Clonidine Transdermal System USP

/Clonidine Transdermal System USP
Clonidine Transdermal System USP2018-09-06T09:12:40+00:00

Prescription Drug Name:

Clonidine Transdermal System USP

ID:

7c40121c-8149-4608-8874-8bd5878a7132

Code:

34391-3

DESCRIPTION


id: e70f488d-5fb1-440b-bbfc-2f639fe69765
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Clonidine transdermal system, USP 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:

CLINICAL PHARMACOLOGY


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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

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% to 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.

INDICATIONS AND USAGE


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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Clonidine transdermal system is indicated in the treatment of hypertension. It may be employed alone or concomitantly with other antihypertensive agents.

CONTRAINDICATIONS


id: de3abc76-0965-40d4-81cf-1cec5e7e63ef
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

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

WARNINGS


id: fc8eebdd-da80-4eb9-bdbb-a9c97c547394
displayName: WARNINGS SECTION
FDA Article Code: 34071-1

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, tremor, 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 clonidine transdermal system, 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 clonidine transdermal 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 clonidine transdermal system.

ADVERSE REACTIONS


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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Clinical
t
rial
e
xperience
w
ith Clonidine Transdermal System
Most systemic adverse effects during clonidine transdermal system therapy have been mild and have tended to diminish with continued therapy. In a 3-month multiclinic trial of clonidine transdermal 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 clonidine transdermal 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 clonidine transdermal 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 clonidine transdermal 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 Clonidine Transdermal System The following adverse reactions have been identified during post-approval use of clonidine transdermal system. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to clonidine transdermal system. 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 (AV) 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; hallucinations (including visual and auditory); 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. Ophthalmological: Blurred vision; burning of the eyes and dryness of the eyes. Adverse Events Associated with Or
al
C
lonidine
Th
erapy: 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 clonidine hydrochloride, USP tablets, but in many cases patients were receiving concomitant medication and a causal relationship has not been established.
Body as a Whole:  Fatigue, fever, headache, pallor, weakness, and withdrawal syndrome. Also reported were a weakly positive Coombs’ test and increased sensitivity to alcohol. Cardiovascular: Bradycardia, congestive heart failure, electrocardiographic abnormalities (i.e., sinus node arrest, junctional bradycardia, high degree AV block and arrhythmias), orthostatic symptoms, palpitations, Raynaud’s phenomenon, syncope, and tachycardia. Cases of sinus bradycardia and AV block have been reported, both with and without the use of concomitant digitalis. Central Nervous System: Agitation, anxiety, delirium, delusional perception, hallucinations (including visual and auditory), insomnia, mental depression, nervousness, other behavioral changes, paresthesia, restlessness, sleep disorder, and vivid dreams or nightmares. Dermatological: Alopecia, angioneurotic edema, hives, pruritus, rash, and urticaria. Gastrointestinal: Abdominal pain, anorexia, constipation, hepatitis, malaise, mild transient abnormalities in liver function tests, nausea, parotitis, pseudo-obstruction (including colonic pseudo-obstruction), salivary gland pain, and vomiting. Genitourinary: Decreased sexual activity, difficulty in micturition, erectile dysfunction, loss of libido, nocturia, and urinary retention. Hematologic: Thrombocytopenia. Metabolic: Gynecomastia, transient elevation of blood glucose or serum creatine phosphokinase, and weight gain. Musculoskeletal: Leg cramps and muscle or joint pain. Oro-otolaryngeal: Dryness of the nasal mucosa. Ophthalmological: Accommodation disorder, blurred vision, burning of the eyes, decreased lacrimation, and dryness of the eyes.

OVERDOSAGE


id: dadb7841-a1c5-40fe-aa9e-a7594e3b0205
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

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 clonidine transdermal 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 clonidine transdermal system 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 LD50 of clonidine is 206 and 465 mg/kg, respectively.

DOSAGE AND ADMINISTRATION


id: f9c2b535-c351-4946-86f3-41068cb2b22e
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Apply clonidine transdermal system once every 7 days to a hairless area of intact skin on the upper outer arm or chest. Each new application of clonidine transdermal 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 7 days to maintain blood pressure control. To initiate therapy, clonidine transdermal system dosage should be titrated according to individual therapeutic requirements, starting with clonidine transdermal system, 0.1 mg per day for one week. If after one or two weeks the desired reduction in blood pressure is not achieved, increase the dosage by adding another clonidine transdermal system, 0.1 mg per day for one week or changing to a larger system. An increase in dosage above two clonidine transdermal systems, 0.3 mg per day for one week is usually not associated with additional efficacy. When substituting clonidine transdermal system for oral clonidine or for other antihypertensive drugs, physicians should be aware that the antihypertensive effect of clonidine transdermal system may not commence until 2 to 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 Patients with renal impairment may benefit from a lower initial dose. 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.

