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Clonidine (Systemic)


VA CLASSIFICATION
Oral
Primary: CV409
Secondary: DX900; CN105; CN900

Transdermal
Primary: CV409


Commonly used brand name(s): Catapres; Catapres-TTS-1; Catapres-TTS-2; Catapres-TTS-3; Dixarit.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antihypertensive—Clonidine Hydrochloride Tablets; Clonidine Transdermal Systems;

Menopausal syndrome therapy adjunct—Clonidine Hydrochloride Tablets;

Vascular headache prophylactic—Clonidine Hydrochloride Tablets;

Antidysmenorrheal—Clonidine Hydrochloride Tablets;

Opioid withdrawal syndrome suppressant—Clonidine Hydrochloride Tablets;

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Hypertension (treatment)—Oral and transdermal dosage forms of clonidine are indicated in the treatment of hypertension . {01} {86} {87} {88} It may be used alone or concomitantly with other antihypertensive agents. {86} {88} Because it causes only mild postural hypotension, clonidine may be useful as a substitute for guanethidine or other adrenergic blockers in patients who cannot tolerate these agents because of severe orthostatic hypotension.
—[Oral clonidine is also used in the urgent treatment of hypertensive emergencies {15} {17} .]1
—For additional information on initial therapeutic guidelines related to the treatment of hypertension, see Appendix III.

[Pheochromocytoma (diagnosis)]1—A clonidine suppression test is used in the diagnosis of pheochromocytoma. {42} {43}

[Headache, vascular (prophylaxis) ]1—Clonidine has been used orally in the prevention of migraine. {30} {47}

[Dysmenorrhea (treatment)]1 or
[Menopause, vasomotor symptoms of (treatment)]—Clonidine is used orally as an adjunct in the treatment of dysmenorrhea and menopausal flushing. {03} {35} {36} {37} {38} {39} {41}

[Opioid (narcotic) abstinence syndrome (treatment)]1—Clonidine is used to control symptoms and aid in {15} rapid detoxification in the treatment of opioid withdrawal. {48} {49} {73} {74} {75} {76} {77}

[Nicotine dependence (treatment adjunct) ]1—Clonidine is used as an adjunct in the treatment of nicotine withdrawal. {26} {34} {44} {45}

[Gilles de la Tourette"s syndrome (treatment)]1—Clonidine is used in the treatment of Gilles de la Tourette"s syndrome. {40} {78} {79} {80}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Clonidine: 230.1 {46}
    Clonidine hydrochloride: 266.56 {46}

Mechanism of action/Effect:

Alpha-adrenergic agonist; also has some alpha-adrenergic antagonist effects.


Antihypertensive:

Thought to be due to central alpha 2-adrenergic {15} {19} {31} stimulation, which results in a decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature; this results in decreased peripheral vascular resistance, decreased systolic and diastolic blood pressure, and decreased heart rate.



Vascular headache prophylactic:

May block central vasomotor reflexes.



Dysmenorrhea therapy adjunct; or menopausal syndrome therapy adjunct:

Unknown, although may act as peripheral vascular stabilizer to reduce menopausal flushing.



Opioid withdrawal syndrome suppressant:

May be result of alpha-adrenergic inhibiting activity in areas of the brain such as the locus ceruleus.



Other actions/effects:

Stimulates the release of growth hormone acutely, but not chronically {31}.

Absorption:

Oral—Well absorbed following oral administration. {16} Bioavailability following chronic administration is approximately 65%. {51}

Transdermal—Greatest from the chest and upper arm, and least from the thigh. Absorbed through the skin at a constant rate {01} {04} {05} {06} {11}.

Protein binding:

Low to moderate (20 to 40%) {16} {23}.

Biotransformation:

Hepatic (about 50% of the absorbed dose) {16} {31}.

Half-life:

Normal renal function—Range, 12 to 16 hours {31} {33} {50} {51}.

Renal function impairment—Up to 41 hours {16} {31}.

Onset of action

Antihypertensive—

Oral—30 to 60 minutes. {16}

Transdermal—2 to 3 days. {01}

Time to peak plasma concentration

Oral—3 to 5 hours. {86} {87}

Transdermal—2 to 3 days. {01} {11}

Time for peak effect

Antihypertensive—Oral: 2 to 4 hours. {86} {87}

Duration of action:

Antihypertensive—


Oral:

Up to 8 hours (24 to 36 hours in some patients).



