CATAPRES-TTS is a transdermal system providing continuous systemic delivery of clonidine for 7 days at an approximately constant rate. Clonidine is a centrally acting alpha-agonist hypotensive agent. It is an imidazoline derivative with the chemical name 2, 6-dichloro-N-2-imidazolidinylidenebenzenamine and has the following chemical structure:

CATAPRES

System Structure and Components

CATAPRES-TTS transdermal therapeutic system is a multi-layered film, 0.2 mm thick, containing clonidine as the active agent. The system areas are 3.5 cm² (CATAPRES-TTS-1), 7.0 cm² (CATAPRES-TTS-2) and 10.5 cm² (CATAPRES-TTS-3) and the amount of drug released is directly proportional to the area (see Release Rate Concept). The composition per unit area is the same for all three doses.

Proceeding from the visible surface towards the surface attached to the skin, there are four consecutive layers: 1) a backing layer of pigmented polyester and aluminum film; 2) a drug reservoir of clonidine, mineral oil, polyisobutylene, and colloidal silicon dioxide; 3) a microporous polypropylene membrane that controls the rate of delivery of clonidine from the system to the skin surface; 4) an adhesive formulation of clonidine, mineral oil, polyisobutylene, and colloidal silicon dioxide. Prior to use, a protective slit release liner of polyester that covers the adhesive layer is removed.

Cross Section of the System:

Release Rate Concept

Catapres-TTS® (clonidine) transdermal therapeutic system is programmed to release clonidine at an approximately constant rate for 7 days. The energy for drug release is derived from the concentration gradient existing between a saturated solution of drug in the system and the much lower concentration prevailing in the skin. Clonidine flows in the direction of the lower concentration at a constant rate, limited by the rate-controlling membrane, so long as a saturated solution is maintained in the drug reservoir.

Following system application to intact skin, clonidine in the adhesive layer saturates the skin site below the system. Clonidine from the drug reservoir then begins to flow through the rate-controlling membrane and the adhesive layer of the system into the systemic circulation via the capillaries beneath the skin. Therapeutic plasma clonidine levels are achieved 2 to 3 days after initial application of CATAPRES-TTS transdermal therapeutic system.

The 3.5, 7.0, and 10.5 cm² systems deliver 0.1, 0.2, and 0.3 mg of clonidine per day, respectively. To ensure constant release of drug for 7 days, the total drug content of the system is higher than the total amount of drug delivered. Application of a new system to a fresh skin site at weekly intervals continuously maintains therapeutic plasma concentrations of clonidine. If the CATAPRES-TTS transdermal therapeutic system is removed and not replaced with a new system, therapeutic plasma clonidine levels will persist for about 8 hours and then decline slowly over several days. Over this time period, blood pressure returns gradually to pretreatment levels.

Last updated on RxList: 7/29/2008

Catapres-TTS® (clonidine) transdermal therapeutic system is indicated in the treatment of hypertension. It may be employed alone or concomitantly with other antihypertensive agents.

Apply CATAPRES-TTS transdermal therapeutic system once every 7 days to a hairless area of intact skin on the upper outer arm or chest. Each new application of CATAPRES-TTS transdermal therapeutic system should be on a different skin site from the previous location. If the system loosens during 7-day wearing, the adhesive cover should be applied directly over the system to ensure good adhesion. There have been rare reports of the need for patch changes prior to 7days to maintain blood pressure control.

To initiate therapy, CATAPRES-TTS transdermal therapeutic system dosage should be titrated according to individual therapeutic requirements, starting with CATAPRES-TTS-1. If after one or two weeks the desired reduction in blood pressure is not achieved, increase the dosage by adding another CATAPRES-TTS-1 or changing to a larger system. An increase in dosage above two CATAPRES-TTS-3 is usually not associated with additional efficacy.

When substituting CATAPRES-TTS transdermal therapeutic system for oral clonidine or for other antihypertensive drugs, physicians should be aware that the antihypertensive effect of CATAPRES-TTS transdermal therapeutic system may not commence until 2-3 days after initial application. Therefore, gradual reduction of prior drug dosage is advised. Some or all previous antihypertensive treatment may have to be continued, particularly in patients with more severe forms of hypertension.

Renal Impairment

Dosage must be adjusted according to the degree of impairment, and patients should be carefully monitored. Since only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis.

CATAPRES-TTS-1, CATAPRES-TTS-2, and CATAPRES-TTS-3 are supplied as 4 pouched systems and 4 adhesive covers per carton. See chart below.

