![]() However, sea studies revealed significantly less reports of a decrement in performance or drowsiness due to prevention of sea sickness. Prolonged or repeated application may cause some impairment of memory storage for new information. Performance is not affected by short-term use. 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. Adverse effects were not correlated with plasma scopolamine concentrations. 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. Low-dose pyridostigmine was found effective in preventing cycloplegia but not mydriasis. ![]() ![]() Transient impairment of ocular accommodation has also been observed, in some cases possibly the result of finger-to-eye contamination. Dry mouth occurs in about 50-60% of subjects, drowsiness in up to 20%, and allergic contact dermatitis in 10%. 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. 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. TTS-S was most effective against motion sickness 8-12 hours after application. The addition of ephedrine or the use of two patches did not improve its efficacy, but rather increased the rate of adverse effects. It was more effective than oral meclizine or cinnarizine, similar to oral scopolamine 0.6 mg or promethazine plus ephedrine, and the same as or superior to dimenhydrinate. TTS-S has proved to be significantly superior to placebo in reducing the incidence and severity of motion sickness by 60-80%. A combination of transdermal and oral scopolamine (0.3 or 0.6 mg) was effective and well tolerated in producing desired plasma concentrations 1-hour post-treatment. Overall, the product appears to be the approximate functional equivalent of a 72-hour slow intravenous infusion. These findings may explain some of the treatment failures. 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. TTS-S attains that concentration after 6 hours a steady state of about 100 pg/mL is achieved 8-12 hours after application. The protective plasma concentration of scopolamine is estimated to be 50 pg/mL. The remainder is released at a constant rate of approximately 5 microg/hour. A priming dose (140 microg) 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 plaster contains a reservoir of 1.5 mg of scopolamine programmed to deliver 0.5 mg over a 3-day period. 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.
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