Transdermal:

About 7 days with the system in place; about 8 hours after removal. {01} {06}


Elimination:
    Renal—40 to 60% (as unchanged drug) in 24 hours {16} {31}.
    Biliary/fecal—20% (probably via enterohepatic circulation).
    In dialysis—Very little (maximum 5%) removable by hemodialysis. {01}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to ophthalmic apraclonidine may be sensitive to clonidine. {02}

Patients sensitive to topical clonidine transdermal system may also be sensitive to oral clonidine hydrochloride. {86} {87} {88}

Carcinogenicity

Studies in rats at doses 32 to 46 times the maximum recommended human dose for 132 weeks found no evidence of carcinogenicity. {31}

Pregnancy/Reproduction
Fertility—
Studies in male and female rats at doses up to three times the maximum recommended human dose found no impairment of fertility. However, fertility was affected in female rats given 10 to 40 times the maximum recommended human dose {31}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

Studies in rats at doses as low as one-third the maximum recommended human dose given for 2 months prior to mating found an increased incidence of resorptions; this effect did not occur at doses of one-third to three times the maximum recommended human dose given on days 6 to 15 of gestation. {33} Increased resorptions also occurred in rats and mice given doses up to 40 times the maximum recommended human dose on days 1 to 14 of gestation. {33} No teratogenicity or embryotoxicity was observed in rabbits given up to three times the maximum recommended human dose. {31} {33}

FDA Pregnancy Category C.

Breast-feeding

Clonidine is distributed into breast milk. {31} However, problems in humans have not been documented. Caution is recommended if clonidine is used in nursing mothers.

Pediatrics

Appropriate studies on the relationship of age to the effects of clonidine have not been performed in the pediatric population. However, there are numerous reports describing accidental clonidine overdose in the pediatric population. {52} {53} {54} {55} {56} {57} {58} {59} {60} {61} {62} These reports seem to indicate that neonates, infants, and children are especially sensitive to the effects of clonidine. Caution is recommended.


Geriatrics


The elderly may be more sensitive than younger adults to clonidine's hypotensive effects. {63} In addition, elderly patients are more likely to have age-related renal function impairment, which may require reduction of dosage in patients receiving clonidine.


Dental

Use of clonidine may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Alcohol or
Central nervous system (CNS) depression-producing medications (see Appendix II) {33}    (concurrent use may enhance the CNS-depressant effects of either these medications or clonidine)


» Antidepressants, tricyclic, {33} or
Appetite suppressants, with the exception of fenfluramine    (concurrent use may decrease the hypotensive effects of clonidine)


Anti-inflammatory drugs, nonsteroidal (NSAIDs), especially indomethacin {64} {65} {66}    (NSAIDs may reduce the antihypertensive effects of clonidine, possibly by inhibiting renal prostaglandin synthesis and/or causing sodium and fluid retention; the patient should be monitored carefully to confirm that the desired effect is being obtained)


» Beta-adrenergic blocking agents, systemic    (discontinuation of clonidine therapy during concurrent use of beta-adrenergic blocking agents may increase the risk of clonidine-withdrawal hypertensive crisis; ideally, beta-adrenergic blocking agents should be discontinued several days {18} {19} before clonidine is discontinued; blood pressure control may also be impaired when the two are combined)


Fenfluramine    (concurrent use may increase the hypotensive effects of clonidine)


Hypotension-producing medications, other (see Appendix II ), with the exception of systemic beta-adrenergic blocking agents and tricyclic antidepressants    (concurrent use may potentiate antihypertensive effects; although some antihypertensive and/or diuretic combinations are frequently used for therapeutic advantage, dosage adjustments may be necessary during concurrent use)


Sympathomimetic agents    (concurrent use may reduce the antihypertensive effects of clonidine; the patient should be carefully monitored to confirm that the desired effect is being obtained)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Catecholamine concentrations, urinary {33} , and
Vanillylmandelic acid (VMA) excretion, urinary    (may be decreased, but may increase on abrupt withdrawal)


Direct antiglobulin (Coombs') tests {33}    (may produce weakly positive results)


Growth hormone concentrations, plasma    (may be increased transiently because of stimulation of growth hormone release, but are not elevated chronically with long-term use of clonidine {31})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Atrioventricular (AV) node function impairment    (vagal effect of clonidine may exacerbate condition)


Cerebrovascular disease or
Coronary insufficiency or
Myocardial infarction, recent {33}    (lowered blood pressure may decrease perfusion and worsen ischemia)


Mental depression, history of or
Raynaud's syndrome {33}    (may be exacerbated by clonidine)


