Long Term Application of Transdermal Clonidine Sustained hypotensive action but a high incidence of local skin reactions

The long term efficacy and tolerability of a clonidine transdermal therapeutic system (clonidine TIS) were assessed in a 2-centre open study. Ten women and 22 men of mean age 48 years with WHO grade I-II essential hypertension were included, some of whom had received previous antihypertensive treatment. No patient had previously received oral clonidine. After a 2-week washout period, all 32 patients were given a placebo TTS for 1 week, before beginning active treatment with a disc containing 2.5mg clonidine (TIS 1) being released at 0.1 mg/24 hours. If BP was satisfactorily controlled the disc was replaced with another TIS 1 after 7 days, but if diastolic BP was> 95mm Hg a disc containing 5mg clonidine (TIS 2) released at a rate of 0.2 mg/24 hours was given. If BP was still uncontrolled oral I)ydrochlorothiazide 50 mg/day was included in the regimen. Following the 4-week dose adjustment period, treatment was continued for up to 19 months.

After 4 weeks of clonidine treatment, BP decreased significantly from 162/107 to 145/91mm Hg, while placebo had caused no significant change. At the end of the titration period, 28 patients had achieved a diastolic BP < 95mm Hg: 6 on clonidine TIS 1; 14 on clonidine TIS 2 and 8 on clonidine + hydrochlorothiazide. Further analysis revealed that patients responding to TIS 1 had significantly lower initial BP values (mean 154/103mm Hg) than those requiring the addition of hydrochlorothiazide (168/110mm Hg). Fifteen patients continued treatment for over 6 months (5 patients for 6-9 months, 4 patients for 9-12 months, 6 patients for> 12 months) and during that time no reduction in efficacy was seen. Plasma clonidine concentrations increased from 0.06 ng/ml to a steady state level of 0.29 ng/ml after 7 days on TTS 1 and ranged between 0.49-0.57 ng/ml on TTS 2. Fifteen (47%) patients developed local skin reactions after 4-22 weeks, necessitating clonidine withdrawal in 11 cases. Seven out of the 8 patients patch-tested with all components of the clonidine TIS showed clonidine-induced allergic contact dermatitis. Twelve patients (38%) reported systemic side effects such as dry mouth (9), fatigue (4), sexual disturbances (2) and Raynaud's phenomenon (1), but treatment was withdrawn only in 1 case, possibly because of a faulty drug release system.

It is concluded that, although displaying an effective and sustained antihypertensive effect, further use of transdermal clonidine application may be limited by the high incidence of allergic contact dermatitis. Groth, H.; Vetter, H.; Knusel, J.; Foerster, E.; Siegenthaler, W. et at.: Klinische Wochenschrift 62: 925-930 (Oct 1984)

8 INPHARMA"" 16 Mar 1985 0156-2703/85/0316-0008/0$01.00/0 © ADIS Press