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Skin Sensitivity and Transdermal Drug Delivery

A Review of the Problem

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Summary

Transdermal devices are now marketed for the delivery of systemic medication through the skin. Advantages associated with transdermal drug delivery include avoidance of first-pass metabolism and improved patient compliance. Drugs currently available by this route include scopolamine (hyoscine), nitroglycerin (glyceryl trinitrate), estradiol, nicotine and clonidine. This novel development has brought in its wake a specific constellation of skin sensitivity problems, which vary widely in incidence between drugs. Varying the site of drug administration to minimise these reactions is important. Any eczematous reaction can be treated with a moderately potent topical steroid. Tolerance to oral challenge in those with topical sensitivity occurs, but caution is still advocated before proceeding to this step.

The increasing use of transdermal drug delivery systems across many specialities means that problems of skin sensitivity are of growing relevance to the dermatologist, the hospital specialist and the primary care physician.

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References

  • Abelin T, Buchler A, Müller P, Vesanen K, Imhof PR. Controlled trial of transdermal nicotine patch in tobacco withdrawal. Lancet 1: 7–10, 1989

    Article  PubMed  CAS  Google Scholar 

  • Anonymous. Nitroglycerine patches may explode during resuscitation attempts, emergency MDs warned. Canadian Medical Association Journal 148: 790, 1993

    Google Scholar 

  • Apted J. Percutaneous nitroglycerin patches. Medical Journal of Australia 148: 482, 1988

    PubMed  CAS  Google Scholar 

  • Bals-Pratsch M, Knuth UA, Yoon Y-D, Nieschlag E. Transdermal testosterone substitution therapy for male hypogonadism. Lancet 2: 943–946, 1986

    Article  PubMed  CAS  Google Scholar 

  • Bircher AJ, Havald H, Rufli T. Adverse reactions to nicotine in a transdermal therapeutic system. Contact Dermatitis 25: 230–236, 1991

    Article  PubMed  CAS  Google Scholar 

  • Boekhorst JC. Allergic contact dermatitis with transdermal clonidine. Lancet 2: 1031–1032, 1983

    Article  PubMed  CAS  Google Scholar 

  • Brown L, Langer R. Transdermal delivery of drugs. Annual Review of Medicine 39: 221–229, 1988

    Article  PubMed  CAS  Google Scholar 

  • Carmichael AJ, Foulds IS. Allergic contact dermatitis from transdermal nitroglycerin. Contact Dermatitis 21: 113–114, 1989

    Article  PubMed  CAS  Google Scholar 

  • Carmichael AJ, Foulds IS. Allergic contact dermatitis to oestradiol in oestrogen patches. Contact Dermatitis 26: 194–195, 1992

    Article  PubMed  CAS  Google Scholar 

  • Chandraratna PAN, O’Dell RE. Allergic reactions to nitroglycerin ointment: report of five cases. Current Therapeutic Research 25: 481–484, 1979

    Google Scholar 

  • Davis GF, Winter L. Cumulative irritation study of placebo transdermal estrogen patches. Current Therapeutic Research 42: 712–719, 1987

    Google Scholar 

  • Dick JBC, Northridge DB, Lawson AAH. Skin reactions to long-term transdermal clonidine. Lancet 1: 516, 1987

    Article  PubMed  CAS  Google Scholar 

  • Ducros B, Bonnin JP, Navaranne A, Colomb D. Eczema due to contact with ethanol in oestradiol transdermal patch (Estraderm TTS 50). Nouvelles Dermatologiques 8: 21–22, 1989

    Google Scholar 

  • Editorial. Nicotine patches. Drug and Therapeutics Bulletin 31: 95–96, 1993

  • Editorial. Transdermal antihypertensive drugs. Lancet 1: 79–80, 1987

  • Falkner B, Thanki B, Lowenthal DY. Transdermal clonidine in the treatment of adolescent hypertension. Journal of Hypertension 3 (suppl. 4): 61–63, 1985