Storage And Handling

Store below 86° F (30° C).

Manufactured by: ALZA Corporation Mountain View, CA 94043, USA. Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877, USA. Licensed from: Boehringer Ingelheim International GmbH. Revised: February 14, 2006. FDA rev date: 04/13/06

Last updated on RxList: 7/29/2008

Clinical trial experience with CATAPRES-TTS

Most systemic adverse effects during Catapres-TTS® (clonidine) transdermal therapeutic system therapy have been mild and have tended to diminish with continued therapy. In a 3-month multiclinic trial of CATAPRES-TTS transdermal therapeutic system in 101 hypertensive patients, the systemic adverse reactions were, dry mouth (25 patients) and drowsiness (12), fatigue (6), headache (5), lethargy and sedation (3 each), insomnia, dizziness, impotence/sexual dysfunction, dry throat (2 each) and constipation, nausea, change in taste and nervousness (1 each).

In the above mentioned 3-month controlled clinical trial, as well as other uncontrolled clinical trials, the most frequent adverse reactions were dermatological and are described below.

In the 3-month trial, 51 of the 101 patients had localized skin reactions such as erythema (26 patients) and/or pruritus, particularly after using an adhesive cover throughout the 7-day dosage interval. Allergic contact sensitization to CATAPRES-TTS transdermal therapeutic system was observed in 5 patients. Other skin reactions were localized vesiculation (7 patients), hyperpigmentation (5), edema (3), excoriation (3), burning (3), papules (1), throbbing (1), blanching (1), and a generalized macular rash (1).

In additional clinical experience, contact dermatitis resulting in treatment discontinuation was observed in 128 of 673 patients (about 19 in 100) after a mean duration of treatment of 37 weeks. The incidence of contact dermatitis was about 34 in 100 among white women, about 18 in 100 in white men, about 14 in 100 in black women, and approximately 8 in 100 in black men. Analysis of skin reaction data showed that the risk of having to discontinue CATAPRES-TTS transdermal therapeutic system treatment because of contact dermatitis was greatest between treatment weeks 6 and 26, although sensitivity may develop either earlier or later in treatment.

In a large-scale clinical acceptability and safety study by 451 physicians in a total of 3539 patients, other allergic reactions were recorded for which a causal relationship to CATAPRES-TTS transdermal therapeutic system was not established: maculopapular rash (10 cases); urticaria (2 cases); and angioedema of the face (2 cases), which also affected the tongue in one of the patients.

Marketing Experience with CATAPRES-TTS

Other adverse effects reported since the drug has been marketed are listed below by body system. In this setting, an incidence or causal relationship cannot always be accurately determined. However, none of the events listed below occurred in a frequency greater than 0.5%.

Body as a Whole: Fever; malaise; weakness; pallor; and withdrawal syndrome.

Cardiovascular: Congestive heart failure; cerebrovascular accident; electrocardiographic abnormalities (i.e., bradycardia, sick sinus syndrome disturbances and arrhythmias); chest pain; orthostatic symptoms; syncope, increases in blood pressure; sinus bradycardia and atrioventricular block with and without the use of concomitant digitalis; Raynaud's phenomenon; tachycardia; bradycardia; and palpitations.

Central and Peripheral Nervous System/Psychiatric: Delirium; mental depression; visual and auditory hallucinations; localized numbness; vivid dreams or nightmares; restlessness; anxiety; agitation; irritability; other behavioral changes; and drowsiness.

Dermatological: Angioneurotic edema; localized or generalized rash; hives; urticaria; contact dermatitis; pruritus; alopecia; and localized hypo or hyper pigmentation.

Gastrointestinal: Anorexia and vomiting.

Genitourinary: Difficult micturition; loss of libido; and decreased sexual activity.

Metabolic: Gynecomastia or breast enlargement and weight gain.

Musculoskeletal: Muscle or joint pain; and leg cramps.

Opthalmological: Blurred vision; burning of the eyes and dryness of the eyes.

Adverse Events Associated with Oral CATAPRES Therapy: Most adverse effects are mild and tend to diminish with continued therapy. The most frequent (which appear to be dose-related) are dry mouth, occurring in about 40 of 100 patients; drowsiness, about 33 in 100; dizziness, about 16 in 100; constipation and sedation, each about 10 in 100. The following less frequent adverse experiences have also been reported in patients receiving CATAPRES (clonidine hydrochloride USP), but in many cases patients were receiving concomitant medication and a causal relationship has not been established.

