For other uses, see Datura (disambiguation).
For other Devil's Trumpet, see Datura (disambiguation).
Datura is a genus of nine species of poisonous vespertineflowering plants belonging to the family Solanaceae. They are commonly known as daturas, but also known as devil's trumpets, not to be confused with angel's trumpets, its closely related genus Brugmansia. They are also sometimes called moonflowers, jimsonweed, devil's weed, hell's bells, thorn-apple, and many more. Its precise and natural distribution is uncertain, owing to its extensive cultivation and naturalization throughout the temperate and tropical regions of the globe. Its distribution within the Americas and North Africa, however, is most likely restricted to the United States, Mexico and Southern Canada in North America, and Tunisia in Africa, where the highest species diversity occurs.
All species of Datura are poisonous, especially their seeds and flowers.
Some South American plants formerly thought of as Datura are now treated as belonging to the distinct genus Brugmansia (Brugmansia differs from Datura in that it is woody, making shrubs or small trees, and it has pendulous flowers, rather than erect ones). Other related taxa include Hyoscyamus niger, Atropa belladonna, Mandragora officinarum, and many more.
The name Datura is taken from Hindi धतूरा dhatūra 'thorn-apple', ultimately from Sanskrit धत्तूर dhattūra 'white thorn-apple' (referring to Datura metel of Asia). In the Ayurvedic text Sushruta different species of Datura are also referred to as kanaka and unmatta. Dhatura is offered to Lord Shiva in Hindu/Santana religion. Record of this name in English dates back to 1662.Nathaniel Hawthorne refers to one type in The Scarlet Letter as apple-Peru. In Mexico, its common name is toloache.
Datura species are herbaceous, leafy annuals and short-lived perennials which can reach up to 2 m in height. The leaves are alternate, 10–20 cm long and 5–18 cm broad, with a lobed or toothed margin. The flowers are erect or spreading (not pendulous like those of Brugmansia), trumpet-shaped, 5–20 cm long and 4–12 cm broad at the mouth; colors vary from white to yellow, pink, and pale purple. The fruit is a spiny capsule 4–10 cm long and 2–6 cm broad, splitting open when ripe to release the numerous seeds. The seeds disperse freely over pastures, fields and even wasteland locations.
Datura belongs to the classic "witches' weeds", along with deadly nightshade, henbane, and mandrake. Most parts of the plants are toxic, and datura has a long history of use for causing delirious states and death. It was well known as an essential ingredient of potions and witches' brews.
In India it has been referred to as "Poisonous" and as an aphrodisiac. In little measures it was used in Ayurveda as a medicine from the ancient times. It is used in rituals and prayers to Shiva. It is also used in Ganesh Chaturthi.
The larvae of some Lepidoptera (butterfly and moth) species, including Hypercompe indecisa, eat some Datura species.
Species and cultivars
It is difficult to classify Datura as to its species, and it often happens that the descriptions of new species are accepted prematurely. Later, these "new species" are found to be simply varieties that have evolved due to conditions at a specific location. They usually disappear in a few years. Contributing to the confusion is the fact that various species, such as D. wrightii and D. inoxia, are very similar in appearance, and the variation within a species can be extreme. For example, Datura species can change size of plant, leaf, and flowers, all depending on location. The same species, when growing in a half-shady, damp location can develop into a flowering bush half as tall as an adult human of average height, but when growing in a very dry location, will only grow into a thin plant not much more than ankle-high, with tiny flowers and a few miniature leaves.
Today, experts classify only nine species of Datura:
American Brugmansia and Datura Society, Inc. (ABADS) is designated in the 2004 edition of the International Code of Nomenclature for Cultivated Plants as the official International Cultivar Registration Authority for Datura. This role was delegated to ABADS by the International Society for Horticultural Science in 2002.
Past classified species
Datura species are usually planted annually from the seed produced in the spiny pods, but with care, plants can be overwintered. Most species are suited to being planted outside or in containers. As a rule, they need warm, sunny places and soil that will keep their roots dry. When grown outdoors in good locations, the plants tend to reseed themselves and may become invasive. In containers, they should have porous, aerated potting soil with adequate drainage. The plants are susceptible to fungi in the root area, so anaerobic organic enrichment such as anaerobically composted organic matter or manure, should be avoided.
