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Traduzido de Scopolamine - Medical Countermeasures Database ↗ (CHEMM, HHS/ASPR — domínio público), fonte capturada em 2026-08-25. Em caso de dúvida, vale o original.

Scopolamine (escopolamina) — banco de contramedidas médicas

• Name of Chemical Defense therapeutic agent/deviceno original (inglês)
• Chemical Defense therapeutic areano original (inglês)
• Evidence-based medicine for Chemical Defenseno original (inglês)
• Pharmacokinetic and toxicokinetics datano original (inglês)
• Indication/dosingno original (inglês)
• Formulation/shelf lifeno original (inglês)
• Off-label use & dosingno original (inglês)
• Route of administrating/monitoringno original (inglês)
• Adverse effectsno original (inglês)
• Contraindicationsno original (inglês)
• Clinical studies in progressno original (inglês)
• Non-clinical studies in progressno original (inglês)
• Needed studies for Chemical Defenseno original (inglês)
• Needed studies for non-Chemical Defenseno original (inglês)
• Study-related ethical concernsno original (inglês)
• Global regulatory statusno original (inglês)
• Other potentially useful informationno original (inglês)
• Publicationsno original (inglês)
• Web sitesno original (inglês)

1. Nome do agente terapêutico/dispositivo de defesa química

Scopolaminedose/fármaco conforme a fonte ↗

2. Área(s) terapêutica(s) de defesa química

A scopolamine é um anticonvulsivante anticolinérgico que foi estudado para uso contra a intoxicação por organofosforados.dose/fármaco conforme a fonte ↗

3. Medicina baseada em evidência para defesa química

A. Resumo

Estrutura

HSDB. Scopolaminedose/fármaco conforme a fonte ↗no original (inglês)

Mecanismo de ação

• A scopolamine é um antagonista de receptor muscarínico de ocorrência natural e um alcaloide da beladona. A scopolamine compete com a acetilcolina (ACh) e com outros agonistas muscarínicos por um sítio de ligação comum no receptor muscarínico. Os antagonistas de receptor muscarínico inibem as respostas à estimulação nervosa colinérgica pós-ganglionar de forma menos eficaz do que inibem as respostas a ésteres de colina injetados. A diferença pode ser explicada pelo fato de a liberação de ACh pelos terminais nervosos colinérgicos ocorrer muito próxima aos receptores, resultando em concentrações muito altas do transmissor nos receptores. A scopolamine é capaz de atravessar a barreira hematoencefálica e é eficaz na prevenção da cinetose, possivelmente por bloquear as vias neurais do ouvido interno até o centro do vômito no tronco encefálico.dose/fármaco conforme a fonte ↗

Brunton LL, Chabner BA, Knollmann BC (eds.) Goodman & Gilman's The Pharmacological Basis of Therapeutics (12th Ed.). McGraw-Hill Medical, New York, NY. (2011) p.226-230no original (inglês)

Resumo dos estudos clínicos e não clínicos

Organophosphates (OP) are commonly used as pesticides and as military nerve agents; the latter include sarin, soman, tabun, and VX. OP intoxication is the result of irreversible inhibition of acetylcholinesterase (AChE) via phosphorylation of the active-site serine. As a result, acetylcholine accumulates at synapses, inducing convulsions, behavioral impairments, and eventually death, if untreated. Current therapy options for acute OP poisoning are atropine, atropine combined with an oxime. While this regimen is effective in preserving the life of the subject, it does not efficiently control the convulsions and behavioral deficits that may arise due to the initial spike in cholinergic activity. The classical anticholinergic anticonvulsant scopolamine, approved for human use against motion sickness, has been successfully used against OP intoxication in animal studies. In oxime-pretreated, soman-intoxicated (1.6×LD 50 ) rats, scopolamine pretreatment was more effective than atropine pretreatment in preventing convulsions (Shih et al., 1991). A study of pretreatment scopolamine (or diazepam) combined with pretreatment pyridostigmine and posttreatment atropine and pralidoxime showed that scopolamine significantly improved survival (p<0.001) and reduced convulsions (p<0.05) in soman-exposed guinea pigs, compared to animals pretreated with diazepam (Anderson et al., 1994; Harris et al., 1994). Even when administered up to 40 minutes after 2×LD 50 soman exposure (in pyridostigmine-pretreated, atropine/pralidoxime-posttreated guinea pigs), scopolamine reduced seizures, though it became less effective at the later time points (McDonough et al., 2000). When scopolamine and pyridostigmine were administered to rats via intramuscular injection prior to soman exposure (1×LD 50 ), convulsions were completely abolished and impairments in learning and memory were partially restored (Raveh et al., 2002).dose/fármaco conforme a fonte ↗no original (inglês)

Nonhuman primate experiments have been similarly promising. Cynomolgus monkeys pretreated with physostigmine and scopolamine were able to completely survive 2×LD 50 of soman exposure without convulsions or loss of consciousness; at a high soman dose (5×LD 50 ), pretreated monkeys experienced a memory/behavioral recovery within 30 minutes, after a brief period of unconsciousness (von Bredow et al., 1991). Two weeks of pretreatment with scopolamine and physostigmine preserved memory and behavioral function in marmosets after injection of sublethal doses of sarin or soman (Muggleton et al., 2003).dose/fármaco conforme a fonte ↗no original (inglês)

More recent experiments with aerosolized scopolamine have yielded encouraging results. Soman-exposed (841 mg/m 3 ) guinea pigs who received only aerosolized scopolamine (0.25 mg/kg) 30 seconds later showed improved lung function and histopathology compared to non-scopolamine (saline)-treated animals (Perkins et al., 2011). Scopolamine treatment resulted in normalization of respiratory flow; AChE levels, cell death, total cell count, and protein levels in broncheoalveolar fluid; epithelial/ subepithelial inflammation; and alveolar edema.dose/fármaco conforme a fonte ↗no original (inglês)

Não há dado clínico disponível demonstrando eficácia da scopolamine contra a intoxicação por organofosforado em humanos.dose/fármaco conforme a fonte ↗

B. Link para os estudos clínicos

Estudos em gravidez e amamentação

• O fármaco é compatível com a amamentação e é considerado não teratogênico (Classe IV).

Renner UD, Oertel R, Kirch W. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit. 2005 Oct;27(5):655-65. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• 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 the newborns. There are no other adequate and well-controlled studies in pregnant women. Other than in the adjunctive use for delivery by cesarean section, Transderm Scōp should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus (Class IV).no original (inglês)

Product label: TRANSDERM SCOP (scopalamine) patch, extended release [Baxter Healthcare Corporation] Last revised: September 2012 [DailyMed]no original (inglês)

C. Link para os estudos não clínicos (por exemplo, em animais)

Estudos em animais adultos

• The protective efficacy of the antimuscarinic agent scopolamine was evaluated against soman (o-pinacolyl methylphosphonofluoridate [GD])-induced respiratory toxicity in guinea pigs. Anesthetized animals were exposed to GD (841 mg/m3) by microinstillation inhalation exposure and treated 30 seconds later with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 hours. Treatment with scopolamine significantly increased survival and reduced clinical signs of toxicity and body weight loss in GD-exposed animals. Analysis of bronchoalveolar lavage (BAL) fluid showed normalization of GD-induced increased cell death, total cell count, and protein following scopolamine treatment. The BAL fluid acetylcholinesterase and butyrylcholinesterase levels were also increased by scopolamine treatment. Respiratory dynamics parameters were normalized at 4 and 24 hours post-GD exposure in scopolamine-treated animals. Lung histology showed that scopolamine treatment reduced bronchial epithelial and subepithelial inflammation and multifocal alveolar septal edema. These results suggest that aerosolized scopolamine considerably protects against GD-induced respiratory toxicity.dose/fármaco conforme a fonte ↗no original (inglês)

