Clonidine


Mayne Pharma Inc.
Human Prescription Drug
NDC 51862-455
Clonidine is a human prescription drug labeled by 'Mayne Pharma Inc.'. National Drug Code (NDC) number for Clonidine is 51862-455. This drug is available in dosage form of Patch, Extended Release. The names of the active, medicinal ingredients in Clonidine drug includes Clonidine - .3 mg/24h . The currest status of Clonidine drug is Active.

Drug Information:

Drug NDC: 51862-455
The labeler code and product code segments of the National Drug Code number, separated by a hyphen. Asterisks are no longer used or included within the product code segment to indicate certain configurations of the NDC.
Proprietary Name: Clonidine
Also known as the trade name. It is the name of the product chosen by the labeler.
Product Type: Human Prescription Drug
Indicates the type of product, such as Human Prescription Drug or Human OTC Drug. This data element corresponds to the “Document Type” of the SPL submission for the listing.
Non Proprietary Name: Clonidine
Also known as the generic name, this is usually the active ingredient(s) of the product.
Labeler Name: Mayne Pharma Inc.
Name of Company corresponding to the labeler code segment of the ProductNDC.
Dosage Form: Patch, Extended Release
The translation of the DosageForm Code submitted by the firm. There is no standard, but values may include terms like `tablet` or `solution for injection`.The complete list of codes and translations can be found www.fda.gov/edrls under Structured Product Labeling Resources.
Status: Active
FDA does not review and approve unfinished products. Therefore, all products in this file are considered unapproved.
Substance Name:CLONIDINE - .3 mg/24h
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.
Route Details:TRANSDERMAL
The translation of the Route Code submitted by the firm, indicating route of administration. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Marketing Information:

An openfda section: An annotation with additional product identifiers, such as NUII and UPC, of the drug product, if available.
Marketing Category: ANDA
Product types are broken down into several potential Marketing Categories, such as New Drug Application (NDA), Abbreviated New Drug Application (ANDA), BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.
Marketing Start Date: 03 Aug, 2016
This is the date that the labeler indicates was the start of its marketing of the drug product.
Marketing End Date: 22 Dec, 2025
This is the date the product will no longer be available on the market. If a product is no longer being manufactured, in most cases, the FDA recommends firms use the expiration date of the last lot produced as the EndMarketingDate, to reflect the potential for drug product to remain available after manufacturing has ceased. Products that are the subject of ongoing manufacturing will not ordinarily have any EndMarketingDate. Products with a value in the EndMarketingDate will be removed from the NDC Directory when the EndMarketingDate is reached.
Application Number: ANDA079090
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.
Listing Expiration Date: 31 Dec, 2023
This is the date when the listing record will expire if not updated or certified by the firm.

OpenFDA Information:

An openfda section: An annotation with additional product identifiers, such as NUII and UPC, of the drug product, if available.
Manufacturer Name:Mayne Pharma Inc.
Name of manufacturer or company that makes this drug product, corresponding to the labeler code segment of the NDC.
RxCUI:998671
998675
998679
The RxNorm Concept Unique Identifier. RxCUI is a unique number that describes a semantic concept about the drug product, including its ingredients, strength, and dose forms.
Original Packager:Yes
Whether or not the drug has been repackaged for distribution.
NUI:N0000009918
N0000175554
Unique identifier applied to a drug concept within the National Drug File Reference Terminology (NDF-RT).
UNII:MN3L5RMN02
Unique Ingredient Identifier, which is a non-proprietary, free, unique, unambiguous, non-semantic, alphanumeric identifier based on a substance’s molecular structure and/or descriptive information.
Pharmacologic Class MOA:Adrenergic alpha2-Agonists [MoA]
Mechanism of action of the drug—molecular, subcellular, or cellular functional activity—of the drug’s established pharmacologic class. Takes the form of the mechanism of action, followed by `[MoA]` (such as `Calcium Channel Antagonists [MoA]` or `Tumor Necrosis Factor Receptor Blocking Activity [MoA]`.
Pharmacologic Class EPC:Central alpha-2 Adrenergic Agonist [EPC]
Established pharmacologic class associated with an approved indication of an active moiety (generic drug) that the FDA has determined to be scientifically valid and clinically meaningful. Takes the form of the pharmacologic class, followed by `[EPC]` (such as `Thiazide Diuretic [EPC]` or `Tumor Necrosis Factor Blocker [EPC]`.
Pharmacologic Class:Adrenergic alpha2-Agonists [MoA]
Central alpha-2 Adrenergic Agonist [EPC]
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

