Withdrawal symptoms after discontinuation of transdermal scopolamine therapy: Treatment with meclizine

Scopolamine, a naturally occurring belladonna alkaloid, is a competitive muscarinic receptor antagonist with activity most similar to that of atropine.^1,2 A transdermal formulation of scopolamine is used for the prevention of nausea and vomiting due to motion sickness and during recovery from anesthesia and surgery. It is thought to work for these indications by blocking cholinergic transmission from the vestibular nuclei to higher centers in the central nervous system and from the reticular formation to the vomiting center.¹ We present the case of a woman who self-treated her trans-dermal scopolamine withdrawal symptoms with oral meclizine.

Case report

A 30-year-old woman was prescribed the transdermal scopolamine patch (Transderm Scop [approximately 1 mg/72 hr], Novartis Consumer Health, Inc.) for prevention of motion sickness during a vacation abroad. Other medications included an oral contraceptive and as-needed zolmitriptan for migraines, though the patient reported not needing the latter during the vacation. She used the patches as prescribed, applying one patch behind the ear every 3 days. After 10 consecutive days of wearing the patch and experiencing no motion sickness, she began to develop dry mouth and uncomfortable, dry eyes, which prompted her to remove the patch. After 24 hours without the patch, she experienced severe nausea that did not subside during a car ride. Due to the intractable nausea, she applied a new patch, which she wore for 3 consecutive days without recurrence of the nausea. Upon returning from the trip, she removed the last patch. Twelve hours after the last patch was removed, the nausea recurred without motion. She felt better while lying down but felt nauseated when standing or walking. After 3 days of this nausea, she started taking nonprescription meclizine hydrochloride 25 mg (Bonine, Insight Pharmaceuticals Corp.) orally every 12 hours. The nausea subsided after two doses, and she was able to resume her normal activities. She continued taking meclizine for an additional four doses. The nausea did not recur after discontinuation of the meclizine. Eight years prior, the patient had used transdermal scopolamine without experiencing any withdrawal symptoms.

Discussion

Use of the Naranjo et al.³ adverse drug reaction probability scale indicated a probable relationship between the removal of the scopolamine patch and the withdrawal symptoms experienced by this patient. To our knowledge, this is the first report of treating scopolamine withdrawal symptoms with meclizine.

Withdrawal and postremoval symptoms associated with antimuscarinics, including dizziness, nausea, vomiting, and headache, are listed in the prescribing information of the transdermal scopolamine patch. Disturbances of equilibrium, which typically do not occur until 24 hours or more after removal of the patch, have been reported specifically for the transdermal scopolamine system.¹ There have been at least two other published reports of a similar withdrawal syndrome after discontinuation of transdermal scopolamine. One report describes the case of a 50-year-old woman who went to the emergency room with extreme nausea, dizziness, and intermittent sweating and parethesias of the hands and feet.⁴ The patient used transdermal scopolamine during a 10-day cruise. Withdrawal symptoms began 48 hours after patch removal. The patient explained the need to lie down periodically in order to tolerate the symptoms. Physical examination of the patient revealed supine and standing blood pressure readings of 90/60 and 88/62 mm Hg, respectively. On follow-up examination (approximately 80 hours after patch removal), the patient was able to function normally. Treatment for this patient was not discussed.

Another report describes the case of a man who experienced dizziness, nausea, hypersalivation, and diarrhea after seven consecutive days of transdermal scopolamine use.⁵ These symptoms emerged approximately 72 hours after removal of the last patch and continued for another 72 hours thereafter. One year after this episode, this patient again used transdermal scopolamine while traveling. During this time, the patient used the scopolamine patch for 12 hours daily for five consecutive days. The same withdrawal symptoms occurred 72 hours after discontinuation of the patch and persisted for 96 hours.

Neither of the published reports nor the prescribing information mentions possible management of the withdrawal symptoms of trans-dermal scopolamine. Our patient self-treated with nonprescription meclizine tablets. Meclizine is a first-generation piperazine antihistamine derivative with anticholinergic properties.^1,6 Other medications in this class include hydroxyzine hydrochloride and hydroxyzine pamoate.⁶ Although meclizine’s exact mechanism of antiemetic effects is unknown, it is thought to decrease excitability of the inner ear (labyrinth) as well as block activity of vestibular–cerebellar pathways.^6,–9 Meclizine has minimal, if any, activity on the chemoreceptor trigger zone in the brain.¹⁰

Meclizine has significant antimuscarinic properties, similar to those of scopolamine. Therefore, meclizine may be a viable treatment for scopolamine withdrawal symptoms. In the case presented here, meclizine successfully treated the patient’s symptoms. Research conducted in humans and animals suggests that the induction of muscarinic receptors caused by antimuscarinic effects of scopolamine may take several days to be down regulated once the drug is removed.^5,11,12 Given the significant antimuscarinic effect of meclizine, it may aid as an “antimuscarinic bridge” while muscarinic receptors are down regulated after discontinuation of scopolamine.

The route of administration through which scopolamine is delivered must also be considered. The transdermal scopolamine delivery system is designed to deliver a priming dose to saturate the skin upon initial administration.¹ The delivery rate of the drug is determined by the skin membrane. Once the patch is removed, a residual amount of the drug remains in the skin membrane; however, specific data on how much drug remains in the skin or how long it remains after patch removal are not available.^1,13 Thus, the pharmacokinetics of the transdermal drug delivery system may explain why withdrawal symptoms typically do not appear until approximately 24 hours after removal of the patch. Administering oral meclizine after patch removal may supplement antimuscarinic activity as the scopolamine is slowly absorbed and removed from the body, thereby helping to reduce withdrawal symptoms. The oral therapy may then be adjusted downward.

The prescribing information for transdermal scopolamine warns of adverse effects after patch removal.¹ However, it does not offer any guidelines on treatment of withdrawal symptoms. Pharmacists need to be aware that these symptoms may occur and should counsel their patients accordingly. Case reports suggest that use of the drug for seven or more days may increase the likelihood of withdrawal symptoms. The case presented here supports the treatment of withdrawal symptoms with oral meclizine. Since the patient waited three days before initiating treatment with meclizine, the decrease in withdrawal symptoms may have temporally coincided with the natural time course of improvement in withdrawal symptoms if meclizine was not used. However, in the case reports noted above, withdrawal symptoms after removal of the patch lasted for up to six days. Therefore, we suggest that meclizine provided treatment of symptoms before they would have resolved without intervention.

Conclusion

Withdrawal symptoms experienced after removal of a transdermal scopolamine patch were successfully treated with oral meclizine.

References

Author notes