    Google Scholar 

  • Fisher AA. Dermatitis due to transdermal therapeutic systems. Cutis 34: 526–531, 1984

    PubMed  CAS  Google Scholar 

  • Fisher AA. Contact dermatitis: highlights from the 1987 Meeting of the American Academy of Dermatology, San Antonio, Texas. Cutis 41: 87–88, 1988

    Google Scholar 

  • Fischer RG, Tyler M. Severe contact dermatitis due to nitroglycerin patches. Southern Medical Journal 78: 1523–1524, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gordon CR, Shupak A, Doweck I, Spitzer O. Allergic contact dermatitis caused by transdermal. hyoscine. British Medical Journal 298: 1220–1221, 1989

    Article  CAS  Google Scholar 

  • Grattan CEH, Kennedy CTC. Allergic contact dermatitis to transdermal clonidine. Contact Dermatitis 12: 225–226, 1985

    Article  PubMed  CAS  Google Scholar 

  • Groth H, Vetter H, Knuesel J, Vetter W. Allergic skin reactions to transdermal clonidine. Lancet 2: 850–851, 1983

    Article  Google Scholar 

  • Harari Z, Sommer I, Knobel B, Multifocal contact dermatitis to Nitroderm TTS 5 with extensive postinflammatory hypermelanosis. Dermatologica 174: 249–252, 1987

    Article  PubMed  CAS  Google Scholar 

  • Hendricks AA, Dec Jr GW. Contact dermatitis due to nitroglycerin ointment. Archives of Dermatology 115: 853–855, 1979

    Article  PubMed  CAS  Google Scholar 

  • Hogan DJ, Maibach HI. Adverse dermatological reactions to transdermal drug delivery systems. Journal of the American Academy of Dermatology 22: 811–814, 1990

    Article  PubMed  CAS  Google Scholar 

  • Holdiness MR. A review of contact dermatitis associated with transdermal therapeutic systems. Contact Dermatitis 20: 3–9, 1989

    Article  PubMed  CAS  Google Scholar 

  • Hollifield J. Clinical acceptability of transdermal clonidine: a large-scale evaluation by practitioners. American Heart Journal 112: 900–906, 1986

    Article  PubMed  CAS  Google Scholar 

  • Homick JL, Kohl RL, Reschke MF, Degionanni J, Cintron-Trevino NM. Transdermal scopolamine in the prevention of motion sickness: evaluation of the time course of efficacy. Aviation Space and Environmental Medicine 54: 994–1000, 1983

    CAS  Google Scholar 

  • Horning JR, Zawada Jr ET, Simmons JL, Williams L, McNutly R. Efficacy and safety of two-year therapy with transdermal clonidine for essential hypertension. Chest 93: 941–945, 1988

    Article  PubMed  CAS  Google Scholar 

  • Hurkmans JFGM, Bodde HE, van Driel LMJ, van Doorne H, Junginger HE. Skin irritation caused by transdermal drug delivery systems during long-term (5 days) application. British Journal of Dermatology 112: 461–467, 1985

    Article  PubMed  CAS  Google Scholar 

  • Kelly HW Controlled-release transdermal drug delivery. Cutis 35: 204–205, 1985

    PubMed  CAS  Google Scholar 

  • Kligman AM. The identification of contact allergens by human assay: III. The maximization test: a procedure for screening and rating contact sensitizers. Journal of Investigative Dermatology 47: 393–409, 1966

    PubMed  CAS  Google Scholar 

  • Letendre PW, Barr C, Wilkens K. Adverse dermatologic reaction to transdermal nitroglycerin. Drug Intelligence and Clinical Pharmacy 18: 69–70, 1984

    PubMed  CAS  Google Scholar 

  • Lindberg M, Forslind B. The effects of occlusion of the skin on the Langerhans’ cell and the epidermal mononuclear cells. Acta Dermato-Venerologica (Stockholm) 61: 201–205, 1981