Packaging Information:

Package NDCDescriptionMarketing Start DateMarketing End DateSample Available
51862-455-044 POUCH in 1 CARTON (51862-455-04) / 1 PATCH in 1 POUCH (51862-455-01) / 24 h in 1 PATCH03 Aug, 2016N/ANo
Package NDC number, known as the NDC, identifies the labeler, product, and trade package size. The first segment, the labeler code, is assigned by the FDA. Description tells the size and type of packaging in sentence form. Multilevel packages will have the descriptions concatenated together.

Product Elements:

Clonidine clonidine clonidine clonidine silicon dioxide light mineral oil polyisobutylene (1100000 mw) clonidine clonidine clonidine clonidine silicon dioxide light mineral oil polyisobutylene (1100000 mw) clonidine clonidine clonidine clonidine silicon dioxide light mineral oil polyisobutylene (1100000 mw)

Drug Interactions:

Drug interactions 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. if a patient receiving clonidine is also taking neuroleptics, orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue) may be induced or exacerbated. monitor heart rate 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. sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil. amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats (see toxicology ).

Indications and Usage:

Indications and usage clonidine transdermal system is indicated in the treatment of hypertension. it may be employed alone or concomitantly with other antihypertensive agents.

Warnings:

Warnings 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.

General Precautions:

General in patients who have developed localized contact sensitization to clonidine transdermal system, continuation of clonidine transdermal 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 clonidine transdermal system, substitution of oral clonidine hydrochloride may also elicit an allergic reaction (including generalized rash, urticaria, or angioedema). the sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular (av) block, especially in patients taking other sympatholytic drugs. there are postmarketing reports of patients with conduction abnormalities and/or taking other sympatholytic drugs who developed severe bradycardia requiring iv atropine, iv isoproterenol and temporary cardiac pacing while taking clonidine. in hypertension caused by pheochromocytoma, no therapeutic effect of clonidine transdermal system can be expected.
in rare instances, loss of blood pressure control has been reported in patients using clonidine transdermal system according to the instructions for use.

Dosage and Administration:

Dosage and administration 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. 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 or changing to a larger system. an increase in dosage above two clonidine transdermal system 0.3 mg is usually not associated with additional efficacy. when subst
ituting 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.

Contraindications:

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

Adverse Reactions:

Adverse reactions clinical trial experience with 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 multi-clinic 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 s
ensitization 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 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 oral clonidine 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 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.

Drug Interactions:

Drug interactions 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. if a patient receiving clonidine is also taking neuroleptics, orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue) may be induced or exacerbated. monitor heart rate 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. sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil. amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats (see toxicology ).

Use in Pregnancy:

Pregnancy teratogenic effects reproduction studies performed in rabbits at doses up to approximately 3 times the oral maximum recommended daily human dose (mrdhd) of 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/m 2 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 to 15. increases in resorption were observed at much higher dose levels (40 times the oral mrdhd on a mg/kg basis; 4 to 8 times the mrdhd on a mg/m 2 basis) in mice and rats treated on gestation days 1 to 14 (lowest dose employed in the study was 500 mcg/kg). no adequate well-controlled studies have been conducted in pregnant women. cl
onidine crosses the placental barrier (see clinical pharmacology, pharmacokinetics ). because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Pediatric Use:

Pediatric use safety and effectiveness in pediatric patients have not been established in adequate and well-controlled trials.