Perkins MW, Pierre Z, Rezk P, Song J, Oguntayo S, Morthole V, Sciuto AM, Doctor BP, Nambiar MP. Protective effects of aerosolized scopolamine against soman-induced acute respiratory toxicity in guinea pigs. Int J Toxicol. 2011 Dec;30(6):639-49. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• There is a requirement to ensure that UK armed forces are provided with the best possible medical countermeasures to prevent or mitigate the effects of exposure to nerve agents. When pretreatments are under consideration, it is of particular importance to ensure that they do not in themselves give rise to adverse effects and do not exacerbate the effects of agent exposure. The present study was designed to address these considerations for a combination of physostigmine and scopolamine as a potential pretreatment regimen. Common marmosets were trained to perform a two-choice discrimination serial reversal task, and baseline data were collected. Subjects received a dose of either soman or sarin after 2 weeks of pretreatment with either saline or physostigmine and scopolamine via miniosmotic pump. No effects of physostigmine and scopolamine were seen on task accuracy or response rates. Neither accuracy of reversal performance nor number of responses made were significantly changed by administration of either soman or sarin subsequent to pretreatment with physostigmine/scopolamine. In the groups pretreated with saline, performance of the behavioural task, in terms of responses made, was virtually abolished on the day the OP was administered, but a significant increase in accuracy of performance was seen over the 2- to 14-day period following administration. A combination of physostigmine and scopolamine, which is known to protect against nerve-agent lethality, offers protection against the effects of soman and sarin on behavioural performance, as measured by a discrimination reversal task. The improved performance observed following nerve agent requires further investigation.dose/fármaco conforme a fonte ↗no original (inglês)

Muggleton NG, Bowditch AP, Crofts HS, Scott EA, Pearce PC. Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus). Psychopharmacology (Berl). 2003 Mar;166(3):212-20. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• Exposure to soman, a toxic organophosphate nerve agent, causes severe adverse effects and long term changes in the peripheral and central nervous systems. The goal of this study was to evaluate the ability of prophylactic treatments to block the deleterious effects associated with soman poisoning. scopolamine, a classical anticholinergic agent, or caramiphen, an anticonvulsant anticholinergic drug with anti-glutamatergic properties, in conjunction with pyridostigmine, a reversible cholinesterase inhibitor, were administered prior to soman (1xLD50). Both caramiphen and scopolamine dramatically attenuated the process of cell death as assessed by the binding of [3H]RoS-4864 to peripheral benzodiazepine receptors (omega3 sites) on microglia and astrocytes. In addition, caramiphen but not scopolamine, blocked the soman-evoked down-regulation of [3H]AMPA binding to forebrain membrane preparations. Moreover, cognitive tests utilizing the Morris water maze, examining learning and memory processes as well as reversal learning, demonstrated that caramiphen abolished the effects of soman intoxication on learning as early as the first trial day, while scopolamine exerted its effect commencing at the second day of training. Whereas the former drug completely prevented memory deficits, the latter exhibited partial protection. Both agents equally blocked the impairment of reversal learning. In addition, there is a significant correlation between behavioral parameters and [3H]RoS-4864 binding to forebrain membrane preparations of rats, which participated in these tests (r(21) = 0.66, P < 0.001; r(21) = 0.66, P < 0.001, -0.62, P < 0.002). These results demonstrate the beneficial use of drugs exhibiting both anti-cholinergic and anti-glutamatergic properties for the protection against changes in cognitive parameters caused by nerve agent poisoning. Moreover, agents such as caramiphen may eliminate the need for multiple drug therapy in organophosphate intoxications.dose/fármaco conforme a fonte ↗no original (inglês)

Raveh L, Weissman BA, Cohen G, Alkalay D, Rabinovitz I, Sonego H, Brandeis R . Caramiphen and scopolamine prevent soman-induced brain damage and cognitive dysfunction. Neurotoxicology. 2002 May;23(1):7-17. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• A total of eight anticholinergic drugs (aprophen, atropine, azaprophen, benactyzine, biperiden, procyclidine, scopolamine, trihexyphenidyl) were tested in parallel with diazepam for the ability to terminate seizure activity induced by the nerve agent soman. Guinea pigs, implanted with electrodes to record cortical electroencephalographic (EEG) activity, were pretreated with pyridostigmine Br (0.026 mg:kg, i.m.) and 30 min later challenged with 2×LD50 soman (56 microg:kg, s.c.) followed 1 min later by treatment with atropine SO4 (2 mg:kg, i.m.) and pralidoxime chloride (2-PAM Cl; 25 mg:kg, i.m.). All guinea pigs developed sustained seizure activity following this treatment. Dose-effect curves were determined for the ability of each drug to terminate seizure activity when anticonvulsant treatment was given either 5 or 40 min after seizure onset. Body weight gain and recovery of behavioral performance of a previously trained one-way avoidance task were measured after exposure. With the exception of atropine, all anticholinergic drugs were effective at lower doses than diazepam in terminating seizures when given 5 min after seizure onset; benactyzine, procyclidine and aprophen terminated seizures most rapidly while scopolamine, trihexyphenidyl, biperiden, and diazepam were significantly slower. When given 40 min after seizure onset, diazepam was the most potent compound tested, followed by scopolamine, benactyzine and biperiden; atropine was not effective when tested 40 min after seizure onset. For diazepam, the time to terminate the seizure was the same whether it was given at the 5- or 40-min delay. In contrast, most anticholinergics were significantly slower in terminating seizure activity when given at the 40-min delay relative to when they were given at the 5-min delay. Successful control of seizure activity, regardless of the drug, was predictive of survival of the lethal effects of nerve agent exposure, a more rapid behavioral recovery (body weight, avoidance performance) and greater protection from neuropathology. In contrast, failure of a drug treatment to terminate seizure activity was closely associated with an increased probability of acute (<24 h) and delayed (10-day survival) lethality, a slower behavioral recovery in survivors, and an increased incidence and degree of neuropathology.dose/fármaco conforme a fonte ↗no original (inglês)

McDonough JH Jr, Zoeffel LD, McMonagle J, Copeland TL, Smith CD, Shih TM. Anticonvulsant treatment of nerve agent seizures: Anticholinergics versus diazepam in soman-intoxicated guinea pigs. Epilepsy Res. 2000 Jan;38(1):1-14. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• Six FDA approved, injectable compounds [benztropine (BZT); biperiden (BIP); dicyclomine (DCL); l-hyoscyamine (HYO); orphenadrine (ORP); scopolamine (SCP)] were each compared to diazepam (DZ, the standard) in male guinea pigs against ongoing soman-induced convulsive or sub-CV (CV/sub-CV) activity. Three trained graders concurrently assigned CV/sub-CV scores to each animal based on signs of intoxication at various times post-soman. Animals received (im) pyridostigmine (26 micrograms/kg) 30 min before soman (56 micrograms/kg; 2 x LD50), atropine (2 mg/kg) admixed with 2-PAM (25 mg/kg) at one min after soman, and the candidate drug preparation at 5.67 min post soman, a time when CV activity was assured. BIP and SCP were effective over dosage ranges between 10 and 0.3, and 1.0 and 0.13 mg/kg, respectively, while the other preparations were less effective at their respective maximum dosages. At the most effective dosages of SCP (1.0 mg/kg) and BIP (10 mg/kg), the CV/sub-CV scores were significantly lower (p < 0.05) than those of DZ. Only 33% survival was observed at each of two doses of ORP and one dose of HYO; therefore, no further testing was done with these compounds. Using freshly prepared solutions, DCL (up to 40 mg/kg) and BZT (up to 96 mg/kg) were tested with mixed results; DCL lowered lethality while BZT increased lethality. CV/sub-CV scores for the most effective dose of DCL and BZT were, however, lower than those of DZ. SCP is an antimuscarinic drug devoid of antinicotinic activity, while BIP possesses antimuscarinic, antinicotinic, antispasmodic and anti-N-methyl-D-aspartate activity. Recent evidence suggests that, in late stages of intoxication by nerve agents, noncholinergic, excitatory amino acid receptors may become involved and necessitate the use of a multi-action drug like BIP. The findings herein suggest that SCP and BIP are superior to DZ, but further studies are needed to determine which drug or drug class should be pursued in more advanced testing.dose/fármaco conforme a fonte ↗no original (inglês)

