Clonidine transdermal system

Antihypertensive drugp are contraindicated in patients with known hypersensitivity to the individual dm. When an antihypertensive is administered by a trans-derrnal system (eg, clonidine), the system is contraindicated if the patient is allergic to any component of the adhesive layer of the transdermal system. Use of the angiotensin II receptor antagonists during the second and third trimester of pregnancy is contraindicated... 

Transdermal system-The system, a 0.2 mm thick film with 4 layers, contains a drug reservoir of clonidine, released at an approximately constant rate for 7 days. 

Hypersensitivity to clonidine or any component of adhesive layer of transdermal system. 

Burris JF. The USA experience with the clonidine transdermal therapeutic system. Clin Auton Res. 1993 3 391-6. 

As little as 0.1 mg of clonidine has produced toxicity in children determination of adult toxicity is based on observation as there is no milligram per kilogram toxic dose established. Clonidine levels are not clinically useful. Toxicity can result from ingestion of used clonidine transdermal patches as residual clonidine remains after full therapeutic use. Symptoms generally begin within 30-90 min and include hypotension, central nervous system depression, bradycardia, and... 

The major adverse effects of clonidine are dry mouth and sedation. These responses occur in at least 50% of patients and may require dmg discontinuation. However, they may diminish in intensity after several weeks of therapy. Sexual dysfunction also may occur. Marked bradycardia is observed in some patients. These and some of the other adverse effects of clonidine frequently are related to dose, and their incidence may be lower with transdermal administration of clonidine because antihypertensive efficacy may be achieved while avoiding the relatively high peak concentrations that occur after oral administration of the drug. About 15 to 20% of patients develop contact dermatitis when using clonidine in the transdermal system. Withdrawal reactions follow abrupt discontinuation of long-term therapy with clonidine in some hypertensive patients. 

Active substances used in membrane diffusion transdermal systems can be the following steroid hormones, clonidine, scopolamine, nicotine, nitroglycerine, dexamethasone, propranolol, and analgesics (e.g. phentanyl, buprenor-phine), [60, 61, 75]. 

Clonidine is an aryl-2-aminoimidazoline that is more selective for a2-adrenoceptors than for I1-IBS (Fig. 29.7) in producing its hypotensive effect. It is available as oral tablets, injection, or a transdermal system. 

Clonidine hydrochloride is readily absorbed by oral route with an absorption time of 2 to 4 hours (9). Drug is well absorbed from the gastro-intestinal tract. It may also be absorbed when applied topically to the eye, clonidine is well absorbed percutaneously following topical application of a transdermal system to the arm or chest. Plasma clonidine concentrations of 2 ng/mL have been detected one hour after administration of a single 0.39 mg oral dose of radiolabeled drug. Peak plasma concentrations following oral administration occur in approximately 3-5 hours (1). 

Despite the limitations imposed by the physiology of the skin, several marketed controUed release transdermal dmg dehvery systems are available in the United States for example, scopolamine [51-34-3] for the treatment of motion sickness, nitroglycerin [55-63-0] for angina, estradiol [50-28-2] for the rehef of postmenopausal symptoms and osteoporosis, clonidine [4205-90-7] for the treatment of hypertension, fentanyl [437-38-7] as an analgesic, and nicotine [54-11-5] as an aid to smoking cessation. These systems are designed to dehver dmg for periods of one to seven days. 

Clonidine is also available as a transdermal patch (Catapres-TTS [transdermal therapeutic system]) that has the advantages of avoiding the need for repeated doses during the day and of reportedly lower rates of dry mouth and drowsiness (Burris, 1993). Steady-state plasma levels are reached within 2-3 days after applying the patch and clonidine concentrations reportedly diminish gradually over 2-3 days following patch removal, without rebound hypertension in adult hyper-... 