Body as a Whole: Weakness, about 10 in 100 patients; fatigue, about 4 in 100; headache and withdrawal syndrome each about 1 in 100. Also reported were pallor; a weakly positive Coombs' test; increased sensitivity to alcohol; and fever.

Cardiovascular: Orthostatic symptoms, about 3 in 100 patients; palpitations and tachycardia, and bradycardia, each about 5 in 1000. Syncope, Raynaud's phenomenon, congestive heart failure, and electrocardiographic abnormalities (i.e., sinus node arrest, functional bradycardia, high degree AV block and arrhythmias) have been reported rarely. Rare cases of sinus bradycardia and AV block have been reported, both with and without the use of concomitant digitalis.

Central Nervous System: Nervousness and agitation, about 3 in 100 patients, mental depression, about 1 in 100 and insomnia, about 5 in 1000. Other behavioral changes, vivid dreams or nightmares, restlessness, anxiety, visual and auditory hallucinations and delirium have rarely been reported.

Dermatological: Rash, about 1 in 100 patients; pruritus, about 7 in 1000; hives, angioneurotic edema and urticaria, about 5 in 1000; alopecia, about 2 in 1000.

Gastrointestinal: Nausea and vomiting, about 5 in 100 patients; anorexia and malaise, each about 1 in 100; mild transient abnormalities in liver function tests, about 1 in 100; hepatitis, parotitis, constipation, pseudo-obstruction, and abdominal pain, rarely.

Genitourinary: Decreased sexual activity, impotence and loss of libido, about 3 in 100 patients; nocturia, about 1 in 100; difficulty in micturition, about 2 in 1000; urinary retention, about 1 in 1000.

Hematologic: Thrombocytopenia, rarely.

Metabolic: Weight gain, about 1 in 100 patients; gynecomastia, about 1 in 1000; transient elevation of blood glucose or serum creatine phosphokinase, rarely.

Musculoskeletal: Muscle or joint pain, about 6 in 1000 and leg cramps, about 3 in 1000.

Oro-otolaryngeal: Dryness of the nasal mucosa was rarely reported.

Ophthalmological: Dryness of the eyes, burning of the eyes and blurred vision were reported.

Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. If a patient receiving clonidine is also taking tricyclic antidepressants, the hypotensive effect of clonidine may be reduced, necessitating an increase in the clonidine dose.

Due to a potential for additive effects such as bradycardia and AV block, caution is warranted in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction e.g., digitalis, calcium channel blockers and beta-blockers.

Amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats (see Toxicology).

Toxicology

In several studies with oral clonidine hydrochloride, a dose-dependent increase in the incidence and severity of spontaneous retinal degeneration was seen in albino rats treated for six months or longer. Tissue distribution studies in dogs and monkeys showed a concentration of clonidine in the choroid.

In view of the retinal degeneration seen in rats, eye examinations were performed during clinical trials in 908 patients before, and periodically after, the start of clonidine therapy. In 353 of these 908 patients, the eye examinations were carried out over periods of 24 months or longer. Except for some dryness of the eyes, no drug-related abnormal ophthalmological findings were recorded and, according to specialized tests such as electroretinography and macular dazzle, retinal function was unchanged.

In combination with amitriptyline, clonidine hydrochloride administration led to the development of corneal lesions in rats within 5 days.

Last updated on RxList: 7/29/2008

Withdrawal

Patients should be instructed not to discontinue therapy without consulting their physician. Sudden cessation of clonidine treatment has, in some cases, resulted in symptoms such as nervousness, agitation, headache, and confusion accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma. The likelihood of such reactions to discontinuation of clonidine therapy appears to be greater after administration of higher doses or continuation of concomitant beta-blocker treatment and special caution is therefore advised in these situations. Rare instances of hypertensive encephalopathy, cerebrovascular accidents and death have been reported after clonidine withdrawal. When discontinuing therapy with CATAPRES, the physician should reduce the dose gradually over 2 to 4 days to avoid withdrawal symptomatology.

An excessive rise in blood pressure following discontinuation of CATAPRES-TTS transdermal therapeutic system therapy can be reversed by administration of oral clonidine hydrochloride or by intravenous phentolamine. If therapy is to be discontinued in patients receiving a beta-blocker and clonidine concurrently, the beta-blocker should be withdrawn several days before the gradual discontinuation of CATAPRES-TTS transdermal therapeutic system.