    CAS  Google Scholar 

  • McBurney EI, Noel SB, Collins JH. Contact dermatitis to transdermal estradiol system. Journal of the American Academy of Dermatology 20: 508–510, 1989

    Article  PubMed  CAS  Google Scholar 

  • McMahon FG, Weber MA. Allergic skin reactions to transdermal clonidine. Lancet 2: 851, 1983

    Google Scholar 

  • Maibach H. Clonidine: irritant and allergic contact dermatitis assays. Contact Dermatitis 12: 192–195, 1985

    Article  PubMed  CAS  Google Scholar 

  • Maibach HI. Oral substitution in patients sensitized by transdermal clonidine treatment. Contact Dermatitis 16: 1–8, 1987

    Article  PubMed  CAS  Google Scholar 

  • Moore L, Chien YW. Transdermal drug delivery: a review of pharmaceutics, pharmacokinetics and pharmacodynamics. Critical Reviews in Therapeutic Drug Carrier Systems 4: 285–349, 1988

    PubMed  CAS  Google Scholar 

  • Müller P, Imhof PR, Burkart F, Chu L-C, Gérardin A. Human pharmacological studies of a new transdermal system containing nitroglycerin. European Journal of Clinical Pharmacology 22: 473–480, 1982

    Article  PubMed  Google Scholar 

  • Murray KB. Hazard of microwave ovens to transdermal delivery system. New England Journal of Medicine 310: 721, 1984

    PubMed  CAS  Google Scholar 

  • Nater JP, de Groot AC (Eds). Unwanted effects of cosmetics and drugs used in dermatology, 2nd ed., p. 60, Elsevier, Amsterdam, 1985

    Google Scholar 

  • Nieboer C, Bruynzeel DP, Boorsma DM. The effect of occlusion of the skin with transdermal therapeutic system on Langerhans’ cells and the induction of skin irritation. Archives of Dermatology 123: 1499–1502, 1987

    Article  PubMed  CAS  Google Scholar 

  • Place VA, Powers M, Darley PE, Schenkel L, Good WR. A double-blind comparative study of Estraderm and Premarin in the amelioration of postmenopausal symptoms. American Journal of Obstetrics and Gynecology 152: 1092–1099, 1985

    PubMed  CAS  Google Scholar 

  • Popli S, Daugirdas JT, Neubauer JA, Hockenberry B, Hano JE, et al. Transdermal clonidine in mild hypertension. Archives of Internal Medicine 146: 2140–2144, 1986

    Article  PubMed  CAS  Google Scholar 

  • Price NM, Schmitt LG, McGuire J, Shaw JE, Trobough G. Transdermal scopolamine in the prevention of motion sickness at sea. Clinical Pharmacology and Therapeutics 29: 414–418, 1981

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld AS, White WB. Allergic contact dermatitis secondary to transdermal nitroglycerin. American Heart Journal 108: 1061–1062, 1984

    Article  PubMed  CAS  Google Scholar 

  • Rowbotham DJ, Wyld R, Peacock JE, Duthie DJ, Nimmo WS. Transdermal fentanyl for the relief of pain after abdominal surgery. British Journal of Anaesthesia 63: 56–59, 1989

    Article  PubMed  CAS  Google Scholar 

  • Russell MAH, Stapleton JA, Feyerabend C, Wiseman SM, Gustavsson G, et al. Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. British Medical Journal 306: 1308–1312, 1993

    Article  PubMed  CAS  Google Scholar 

  • Sausker WF, Frederick FD. Allergic contact dermatitis secondary to topical nitroglycerin. Journal of the American Medical Association 239: 1743–1744, 1978

    Article  PubMed  CAS  Google Scholar 

  • Schenkel L, Barlier D, Riera M, Banner A. Transdermal absorption of estradiol from different sites is comparable. Journal of Controlled Release 4: 195–201, 1986

