Abstract
The clonidine transdermal therapeutic system is being used as a therapy for blood pressure treatment. Systemic side effects seem to be fewer than with oral clonidine. However, localized skin reactions occur frequently and the incidence increases with the dose and duration of use. Common signs include erythema, scaling, vesiculation, excoriation, and induration. Allergic contact dermatitis is less frequent but common. Hyperpigmentation and depigmentation also occur. Pretreatment with 0.5% hydrocortisone is associated with less skin irritation and higher blood levels. Although oral clonidine is no longer widely used in the management of hypertension, awareness of these reactions to the transdermal delivery of this agent is important.
Transdermal clonidine was introduced in 1984 as a transcutaneous antihypertensive drug that can be delivered for up to 168 hours. 1 , 2 The transdermal therapeutic system (TTS) for Catapres‐TTS consists of a 0.2‐mm adhesive patch with a drug reservoir and a rate‐controlling membrane. Figure 3 shows the design of the delivery system. The patient is advised to place the patch on the upper arm or torso and to rotate the site. 3
Figure 3.
Diagram of transdermal clonidine delivery system
The α2 stimulant in this delivery system, which results in decreased sympathetic nerve activity, seems to be better tolerated than oral clonidine in terms of dry mouth and drowsiness. 4 , 5 It takes 2–3 days to achieve initial therapeutic blood levels. 6 On discontinuation, rebound and/or overshoot hypertension is less likely to occur, due to the skin depot of clonidine, except in elderly patients. 7 , 8 However, dermatologic reactions occur commonly (Figures 1 and 2 and Table). The patient may complain of pruritus, and the objective signs include erythema, scaling, vesiculation, excoriation, and induration.
Figure 1.
Examine the arms and upper chest. What do you notice?
Figure 2.
A close‐up view of erythematous squares on the chest, showing varying stages of erythema and scaling in squares due to transdermal clonidine
Table.
Adverse Skin Reactions With Transdermal Clonidine
| Author (Year) | n | Duration (WK) | Skin Reaction | Dermatitis |
|---|---|---|---|---|
| Boekhorst (1983) 19 | 21 | 4–28 | 52% | 14% |
| Groth et al. (1983) 20 | 29 | 4 | ? | 38% |
| McMahon (1983) 20 | 73 | 12 | ? | 6% |
| Weber et al. (1984) 5 | 20 | 12 | 10% | 0% |
| Weber et al. (1984) 21 | 85 | 12 | 9% | ? |
| Schaller et al.(1985) 22 | 7 | 4 | 43% | 0% |
| Burris and Mroczek (1986) 4 | 25 | 4 | 64% | 8% |
| Hollifield (1986) 10 | 2681 | 12 | ? | 15% |
| Kellaway and Lubbe (1986) 15 | 135 | 12 | 51% | 15% |
| Popli et al. (1986) 23 | 30 | 5 | ? | 0% |
| McChesney et al. (1987) 24 | 28 | 12–36 | 39% | 12% |
| Horning et al. (1988) 9 | 20 | 104 | 50% | ? |
| Fillingim et al. (1989) 25 | 41 | 88 | 41% | 5% |
| Schmidt et al. (1989) 8 | 22 | 12–20 | 50% | 23% |
| McMahon et al. (1990) 26 | 39 | 8 | 33% | 9% |
| Burris et al. (1991) 27 | 23 | 8 | ? | 13% |
| Lueg et al. (1991) 28 | 60 | 8 | 20% | 2% |
| Houston and Hays (1993) 29 | 35 | 8 | 29% | 9% |
| Weidler et al. (1992) 30 | 66 | 20 | ? | 5% |
Several types of dermatologic reactions have been reported, including early erythema associated with pruritus, allergic contact dermatitis, and alterations in skin pigmentation. 3 Allergic dermatitis occurs more commonly in whites than in blacks 9 and in women than in men. 10 One report 11 indicated that the sensitization rate with clonidine TTS is 34% in white women, 18% in white men, 14% in black women, and 8% in black men. Depigmentation and hyperpigmentation have been observed in African Americans. 12 There is a relationship between duration of patch use and the rate of development of allergic dermatitis. 13 , 14
In a single‐blind study with a 2‐week placebo patch run‐in and a 12‐week maintenance period, 15 the rates of erythema and induration were 52% vs. 11% and 24% vs. 0% for active drug vs. placebo, respectively. Fifteen percent of patients discontinued treatment due to severe skin reactions. 8
Potential causes of the allergic contact dermatitis could be from the active drug, the adhesive, the diffusion membrane, the solvent, or the enhancer. 16 Most studies have indicated that the skin reactions are related to the drug itself and not other factors. 13 , 17 Other transdermal delivery systems are used with nicotine, nitroglycerin, scopolamine, estradiol, and testosterone; cutaneous and allergic reactions are less frequent. 16 Treatment with 0.5% hydrocortisone or over‐the‐counter antacids (magnesium‐aluminum hydroxide suspension) has been used to ameliorate skin reactions. 18
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