General

In patients who have developed localized contact sensitization to CATAPRES-TTS transdermal therapeutic system continuation of CATAPRES-TTS transdermal therapeutic system or substitution of oral clonidine hydrochloride therapy may be associated with development of a generalized skin rash.

In patients who develop an allergic reaction to CATAPRES-TTS transdermal therapeutic system, substitution of oral clonidine hydrochloride may also elicit an allergic reaction (including generalized rash, urticaria, or angioedema).

CATAPRES-TTS transdermal therapeutic system should be used with caution in patients with severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease, or chronic renal failure.

In rare instances, loss of blood pressure control has been reported in patients using CATAPRES-TTS transdermal therapeutic system according to the instructions for use.

Perioperative Use

CATAPRES-TTS transdermal therapeutic system therapy should not be interrupted during the surgical period. Blood pressure should be carefully monitored during surgery and additional measures to control blood pressure should be available if required. Physicians considering starting CATAPRES-TTS transdermal therapeutic system therapy during the perioperative period must be aware that therapeutic plasma clonidine levels are not achieved until 2 to 3 days after initial application of Catapres-TTS® (clonidine) transdermal therapeutic system (see DOSAGE AND ADMINISTRATION).

Defibrillation or Cardioversion

The transdermal clonidine systems should be removed before attempting defibrillation or cardioversion because of the potential for altered electrical conductivity which may increase the risk of arcing, a phenomenon associated with the use of defibrillators.

MRI

Skin burns have been reported at the patch site in several patients wearing an aluminized transdermal system during a magnetic resonance imaging scan (MRI). Because the CATAPRES-TTS PATCH contains aluminum, it is recommended to remove the system before undergoing an MRI.

Information for Patients

Patients should be cautioned against interruption of CATAPRES-TTS transdermal therapeutic system therapy without their physician's advice.

Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of a possible sedative effect of clonidine. They should also be informed that this sedative effect may be increased by concomitant use of alcohol, barbiturates, or other sedating drugs.

Patients should be instructed to consult their physicians promptly about the possible need to remove the patch if they observe moderate to severe localized erythema and/or vesicle formation at the site of application or generalized skin rash.

If a patient experiences isolated, mild localized skin irritation before completing 7 days of use, the system may be removed and replaced with a new system applied to a fresh skin site.

If the system should begin to loosen from the skin after application, the patient should be instructed to place the adhesive cover directly over the system to ensure adhesion during its 7-day use.

Used CATAPRES-TTS PATCHES contain a substantial amount of their initial drug content which may be harmful to infants and children if accidentally applied or ingested. THEREFORE, PATIENTS SHOULD BE CAUTIONED TO KEEP BOTH USED AND UNUSED CATAPRES-TTS PATCHES OUT OF THE REACH OF CHILDREN. After use, CATAPRES-TTS should be folded in half with the adhesive sides together and discarded away from children's reach.

Instructions for use, storage and disposal of the system are provided at the end of this monograph. These instructions are also included in each box of CATAPRES-TTS transdermal therapeutic system.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Chronic dietary administration of clonidine was not carcinogenic to rats (132 weeks) or mice (78 weeks) dosed, respectively, at up to 46 to 70 times the maximum recommended daily human dose as mg/kg (9 or 6 times the MRDHD on a mg/m² basis). There was no evidence of genotoxicity in the Ames test for mutagenicity or mouse micronucleus test for clastogenicity.

Fertility of male and female rats was unaffected by clonidine doses as high as 150 mcg/kg (approximately 3 times the MRDHD). In a separate experiment, fertility of female rats appeared to be affected at dose levels of 500 to 2000 mcg/kg (10 to 40 times the oral MRDHD on a mg/kg basis; 2 to 8 times the MRDHD on a mg/m² basis).

Pregnancy

Teratogenic Effects: Pregnancy Category C.

Reproduction studies performed in rabbits at doses up to approximately 3 times the oral maximum recommended daily human dose (MRDHD) of CATAPRES® (clonidine hydrochloride) produced no evidence of a teratogenic or embryotoxic potential in rabbits. In rats, however, doses as low as 1/3 the oral MRDHD (1/15 the MRDHD on a mg/m² basis) of clonidine were associated with increased resorptions in a study in which dams were treated continuously from 2 months prior to mating. Increased resorptions were not associated with treatment at the same or at higher dose levels (up to 3 times the oral MRDHD) when the dams were treated on gestation days 6-15. Increases in resorption were observed at much higher dose levels (40 times the oral MRDHD on mg/kg basis; 4 to 8 times the MRDHD on a mg/m² basis) in mice and rats treated on gestation days 1-14 (lowest dose employed in the study was 500 mcg/kg).