Renal function impairment, chronic    (reduces the elimination of clonidine and may increase the risk of toxicity; dosage reduction may be necessary)


Sensitivity to clonidine
Sinus node function impairment    (function may be further impaired)


Thromboangiitis obliterans
For transdermal dosage form only (in addition to above):
Polyarteritis nodosa or
Scleroderma or
Systemic lupus erythematosus (SLE)    (absorption may be decreased; placement of patches on affected areas should be avoided {25})


Skin irritation or abrasion    (absorption may be increased; placement of patches on irritated or abraded areas should be avoided)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Blood pressure measurements    (recommended at periodic intervals in patients being treated for hypertension; selected patients may be taught to monitor their blood pressure at home and report the results at regular physician visits)




Side/Adverse Effects

Note: Incidence and severity of adverse systemic effects may be reduced with the transdermal dosage form {01} {04} {05} {07} {08} {09}, possibly because this form of administration maintains lower peak blood concentrations than occur with oral administration and decreases fluctuation in blood concentration {01} {07} {09} {12}.
Administration of clonidine for 6 months or longer to albino rats has resulted in a dose-related increase in the incidence and severity of spontaneously occurring retinal degeneration. These effects have not been observed in humans. {13}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
—about 15 to 20%, with transdermal systems only    
Itching or redness of skin{01}{05}{06}{07}{08}{12}

Note: Patients who develop either a localized or an extended allergic reaction to the transdermal system may also experience a generalized allergic skin rash if oral clonidine is substituted. {01}


Incidence less frequent
    
Mental depression
    
sodium and water retention or edema (swelling of feet and lower legs)

Incidence rare
    
Raynaud's phenomenon (paleness or cold feeling in fingertips and toes)
    
vivid dreams or nightmares



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Constipation{86} —about 10%{31}
    
dizziness{86} —about 16% with oral use{31}
    
drowsiness{86} —about 33% with oral use{31}
    
dryness of mouth{86} —about 40% with oral use
    
unusual tiredness or weakness{86} —about 10%{31}

Incidence less frequent
—1 to 5%{01}    
Anorexia (loss of appetite)
    
darkening of skin —with transdermal systems only{01}{05}{10}
    
decreased sexual ability
    
dry, itching, or burning eyes{13}
    
orthostatic hypotension (dizziness, lightheadedness, or fainting, especially when getting up from a lying or sitting position)
    
nausea or vomiting
    
nervousness{31}



Those indicating possible rebound hypertension and need for medical attention if they occur after medication is abruptly discontinued
    
Angina (chest pain)
    
anxiety or tenseness
    
headache
    
increased salivation
    
nausea
    
nervousness
    
palpitations (pounding heartbeat)
    
restlessness
    
shaking or trembling of hands and fingers
    
stomach cramps
    
sweating
    
tachycardia (fast heartbeat)
    
trouble in sleeping
    
vomiting

Note: Rebound hypertension may occur but is symptomatic in only 5 to 20% of patients. It is more likely to occur after abrupt withdrawal of clonidine in patients who had been receiving doses exceeding 1.2 mg per day or if clonidine therapy is discontinued before or at the same time as concurrent beta-adrenergic blocking agent therapy.





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose {52} {53} {54} {55} {56} {57} {58} {59} {60} {61} {62} {72}
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Apnea or respiratory depression (difficulty in breathing)

bradycardia (slow heartbeat)

hypotension (dizziness or faintness)

hypothermia (feeling cold)

lethargy (unusual tiredness or weakness, extreme)

miosis (pinpoint pupils of eyes)

Note: Overdose may result in hypertension, especially in pediatric patients. {53} {54} {55}
Toxicity may occur with ingestion of 100 mcg (0.1 mg) in children {16} {53} {54}.


Treatment of overdose


Specific treatment:
Recommended treatment for clonidine overdose is usually symptomatic and supportive and may include use of intravenous fluids.

For significant bradycardia: Atropine. {33} {54} {57} {59} {71}

For hypotension: Dopamine infusion {31}.

For hypertension: Intravenous furosemide, diazoxide, phentolamine, {33} or nitroprusside {54} {31}.