Anderson DR, Harris LW, Bowersox SL, Lennox WJ, Anders JC. Efficacy of injectable anticholinergic drugs against soman-induced convulsive/subconvulsive activity. Drug Chem Toxicol. 1994;17(2):139-48. [PubMed Citation]no original (inglês)

• Diazepam (DZ) and scopolamine (SCP) are known to be beneficial when each is used in combination with atropine (AT) + oxime therapy against intoxication by soman, but the efficacy of each might be expected to vary with the dosage of AT. Thus the therapeutic efficacy of SCP (5 doses; 0-0.86 mg/kg) versus DZ (5 doses; 0-5 mg/kg), when used in conjunction with AT (3 doses; 0.5-8 mg/kg) + 2-PAM (25 mg/kg) therapy, was tested in groups of pyridostigmine pretreated guinea pigs exposed to 1.6, 2.0, 2.5 or 3.2 LD50s of soman. Response surface methodology was employed to describe the relationship between lethality and the AT/DZ or AT/SCP dosages. Results show that within the indicated dose ranges used, the efficacy of SCP is not dependent on the presence of AT, whereas AT is needed for DZ to maintain the lowest probability of death. These findings suggest that in guinea pigs SCP could supplement AT or replace DZ as therapy against nerve agent intoxication.dose/fármaco conforme a fonte ↗no original (inglês)

Harris LW, Gennings C, Carter WH, Anderson DR, Lennox WJ, Bowersox SL, Solana RP. Efficacy comparison of scopolamine (SCP) and diazepam (DZ) against soman-induced lethality in guinea pigs. Drug Chem Toxicol. 1994;17(1):35-50. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• Exposure to high doses of organophosphorus nerve agents such as soman, even with carbamate pretreatment, produces a variety of toxic cholinergic signs, including secretions, convulsions and death. Evidence suggests that soman-induced convulsions may be associated with postexposure brain neuropathology. The purpose of this study was to investigate the pharmacologic mechanism of action of soman-induced convulsions and of anticonvulsant drugs. Various classes of compounds were evaluated for their efficacy in preventing soman-induced convulsions in rats pretreated with the oxime HI-6 to increase survival time, along with various doses of the test compounds (IM) either in the absence or presence of atropine sulfate (16 mg/kg, IM) 30 minutes prior to a soman challenge dose (180 micrograms/kg, SC; equivalent to 1.6 x LD50) that produced 100% convulsions. Without atropine sulfate, only tertiary anticholinergics (scopolamine, trihexyphenidyl, biperiden, benactyzine, benztropine, azaprophen and aprophen), caramiphen, carbetapentane and MK-801 were effective anticonvulsants. In the presence of atropine sulfate, the benzodiazepines (diazepam, midazolam, clonazepam, loprazolam and alprazolam), mecamylamine, flunarizine, diphenylhydantoin, clonidine, CGS 19755 and Organon 6370 studied were effective. We have examined the possibility that diazepam may exert some of its anticonvulsant effects through cholinergic mechanisms and found that a reduced release of ACh into synapses after diazepam and atropine treatment may account for diazepam's anticonvulsant activity against soman. We also found that at anticonvulsant doses biperiden and trihexyphenidyl each significantly reversed the effects of soman on striatal levels of DOPAC and HVA, the metabolites of dopamine, and have concluded that in addition to actions on muscarinic receptors, the anticonvulsant effects of these anticholinergics in soman poisoning may be partially related to their actions on the striatal dopaminergic system. These findings allow us to postulate that central muscarinic cholinergic mechanisms are primarily involved in eliciting the convulsions following exposure to soman and that subsequent recruitment of other excitatory neurotransmitter systems and loss of inhibitory control may be responsible for sustaining the convulsions and for producing the subsequent brain damage. Future studies to confirm these neuropharmacological mechanisms are proposed.dose/fármaco conforme a fonte ↗no original (inglês)

Shih, T-M., T.A. Koviak, B.R. Capacio. Anticonvulsants for poisoning by the organophosphorus compound soman: Pharmacological mechanisms. Neurosci Biobehav Rev. 1991 Fall;15(3):349-62. [PubMed Citation]no original (inglês)

• Pretreatment of nonhuman primates with physostigmine (Phy) and scopolamine or physostigmine and trihexyphenidyl 25 min before exposure to 2 LD50 soman im resulted in complete survival without convulsions or loss of consciousness. When identically pretreated animals were challenged with 5 LD50s of soman followed by atropine and 2-PAM therapy 1 min later, all animals experienced a loss of consciousness for approximately 10 min followed by functional recovery within an additional 20 min. These findings indicated that a pretreatment regimen composed of Phy and cholinolytic is capable of protecting primates from an absolute lethal dose of soman with rapid recovery from incapacitation.dose/fármaco conforme a fonte ↗no original (inglês)

von Bredow J, Corcoran K, Maitland G, Kaminskis A, Adams N, Wade J. Efficacy evaluation of physostigmine and anticholinergic adjuncts as a pretreatment for nerve agent intoxication. Fundam Appl Toxicol. 1991 Nov;17(4):782-9. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Estudos em animais gestantes

• Teratogenic studies were performed in pregnant rats and rabbits with scopolamine hydrobromide administered by daily intravenous injection. No adverse effects were recorded in rats. Scopolamine hydrobromide has been shown to have a marginal embryotoxic effect in rabbits when administered by daily intravenous injection at doses producing plasma levels approximately 100 times the level achieved in humans using a transdermal system.dose/fármaco conforme a fonte ↗no original (inglês)

Product label: TRANSDERM SCOP (scopalamine) patch, extended release [Baxter Healthcare Corporation] Last revised: September 2012 [DailyMed]no original (inglês)