Nicotine dependence may respond to replacement therapy with either nicotine gum or transdermal patches, and detoxification from nicotine dependence has been described using clonidine. Bupropion, an antidepressant, also shows efficacy for smoking cessation. The nicotinic receptor blocker mecamylamine, which has good central nervous system access, has been used with limited efficacy. Overall, success rates for smoking abstinence at 1 year are about 20%, with even less success for depressed smokers. 

Transdermal therapeutic systems (TTS) of nitroglycerin (1), isosorbide dinitrate (2), scopolamine (3) or clonidine (4) have been throughly investigated in vitro and in vivo. However, there have been few studies of skin permeation of ionizable water soluble drugs. 

Clonidine is a potent antihypertensive agent which is well absorbed from the GI tract (95%). The dmg has a relatively long half-life (6-20 h) and a modest clearance (13 L h ). The rationale for the development of transdermal clonidine was to reduce side-effects and to improve patient compliance. Catapres-TTS, a reservoir-type patch, reached the market in 1985 in a form designed to remain in place and to deliver dmg for 7 days. Dose titration was possible via the use of systems of different active areas (3.5, 7.0, and 10.5 cm2). The control of dmg delivery over 7 days is impressive, and avoids the peaks and valleys of conventional (twice-a-day) oral administration (Figure 8.7). However, this system has not achieved as wide a success as first seemed likely because of skin sensitization. Clonidine itself, when administered transdermally on a chronic, repetitive basis, induces in a significant fraction of patients a classic immunologic skin reaction, and this has severely attenuated its use. 

Advances in transdermal delivery systems (TDSs) and the technology involved have been rapid because of the sophistication of polymer science, which now allows incorporation of polymeric additives in TDSs in adequate quantity. Drugs with which transdermal therapy was pioneered include scopolamine, nitroglycerine, iso-sorbide dinitrite, clonidine, estradiol, nicotine, and testosterone [74],... 

Catapres TTS is the first and only transdermal patch approved by the FDA for the treatment of hypertension. Catapres TTS contains the active ingredient clondidine and was approved in 1985 [27], Catapres TTS is a seven-day patch and is a membrane-moderated transdermal patch. The patch comes in three sizes, 0.1, 0.2, and 0.3 mg/day. In addition there is also a burst dose of clonidine in the adhesive layer. The presence of the burst doses provides an immediate-release dose of clonidine which promotes rapid systemic levels of the drug. 

Transdermal administration can avoid first-pass metabolism as well as provide a large surface area for continuous-controlled administration of drugs with short biological half-lives and narrow therapeutical indices. The route has been used for nitroglycerin ointments, and transdermal therapeutical systems (patches) have been developed for scopolamine, nitroglycerin, clonidine, estradiol, and nicotine. 

Currently approved therapies of systemic drug delivery via the transdermal route include aprostadil for erectile dysfunction, clonidine for hypertension, estradiol and... 

Transdermal clonidine (clonidine TTS) has been used with some success for the treatment of mild hypertension. Systemic adverse effects are similar to those seen after oral administration, but are less frequent and milder. They include dry mouth, drowsiness, headache, sexual disturbance, cold extremities, obstipation, and fatigue (31-33). These adverse effects rarely necessitate withdrawal of clonidine TTS. 

A 47-year-old woman was given transdermal, oral, and intravenous clonidine at different times, separated by several months. The patches were withdrawn after 2 months because of pruritic erythematous vesiculation at the site of application. Oral clonidine (0.3 mg/day) had to be withdrawn when a generalized maculopapular rash appeared on the third day, and was promptly exacerbated by each dose. Intravenous clonidine 0.150 mg was followed within 30 minutes by a severe, generalized, maculopapular reaction requiring systemic steroids and antihistamines. 

Membrane permeation-controlled transdermal drug delivery (Fig. 5.2) has been successfully applied in therapeutic systems for scopolamine (prevention of motion sickness for a 3-day period), nitroglycerin (prophylaxis against attack of angina pectoris over a 24-h period), clonidine (control of hypertension for a 7-day period), and fentanyl (control of constant pain for 72 h). 

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