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Description of key information

The following is related to CSR section skin sensitization 5.5.1.2 Human information:

Regarding skin sensitization, three sources reported positive findings whereas three sources reported negative findings, indicating a inconclusive result.

Additional information

There are seven published unique clinical reports with information relevant to scopolamine and skin sensitization. However, all of the reports had inherent limitations which prevented conclusions regarding the sensitization potential of scopolamine. Three publications reported positive findings and four reported no clinical findings of sensitization – see table 1. Two of the positive studies (Trozak and Modesto 1985, van der Willigenet al1988) were single-case reports with no indication of prior medical history or history of exposure to other potentially cross-reacting materials. One of the positive studies (Gordon et al, 1989) reported a 10% rate of elicitation of delayed-contact hypersensitivity also with no information on prior medical history of the subjects who tested positive. 

Of the four publications with no clinical findings of delayed contact hypersensitivity, the duration of the studies may have been too short to allow for induction of sensitization if scopolamine were to be a weak sensitizer.

Finally, all of the reports available with human data were evaluated against the Klimisch study quality criteria and scored 3 or 4 (see table 1). This limits the usefulness of these reports for evaluated the sensitization potential of scopalomine.

Table 1: Data for Skin sensitization for scopolamine (CAS 51-34-3)

Route

Effect

Reference

Result and Justification

Application of transdermal patch, human

Allergic contact dermatitis occurred in 16 out of 164 men being treated for seasickness with transdermal hyoscine for 6 weeks to 15 months. All 16 men showed pruritus after several hours and erythema after 24-48 hours after exposure. All reactions resolved upon patch removal and reappeared when patches were reapplied. Allergic contact dermatitis (type IV hypersensitivity) was diagnosed by well-established clinical criteria.

Gordon CR, et al.Allergic contact dermatitis caused by transdermal hyoscine.

 

BMJ 1989;298: 1220–1

 

 

Positive

Did not rule out prior induction of sensitization by cross-reactive molecules. 

Klimisch 4

Results have not been duplicated despite ongoing use of transdermal hyoscine. FDA surveillance reports do not support the conclusions of this study.

Application of transdermal patch, human

One case of delayed hypersensitivity to transdermal hyoscine has been reported during standardized patch testing, carried out following daily use of the patch for 3 months. Reactions to other components of the device were all negative apart from a transient erythema (irritation) to mineral oil at 72 hours. 

Trozak DJ, Modesto MD. Delayed hypersensitivity to scopolamine delivered by a transdermal device. IAm Acad Dermatol 1985;13:247-51.

Positive

Limited data on the study are available and only 1 case study was reported. Cross reactivity from prior induction of sensitization to another material was not ruled out.

This study cannot be used to make a determination of the dermal sensitization potential of scopolamine

Klimisch 4

Application of transdermal patch, human

Positive reactions were reported in one 10 year old child following continuous treatment for 2 weeks with scopoloamine patches. Standardized patch testing was consequently carried out with different concentrations of scopolamine and again showed positive reactions. No reaction was seen with the test battery. Reactions were considered extremely positive (erythema, induration, papules,

vesicles exceeding the border of the test area).

Van der Willigen AH, Oranje AP, Stolz E, Van Joost T. Delayed hypersensitivity to scopolamine in transdermal therapeutic systems. J Am Acad Dermatol 1988;18:146-7.

Positive

Limited data on the study are available and only 1 case study was reported.

Klimisch 4

Application of transdermal patch, human

No delayed contact sensitization occurred in studies conducted by manufacturer of transdermal patches (Alza Corporation, Calafornia). 203 subjects were subjected to consecutive application of 9 hyoscine patches followed by application of the tenth patch 2 weeks later. The design of the studies does not rule out the possibility of delayed type IV sensitivity occurring due to a more prolonged use of the patches.

Alza Corporation, California, United States

Negative

No sufficient data on the study are available

Klimisch 4

Application of transdermal patch, human

No irritation or contact allergy were reported in

36 healthy men and women with either the scopoloamine Transderm Scop or placebo patch used for 3 days. This may be due to low antigenicity of scopolamine, the short-term applications and limited repeat exposures employed, or the lack or reporting of such effects as participants were only asked

about any symptoms of drowsiness, dry

mouth and blurred vision.

Price N, Schmitt RN, Shaw JE: Transdermal delivery of

scopolamine for prevention of motion-induced nausea in

rough seas. Clin Ther 2:258-262, 1979.

 

 

 

Negative

Limited study as sensitization effects may not have been recorded

 

Klimisch 3

Application of transdermal patch, human

No irritation or contact allergy were reported in

35 healthy men and women with either the scopoloamine Transderm Scop or placebo patch was used for 12-24 hours, three times at least a week apart. This may be due to low antigenicity of scopolamine, the short-term applications and limited repeat exposures employed or the lack or reporting of such effects as participants were not asked to report any side effects.

McCauley ME, Royal JW, Shaw JE, Schmitt LG: Effect

of transdermally administered scopolamine in preventing

motion sickness. Aviat Space Environ Med 50: 11081111,

1979.

 

Negative

Limited study as sensitization effects may not have been recorded

Klimisch 3

 

Application of transdermal patch, human

No irritation or contact allergy were reported in

163 healthy men and women with either the scopoloamine or placebo patch Transderm Scop used for 14-16 hours. This may be due to the short-term applications and limited repeat exposures employed or reporting of such effects as participants were not asked to report any side effects.

Price N, Schmitt L, McGuire J, et al: Transdermal scopolamine

jn the prevention of motion sickness at sea.

Clin Pharmacol Ther 29:414-419, 1981.

Negative

Limited study as sensitization effects may not have been recorded and due to the short exposure period

 

Klimisch 3