    Article  CAS  Google Scholar 

  • Scheper RJ, von Blomberg BME, de Groot J, Geoptar AR, Lang M, et al. Low allergenicity of clonidine impedes studies of sensitization mechanisms in guinea pig models. Contact Dermatitis 23: 81–89, 1990

    Article  PubMed  CAS  Google Scholar 

  • Scheuplein RJ, Blank IH. Permeability of the skin. Physiological Reviews 51: 702–747, 1971

    PubMed  CAS  Google Scholar 

  • Schwartz BK, Clendenning WE. Allergic contact dermatitis from hydroxypropyl cellulose in a transdermal estradiol patch. Contact Dermatitis 18: 106–107, 1988

    Article  PubMed  CAS  Google Scholar 

  • Sebel PS, Barrett CW, Kirk CJC, Heykants J. Transdermal absorption of fentanyl and sufentanil in man. European Journal of Clinical Pharmacology 32: 529–531, 1987

    Article  PubMed  CAS  Google Scholar 

  • Shaw JE, Prevo ME, Amkraut AA. Testing of controlled-release transdermal dosage forms. Archives of Dermatology 123: 1548–1556, 1987

    Article  PubMed  CAS  Google Scholar 

  • Shaw JE, Urquhart J. Transdermal drug administration — a nuisance becomes an opportunity. British Medical Journal 283: 875–876, 1981

    Article  PubMed  CAS  Google Scholar 

  • Topaz O, Abraham D. Severe allergic contact dermatitis secondary to nitroglycerin in a transdermal therapeutic system. Annals of Allergy 59: 365–366, 1987

    PubMed  CAS  Google Scholar 

  • Trozak DJ. Delayed hypersensitivity to scopolamine delivered by a transdermal device. Journal of the American Academy of Dermatology 13: 247–251, 1985

    Article  PubMed  CAS  Google Scholar 

  • Utian WH. Transdermal estradiol overall safety profile. American Journal of Obstetrics and Gynecology 156: 1335–1338, 1987a

    PubMed  CAS  Google Scholar 

  • Utian WH. In discussion: Judd H, Ravaikar V, Utian WH, Lawrence W. Panel discussion III. American Journal of Obstetrics and Gynecology 156: 1338–1341, 1987b

    Google Scholar 

  • van der Willigen AH, de Graaf YP, van Joost Th. Peri-ocular dermatitis from atropine. Contact Dermatitis 17: 56–57, 1987

    Article  PubMed  Google Scholar 

  • van der Willigen AH, Oranje AP, Stolz E, van Joost Th. Delayed hypersensitivity to scopolamine in transdermal therapeutic systems. Journal of the American Academy of Dermatology 18: 146–147, 1988

    Article  PubMed  Google Scholar 

  • Weber MA. Transdermal antihypertensive therapy: clinical and metabolic considerations. American Heart Journal 112: 906–912, 1986

    Article  PubMed  CAS  Google Scholar 

  • Weickel R, Frosch PJ. Kontaktallergie auf Glyceroltriniträt (Nitroderm TTS). Hautarzt 37: 511–512, 1986

    PubMed  CAS  Google Scholar 

  • White TM, Guidry JR. Rebound hypertension associated with transdermal clonidine and contact dermatitis. Western Journal of Medicine 145: 104, 1986

    PubMed  CAS  Google Scholar 

  • Wrenn K. The hazards of defibrillation through nitroglycerin patches. Annals of Emergency Medicine 19: 1327–1328, 1990

    Article  PubMed  CAS  Google Scholar 

  • Zugerman C, Zheutlin T, Giacobetti R. Allergic contact dermatitis secondary to nitroglycerin in Nitro-Bid ointment. Contact Dermatitis 5: 270–271, 1979

    Article  PubMed  CAS  Google Scholar 

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Carmichael, A.J. Skin Sensitivity and Transdermal Drug Delivery. Drug-Safety 10, 151–159 (1994). https://doi.org/10.2165/00002018-199410020-00004

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