Scopolamine (Hyoscine)

Scopolamine (hyoscine) for preventing and treating motion sickness

Background: This is an update of a Cochrane Review first published in The Cochrane Library in Issue 3, 2004 and previously updated in 2007 and 2009.Motion sickness, the discomfort experienced when perceived motion disturbs the organs of balance, may include symptoms such as nausea, vomiting, pallor, cold sweats, hypersalivation, hyperventilation and headaches. The control and prevention of these symptoms has included pharmacological, behavioural and complementary therapies. Although scopolamine (hyoscine) has been used in the treatment and prevention of motion sickness for decades, there have been no systematic reviews of its effectiveness. Objectives: To assess the effectiveness of scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination for motion sickness in persons (both adults and children) without known vestibular, visual or central nervous system pathology. Search strategy: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 14 April 2011. Selection criteria: All parallel-arm, randomised controlled trials (RCTs) focusing on scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination. We considered outcomes relating to the prevention of onset or treatment of clinically-defined motion sickness, task ability and psychological tests, changes in physiological parameters and adverse effects. Data collection and analysis: Two authors independently extracted data from the studies using standardised forms. We assessed study quality. We expressed dichotomous data as odds ratio (OR) and calculated a pooled OR using the random-effects model. Main results: Of 35 studies considered potentially relevant, 14 studies enrolling 1025 subjects met the entry criteria. Scopolamine was administered via transdermal patches, tablets or capsules, oral solutions or intravenously. Scopolamine was compared against placebo, calcium channel antagonists, antihistamine, methscopolamine or a combination of scopolamine and ephedrine. Studies were generally small in size and of varying quality.Scopolamine was more effective than placebo in the prevention of symptoms. Comparisons between scopolamine and other agents were few and suggested that scopolamine was superior (versus methscopolamine) or equivalent (versus antihistamines) as a preventative agent. Evidence comparing scopolamine to cinnarizine or combinations of scopolamine and ephedrine is equivocal or minimal.Although sample sizes were small, scopolamine was no more likely to induce drowsiness, blurring of vision or dizziness compared to other agents. Dry mouth was more likely with scopolamine than with methscopolamine or cinnarizine.No studies were available relating to the therapeutic effectiveness of scopolamine in the management of established symptoms of motion sickness. Authors' conclusions: The use of scopolamine versus placebo in preventing motion sickness has been shown to be effective. No conclusions can be made on the comparative effectiveness of scopolamine and other agents such as antihistamines and calcium channel antagonists. In addition, we identified no randomised controlled trials that examined the effectiveness of scopolamine in the treatment of established symptoms of motion sickness.

Pharmacokinetics and pharmacodynamics in clinical use of scopolamine

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 biozlogic 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. The alkaloid readily crosses the placenta. Therefore, scopolamine should be administered to pregnant women only under observation. The drug is compatible with nursing and is considered to be nonteratogenic. 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.

Scopolamine (hyoscine) for preventing and treating motion sickness

Background: Motion sickness - the discomfort experienced when perceived motion disturbs the organs of balance - may include symptoms such as nausea, vomiting, pallor, cold sweats, hypersalivation, hyperventilation and headaches. The control and prevention of these symptoms have included pharmacological, behavioural and complementary therapies. Although scopolamine (hyoscine) has been used in the treatment and prevention of motion sickness for decades, there have been no systematic reviews of its effectiveness.
Objectives: To assess the effectiveness of scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination for motion sickness in persons (both adults and children) without known vestibular, visual or central nervous system pathology.
Search strategy: The Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2007), MEDLINE (OVID, 1966 to May 2007), EMBASE (1974 to May 2007) CINAHL (OVID, 1982 to May 2007) and reference lists of retrieved studies were searched for relevant studies. No language restrictions were applied. The date of the last search was May 2007.
Selection criteria: All parallel-arm, randomised controlled trials (RCTs) focusing on scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination were included. Outcomes relating to the prevention of onset or treatment of clinically-defined motion sickness, task ability and psychological tests, changes in physiological parameters and adverse effects were considered.
Data collection and analysis: Data from the studies were extracted independently by two authors using standardised forms. Study quality was assessed. Dichotomous data were expressed as odds ratio (OR) and a pooled OR was calculated using the random-effects model.
Main results: Of 35 studies considered potentially relevant, 14 studies enrolling 1025 subjects met the entry criteria. Scopolamine was administered via transdermal patches, tablets or capsules, oral solutions or intravenously. Scopolamine was compared against placebo, calcium channel antagonists, antihistamine, methscopolamine or a combination of scopolamine and ephedrine. Studies were generally small in size and of varying quality. Scopolamine was more effective than placebo in the prevention of symptoms. Comparisons between scopolamine and other agents were few and suggested that scopolamine was superior (versus methscopolamine) or equivalent (versus antihistamines) as a preventative agent. Evidence comparing scopolamine to cinnarizine or combinations of scopolamine and ephedrine is equivocal or minimal. Although sample sizes were small, scopolamine was no more likely to induce drowsiness, blurring of vision or dizziness compared to other agents. Dry mouth was more likely with scopolamine than with methscopolamine or cinnarizine. No studies were available relating to the therapeutic effectiveness of scopolamine in the management of established symptoms of motion sickness.
Authors' conclusions: The use of scopolamine versus placebo in preventing motion sickness has been shown to be effective. No conclusions can be made on the comparative effectiveness of scopolamine and other agents such as antihistamines and calcium channel antagonists. In addition, no randomised controlled trials were identified that examined the effectiveness of scopolamine in the treatment of established symptoms of motion sickness.

Transdermal hyoscine (Scopolamine). A preliminary review of its pharmacodynamic properties and therapeutic efficacy

Hyoscine (scopolamine) is a competitive inhibitor of the muscarinic receptors of acetylcholine and it has been shown to be one of the most effective agents for preventing motion sickness. However, a relatively high incidence of side effects and a short duration of action has restricted the usefulness of this agent when administered orally or parenterally, and to counter this a novel transdermal preparation of hyoscine has been developed. Pharmacokinetic studies indicate that this new method for administering hyoscine controls the absorption process and the rate of drug entry into the systemic circulation over an extended period (72 hours), providing a means of delivery which is similar to a slow intravenous infusion. However, recent evidence suggests that the response to transdermal hyoscine treatment is variable and this may reflect pharmacokinetic differences between individuals. Controlled therapeutic trials have indicated that a single transdermal hyoscine patch is significantly superior to placebo and oral meclozine (meclizine) in preventing motion sickness. Trials comparing transdermal hyoscine with oral dimenhydrinate have failed to establish any significant differences in efficacy between the 2 drugs in small numbers of subjects, although there was always a more favourable trend towards the transdermal system. In patients with acute vertigo, transdermal hyoscine and oral meclozine were equally efficacious and both were significantly better than placebo in reducing the number of attacks of vertigo. Although transdermal hyoscine has been associated with a lower incidence of side effects than orally or parenterally administered hyoscine hydrobromide, adverse systemic effects have still been frequently reported. Most commonly cited have been dry mouth, drowsiness and impairment of ocular accommodation, including blurred vision and mydriasis (some ocular effects reported may be due to finger-to-eye contamination). Adverse central nervous system (CNS) effects, difficulty in urinating, rashes and erythema have been reported only occasionally. Thus, preliminary evidence suggests transdermal hyoscine may offer an effective and conveniently administered alternative for the prevention of motion-induced nausea and vomiting in certain situations. However, the duration of its clinical effectiveness, and its relative efficacy and tolerability compared with other agents needs to be confirmed in a few additional well-designed studies.

Transdermal hyoscine (scopolamine) and postoperative vomiting