Clonidine Transdermal System, (clonidine)

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Clonidine Transdermal System is a transdermal system (patch) 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%-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: e26a64e6-c839-446b-8547-483690eba889
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 transdermal system.

OVERDOSAGE

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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, semi-coma, 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

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Apply Clonidine Transdermal Systems 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 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 2-3 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.

HOW SUPPLIED

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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Clonidine Transdermal Systems 0.1 mg, Clonidine Transdermal Systems 0.2 mg, and Clonidine Transdermal Systems 0.3 mg are supplied as 4 pouched systems and 4 adhesive covers per carton.

STORAGE AND HANDLING

id: 72eb4155-5ac1-4647-ad49-14c4c799e6b6
displayName: STORAGE AND HANDLING SECTION
FDA Article Code: 44425-7

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature] Manufactured by:       AVEVA
                                     Drug Delivery Systems
                                     A Nitto Denko Company
                                     Miramar, FL 33025 Manufactured for:       PAR PHARMACEUTICAL COMPANIES, INC.

                                     Spring Valley, NY 10977 3001690
OS774-86-1-06
Rev. 11/08 Relabeling of additional barcode by:

Physicians Total Care, Inc.
Tulsa, OK      74146