4. Dados farmacocinéticos e toxicocinéticos

Adulto

• The objective was to develop a microdialysis set-up to measure the concentration-time course of scopolamine in the interstitium of subcutaneous adipose tissue. Six healthy male volunteers were eligible for data analysis. Subjects received 0.5 mg scopolamine as a 15-minute intravenous infusion. Microdialysis samples from interstitial space fluid of subcutaneous adipose tissue and blood samples were taken at predefined intervals over a period of 360 minutes. Scopolamine concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS). High inter-individual variability was observed in all pharmacokinetic parameters. The mean peak serum concentration (C(max)) of 6.5 +/- 3.9 ng/ml (data in mean +/- SD) was attained after 15 +/- 3 minutes (t(max)), whereas in dialysate, a mean peak concentration of 2.7 +/- 1.7 ng/ml was measured after 27 +/- 8 minutes. The ratio of the area under the concentration versus time curve from 0-360 min for interstitium (AUC(interstitium 0-360 min0) to the AUC for serum (AUC(serum 0-360 min)) was 0.96 +/- 0.7. The elimination half-life of scopolamine was 121 +/- 85 minutes in serum and 166 +/- 117 minutes in dialysate. Values for total clearance and volume of distribution in serum were 99.1 +/- 35.0 1/h and 188 +/- 76 1, respectively. In the present study, we were able to define a microdialysis set-up, which allows for the measurement of scopolamine concentrations in target tissues. In addition, we demonstrated that the concentrations of scopolamine in subcutaneous adipose tissue resemble closely the concentration-time course in serum of healthy volunteers.dose/fármaco conforme a fonte ↗no original (inglês)

Stetina PM, Madai B, Kulemann V, Kirch W, Joukhadar C. Pharmacokinetics of scopolamine in serum and subcutaneous adipose tissue in healthy volunteers. Int J Clin Pharmacol Ther. 2005 Mar;43(3):134-9. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• The effects of subcutaneously administered scopolamine on quantitative electroencephalogram (qEEG) and cognitive performance were evaluated and correlated with pharmacokinetic parameters in a randomized, double-blind placebo-controlled crossover study of 10 healthy male volunteers. Changes in qEEG and cognition were determined for 8 hours after drug administration. Scopolamine produced dose- and time-dependent impairments of attention and memory and a time-dependent increase in delta power (1.25-4.50 Hz) and a decrease in fast alpha power (9.75-12.50 Hz) on qEEG compared with placebo. Maximum serum concentrations of scopolamine occurred 10 to 30 minutes after drug administration. Mean peak serum concentrations (free base) were 3.27, 8.99, and 18.81 ng/mL after administration of 0.4, 0.6 mg, and 0.8 mg scopolamine, respectively. Elimination half-life was approximately 220 minutes. The findings indicate temporary changes in qEEG and psychometric tests, and support the possible use of such a testing model for impaired cognitive functions such as age-related memory disturbances.dose/fármaco conforme a fonte ↗no original (inglês)

Ebert U, Siepmann M, Oertel R, Wesnes KA, Kirch W. Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration. J Clin Pharmacol. 1998 Aug;38(8):720-6. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• The alkaloid L-(-)-scopolamine [L-(-)-hyoscine] competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. The parasympatholytic scopolamine, structurally very similar to atropine (racemate of hyoscyamine), is used in conditions requiring decreased parasympathetic activity, primarily for its effect on the eye, gastrointestinal tract, heart, and salivary and bronchial secretion glands, and in special circumstances for a CNS action. Therefore, scopolamine is most suitable for premedication before anesthesia and for antiemetic effects. This alkaloid is the most effective single agent to prevent motion sickness. Scopolamine was the first drug to be made commercially available in a transdermal therapeutic system (TTS-patch) delivering alkaloid. Recently, pharmacokinetic data on scopolamine in different biologic matrices were obtained most efficiently using liquid chromatographic-tandem mass spectrometric (LC-MS/MS) or gas chromatography online coupled to mass spectrometry. Pharmacokinetic parameters are dependent on the dosage form (oral dose, tablets; parenteral application; IV infusion; SC and IM injection). Scopolamine has a limited bioavailability if orally administered. The maximum drug concentration occurs approximately 0.5 hours after oral administration. Because only 2.6% of nonmetabolized L-(-)-scopolamine is excreted in urine, a first-pass metabolism is suggested to occur after oral administration of scopolamine. Because of its short half-life in plasma and dose-dependent adverse effects (in particular hallucinations and the less serious reactions, eg, vertigo, dry mouth, drowsiness), the clinical use of scopolamine administered orally or parenterally is limited. To minimize the relatively high incidence of side effects, the transdermal dosage form has been developed. The commercially available TTS-patch contains a 1.5-mg drug reservoir and a priming dose (140 microg) to reach the steady-state concentration of scopolamine quickly. The patch releases 0.5 mg alkaloid over a period of 3 days (releasing rate 5 microg/h). Following the transdermal application of scopolamine, the plasma concentrations of the drug indicate major interindividual variations. Peak plasma concentrations (Cmax) of approximately 100 pg/mL (range 11-240 pg/mL) of the alkaloid are reached after about 8 hours and achieve steady state. During a period of 72 hours the plaster releases scopolamine, so constantly high plasma levels (concentration range 56-245 pg/mL) are obtained, followed by a plateau of urinary scopolamine excretion. Although scopolamine has been used in clinical practice for many years, data concerning its metabolism and the renal excretion in man are limited. After incubation with beta-glucuronidase and sulfatase, the recovery of scopolamine in human urine increased from 3% to approximately 30% of the drug dose (intravenously administered). According to these results from enzymatic hydrolysis of scopolamine metabolites, the glucuronide conjugation of scopolamine could be the relevant pathway in healthy volunteers. However, scopolamine metabolism in man has not been verified stringently. An elucidation of the chemical structures of the metabolites extracted from human urine is still lacking. Scopolamine has been shown to undergo an oxidative demethylation during incubation with CYP3A (cytochrome P-450 subfamily). To inhibit the CYP3A located in the intestinal mucosa, components of grapefruit juice are very suitable. When scopolamine was administered together with 150 mL grapefruit juice, the alkaloid concentrations continued to increase, resulting in an evident prolongation of tmax (59.5 +/- 25.0 minutes; P < 0.001). The AUC0-24h values of scopolamine were higher during the grapefruit juice period. They reached approximately 142% of the values associated with the control group (P < 0.005). Consequently, the related absolute bioavailabilities (range 6% to 37%) were significantly higher than the corresponding values of the drug orally administered together with water (range 3% to 27%). The effect of the alkaloid on quantitative electroencephalogram (qEEG) and cognitive performance correlated with pharmacokinetics was shown in studies with healthy volunteers. From pharmacokinetic-pharmacodynamic modeling techniques, a direct correlation between serum concentrations of scopolamine and changes in total power in alpha-frequency band (EEG) in healthy volunteers was provided. In conclusion, scopolamine is used for premedication in anesthesia and for the prevention of nausea and vomiting associated with motion sickness. Pharmacokinetics and pharmacodynamics of scopolamine depend on the dosage form. Effects on different cognitive functions have been extensively documented.dose/fármaco conforme a fonte ↗no original (inglês)

Renner UD, Oertel R, Kirch W. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit. 2005 Oct;27(5):655-65. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Gravidez

• O alcaloide atravessa facilmente a placenta. Por isso, a scopolamine só deve ser administrada a gestantes sob observação.dose/fármaco conforme a fonte ↗

Renner UD, Oertel R, Kirch W. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit. 2005 Oct;27(5):655-65. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Animais