Overdosage:

Overdosage 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 ld 50 of clonidine is 206 and 465 mg/kg, respectively.

Description:

Description clonidine transdermal system usp provides continuous systemic delivery of clonidine usp for 7 days at an approximately constant rate. clonidine usp 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: c 9 h 9 cl 2 n 3 m.w. 230.10 chemical structure system structure and components clonidine transdermal system usp is a multi-layered film, 0.2 mm thick, containing clonidine usp as the active agent. the system areas are 4.33 cm 2 (clonidine usp 0.1 mg per day), 8.67 cm 2 (clonidine usp 0.2 mg per day) and 13 cm 2 (clonidine usp 0.3 mg per day) 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. the inactive ingredients are: aluminum, colloidal silicon dioxide, ethylene vinyl acetate copolymer, light mineral oil, microporous polypropylene membrane, pigmented polyethylene polyester film, polyisobutylene and silicon coated polyester film. proceeding from the visible surface towards the surface attached to the skin, there are four consecutive layers: 1) a backing layer of polyester film; 2) a drug reservoir; 3) a microporous polypropylene membrane that controls the rate of delivery of clonidine usp from the system to the skin surface; 4) an adhesive formulation. prior to use, a protective slit release liner of silicone coated polyester film that covers the adhesive layer is removed. cross section of the system: figure release rate concept clonidine transdermal system usp is programmed to release clonidine usp 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 usp 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 usp in the adhesive layer saturates the skin site below the system. clonidine usp 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 usp levels are achieved 2 to 3 days after initial application of clonidine transdermal system usp. the 4.33, 8.67 and 13 cm 2 systems deliver 0.1, 0.2, and 0.3 mg of clonidine usp 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 usp. if the clonidine transdermal system usp is removed and not replaced with a new system, therapeutic plasma clonidine usp 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.

Clinical Pharmacology:

Clinical pharmacology 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 ex
ercise. 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 clonidine transdermal system delivers clonidine at an approximately constant rate for 7 days. the absolute bioavailability of clonidine from the clonidine transdermal system dosage form is approximately 60%. steady-state clonidine plasma levels are obtained within 3 days after transdermal application to the upper outer arm and increase linearly with increasing size of the transdermal patch. mean steady-state plasma concentrations with the 4.33 cm 2 , 8.67 cm 2 and 13 cm 2 systems are approximately 0.4 ng/ml, 0.8 ng/ml, and 1.1 ng/ml, respectively. similar clonidine steady-state concentrations are reached after application to the chest. steady-state clonidine plasma levels remain constant after removal of one system and application of a new system of the same size. following intravenous administration, clonidine displays biphasic disposition with a distribution half-life of about 20 minutes and an elimination half-life ranging from 12 to 16 hours. the half-life increases up to 41 hours in patients with severe impairment of renal function. clonidine has a total clearance of 177 ml/min and a renal clearance of 102 ml/min. the apparent volume of distribution (v z ) of clonidine is 197 l (2.9 l/kg). clonidine crosses the placental barrier. it has been shown to cross the blood brain barrier in rats. following oral administration, about 40% to 60% of the absorbed dose is recovered in the urine as unchanged drug within 24 hours. about 50% of the absorbed dose is metabolized in the liver. after removal of the clonidine transdermal system, clonidine plasma concentrations decline slowly with a half-life of approximately 20 hours.

Pharmacokinetics:

Pharmacokinetics clonidine transdermal system delivers clonidine at an approximately constant rate for 7 days. the absolute bioavailability of clonidine from the clonidine transdermal system dosage form is approximately 60%. steady-state clonidine plasma levels are obtained within 3 days after transdermal application to the upper outer arm and increase linearly with increasing size of the transdermal patch. mean steady-state plasma concentrations with the 4.33 cm 2 , 8.67 cm 2 and 13 cm 2 systems are approximately 0.4 ng/ml, 0.8 ng/ml, and 1.1 ng/ml, respectively. similar clonidine steady-state concentrations are reached after application to the chest. steady-state clonidine plasma levels remain constant after removal of one system and application of a new system of the same size. following intravenous administration, clonidine displays biphasic disposition with a distribution half-life of about 20 minutes and an elimination half-life ranging from 12 to 16 hours. the half-life increase
s up to 41 hours in patients with severe impairment of renal function. clonidine has a total clearance of 177 ml/min and a renal clearance of 102 ml/min. the apparent volume of distribution (v z ) of clonidine is 197 l (2.9 l/kg). clonidine crosses the placental barrier. it has been shown to cross the blood brain barrier in rats. following oral administration, about 40% to 60% of the absorbed dose is recovered in the urine as unchanged drug within 24 hours. about 50% of the absorbed dose is metabolized in the liver. after removal of the clonidine transdermal system, clonidine plasma concentrations decline slowly with a half-life of approximately 20 hours.

Carcinogenesis and Mutagenesis and Impairment of Fertility:

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/m 2 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/m 2 basis).

How Supplied:

How supplied clonidine transdermal system usp 0.1 mg/day, 0.2 mg/day or 0.3 mg/day are available as 4 pouched systems and 4 adhesive covers per carton. each system is a round corner, rectangular flexible transdermal system with a tan matte backing and clear membrane. *programmed delivery - clonidine in vivo per day over 1 week debossed total clonidine content size ndc (for 4 systems) clonidine transdermal system 0.1 mg/day 0.1 mg 453 clonidine 0.1 mg/day 3.09 mg 4.33 cm 2 ndc 51862-453-04 clonidine transdermal system 0.2 mg/day 0.2 mg 454 clonidine 0.2 mg/day 6.19 mg 8.67 cm 2 ndc 51862-454-04 clonidine transdermal system 0.3 mg/day 0.3 mg 455 clonidine 0.3 mg/day 9.28 mg 13 cm 2 ndc 51862-455-04 storage and handling store at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. keep this and all medications out of the reach of children.

Information for Patients:

Information for patients patients should be cautioned against interruption of clonidine transdermal system therapy without their physician's advice. since patients may experience a possible sedative effect, dizziness, or accommodation disorder with use of clonidine, caution patients about engaging in activities such as driving a vehicle or operating appliances or machinery. also, inform patients that this sedative effect may be increased by concomitant use of alcohol, barbiturates, or other sedating drugs. patients who wear contact lenses should be cautioned that treatment with clonidine transdermal system may cause dryness of eyes. 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 clonidine transdermal system 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 clonidine transdermal system patches out of the reach of children. after use, clonidine transdermal system 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 brochure. these instructions are also included in each box of clonidine transdermal system.

Package Label Principal Display Panel:

Principal display panel - 0.1 mg patch pouch carton ndc 51862-453-04 clonidine transdermal system usp 0.1 mg/day programmed in vivo delivery of 0.1 mg per day for one week. to avoid possible burns, remove the clonidine transdermal system patch before undergoing an mri (magnetic resonance imaging) procedure. rx only 4 systems and 4 adhesive covers mayne pharma principal display panel - 0.1 mg patch pouch carton

Principal display panel - 0.2 mg patch pouch carton ndc 51862-454-04 clonidine transdermal system usp 0.2 mg/day programmed in vivo delivery of 0.2 mg per day for one week. to avoid possible burns, remove the clonidine transdermal system patch before undergoing an mri (magnetic resonance imaging) procedure. rx only 4 systems and 4 adhesive covers mayne pharma principal display panel - 0.2 mg patch pouch carton

Principal display panel - 0.3 mg patch pouch carton ndc 51862-455-04 clonidine transdermal system usp 0.3 mg/day programmed in vivo delivery of 0.3 mg per day for one week. to avoid possible burns, remove the clonidine transdermal system patch before undergoing an mri (magnetic resonance imaging) procedure. rx only 4 systems and 4 adhesive covers mayne pharma principal display panel - 0.3 mg patch pouch carton


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