Tolazoline infusion if necessary. {57} {58}



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Clonidine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to clonidine or to ophthalmic apraclonidine

Pregnancy—Increased resorptions in rats and mice





Breast-feeding—Distributed into human breast milk





Use in children—Caution recommended in children because accidental overdoses have been reported






Use in the elderly—Hypotensive effects may be more likely
Other medications, especially tricyclic antidepressants or beta-adrenergic blocking agents

Proper use of this medication
Proper administration of the transdermal dosage form:

» Compliance with therapy; reading patient instructions carefully

Not trimming or cutting patch {01} {02}

Applying to clean, dry skin area on upper arm or torso; area should be free of hair, scars, cuts, or irritation {01} {02}

Should remain in place even during showering, bathing, or swimming {01} {02} {08}; applying adhesive overlay to loose systems; replacing systems that have loosened excessively or fallen off {01}

Alternating application sites {01}

Folding used patches in half with adhesive sides together; disposing of patch carefully, out of reach of children {25}

Taking or applying medication at the same time(s) each day or week to maintain the therapeutic effect

» Proper dosing
Missed dose: Taking or using as soon as possible; checking with physician if miss two or more oral doses in a row or if are late in changing the transdermal system by 3 or more days {11}; possible {19} severe reaction if stopped abruptly

» Proper storage

For use as an antihypertensive
Possible need for control of weight and diet, especially sodium intake

» Patient may not experience symptoms of hypertension; importance of taking medication even if feeling well

» Does not cure, but helps control hypertension; possible need for lifelong therapy; serious consequences of untreated hypertension

Precautions while using this medication
Regular visits to physician to check progress

» Checking with physician before discontinuing medication; gradual dosage reduction may be necessary to avoid serious rebound hypertension

» Having enough medication on hand to get through weekends, holidays, and vacations; possibly carrying second prescription for emergency use

» Caution in taking alcohol or other CNS depressants

» Caution when driving or doing things requiring alertness, because of possible drowsiness

» Caution if any kind of surgery or emergency treatment is required

Caution when getting up suddenly from a lying or sitting position

Caution in using alcohol, while standing for long periods or exercising, and during hot weather, because of enhanced orthostatic hypotensive effects

Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks

For use as an antihypertensive
» Not taking other medications, especially nonprescription sympathomimetic agents, unless discussed with physician


Side/adverse effects
Signs of potential side effects, especially itching or redness of skin (transdermal), mental depression, sodium and water retention, edema, Raynaud"s phenomenon, vivid dreams or nightmares, and withdrawal reaction


General Dosing Information
With continued use, apparent tolerance to the antihypertensive effects of clonidine may develop as a result of fluid retention and expanded plasma volume {31}. Concurrent administration of a diuretic may decrease this likelihood and will enhance the antihypertensive effects of clonidine. Other antihypertensives have also been used concurrently with clonidine. If combination therapy is indicated, individual titration is required to ensure the lowest possible therapeutic dose of each drug.

The abrupt interruption of clonidine therapy, including several consecutive missed doses, may result in rebound hypertension, which may be severe (acute post-treatment syndrome), or, in rare cases, overshoot hypertension, occurring within 12 to 48 hours of discontinuing therapy and lasting several days. Some patients may experience associated symptoms such as nervousness, agitation, and headache. At cessation of therapy, dosage should be gradually reduced (in the case of the transdermal system, by reducing patch strength and, if necessary, administering oral clonidine {25}) over a 2- to 4-day {32} period. Alternative therapy should be considered for unreliable or noncompliant patients. An excessive rise in blood pressure may be treated by resumption of oral clonidine therapy or by intravenous administration of diazoxide or an alpha-adrenergic blocking agent.

It is recommended that this medication be discontinued if mental depression occurs.

For oral dosage form only
It is recommended that the last daily dose be taken at bedtime to ensure overnight control of blood pressure and reduce daytime drowsiness.

If clonidine therapy must be interrupted for surgery, it is recommended that the last dose be given no later than 4 to 6 hours prior to surgery, that parenteral hypotensive medication be administered throughout the procedure, and that clonidine therapy be reinstituted as soon as possible afterwards.

Clonidine has been used investigationally for rapid detoxification in the treatment of opioid withdrawal. One protocol used consists of a test dose of 5 to 6 mcg (0.005 to 0.006 mg) of clonidine hydrochloride per kg of body weight on the first day. Patients showing a positive response then receive 17 mcg (0.017 mg) of clonidine hydrochloride per kg of body weight in divided daily doses for 9 or 10 days (adjusted to avoid hypotension and oversedation), followed by a reduction to 50% of the dose on Days 11, 12, and 13, and no medication on Day 14. Dosage must be individualized according to each patient's tolerance.