• A rapid and sensitive method is described for the determination of scopolamine and its metabolites in rat urine by combining liquid chromatography and tandem mass spectrometry (LC-MS/MS). Various extraction techniques (free fraction, acid hydrolyses and enzyme hydrolyses) and their comparison were carried out for investigation of the metabolism of scopolamine. After extraction procedure, the pretreated samples were injected into a reversed-phase C18 column with mobile phase of methanol/ ammonium acetate (2mM, adjusted to pH 3.5 with formic acid) (70:30, v/v) and detected by an on-line MS/MS system. Identification and structural elucidation of the metabolites were performed by comparing their changes in molecular masses (DeltaM), retention-times and full scan MS(n) spectra with those of the parent drug. The results revealed that at least 18 metabolites (norscopine, scopine, tropic acid, aponorscopolamine, aposcopolamine, norscopolamine, hydroxyscopolamine, hydroxyscopolamine N-oxide, p-hydroxy-m-methoxyscopolamine, trihydroxyscopolamine, dihydroxy-methoxyscopolamine, hydroxyl-dimethoxyscopolamine, glucuronide conjugates and sulfate conjugates of norscopolamine, hydroxyscopolamine and the parent drug) and the parent drug existed in urine after ingesting 55mg/kg scopolamine to healthy rats. Hydroxyscopolamine, p-hydroxy-m-methoxyscopolamine and the parent drug were detected in rat urine for up to 106 h after ingestion of scopolamine.dose/fármaco conforme a fonte ↗no original (inglês)

Chen H, Chen Y, Wang H, Du P, Han F, Zhang H. Analysis of scopolamine and its eighteen metabolites in rat urine by liquid chromatography-tandem mass spectrometry. Talanta. 2005 Oct 31;67(5):984-91. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• In vivo and in vitro metabolism of scopolamine is investigated using a highly specific and sensitive liquid chromatography-mass spectrometry (LC-MSn) method. Feces, urine, and plasma samples are collected individually after ingestion of 55 mg/kg scopolamine by healthy rats. Rat feces and urine samples are cleaned up by a liquid-liquid extraction and a solid-phase extraction procedure (C18 cartridges), respectively. Methanol is added to rat plasma samples to precipitate plasma proteins. Scopolamine is incubated with homogenized liver and intestinal flora of rats in vitro, respectively. The metabolites in the incubating solution are extracted with ethyl acetate. Then these pretreated samples are injected into a reversed-phase C18 column with mobile phase of methanol-ammonium acetate (2 mM, adjusted to pH 3.5 with formic acid) (70:30, v/v) and detected by an on-line MSn system. Identification and structural elucidation of the metabolites are performed by comparing their changes in molecular masses (DeltaM), retention-times and full scan MSn spectra with those of the parent drug. The results reveal that at least 8 metabolites (norscopine, scopine, tropic acid, aponorscopolamine, aposcopolamine, norscopolamine, hydroxyscopolamine, and hydroxyscopolamine N-oxide) and the parent drug exist in feces after administering 55 mg/kg scopolamine to healthy rats. Three new metabolites (tetrahydroxyscopolamine, trihydroxy-methoxyscopolamine, and dihydroxy-dimethoxyscopolamine) are identified in rat urine. Seven metabolites (norscopine, scopine, tropic acid, aponorscopolamine, aposcopolamine, norscopolamine, and hydroxyscopolamine) and the parent drug are detected in rat plasma. Only 1 hydrolyzed metabolite (scopine) is found in the rat intestinal flora incubation mixture, and 2 metabolites (aposcopolamine and norscopolamine) are identified in the homogenized liver incubation mixture.dose/fármaco conforme a fonte ↗no original (inglês)

Chen H, Chen Y, Du P, Han F. Liquid chromatography-electrospray ionization ion trap mass spectrometry for analysis of in vivo and in vitro metabolites of scopolamine in rats. J Chromatogr Sci. 2008 Jan;46(1):74-80. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

5. Indicações e posologia atualmente aprovadas pela FDA/EUA

Adultos (FDA)

Dose parenteral: a dose usual do adulto por via IM, IV ou subcutânea de scopolamine hydrobromide é de 0.3-0.65 mg; se necessário, essas doses podem ser repetidas 3 ou 4 vezes ao dia. Alternativamente, sugerem-se doses parenterais no adulto de scopolamine hydrobromide de 0.2-1 mg para efeito antiemético, 0.2-0.6 mg para inibição da salivação, 0.32-0.65 mg para efeito amnésico, ou 0.6 mg para sedação ou tranquilização.dose/fármaco conforme a fonte ↗

Cinetose: a dose usual do adulto do sistema transdérmico de scopolamine é de um sistema programado para liberar aproximadamente 1 mg de scopolamine ao longo de 72 hours (72 horas).dose/fármaco conforme a fonte ↗

Náusea e vômito pós-operatórios: o sistema transdérmico de scopolamine deve ser aplicado na noite anterior à cirurgia programada. O sistema transdérmico deve permanecer no lugar por 24 hours (24 horas) após a cirurgia, sendo então removido e descartado.dose/fármaco conforme a fonte ↗

A faixa usual de dose oral dos comprimidos solúveis de scopolamine hydrobromide é de 0.4-0.8 mg. Cinetose: 0.25-0.8 mg do fármaco podem ser administrados 1 hour (1 hora) antes da exposição ao movimento; doses subsequentes de 0.25-0.8 mg podem ser dadas 3 vezes ao dia, conforme a necessidade e a tolerância.dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

Crianças (FDA)

Dose parenteral: a dose pediátrica usual por via IM, IV ou subcutânea de scopolamine hydrobromide é de 0.006 mg/kg (6 mcg/kg) ou 0.2 mg/m 2 .dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

A segurança e a eficácia do Transderm Scōp em crianças não estão estabelecidas. As crianças são particularmente suscetíveis aos efeitos colaterais dos alcaloides da beladona. O Transderm Scōp não deve ser usado em crianças, porque não se sabe se esse sistema liberará quantidade de scopolamine capaz de produzir efeitos adversos graves em crianças.dose/fármaco conforme a fonte ↗

Product label: TRANSDERM SCOP (scopalamine) patch, extended release [Baxter Healthcare Corporation] Last revised: September 2012 [DailyMed]no original (inglês)

Gravidez (FDA)

Cesariana: se o sistema transdérmico de scopolamine for usado profilaticamente em pacientes submetidas a cesariana, o sistema deve ser aplicado uma hora antes da cirurgia, para minimizar a exposição do recém-nascido ao fármaco. O sistema transdérmico deve permanecer no lugar por 24 hours (24 horas) após a cirurgia, sendo então removido e descartado.dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

Categoria de gravidez C

A scopolamine administrada por via parenteral em doses maiores que a liberada pelo Transderm Scōp não aumenta a duração do trabalho de parto nem afeta as contrações uterinas. A scopolamine atravessa a placenta.dose/fármaco conforme a fonte ↗

Product label: TRANSDERM SCOP (scopalamine) patch, extended release [Baxter Healthcare Corporation] Last revised: September 2012 [DailyMed]no original (inglês)

Lactantes (FDA)

Como a scopolamine é excretada no leite humano, deve-se ter cautela quando o Transderm Scōp é administrado a uma lactante.dose/fármaco conforme a fonte ↗

Product label: TRANSDERM SCOP (scopalamine) patch, extended release [Baxter Healthcare Corporation] Last revised: September 2012 [DailyMed]no original (inglês)

6. Formulações disponíveis atualmente / prazo de validade

Formulação

Sistema transdérmico tópico de scopolamine, aproximadamente 1 mg/72 hours (1.5 mg/2.5 cm2)dose/fármaco conforme a fonte ↗

Scopolamine Hydrobromide comprimidos solúveis 0.4 mgdose/fármaco conforme a fonte ↗

Scopolamine Hydrobromide pó a graneldose/fármaco conforme a fonte ↗

Scopolamine Hydrobromide injeção parenteral 0.4 mg/mLdose/fármaco conforme a fonte ↗

Scopolamine Hydrobromide (EENT) solução oftálmica 0.25%dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