No adequate well-controlled studies have been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

As clonidine is excreted in human milk, caution should be exercised when Catapres-TTS® (clonidine) transdermal therapeutic system is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of twelve have not been established (see WARNINGS, Withdrawal).

Last updated on RxList: 7/29/2008

Hypertension may develop early and may be followed by hypotension, bradycardia, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, weakness, irritability and miosis. The frequency of CNS depression may be higher in children than adults. Large overdoses may result in reversible cardiac conduction defects or dysrhythmias, apnea, coma and seizures. Signs and symptoms of overdose generally occur within 30 minutes to two hours after exposure. As little as 0.1 mg of clonidine has produced signs of toxicity in children.

If symptoms of poisoning occur following dermal exposure, remove all Catapres-TTS® (clonidine) transdermal therapeutic systems. After their removal, the plasma clonidine levels will persist for about 8 hours, then decline slowly over a period of several days. Rare cases of CATAPRES-TTS poisoning due to accidental or deliberate mouthing or ingestion of the patch have been reported, many of them involving children.

There is no specific antidote for clonidine overdosage. Ipecac syrup-induced vomiting and gastric lavage would not be expected to remove significant amounts of clonidine following dermal exposure. If the patch is ingested, whole bowel irrigation may be considered and the administration of activated charcoal and/or cathartic may be beneficial. Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension and vasodilators for hypertension. Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension and/or coma; blood pressure should be monitored since the administration of naloxone has occasionally resulted in paradoxical hypertension. Tolazoline administration has yielded inconsistent results and is not recommended as first-line therapy. Dialysis is not likely to significantly enhance the elimination of clonidine.

The largest overdose reported to date, involved a 28-year old male who ingested 100 mg of clonidine hydrochloride powder. This patient developed hypertension followed by hypotension, bradycardia, apnea, hallucinations, semicoma, and premature ventricular contractions. The patient fully recovered after intensive treatment. Plasma clonidine levels were 60 ng/mL after 1 hour, 190 ng/mL after 1.5 hours, 370 ng/mL after 2 hours, and 120 ng/mL after 5.5 and 6.5 hours. In mice and rats, the oral LD₅₀of clonidine is 206 and 465 mg/kg, respectively.

CATAPRES-TTS transdermal therapeutic system should not be used in patients with known hypersensitivity to clonidine or to any other component of the therapeutic system.

Last updated on RxList: 7/29/2008

Clonidine stimulates alpha-adrenoreceptors in the brain stem. This action results in reduced sympathetic outflow from the central nervous system and in decreases in peripheral resistance, renal vascular resistance, heart rate, and blood pressure. Renal blood flow and glomerular filtration rate remain essentially unchanged. Normal postural reflexes are intact; therefore, orthostatic symptoms are mild and infrequent.

Acute studies with clonidine hydrochloride in humans have demonstrated a moderate reduction (15% - 20%) of cardiac output in the supine position with no change in the peripheral resistance; at a 45° tilt there is a smaller reduction in cardiac output and a decrease of peripheral resistance.

During long-term therapy, cardiac output tends to return to control values, while peripheral resistance remains decreased. Slowing of the pulse rate has been observed in most patients given clonidine, but the drug does not alter normal hemodynamic responses to exercise.

Tolerance to the antihypertensive effect may develop in some patients, necessitating a reevaluation of therapy.

Other studies in patients have provided evidence of a reduction in plasma renin activity and in the excretion of aldosterone and catecholamines. The exact relationship of these pharmacologic actions to the antihypertensive effect of clonidine has not been fully elucidated.

Clonidine acutely stimulates the release of growth hormone in children as well as adults but does not produce a chronic elevation of growth hormone with long-term use.

Pharmacokinetics

The plasma half-life of clonidine is 12.7 ± 7 hours. Following oral administration, about 40-60% of the absorbed dose is recovered in the urine as unchanged drug within 24 hours. The remainder of the absorbed dose is metabolized in the liver.

Last updated on RxList: 7/29/2008

Catapres-TTS®
(clonidine)

Transdermal Therapeutic System

(Read the following instructions carefully before using this medication. If you have any questions, please consult with your doctor.)