For transdermal dosage form only
Because the onset of action of transdermal clonidine is 2 to 3 days, when a patient is being switched from oral to transdermal therapy, the dose of oral clonidine should be gradually reduced over 2 to 3 days after transdermal therapy is begun, to avoid a withdrawal reaction {27}.

Application should preferably be made at the same time of day each week to areas of clean, dry, hairless skin on the upper arm or torso. Skin areas with extensive scarring, calluses, or irritation should be avoided. {70} Application sites should be alternated to avoid causing skin irritation. {01}

The transdermal units should not be cut or trimmed in an attempt to adjust dosage. {01}

If the transdermal system begins to loosen, the adhesive overlay provided by the manufacturer should be applied over the unit to hold it in place. A new dosage unit should be applied if the first becomes overly loosened or falls off. {01}

If local skin irritation occurs before the system has been in place for 7 days, the system may be removed and a new one placed on a different site {01} {07}. If contact sensitization persists, withdrawal of transdermal therapy may be necessary {25}.


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

CLONIDINE HYDROCHLORIDE TABLETS USP

Usual adult dose
Antihypertensive
Initial: Oral, 100 mcg (0.1 mg) two times a day, {33} the dosage being increased by 100 mcg (0.1 mg) per day at weekly intervals if necessary for control of blood pressure. {86}

Maintenance: Oral, 200 to 600 mcg (0.2 to 0.6 mg) per day, in divided doses {31} {33} {86} {87}.

Severe hypertension in the urgent but not emergency situation (loading dose): Oral, 200 mcg (0.2 mg), followed by 100 mcg (0.1 mg) every hour until diastolic blood pressure is controlled or a total of 800 {17} mcg (0.8 mg) has been given; the patient is then controlled on a normal maintenance dose.

[Vascular headache prophylactic]1
Oral, 25 mcg (0.025 mg) two to four times a day up to 50 mcg (0.05 mg) three times a day.

[Antidysmenorrheal]1
Severe dysmenorrhea: Oral, 25 mcg (0.025 mg) two times a day for fourteen days before and during menses.

[Menopausal syndrome therapy adjunct]
Oral, 25 to 75 mcg (0.025 to 0.075 mg) two times a day. {35} {36} {38} {39}


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose and may benefit from a lower initial dose. {86} {87}


Usual adult prescribing limit
Antihypertensive—2.4 mg daily. {33}

Usual pediatric dose
Children under 12 years of age—Safety and efficacy have not been established. {86} {87}

Strength(s) usually available
U.S.—


100 mcg (0.1 mg) (Rx) [Catapres{86} (scored) (lactose)][Generic] (may be scored)(may contain lactose)


200 mcg (0.2 mg) (Rx) [Catapres{86} (scored) (lactose)][Generic] (may be scored)(may contain lactose)


300 mcg (0.3 mg) (Rx) [Catapres{86} (scored) (lactose)][Generic] (may be scored)(may contain lactose)

Note: Not commercially available in 25-mcg (0.025-mg) strength used for indications other than hypertension; extemporaneous compounding required.


Canada—


25 mcg (0.025 mg) (Rx) [Dixarit (lactose)]


100 mcg (0.1 mg) (Rx) [Catapres{87} (scored) (lactose)]


200 mcg (0.2 mg) (Rx) [Catapres{87} (scored) (lactose)]

Note: 100 mcg of the hydrochloride salt is equivalent to 87 mcg of the free base.


Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), {86} {87} unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • Do not miss doses.
   • Do not take other medicines without your doctor's advice.

Note: Check refill frequency to determine compliance in hypertensive patients.




Topical Dosage Forms

CLONIDINE TRANSDERMAL SYSTEM

Usual adult dose
Antihypertensive
Topical, to the intact skin, 1 transdermal dosage system, beginning with the system delivering 100 mcg (0.1 mg) per day, once a week. {88} Dosage adjustments may be made every one or two weeks {15} {19} {88} by changing to the next larger dosage system or a combination of systems. {01} {88}


Usual pediatric dose
Children under 12 years of age—Safety and efficacy have not been established. {88}

Strength(s) usually available
U.S.—


2.5 mg (delivering 100 mcg [0.1 mg] per day) (Rx) [Catapres-TTS-1{88}]


5.0 mg (delivering 200 mcg [0.2 mg] per day) (Rx) [Catapres-TTS-2{88}]


7.5 mg (delivering 300 mcg [0.3 mg] per day) (Rx) [Catapres-TTS-3{88}]

Note: All systems are designed to release a constant, controlled dose of clonidine. The actual dose delivered will be as labeled and as intended, but less than the total content of each system.


