a careful history is crucial to making the correct diagnosis.

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.