Prazo de validade

Estabilidade

• Quando misturada na mesma seringa, a injeção de scopolamine hydrobromide é relatada como fisicamente compatível por pelo menos 15 minutes (15 minutos) com as seguintes injeções: atropine sulfate, butorphanol tartrate, chlorpromazine hydrochloride, dimenhydrinate, diphenhydramine hydrochloride, droperidol, fentanyl citrate, glycopyrrolate, hydromorphone hydrochloride, hydroxyzine hydrochloride, meperidine hydrochloride, metoclopramide, morphine sulfate, cloridratos concentrados de alcaloides do ópio, pentazocine lactate, pentobarbital sodium, perphenazine, prochlorperazine edisylate, promazine hydrochloride, promethazine hydrochloride ou thiopental sodium. Como a compatibilidade dessas e de outras misturas com a injeção de scopolamine hydrobromide depende de vários fatores (por exemplo, concentração dos fármacos, pH resultante, temperatura), referências especializadas devem ser consultadas para informação específica de compatibilidade. Pode se formar turvação em até 1 hour (1 hora) quando a injeção de scopolamine hydrobromide é misturada a soluções de methohexital sodium.dose/fármaco conforme a fonte ↗
• A scopolamine racemiza facilmente na presença de álcali diluído. As soluções de scopolamine hydrobromide são incompatíveis com álcalis.dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

Armazenamento

O sistema transdérmico de scopolamine disponível comercialmente (Transderm Scop) deve ser guardado em temperatura ambiente controlada, entre 20-25&deg;C. A scopolamine hydrobromide deve ser guardada em recipientes hermeticamente fechados e resistentes à luz. As injeções de scopolamine hydrobromide devem ser guardadas em recipientes resistentes à luz, de dose única ou múltipla, preferencialmente de vidro USP Tipo I, a 15-30&deg;C; o congelamento das injeções deve ser evitado. Os comprimidos solúveis de scopolamine hydrobromide disponíveis comercialmente devem ser guardados em temperatura ambiente controlada (15-30&deg;C).dose/fármaco conforme a fonte ↗

A solução oftálmica de scopolamine hydrobromide deve ser guardada em recipientes hermeticamente fechados, a temperatura inferior a 40&deg;C, preferencialmente entre 15-30&deg;C; o congelamento deve ser evitado.dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

7. Utilização e posologia off-label atuais

Adulto

• The effect of oral anticholinergic drugs has been limited in the treatment of drooling. Transdermal scopolamine (1.5 mg/2.5 cm2) offers advantages. One single application is considered to render a stable serum concentration for 3 days. A distinct reduction of basal salivation was demonstrated in an open trial of six healthy volunteers. Eighteen mentally retarded patients with a drooling problem were studied in a double-blind, placebo-controlled cross-over trial. The therapeutic effect of transdermal scopolamine was assessed by a visual analogue scale. Three patients dropped out due to loss of the system. In the remaining 15 patients, the active drug caused a reduction of drooling which was significant in the period from 24 to 72 h. There were few and slight objective signs of unwanted effects. Scopoderm may cause drowsiness and affect tooth health. The management of drooling should primarily be focused on the cause. Sensomotor training is often valuable in cerebral palsy. Factors such as nasal obstruction, mucosal irritation, and drug-induced parkinsonism should be given attention. Sometimes, however, a temporary symptomatic treatment is indicated, for example on special occasions or in order to cure perioral skin lesions. Transdermal scopolamine may offer this possibility.dose/fármaco conforme a fonte ↗no original (inglês)

Brodtkorb E, Wyzocka-Bakowska MM, Lillevold PE, Sandvik L, Saunte C, Hestnes A. Transdermal scopolamine in drooling. J Ment Defic Res. 1988 Jun;32 ( Pt 3):233-7. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

• Scopoderm transdermal therapeutic system (TTS) is applied to prevent nausea and vomiting associated with motion sickness. Dry mouth is the most common side effect, appearing in up to two thirds of the patients treated. We have used this side effect to the benefit of patients with sialorrhea or with difficulties swallowing normally secreted amounts of saliva. More than 100 patients with tumors of the aerodigestive tract before and after surgery, and patients after parotidectomies, after tracheotomies, with peritonsillar abscesses, tonsillitis and pharyngitis, and neurologic disorders were thus treated. Reduced secretion of saliva was seen in 50% to 100% of the treatment groups. Other side effects were minimal and we recommend the use of scopoderm TTS for reduction of salivary flow.dose/fármaco conforme a fonte ↗no original (inglês)

Talmi YP, Finkelstein Y, Zohar Y. Reduction of salivary flow with transdermal scopolamine: a four-year experience. Otolaryngol Head Neck Surg. 1990 Oct;103(4):615-8. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Crianças

• Sialorreia (baba): adesivo de 1.5 mg (scopolamine transdérmica) a cada 3 days (3 dias).dose/fármaco conforme a fonte ↗

Kastrup EK et al., eds. Drug Facts and Comparisons St Louis, MO: Wolters Kluwer Health, 2012 p.1480-1no original (inglês)

• Transdermal scopolamine patches (1.5 mg) were used to control drooling in a two-year-old boy with severe spastic quadriparetic cerebral palsy and developmental delay. He responded well to the continuous scopolamine therapy, with a decrease in drooling, and a secondary decrease in respiratory distress and frequency of suctioning. No significant side-effects were noted.dose/fármaco conforme a fonte ↗no original (inglês)

Siegel LK, Klingbeil MA. Control of drooling with transdermal scopolamine in a child with cerebral palsy. Dev Med Child Neurol. 1991 Nov;33(11):1013-4. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

8. Via de administração / monitorização

• A scopolamine hydrobromide é administrada por via oral, IM, IV direta ou por injeção subcutânea. A scopolamine é administrada por via percutânea, pela aplicação tópica de um sistema transdérmico.dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

