Clinical Pharmacokinetics

, Volume 45, Issue 6, pp 543–566 | Cite as

Transdermal Scopolamine for Prevention of Motion Sickness

Clinical Pharmacokinetics and Therapeutic Applications
Review Article

Abstract

A transdermal therapeutic system for scopolamine (TTS-S) was developed to counter the adverse effects and short duration of action that has restricted the usefulness of scopolamine when administered orally or parenterally. The plaster contains a reservoir of 1.5mg of scopolamine programmed to deliver 0.5mg over a 3-day period. A priming dose (140μg) is incorporated into the adhesive layer to saturate certain binding sites within the skin and to accelerate the achievement of steady-state blood levels. The remainder is released at a constant rate of approximately 5 μg/hour. The protective plasma concentration of scopolamine is estimated to be 50 pg/mL. TTS-S attains that concentration after 6 hours; a steady state of about 100 pg/mL is achieved 8–12 hours after application. Yet 20–30% of subjects failed to attain the estimated protective concentration, and plasma concentrations measured in subjects who failed to respond to TTS-S were lower than in responders. These findings may explain some of the treatment failures. Overall, the product appears to be the approximate functional equivalent of a 72-hour slow intravenous infusion. A combination of transdermal and oral scopolamine (0.3 or 0.6mg) was effective and well tolerated in producing desired plasma concentrations 1-hour post-treatment.

TTS-S has proved to be significantly superior to placebo in reducing the incidence and severity of motion sickness by 60–80%. It was more effective than oral meclizine or cinnarizine, similar to oral scopolamine 0.6mg or promethazine plus ephedrine, and the same as or superior to dimenhydrinate. The addition of ephedrine or the use of two patches did not improve its efficacy, but rather increased the rate of adverse effects. TTS-S was most effective against motion sickness 8–12 hours after application. Despite previous evidence to the contrary, a recent bioavailability study demonstrated similar intraindividual absorption and sustained clinical efficacy with long-term use of the drug.

The adverse effects produced by TTS-S, although less frequent, are qualitatively typical of those reported for the oral and parenteral formulations of this agent. Dry mouth occurs in about 50–60% of subjects, drowsiness in up to 20%, and allergic contact dermatitis in 10%. Transient impairment of ocular accommodation has also been observed, in some cases possibly the result of finger-to-eye contamination. Low-dose pyridostigmine was found effective in preventing cycloplegia but not mydriasis. Adverse CNS effects, including toxic psychosis (mainly in elderly and paediatric patients), have been reported only occasionally, as have difficulty in urinating, headache, rashes and erythema. Adverse effects were not correlated with plasma scopolamine concentrations. TTS-S produced only about half the incidence of drowsiness caused by oral dimenhydrinate or cinnarizine, and a level of adverse effects similar to that found with oral meclizine. Performance is not affected by short-term use. Prolonged or repeated application may cause some impairment of memory storage for new information. However, sea studies revealed significantly less reports of a decrement in performance or drowsiness due to prevention of sea sickness.

The recommended dosage is a single TTS-S patch applied to the postauricular area at least 6–8 hours before the anti-motion sickness effect is required. For faster protection, the patch may be applied 1 hour before the journey in combination with oral scopolamine (0.3 or 0.6mg). After 72 hours, the patch should be removed and a new one applied behind the opposite ear. Its place in therapy is mainly on long journeys (6–12 hours or longer), to avoid repeated oral doses, or when oral therapy is ineffective or intolerable.

Notes

Acknowledgements

The authors are grateful to Mr Richard Lincoln for his assistance in the preparation of the manuscript.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Zohar Nachum
    • 1
    • 2
  • Avi Shupak
    • 1
    • 3
  • Carlos R. Gordon
    • 1
    • 4
  1. 1.Motion Sickness and Human Performance Laboratory, Israel Naval Medical InstituteIDF Medical CorpsHaifaIsrael
  2. 2.Department of Obstetrics and GynecologyHa’Emek Medical CenterAfulaIsrael
  3. 3.Department of Otolaryngology-Head and Neck Surgery, Carmel Medical Center and the Otoneurology UnitLin Medical CenterHaifaIsrael
  4. 4.Department of Neurology, Meir General Hospital, Kfar Saba and Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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