Information for Medical Professionals

PRESCRIBING INFORMATION

   
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Drug Abuse and Dependence
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
How Supplied/ Storage and Handling
Patient Counseling Information

INDICATIONS AND USAGE

Motion Sickness

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

Post Operative Nausea and Vomiting (PONV)

Transderm Scōp® is indicated in adults for prevention of nausea and vomiting associated with recovery from anesthesia and/or opiate analgesia and surgery.

DOSAGE AND ADMINISTRATION

Each Transderm Scōp® patch is formulated to deliver in-vivo approximately 1 mg 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 Scōp® patch (formulated to deliver approximately 1 mg 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 Scōp® 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.

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.

DOSAGE FORMS AND STRENGTHS

The Transderm Scōp® system is a tan-colored circular flat patch which contains 1.5 mg of scopolamine base and is formulated to deliver in-vivo approximately 1 mg of scopolamine over 3 days.

CONTRAINDICATIONS

Transderm Scōp® 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 AND 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 Scōp® 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 Scōp® 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 Scōp®, 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 Scōp® 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, amblyopia, 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 Scōp® 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 Scōp® 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 Scōp® should be used with caution in individuals with impaired renal or hepatic functions because of the increased likelihood of CNS effects. Transderm Scōp® 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). Since Transderm Scōp® contains aluminum, it is recommended to remove the system before undergoing an MRI.

ADVERSE REACTIONS

Clinical Trials Experience

Clinical trials are conducted under widely varying conditions, therefore 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 Scōp®, the most frequent adverse reaction was dry mouth. This occurred in about two thirds of patients on the drug. A less frequent adverse drug reaction was drowsiness, which occurred in less than one sixth of patients on the 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 Scōp® 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 the drug. Dizziness was reported by approximately 12% of patients on the drug. Other adverse drug reactions reported from these studies, with a frequency of ≥3% of patients treated with Transderm Scōp® 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 Scōp®. Since 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 Scōp®, 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 Scōp®. Similar symptoms, including disturbances of equilibrium, have been reported in some patients following discontinuation of use of the Transderm Scōp® 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.

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.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C
Based on data from one prospective study of Transderm Scōp® in cesarean delivery, the rate of newborn adverse events in both the Transderm Scōp® 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 Scōp® 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 Scōp® 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 Scōp® 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 Scōp® 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 Scōp® 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 Scōp® is administered to a nursing woman.

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

Geriatric Use
Transderm Scōp® 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 Scōp® 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 Scōp® should be used with caution in individuals with impaired renal or hepatic functions because of the increased likelihood of CNS effects.

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 Scōp® 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.

OVERDOSAGE

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 Scōp® 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.

DESCRIPTION

The Transderm Scōp® (transdermal scopolamine) 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 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 Scōp® 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:

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 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 TOXICOLOGY

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 Scōp® (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 Scōp® as compared to 59% of placebo-treated patients.

HOW SUPPLIED/STORAGE AND HANDLING

The Transderm Scōp® 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 Scōp® system contains 1.5 mg of scopolamine and is formulated to deliver in-vivo approximately 1 mg of scopolamine over 3 days. Transderm Scōp® 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 us ed patches be disposed of properly to avoid contact indexwith children or pets.

PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information)
Please read this instruction sheet carefully before opening the system package.
Transderm Scōp® Transdermal System
Generic Name: scopolamine, pronounced skoe-POL-a-meen

  • Elderly patients should be informed that Transderm Scōp® 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 Scōp® 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 Scōp®.
  • 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 Scōp®:

    • 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 Scōp®:

    • 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 Scōp® 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 Scōp®.
  • Patients should be informed that Transderm Scōp® 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 Scōp® 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.

Manufactured by: ALZA Corporation
Vacaville, CA 95688

Distributed by:
Novartis Consumer Health, Inc.
Parsippany, NJ 07054-0622
©2014

46114066 (Rev. 12/13)