All Datura plants contain tropane alkaloids such as scopolamine, hyoscyamine, and atropine, primarily in their seeds and flowers. Because of the presence of these substances, Datura has been used for centuries in some cultures as a poison. There can be a 5:1 toxin variation between plants, and a given plant's toxicity depends on its age, where it is growing, and the local weather conditions. These variations make Datura exceptionally hazardous as a drug.
In traditional cultures, a great deal of experience with and detailed knowledge of Datura was critical to minimize harm. Many tragic incidents result from modern users ingesting Datura. For example, in the 1990s and 2000s, the United States media contained stories of adolescents and young adults dying or becoming seriously ill from intentionally ingesting Datura. There are also several reports in the medical literature of deaths from D. stramonium and D. ferox intoxication. Children are especially vulnerable to atropine poisoning.
Datura toxins may be ingested accidentally by consumption of honey produced by several wasp species, including Brachygastra lecheguana, during the Datura blooming season. It appears that these semi-domesticated honey wasps collect Datura nectar for honey production which can lead to poisoning.
In some parts of Europe and India, Datura has been a popular poison for suicide and murder. From 1950 to 1965, the State Chemical Laboratories in Agra, India, investigated 2,778 deaths caused by ingesting Datura.
The US Centers for Disease Control and Prevention reported accidental poisoning resulting in hospitalization for a family of six who inadvertently ingested Datura used as an ingredient in stew.
In some places, it is prohibited to buy, sell, or cultivate Datura plants.
Effects of ingestion
Due to the potent combination of anticholinergic substances it contains, Datura intoxication typically produces effects similar to that of an anticholinergic delirium (usually involving a complete inability to differentiate reality from fantasy); hyperthermia; tachycardia; bizarre, and possibly violent behavior; and severe mydriasis (dilated pupils) with resultant painful photophobia that can last several days. Pronounced amnesia is another commonly reported effect.
In Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs, Freye asserts: Few substances have received as many severely negative recreational experience reports as has Datura. The overwhelming majority of those who describe their use of Datura find their experiences extremely unpleasant both mentally and often physically dangerous. However, anthropologists have found that indigenous groups, with a great deal of experience with and detailed knowledge of Datura, have been known to use Datura spiritually (including the Navajo and especially the Havasupai). The knowledge of Datura's properties was critical to minimize harm. Datura was used to locate missing objects by southern Paiute Indians.
Due to their agitated behavior and confused mental state, victims of Datura poisoning are typically hospitalized. Gastric lavage and the administration of activated charcoal can be used to reduce the stomach's absorption of the ingested material. The drug physostigmine is used to reverse the effect of the poisons. Benzodiazepines can be given to curb the patient's agitation, and supportive care with oxygen, hydration, and symptomatic treatment is often provided. Observation of the patient is indicated until the symptoms resolve, usually from 24–36 hours after ingestion of the Datura.
Datura flower on the plant (lateral view) near Hyderabad, Andhra Pradesh, India
Datura flower on the plant (top view) near Hyderabad, Andhra Pradesh, India
Main article: Legal status of deliriant plants
- Donnatal, a pharmaceutical containing the active alkaloids in Belladonna, a plant similar to Datura: scopolamine, hyoscyamine, and atropine, as a drug
- ^"Datura metel". plants.ces.ncsu.edu. Retrieved 2016-01-17.
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- ^American Heritage Dictionary: datura
- ^ abMonier-Williams, Monier (1899). A Sanskrit-English dictionary : etymologically and philologically arranged with special reference to cognate Indo-European languages. Oxford: Clarendon Press.
- ^the Oxford English Dictionary or OED
- ^ abcdefghijPreissel, U.; Preissel, H.-G. (2002). Brugmansia and Datura: Angel's Trumpets and Thorn Apples. Buffalo, NY: Firefly Books. pp. 106–129. ISBN 1-55209-598-3.