General Information

CATAPRES-TTS transdermal therapeutic system is a square, tan adhesive PATCH containing an active blood-pressure- lowering medication. It is designed to deliver the drug into the body through the skin smoothly and consistently for one full week. Normal exposure to water, as in showering, bathing, and swimming, should not affect the PATCH.

The optional white, round ADHESIVE COVER should be applied directly over the PATCH, should the PATCH begin to separate from the skin. The ADHESIVE COVER ensures that the PATCH sticks to the skin. The CATAPRES-TTS PATCH must be replaced with a new one on a fresh skin site if the one in use significantly loosens or falls off.

Figure 1

Skin burns have been reported at the patch site in several patients wearing an aluminized transdermal system during a magnetic resonance imaging scan (MRI). Because the Catapres-TTS® PATCH contains aluminum, it is recommended to remove the system before undergoing an MRI.

How to Apply the CATAPRES-TTS PATCH

1) Apply the square, tan CATAPRES-TTS PATCH once a week, preferably at a convenient time on the same day of the week (i.e., prior to bedtime on Tuesday of week one; prior to bedtime on Tuesday of week two, etc.).

2) Select a hairless area such as on the upper, outer arm or upper chest. The area chosen

Figure 2

should be free of cuts, abrasions, irritation, scars or calluses and should not be shaved before applying the Catapres-TTS® (clonidine) PATCH. Do not place the CATAPRES-TTS PATCH on skin folds or under tight undergarments, since pre-mature loosening may occur.

3) Wash hands with soap and water and thoroughly dry them.

4) Clean the area chosen with soap and water. Rinse and wipe dry with a clean, dry tissue.

5) Select the pouch with the red and orange colors labeled CATAPRES-TTS (clonidine) and open it as illus- trated in Figure 3. Remove the square, tan PATCH from the pouch.

Figure 3

6) Remove the clear plastic protective backing from the PATCH by gently peeling off one half of the backing at a time as shown in Figure 4. Avoid touching the sticky side of the Catapres-TTS® (clonidine) PATCH.

Figure 4

7) Place the CATAPRES-TTS PATCH on the prepared skin site (sticky side down) by applying firm pressure over the PATCH to ensure good contact with the skin, especially around the edges (Figure 5). Discard the clear plastic protective backing and wash your hands with soap and water to remove any drug from your hands.

Figure 5

8)After one week, remove the old PATCH and discard it (refer to Instructions for Disposal). After choosing a different skin site, repeat instructions 2 through 7 for the application of your next CATAPRES-TTS PATCH.

What to do if your CATAPRES-TTS PATCH becomes loose while wearing:

How to Apply the ADHESIVE COVER

Note: The white, round, ADHESIVE COVER does not contain any drug and should not be used alone. The COVER should be applied directly over the CATAPRES-TTS PATCH only if the PATCH begins to separate from the skin, thereby ensuring that it sticks to the skin for seven full days.

Figure 6

1) Wash hands with soap and water and thoroughly dry them.

2) Using a clean, dry tissue, make sure that the area around the square, tan Catapres-TTS® (clonidine) PATCH is clean and dry. Press gently on the CATAPRES-TTS PATCH to ensure that the edges are in good contact with the skin.

3) Take the white, round, ADHESIVE COVER (Figure 6) from the plain white pouch and remove the paper liner backing from the COVER.

4) Carefully center the round, white ADHESIVE COVER over the square, tan CATAPRES-TTS PATCH and apply firm pressure, especially around the edges in contact with the skin.

Instructions for Disposal

KEEP OUT OF REACH OF CHILDREN

During or even after use, a PATCH contains active medication which may be harmful to infants and children if accidentally applied or ingested. After use, fold in half with the sticky sides together. Dispose of carefully out of reach of children.

Last updated on RxList: 7/29/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CLONIDINE - TRANSDERMAL

(KLAHN-eh-deen)

COMMON BRAND NAME(S): Catapres-TTS

USES: This medication is used to treat high blood pressure. It works by stimulating certain brain receptors (alpha adrenergic type) which results in the relaxing of blood vessels in other parts of your body, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to ease withdrawal symptoms associated with the long-term use of narcotics, alcohol and nicotine (smoking). In addition, clonidine may also be used for migraine headaches, hot flashes associated with menopause, attention deficit hyperactivity disorder, and other conditions as determined by your doctor.