HOW SUPPLIED


id: 70df7189-4680-436d-b25f-28a62ad446e4
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Clonidine transdermal systems USP, 0.1 mg per day for one week, 0.2 mg per day for one week, and 0.3 mg per day for one week are supplied as 4 pouched systems and 4 adhesive covers per carton. Each system contains 1.97 mg, 3.94 mg, or 5.90 mg clonidine.  See chart below.

 
   Programmed Delivery
Clonidine
in vivo
 

Per Day Over 1 Week

 Clonidine
Content
 Size  Code
 Clonidine Transdermal System, USP (clonidine)
 
NDC 0591-3508-04
 0.1 mg  1.97 mg  4.1 cm2  WPI
3508
 Clonidine Transdermal System, USP (clonidine)

NDC 0591-3509-04

 0.2 mg  3.94 mg  8.2 cm2  WPI
3509
 Clonidine Transdermal System, USP (clonidine)

NDC 0591-3510-04

 0.3 mg  5.90 mg  12.3 cm2  WPI
3510

STORAGE AND HANDLING


id: e4241b52-101f-4790-a7fc-1965060c210a
displayName: STORAGE AND HANDLING SECTION
FDA Article Code: 44425-7

Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. Manufactured by:
Actavis Laboratories UT, Inc.
Salt Lake City, UT 84108 USA
Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA
Address medical inquiries to Watson Laboratories, Inc. at 1-800-272-5525. Revised: October 2015

PATIENT INSTRUCTIONS


id: 893da59a-ea00-4abf-9ae3-30e4a3d8a714
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

Clonidine Transdermal System, USP
(0.1 mg*, 0.2 mg*, or 0.3 mg* clonidine
per day for one week)
Rx only Clonidine Transdermal System
, USP

*In vivo

delivery

 

of 0.1 mg, 0.2 mg, or 0.3 mg clonidine per day for one week. Each system contains 1.97 mg, 3.94 mg, or 5.90 mg clonidine.
(Read the following instructions carefully before using this medication. If you have any questions, please consult with your doctor.) General Information Clonidine transdermal system is a square to rectangular, 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 to slightly yellow, round to elliptical 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 clonidine transdermal PATCH must be replaced with a new one on a fresh skin site if the one in use significantly loosens or falls off. 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 clonidine transdermal PATCH contains aluminum, it is recommended to remove the system before undergoing an MRI. How to Apply the
C
lonidine
T
ransdermal
PATCH
1) Apply the square to rectangular, tan clonidine transdermal 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 should be free of cuts, abrasions, irritation, scars or calluses and should not be shaved before applying the clonidine transdermal PATCH. Do not place the clonidine transdermal PATCH on skin folds or under tight undergarments, since premature loosening may occur. Each box of clonidine transdermal system contains two types of pouches: 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 blue, red or yellow colors labeled clonidine transdermal system and open it as illustrated in Figure 3. Remove the square to rectangular, tan PATCH from the pouch. Remove the translucent to clear secondary protective liner card that rests over the PATCH. 6) Remove the translucent to clear protective backing from the PATCH by gently peeling it off as shown in Figure 4.  Avoid prolonged touching of the sticky side of the clonidine transdermal PATCH.  7) Place the clonidine transdermal 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 translucent to clear protective backing and wash your hands with soap and water to remove any drug from your hands. 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 clonidine transdermal PATCH.  What to do if your clonidine transderm
al
PATCH
 
becomes loose while wearing:
How to Apply the
ADHESIVE COVER
 
Note: The white to slightly yellow, round to elliptical, ADHESIVE COVER does not contain any drug and should not be used alone. The COVER should be applied directly over the clonidine transdermal PATCH only if the PATCH begins to separate from the skin, thereby ensuring that it sticks to the skin for seven full days. 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 to rectangular, tan clonidine transdermal PATCH is clean and dry. Press gently on the clonidine transdermal PATCH to ensure that the edges are in good contact with the skin. 3) Take the white to slightly yellow, round to elliptical, ADHESIVE COVER (Figure 6) from the plain white pouch and remove the paper liner backing from the COVER. 4) Carefully center the round to elliptical, white to slightly yellow, ADHESIVE COVER over the square to rectangular, tan clonidine transdermal PATCH and apply firm pressure, especially around the edges in contact with the skin. STORAGE AND HANDLING Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. 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. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Manufactured by:
Actavis Laboratories Ut, Inc.
Salt Lake City, UT 84108 USA
Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA
Revised: October 2015

PRINCIPAL DISPLAY PANEL – 0.1 mg/day


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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 0591-3508-04 
Rx
Clonidine
Transdermal System, USP
0.1 mg/day

PRINCIPAL DISPLAY PANEL – 0.2 mg/day


id: 7bc95d2b-57a3-455b-a209-bf09550bd1ad
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 0591-3509-04 
Clonidine
Transdermal System, USP
0.2 mg/day

PRINCIPAL DISPLAY PANEL – 0.3 mg/day


id: d08cbe18-55a8-45db-ac6b-133f569eb545
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 0591-3510-04 
Clonidine
Transdermal System, USP
0.3 mg/day