Label: CLONIDINE HYDROCHLORIDE tablet

Rx only

Clonidine hydrochloride, USP is a centrally acting alpha-agonist hypotensive agent available as tablets for oral administration in three dosage strengths: 0.1 mg, 0.2 mg, and 0.3 mg. The 0.1 mg tablet is equivalent to 0.087 mg of the free base.

The following inactive ingredients are contained in these products: corn starch, D&C Yellow #10 Aluminum Lake, FD&C Yellow #6 Aluminum Lake (Sunset Yellow Lake), lactose monohydrate, magnesium stearate, and sodium starch glycolate.

Clonidine hydrochloride, USP is an imidazoline derivative and exists as a mesomeric compound. The chemical name is 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride. The following is the structural formula:

Clonidine hydrochloride, USP is an odorless, bitter, white, crystalline substance soluble in water and alcohol.

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. Clonidine hydrochloride tablets act relatively rapidly. The patient’s blood pressure declines within 30 to 60 minutes after an oral dose, the maximum decrease occurring within 2 to 4 hours. 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 degree 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 response 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 growth hormone release in both children and adults, but does not produce a chronic elevation of growth hormone with long-term use.

Clonidine hydrochloride tablets are indicated in the treatment of hypertension. Clonidine hydrochloride tablets may be employed alone or concomitantly with other antihypertensive agents.

Clonidine hydrochloride tablets should not be used in patients with known hypersensitivity to clonidine (see PRECAUTIONS).

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 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 atrioventricular 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 eyes.

To report SUSPECTED ADVERSE EVENTS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

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.

There is no specific antidote for clonidine overdosage. Clonidine overdosage may result in the rapid development of CNS depression; therefore, induction of vomiting with ipecac syrup is not recommended. Gastric lavage may be indicated following recent and/or large ingestions. Administration of activated charcoal and/or a 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 50of clonidine is 206 and 465 mg/kg, respectively.

Adults:The dose of clonidine hydrochloride tablets must be adjusted according to the patient’s individual blood pressure response. The following is a general guide to its administration.

Initial Dose:0.1 mg tablet twice daily (morning and bedtime). Elderly patients may benefit from a lower initial dose.

Maintenance Dose:Further increments of 0.1 mg per day may be made at weekly intervals if necessary until the desired response is achieved. Taking the larger portion of the oral daily dose at bedtime may minimize transient adjustment effects of dry mouth and drowsiness. The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day given in divided doses.

Studies have indicated that 2.4 mg is the maximum effective daily dose, but doses as high as this have rarely been employed.

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.

For questions regarding this product, call Teva at 1-888-838-2872.

Clonidine hydrochloride tablets, USP are supplied as follows:

0.1 mg — Each orange, round tablet imprinted with and 127 on one side and bisect on the other side contains 0.1 mg of clonidine hydrochloride, USP and is supplied in bottles of 100 (NDC 68001-237-00) and 500 (NDC 68001-237-03).

0.2 mg — Each orange, round tablet imprinted with on one side and 128 and bisect on the other side contains 0.2 mg of clonidine hydrochloride, USP and is supplied in bottles of 100 (NDC 68001-238-00) and 500 (NDC 68001-238-03).

0.3 mg — Each orange, round tablet imprinted with on one side and 129 and bisect on the other side contains 0.3 mg of clonidine hydrochloride, USP and is supplied in bottles of 100 (NDC 68001-239-00).

Dispense in a tight, light-resistant container as defined in the USP.

Store at 25°C (77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature].

Manufactured In Croatia By:

Pliva Hrvatska d.o.o.

Zagreb, Croatia

For BluePoint Laboratories

Rev. A 9/2022