9. Efeitos adversos

• Embora a scopolamine transdérmica tenha sido associada a menos efeitos adversos que a scopolamine hydrobromide administrada por via oral, efeitos sistêmicos adversos ocorreram após a aplicação do sistema transdérmico na pele.dose/fármaco conforme a fonte ↗
• O efeito adverso mais frequente da scopolamine administrada por via transdérmica é a boca seca, ocorrendo em cerca de 67 ou 29% dos pacientes que recebem o fármaco para prevenção de cinetose ou de náusea e vômito pós-operatórios, respectivamente.dose/fármaco conforme a fonte ↗
• Sonolência foi relatada em cerca de 17% dos pacientes nos estudos clínicos que usaram o sistema transdérmico para prevenção de cinetose. Tontura foi relatada por cerca de 12% dos pacientes nos estudos clínicos que receberam o sistema transdérmico de scopolamine no perioperatório para prevenção de náusea e vômito.dose/fármaco conforme a fonte ↗
• Comprometimento transitório da acomodação ocular, incluindo visão borrada e midríase, também ocorreu após a aplicação transdérmica de scopolamine.dose/fármaco conforme a fonte ↗
• Cicloplegia induzida por scopolamine, manifestada como pupilas fixas e dilatadas, ocorreu após a aplicação transdérmica do fármaco; a cicloplegia pode ser bilateral ou unilateral e persistiu por 48 hours (48 horas) ou mais em alguns pacientes. Sugere-se que a cicloplegia unilateral provavelmente resulte de tocar o olho ou a lente de contato com os dedos contaminados por scopolamine após manusear o sistema transdérmico. Como a midríase neurogênica (por exemplo, causada por traumatismo craniano, tumor) responde (com constrição pupilar) à instilação local de um parassimpatomimético, a falha do esfíncter pupilar em contrair em 30 minutes (30 minutos) após a instilação de algumas gotas de solução oftálmica de pilocarpine a 0.5 ou 1%, na ausência de lesão ocular local (iridoplegia traumática) ou de pressão intraocular aumentada (glaucoma de ângulo fechado), geralmente indica bloqueio do esfíncter induzido quimicamente (por exemplo, por scopolamine).dose/fármaco conforme a fonte ↗
• A aplicação transdérmica de scopolamine também precipitou glaucoma de ângulo fechado em vários pacientes; pelo menos um paciente precisou de cirurgia.dose/fármaco conforme a fonte ↗
• Ressecamento ocular, prurido ou injeção conjuntival dos olhos ocorreram ocasionalmente após a administração transdérmica do fármaco.
• Com menos frequência, efeitos adversos no SNC — incluindo desorientação, distúrbios de memória, tontura, inquietação, vertigem, alucinações, delirium e confusão — ocorreram após a administração transdérmica de scopolamine.dose/fármaco conforme a fonte ↗
• Sinais e sintomas de psicose tóxica aguda, incluindo confusão, agitação, fala arrastada e pressionada, alucinações visuais, comportamento paranoide e delírios, ocorreram em alguns pacientes que receberam scopolamine transdérmica; os sinais e sintomas psicóticos se resolveram em 3 hours (3 horas) após administração IM de physostigmine em um paciente, e em 24-36 hours (24 a 36 horas) após a remoção do sistema transdérmico em vários outros.dose/fármaco conforme a fonte ↗
• Sintomas de abstinência do fármaco, incluindo náusea, vômito, cefaleia, tontura e distúrbios do equilíbrio, foram relatados em alguns pacientes após a descontinuação do sistema transdérmico. Esses sintomas geralmente só aparecem 24 hours (24 horas) ou mais depois de o sistema transdérmico ter sido removido. Alguns desses sintomas podem estar relacionados à adaptação a um ambiente sem movimento a partir de um ambiente em movimento.dose/fármaco conforme a fonte ↗
• Sintomas mais graves, incluindo fraqueza muscular, bradicardia e hipotensão, também podem ocorrer após a descontinuação do sistema transdérmico. É necessário distinguir os sinais e sintomas de abstinência após a descontinuação do sistema transdérmico de scopolamine da superdosagem de scopolamine. Embora confusão mental e tontura possam ser observadas tanto na toxicidade aguda quanto na abstinência, os pacientes com sintomas de abstinência tipicamente apresentam bradicardia, cefaleia, náusea, cólicas abdominais e sudorese, enquanto taquiarritmias, pele seca e ruídos hidroaéreos diminuídos sugerem toxicidade anticolinérgica.dose/fármaco conforme a fonte ↗
• Dermatite de contato alérgica tardia, manifestada como prurido e eritema no local de aplicação, ocorreu com a administração transdérmica de scopolamine.dose/fármaco conforme a fonte ↗
• A reação se desenvolveu 1.5-15 months (1,5 a 15 meses) após o início da terapia transdérmica de longo prazo, cedeu em 2 weeks (2 semanas) após a remoção do sistema transdérmico e foi atribuída à scopolamine, e não aos componentes do sistema transdérmico.dose/fármaco conforme a fonte ↗
• Erupção cutânea e eritema também ocorreram ocasionalmente após a administração transdérmica do fármaco.
• Dificuldade para urinar e alterações transitórias da frequência cardíaca ocorreram ocasionalmente após a administração transdérmica de scopolamine. Contudo, não se estabeleceu relação causal com a scopolamine transdérmica.dose/fármaco conforme a fonte ↗
• A segurança e a eficácia dos comprimidos solúveis de scopolamine hydrobromide ou do sistema transdérmico de scopolamine em crianças não estão estabelecidas. O fabricante afirma que o sistema transdérmico de scopolamine não deve ser usado em crianças, pois não se sabe se o sistema pode liberar quantidade de fármaco capaz de causar efeitos adversos graves na criança. Além disso, o fabricante alerta que as crianças são particularmente suscetíveis aos efeitos adversos da scopolamine.dose/fármaco conforme a fonte ↗
• O fabricante da scopolamine transdérmica afirma que, se ocorrerem sintomas de superdosagem, deve-se estabelecer via aérea adequada e instituir suporte cardíaco e respiratório, seguidos da remoção rápida de todos os sistemas transdérmicos da pele e/ou da boca. Se houver evidência de ingestão do sistema transdérmico, deve-se considerar lavagem gástrica, remoção endoscópica dos adesivos engolidos ou administração de activated charcoal (carvão ativado), conforme a situação clínica. Além disso, tratamento sintomático apropriado deve ser iniciado.dose/fármaco conforme a fonte ↗
• A scopolamine hydrobromide pode causar aumento da pressão intraocular.dose/fármaco conforme a fonte ↗
• A administração prolongada de scopolamine hydrobromide no olho pode causar irritação local, caracterizada por conjuntivite folicular, congestão vascular e edema, exsudato e dermatite eczematoide.dose/fármaco conforme a fonte ↗
• A aplicação tópica de scopolamine hydrobromide no olho pode causar efeitos sistêmicos adversos. Após a aplicação tópica no olho de algumas gotas de scopolamine hydrobromide a 1%, sinais e sintomas de psicose confusional — incluindo inquietação, confusão mental, alucinações, incoerência, comportamento violento, amnésia, inconsciência, extremidades espásticas, vômito e incontinência urinária — ocorreram em vários pacientes.dose/fármaco conforme a fonte ↗
• Sonolência também foi relatada.
• Toxicidade sistêmica manifestada como efeitos antimuscarínicos sistêmicos também ocorreu em um paciente após a aplicação tópica no olho de solução do fármaco a 0.25% a cada 10 minutes (10 minutos) por 2 hours (2 horas) antes de cirurgia de descolamento de retina.dose/fármaco conforme a fonte ↗
• A solução oftálmica de scopolamine hydrobromide é contraindicada em pacientes com glaucoma de ângulo fechado conhecido ou suspeito.dose/fármaco conforme a fonte ↗
• Deve-se considerar a possibilidade de glaucoma não diagnosticado em pacientes idosos.
• A scopolamine hydrobromide deve ser usada com extrema cautela, se é que deve, em lactentes e crianças pequenas.dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

10. Contraindicação(ões)

• A scopolamine é geralmente contraindicada em pacientes com glaucoma (isto é, de ângulo fechado), obstrução pilórica ou obstrução do colo vesical.dose/fármaco conforme a fonte ↗
• A scopolamine também é geralmente contraindicada em pacientes com taquicardia secundária a insuficiência cardíaca ou tireotoxicose, e naqueles com íleo paralítico.dose/fármaco conforme a fonte ↗
• O fabricante afirma que os comprimidos solúveis de scopolamine hydrobromide são contraindicados em pacientes com hipertrofia prostática ou com função renal ou hepática comprometida.dose/fármaco conforme a fonte ↗
• A scopolamine é contraindicada em pacientes hipersensíveis ao fármaco, a qualquer outro alcaloide da beladona, ou a qualquer ingrediente ou componente da formulação ou do sistema de administração.dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904 Obtained online through https://about.medicinescomplete.com/#/browse/ahfsno original (inglês)

11. Estudos clínicos em andamento

• Nenhum dado disponível no momento.