Canada—
Not commercially available.

Packaging and storage:
Store below 30 °C (86 °F), {88} unless otherwise specified by manufacturer.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • For external use only.
   • Do not miss doses.
   • Do not take other medicines without your doctor's advice.

Note: Include patient instructions when dispensing.
Check refill frequency to determine compliance in hypertensive patients.




Revised: 05/21/1999



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. Catapres-TTS package insert (Boehringer Ingelheim—US), 6/85.
  1. Catapres-TTS patient information (Boehringer Ingelheim—US), 3/84.
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  1. Catapres (Clonidine): Pathways in the development of a pharmaceutical. Aulendorf, FRG: Editio Cantor, 1983: 126-32.
  1. Popli S, Stroka G, Ing TS, et al. Transdermal clonidine for hypertensive patients. Clin Ther 1983; 5: 624-8.
  1. Shaw JE. Pharmacokinetics of nitroglycerin and clonidine delivered by the transdermal route. Am Heart J 1984; 108: 217-23.
  1. Weber MA, Drayer JI. Clinical experience with rate-controlled delivery of antihypertensive therapy by a transdermal system. Am Heart J 1984; 108: 231-6.
  1. Weber MA, Drayer JI, McMahon FG, Hamburger R, Shah AR, Kirk LN. Transdermal administration of clonidine for treatment of high BP. Arch Intern Med 1984; 144: 1211-3.
  1. Weber MA, Brewer DD, Drayer JM, Lipson JL. Transdermal continuous antihypertensive therapy. Lancet 1984; 1: 9-11.
  1. Weber MA, et al (editors). Low dose oral and transdermal therapy of hypertension 1985: 86-92.
  1. MacGregor TR, Matzek KM, Keirns JJ, et al. Pharmacokinetics of transdermally delivered clonidine. Clin Pharmacol Ther 1985; 38: 278-84.
  1. Schaller MD, Nussberger J, Waeber B, Porchet M, Brunner HR. Transdermal clonidine therapy in hypertensive patients. JAMA 1985; 253: 233-5.
  1. Clonidine hydrochloride package insert (Par—US), 12/85.
  1. Panel comments, 1986 revision.
  1. Panel comments, addition of transdermal clonidine.
  1. Lowenthal DT. Pharmacokinetics of clonidine. J Cardiovasc Pharmacol 1980; 2(Suppl 1): S29-S37.
  1. Med Lett Drugs Ther 1985 Mar 1; 27: 24.
  1. Transdermal clonidine for hypertension. Med Lett Drugs Ther 1985 Nov 8; 27: 95-6.
  1. Review comments, addition of transdermal clonidine.
  1. Clonidine hydrochloride tablets package insert (Barr—US), 2/87.
  1. Arch Intern Med 1984 May; 144: 1045-57.
  1. Dixarit product monograph (Boehringer Ingelheim—Canada), 8/18/80.
  1. Manufacturer comment Boehringer Ingelheim, 1990 revision (ref. Clin Pharmacokinet 1988; 14: 287-310).
  1. Catapres-TTS package insert (Boehringer Ingelheim—US), 7/88.
  1. Comment from Boehringer Ingelheim (U.S.), 1990 revision.
  1. Sees KL, Stalcup SA. Combining clonidine and nicotine replacement for treatment of nicotine withdrawal. J Psychoact Drugs 1989; 21(3): 355-9.
  1. Per responses to panel question #4, 1990 revision.
  1. Per responses to panel question #5, 1990 revision.
  1. Dixarit product information (Boehringer Ingelheim—Canada), CPS 1987.
  1. Bredfeldt RC, Sutherland JE, Kruse JE. Efficacy of transdermal clonidine for headache prophylaxis and reduction of narcotic use in migraine patients: a randomized crossover trial. J Fam Prac 1989; 29(2): 153-8.
  1. Catapres package insert (Boehringer Ingelheim—US), 5/87.
  1. Catapres package insert (Boehringer Ingelheim—US), 4/88.
  1. Catapres package insert (Boehringer Ingelheim—US), Rev 9/89, Rec 4/92.
  1. Glassman AH, Covey LS. Future trends in the pharmacological treatment of smoking cessation. Drugs 1990; 40(1): 1-5.
  1. Clayden JR. Effect of clonidine on menopausal flushing. Lancet 1972; Dec: 1361.
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