CLONIDINE HYDROCHLORIDE

Main information

  • Trade name:
  • CLONIDINE HYDROCHLORIDE- clonidine hydrochloride tablet
  • Composition:
  • CLONIDINE HYDROCHLORIDE 0.3 mg
  • Administration route:
  • ORAL
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLONIDINE HYDROCHLORIDE- clonidine hydrochloride tablet
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • Clonidine hydrochloride tablets, USP 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 ).
  • Product summary:
  • 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 0228-2127-10) and 500 (NDC 0228-2127-50). 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 0228-2128-10) and 500 (NDC 0228-2128-50). 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 0228-2129-10). Dispense in a tight, light-resistant container as defined in the USP. Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Manufactured by: Actavis Elizabeth LLC Elizabeth, NJ 07207 USA Distributed by: Actavis Pharma, Inc. Parsippany, NJ 07054 USA 40-9183 Revised — October 2015

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 43353-316-09
  • Last update:
  • 15-06-2019

Summary of Product characteristics: dosage, interactions, side effects

CLONIDINE HYDROCHLORIDE- clonidine hydrochloride tablet

Aphena Pharma Solutions - Tennessee, LLC

----------

CLONIDINE HYDROCHLORIDE TABLETS, USP

40-9183

Revised — October 2015

Rx only

DESCRIPTION

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.

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. 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.

Pharmacokinetics: The pharmacokinetics of clonidine is dose-proportional in the range of 100 to 600

mcg. The absolute bioavailability of clonidine on oral administration is 70% to 80%. Peak plasma

clonidine levels are attained in approximately 1 to 3 hours.

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 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 in 24 hours. About 50% of the absorbed dose is metabolized in the liver. Neither food

nor the race of the patient influences the pharmacokinetics of clonidine.

The antihypertensive effect is reached at plasma concentrations between about 0.2 and 2 ng/mL in

patients with normal excretory function. A further rise in the plasma levels will not enhance the

antihypertensive effect.

INDICATIONS AND USAGE

Clonidine hydrochloride tablets, USP are indicated in the treatment of hypertension. Clonidine

hydrochloride tablets may be employed alone or concomitantly with other antihypertensive agents.

CONTRAINDICATIONS

Clonidine hydrochloride tablets should not be used in patients with known hypersensitivity to clonidine

(see PRECAUTIONS).

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, and tremor 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 hydrochloride tablets, 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 hydrochloride tablets

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 hydrochloride tablets.

Because children commonly have gastrointestinal illnesses that lead to vomiting, they may be

particularly susceptible to hypertensive episodes resulting from abrupt inability to take

medication.

PRECAUTIONS

General: In patients who have developed localized contact sensitization to transdermal clonidine,

continuation of transdermal clonidine or substitution of oral clonidine hydrochloride therapy may be

associated with the development of a generalized skin rash.

In patients who develop an allergic reaction to transdermal clonidine, 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 post-marketing 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 hydrochloride tablets

can be expected.

Perioperative Use: Administration of clonidine hydrochloride tablets should be continued to within 4

hours of surgery and resumed as soon as possible thereafter. Blood pressure should be carefully

monitored during surgery and additional measures to control blood pressure should be available if

required.

Information for Patients: Patients should be cautioned against interruption of clonidine hydrochloride

tablets 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 hydrochloride tablets

may cause dryness of eyes.

Drug Interactions: Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or

other sedating drugs. If a patient receiving clonidine hydrochloride 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

T oxicology).

Based on observations in patients in a state of alcoholic delirium it has been suggested that high

intravenous doses of clonidine may increase the arrhythmogenic potential (QT-prolongation, ventricular

fibrillation) of high intravenous doses of haloperidol. Causal relationship and relevance for clonidine

oral tablets have not been established.

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.

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 or 70

times the maximum recommended daily human dose as mg/kg (9 or 6 times the MRDHD on a mg/m

basis). There was no evidence of genotoxicity in the Ames test for mutagenicity or mouse micronucleus

test for clastogenicity.

Fertility of male or female rats was unaffected by clonidine doses as high as 150 mcg/kg (approximately

3 times 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 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 clonidine hydrochloride tablets 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 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 time 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

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. Clonidine 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.

Nursing Mothers: As clonidine hydrochloride is excreted in human milk, caution should be exercised

when clonidine hydrochloride tablets are administered to a nursing woman.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established in adequate and

well-controlled trials (see WARNINGS, Withdrawal).

ADVERSE REACTIONS

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 Actavis at 1-800-432-8534 or FDA at 1-

800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

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.

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 of

clonidine is 206 and 465 mg/kg, respectively.

DOSAGE AND ADMINISTRATION

Adults: The dose of clonidine hydrochloride tablets, USP 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 Actavis at 1-800-432-8534.

HOW SUPPLIED

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 0228-2127-10)

and 500 (NDC 0228-2127-50).

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 0228-2128-10)

and 500 (NDC 0228-2128-50).

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 0228-2129-

10).

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

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room

Temperature].

Manufactured by:

Actavis Elizabeth LLC

Elizabeth, NJ 07207 USA

Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA

40-9183

Revised — October 2015

Repackaging Information

Please reference the How Supplied section listed above for a description of individual tablets. This

drug product has been received by Aphena Pharma - TN in a manufacturer or distributor packaged

configuration and repackaged in full compliance with all applicable cGMP regulations. The package

configurations available from Aphena are listed below:

Count

0.3 mg

9000

43353-316-09

Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-

resistant container as defined by USP. Keep this and all drugs out of the reach of children.

Repackaged by:

Cookeville, TN 38506

20171024DKJ

PRINCIPAL DISPLAY PANEL - 0.3mg

NDC 43353-316 Clonidine HCL 0.3mg - Rx Only

CLONIDINE HYDROCHLORIDE

clonidine hydrochloride tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:43353-316 (NDC:0 228 -2129 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

CLO NIDINE HYDRO CHLO RIDE (UNII: W76 I6 XXF0 6 ) (CLONIDINE -

UNII:MN3L5RMN0 2)

CLONIDINE

HYDROCHLORIDE

0 .3 mg

Inactive Ingredients

Aphena Pharma Solutions - Tennessee, LLC

Inactive Ingredients

Ingredient Name

Stre ng th

STARCH, CO RN (UNII: O8 232NY3SJ)

D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)

Product Characteristics

Color

ORANGE

S core

2 pieces

S hap e

ROUND

S iz e

9 mm

Flavor

Imprint Code

R129

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:43353-316 -0 9

9 0 0 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/0 3/20 17

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 70 9 76

0 1/0 3/19 9 5

Labeler -

Aphena Pharma Solutions - T ennessee, LLC (128385585)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Aphena Pharma So lutio ns - Tennessee, LLC

128 38 558 5

REPACK(43353-316 )

Revised: 5/2017