12. Estudos não clínicos em andamento

• Nenhum dado disponível no momento.

13. Estudos necessários para a indicação clínica de defesa química

• Teste contra a atropine; a scopolamine pode ter melhor penetração no SNC com perfil menor de efeitos colaterais graves. Atropine mais pralidoxime, com scopolamine como acréscimo.dose/fármaco conforme a fonte ↗

Biodefense Meeting. Best Pharmaceuticals for Children Act. Eunice Kennedy Shriver National Institute of Child Health and Human Development , September 8-9, 2008, Rockville, MD (NICHD)no original (inglês)

14. Estudos necessários para indicações clínicas fora da defesa química

• País em desenvolvimento; encontrar/integrar um grupo de pesquisa, metodologia a ser identificada.

Biodefense Meeting. Best Pharmaceuticals for Children Act. Eunice Kennedy Shriver National Institute of Child Health and Human Development , September 8-9, 2008, Rockville, MD (NICHD)no original (inglês)

15. Questões éticas relacionadas aos estudos

• Resolver as questões éticas.

Biodefense Meeting. Best Pharmaceuticals for Children Act. Eunice Kennedy Shriver National Institute of Child Health and Human Development , September 8-9, 2008, Rockville, MD (NICHD)no original (inglês)

16. Situação regulatória global

EUA

• A scopolamine é usada principalmente para a prevenção de náusea e vômito induzidos por movimento ou pela recuperação de anestesia e cirurgia. O fármaco também é usado como adjuvante da anestesia. A utilidade da scopolamine em formas crônicas de terapia (por exemplo, no tratamento adjuvante da doença ulcerosa péptica) é geralmente limitada por seus efeitos adversos, especialmente os efeitos no SNC.dose/fármaco conforme a fonte ↗

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

17. Outras informações potencialmente úteis

• Coeficiente de partição octanol/água: log Kow = 0.98

HSDB. Scopolaminedose/fármaco conforme a fonte ↗no original (inglês)

18. Publicações

Anderson DR, Harris LW, Bowersox SL, Lennox WJ, Anders JC. Efficacy of injectable anticholinergic drugs against soman-induced convulsive/subconvulsive activity. Drug Chem Toxicol. 1994;17(2):139-48. [PubMed Citation]no original (inglês)

Biodefense Meeting. Best Pharmaceuticals for Children Act. Eunice Kennedy Shriver National Institute of Child Health and Human Development , September 8-9, 2008, Rockville, MD (NICHD)no original (inglês)

Brodtkorb E, Wyzocka-Bakowska MM, Lillevold PE, Sandvik L, Saunte C, Hestnes A. Transdermal scopolamine in drooling. J Ment Defic Res. 1988 Jun;32 ( Pt 3):233-7. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Brunton LL, Chabner BA, Knollmann BC (eds.) Goodman & Gilman's The Pharmacological Basis of Therapeutics (12th Ed.). McGraw-Hill Medical, New York, NY. (2011) p.226-230no original (inglês)

Chen H, Chen Y, Wang H, Du P, Han F, Zhang H. Analysis of scopolamine and its eighteen metabolites in rat urine by liquid chromatography-tandem mass spectrometry. Talanta. 2005 Oct 31;67(5):984-91. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Chen H, Chen Y, Du P, Han F. Liquid chromatography-electrospray ionization ion trap mass spectrometry for analysis of in vivo and in vitro metabolites of scopolamine in rats. J Chromatogr Sci. 2008 Jan;46(1):74-80. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Ebert U, Siepmann M, Oertel R, Wesnes KA, Kirch W. Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration. J Clin Pharmacol. 1998 Aug;38(8):720-6. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Harris LW, Gennings C, Carter WH, Anderson DR, Lennox WJ, Bowersox SL, Solana RP. Efficacy comparison of scopolamine (SCP) and diazepam (DZ) against soman-induced lethality in guinea pigs. Drug Chem Toxicol. 1994;17(1):35-50. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

HSDB. Scopolaminedose/fármaco conforme a fonte ↗no original (inglês)

Kastrup EK et al., eds. Drug Facts and Comparisons St Louis, MO: Wolters Kluwer Health, 2012 p.1480-1no original (inglês)

Marrs TC, Maynard RL, Sidell FR. (ed.s). Chemical warfare agents toxicology and treatment 2nd ed. John Wiley and Sons Ltd. (2007) p.258no original (inglês)

McDonough JH Jr, Zoeffel LD, McMonagle J, Copeland TL, Smith CD, Shih TM. Anticonvulsant treatment of nerve agent seizures: Anticholinergics versus diazepam in soman-intoxicated guinea pigs. Epilepsy Res. 2000 Jan;38(1):1-14. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

McEvoy GK, ed. Drug Information 2012. Bethesda, MD: American Society of Health-System Pharmacists, 2012 p.1299-1303, 2903-2904no original (inglês)

Muggleton NG, Bowditch AP, Crofts HS, Scott EA, Pearce PC. Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus). Psychopharmacology (Berl). 2003 Mar;166(3):212-20. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Perkins MW, Pierre Z, Rezk P, Song J, Oguntayo S, Morthole V, Sciuto AM, Doctor BP, Nambiar MP. Protective effects of aerosolized scopolamine against soman-induced acute respiratory toxicity in guinea pigs. Int J Toxicol. 2011 Dec;30(6):639-49. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Product label: TRANSDERM SCOP (scopalamine) patch, extended release [Baxter Healthcare Corporation] Last revised: September 2012 [DailyMed]no original (inglês)

Raveh L, Weissman BA, Cohen G, Alkalay D, Rabinovitz I, Sonego H, Brandeis R . Caramiphen and scopolamine prevent soman-induced brain damage and cognitive dysfunction. Neurotoxicology. 2002 May;23(1):7-17. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Renner UD, Oertel R, Kirch W. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit. 2005 Oct;27(5):655-65. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Shih, T-M., T.A. Koviak, B.R. Capacio. Anticonvulsants for poisoning by the organophosphorus compound soman: Pharmacological mechanisms. Neurosci Biobehav Rev. 1991 Fall;15(3):349-62. [PubMed Citation]no original (inglês)

Siegel LK, Klingbeil MA. Control of drooling with transdermal scopolamine in a child with cerebral palsy. Dev Med Child Neurol. 1991 Nov;33(11):1013-4. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Stetina PM, Madai B, Kulemann V, Kirch W, Joukhadar C. Pharmacokinetics of scopolamine in serum and subcutaneous adipose tissue in healthy volunteers. Int J Clin Pharmacol Ther. 2005 Mar;43(3):134-9. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

Talmi YP, Finkelstein Y, Zohar Y. Reduction of salivary flow with transdermal scopolamine: a four-year experience. Otolaryngol Head Neck Surg. 1990 Oct;103(4):615-8. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

von Bredow J, Corcoran K, Maitland G, Kaminskis A, Adams N, Wade J. Efficacy evaluation of physostigmine and anticholinergic adjuncts as a pretreatment for nerve agent intoxication. Fundam Appl Toxicol. 1991 Nov;17(4):782-9. [PubMed Citation]dose/fármaco conforme a fonte ↗no original (inglês)

19. Sites

NIH CounterACT Program (HHS/NIH)no original (inglês)

NIH RePORTER (HHS/NIH)no original (inglês)

ClinicalTrials.gov (HHS/NIH)no original (inglês)

PubMed (HHS/NIH)no original (inglês)

DailyMed (HHS/NIH)no original (inglês)

Record last updated 1/2/2013no original (inglês)