HOW TO USE: Read the Patient Information Leaflet available from your pharmacist. Consult your doctor or pharmacist if you have any questions.

Before using, remove the clear plastic backing to expose the sticky surface of the medicated patch. Apply the patch to a hairless area of the skin on the upper outer arm or chest every 7 days. Do not use on broken or irritated skin. After 7 days, remove the used patch and apply a new patch to a different area than the previous one to avoid skin irritation.

If the medicated patch peels away from the skin, you may cover it with the large non-medicated adhesive overlay to keep it on for the full 7 days.

Even after 7 days, the used patch still has some medication in it. To prevent an accidental overdose, after you remove a used patch, fold it in half with the sticky sides together and discard in the trash away from children and pets.

The dosage is based on your medical condition and response to therapy.

Use this medication regularly in order to get the most benefit from it. Remember to replace the old patch with a new one on the same day every week, or use as directed by your doctor. It is important to continue using this medication even if you feel well. Most people with high blood pressure do not feel sick.

Do not suddenly stop using this medication without consulting your doctor because your condition may become worse. A serious rapid increase in your blood pressure (rebound hypertension) may occur when this drug is suddenly stopped or if you miss replacing the patch for 3 or more days, especially if you have been taking it for a long time, at higher doses, or with a beta-blocker medication. Therefore it is important that you do not run out of clonidine. There have been reports of rare, but very serious (possibly fatal) results, including stroke, from stopping this drug too quickly. If you must stop using this drug, your dose should be gradually decreased as directed by your doctor.

When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well (e.g., your routine blood pressure readings increase).

SIDE EFFECTS: Dizziness, lightheadedness, drowsiness, dry mouth, unusual tiredness, or headache may occur as your body adjusts to the medication. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water or use a saliva substitute.

If you notice mild skin redness or itching around the patch area before finishing the full 7 days of use, remove the patch and replace it with a new one on a new skin site. These effects seem to occur more frequently in patients who use the overlay cover. If the symptoms persist or worsen into a rash, consult your doctor promptly for further instructions to see if you need to remove the patch.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fast/slow/irregular heartbeat, depression.

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: severe or persistent rash, severe or persistent itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking clonidine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

The patch should be removed before you have certain procedures (e.g., cardioversion, defibrillation) to correct heart conduction disorders. Consult your doctor for more information.

If you are going to have an MRI test, notify testing personnel that you are using this patch. Serious burns may occur during MRI tests because of the aluminum contained in these patches. It should be removed just before the MRI test or consult your doctor for specific instructions.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, heart disease (e.g., severe coronary insufficiency, conduction disorders, recent heart attack), depression, blood circulation disorders (e.g., Raynaud's disease).

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy or drowsy; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

To minimize dizziness and lightheadedness, get up slowly when rising from a seated or lying position.

Caution is advised when using this drug in the elderly because they may be more sensitive to its effects, especially dizziness.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: beta-blocker drugs (e.g., metoprolol, propranolol), cyclobenzaprine, other drugs which can slow the heart rate (e.g., digoxin, calcium channel blockers, guanethidine), MAO inhibitors (e.g., furazolidone, linezolid, moclobemide, phenelzine, procarbazine, selegiline, isocarboxazid, tranylcypromine), tricyclic antidepressants (e.g., amitriptyline, desipramine).

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs - NSAIDs for pain/fever reduction) because they may contain ingredients that could increase your blood pressure. Many cough-and-cold products may also contain ingredients that cause drowsiness. Ask your pharmacist about the safe use of those products.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: antihistamines (e.g., diphenhydramine), anti-anxiety drugs (e.g., diazepam), anti-seizure drugs (e.g., carbamazepine, phenobarbital), medicine for sleep (e.g., sedatives), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., phenothiazines such as chlorpromazine), tranquilizers.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: See also How to Use section.

If overdose is suspected, remove the patch. Contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include fainting, severe weakness, fast/slow/irregular heartbeat, slowed breathing, seizures, coma.

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise, and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Have your blood pressure and pulse checked regularly while taking this medication. Discuss with your doctor how to monitor your own blood pressure and pulse.

MISSED DOSE: See also How to Use section.

If you miss a dose, use it as soon as you remember. Do not double the dose to catch up. Call your doctor immediately if you are late replacing a patch by 3 or more days.

STORAGE: Store at room temperature below 86 degrees F (30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed (See How to Use section).

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA), or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.