- ^Adams, J. D. Jr.; Garcia, C. (2005). "Spirit, Mind and Body in Chumash Healing". Evidence-based Complementary and Alternative Medicine. 2 (4): 459–463. doi:10.1093/ecam/neh130. PMC 1297503. PMID 16322802. Archived from the original on 12 October 2007.
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- ^Leinwand, D. (2006-11-01). "Jimson weed users chase high all the way to hospital". USA TODAY. Retrieved 2009-02-15.
- ^Michalodimitrakis, M.; Koutselinis, A. (1984). "Discussion of "Datura stramonium: A fatal poisoning"". Journal of Forensic Sciences. 29 (4): 961–962. PMID 6502123.
- ^Boumba, V. A.; Mitselou, A.; Vougiouklakis, T. (2004). "Fatal poisoning from ingestion of Datura stramonium seeds". Veterinary and Human Toxicology. 46 (2): 81–82. PMID 15080209.
- ^Steenkamp, P. A.; Harding, N. M.; Van Heerden, F. R.; Van Wyk, B.-E. (2004). "Fatal Datura poisoning: Identification of atropine and scopolamine by high performance liquid chromatography / photodiode array / mass spectrometry". Forensic Science International. 145 (1): 31–39. doi:10.1016/j.forsciint.2004.03.011. PMID 15374592.
- ^Taha, S. A.; Mahdi, A. H. (1984). "Datura intoxication in Riyadh". Transactions of the Royal Society of Tropical Medicine and Hygiene. 78 (1): 134–135. doi:10.1016/0035-9203(84)90196-2. PMID 6710568.
- ^Djibo, A.; Bouzou, S. B. (2000). "[Acute intoxication with "sobi-lobi" (Datura). Four cases in Niger]". Bulletin de la Société de Pathologie Exotique (in French). 93 (4): 294–297. PMID 11204734.
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- ^Bontoyan, W.; et al. (2010-02-05). "Jimsonweed Poisoning Associated with a Homemade Stew – Maryland, 2008"(pdf). Centers for Disease Control and Prevention – Morbidity and Mortality Weekly Report. 59 (4): 102–103. Retrieved 2010-02-11.
- ^ abFreye, E. (2010). "Toxicity of Datura Stramonium". Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs. Netherlands: Springer. pp. 217–218. doi:10.1007/978-90-481-2448-0_34. ISBN 978-90-481-2447-3.
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Dosage and Administration
Dosage Forms and Strengths
Warnings and Precautions
Use in Specific Populations
Drug Abuse and Dependence
How Supplied/ Storage and Handling
Patient Counseling Information
INDICATIONS AND USAGE
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.
DOSAGE AND ADMINISTRATION
Each Transderm Scop® 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.
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
- To prevent the nausea and vomiting associated with motion sickness, one Transderm Scop® 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 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.
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.
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 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 1 mg of scopolamine over 3 days.
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 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 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 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.
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.
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.
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.
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 Scop® contains aluminum, it is recommended to remove the system before undergoing an MRI.
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.
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 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 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 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 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
The following adverse drug reactions, further to those reported from clinical trials, have been identified during postapproval use of Transderm Scop®. 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 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
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.
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
USE IN SPECIFIC POPULATIONS
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.
Scopolamine is excreted in human milk. Caution should be exercised when Transderm Scop® is administered to a nursing woman.
A safe and effective dose has not been established in the pediatric population.
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.
DRUG ABUSE AND DEPENDENCE
Controlled Substance Class
Scopolamine is not a controlled substance.
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.
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.
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 Transderm Scop® (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 Scop® 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:
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.
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.
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).
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.
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.
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.
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 Scop® (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 Scop® as compared to 59% of placebo-treated patients.
HOW SUPPLIED/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
The system should be stored at controlled room temperature between 20°C - 25°C(68°F - 77°F).
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 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.
Manufactured by: ALZA Corporation
Vacaville, CA 95688
Princeton, NJ 08540
46114066 (Rev. 12/13)