Catapres® (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 inactive ingredients are colloidal silicon dioxide, corn starch, dibasic calcium phosphate, FD&C Yellow No. 6, gelatin, glycerin, lactose, and magnesium stearate. The Catapres 0.1 mg tablet also contains FD&C Blue No.1 and FD&C Red No.3.

Clonidine hydrochloride 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:

C₉H₉C_l2N₃• HCl             Mol. Wt. 266.56

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

Last updated on RxList: 8/27/2009

Catapres® (clonidine hydrochloride, USP) tablets are indicated in the treatment of hypertension. CATAPRES tablets may be employed alone or concomitantly with other antihypertensive agents.

Adults

The dose of Catapres® (clonidine hydrochloride, USP) 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

Dosage must be adjusted according to the degree of impairment, and 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.

Catapres® (clonidine hydrochloride, USP) tablets are supplied as follows:

Dose (mg)	Color	Marking	Bottle of 100
0.1	Tan	BI 6	NDC 0597-0006-01
0.2	Orange	BI 7	NDC 0597-0007-01
0.3	Peach	BI 11	NDC 0597-0011-01

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

Dispense in tight, light-resistant container.

Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877 USA. Manufactured by: Boehringer Ingelheim Promeco S.A. de C.V., Mexico City, Mexico. Licensed from: Boehringer Ingelheim International GmbH. Address medical inquiries to: (800) 542-6257 or (800) 459-9906 TTY. Rev: March 2009.

Last updated on RxList: 8/27/2009

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 CATAPRES 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.

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.

Due to a potential for additive effects such as bradycardia and AV block, caution is warranted 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.

Amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats (see Toxicology).

Serious adverse events, including death, have been reported in concomitant use with methylphenidate, although no causality for the combination has been established. The safety of using clonidine in combination with methylphenidate has not been systematically evaluated.

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.

Last updated on RxList: 8/27/2009

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 Catapres® (clonidine hydrochloride, USP) 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 CATAPRES 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 CATAPRES 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.

General

In patients who have developed localized contact sensitization to Catapres-TTS® (clonidine), continuation of Catapres-TTS 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 Catapres-TTS, substitution of oral clonidine hydrochloride may also elicit an allergic reaction (including generalized rash, urticaria, or angioedema).

CATAPRES tablets should be used with caution in patients with severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease or chronic renal failure.

Perioperative Use

Administration of CATAPRES tablets should be continued to within four 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.

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/m² 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/m² 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 Catapres® (clonidine hydrochloride, USP) 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/m² 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 6-15. 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/m² basis) in mice and rats treated on gestation days 1-14 (lowest dose employed in the study was 500 mcg/kg).

No adequate, well-controlled studies have been conducted in pregnant women. 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 Catapres® (clonidine hydrochloride, USP) 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).

Last updated on RxList: 8/27/2009

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 LD50 of clonidine is 206 and 465 mg/kg, respectively.

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

Last updated on RxList: 8/27/2009

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. CATAPRES 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° 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 plasma level of clonidine peaks in approximately 3 to 5 hours and the plasma half-life ranges from 12 to 16 hours. The half-life increases up to 41 hours in patients with severe impairment of renal function. Following oral administration about 40-60% 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.

Last updated on RxList: 8/27/2009

Patients should be cautioned against interruption of CATAPRES tablets therapy without their physician's advice.

Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of a possible sedative effect of clonidine. They should also be informed 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 Catapres® (clonidine hydrochloride, USP) tablets may cause dryness of eyes.

Last updated on RxList: 8/27/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CLONIDINE - ORAL

(KLAHN-eh-deen)

COMMON BRAND NAME(S): Catapres

USES: This medication is used alone or with other medications to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Clonidine belongs to a class of drugs (central alpha agonists) that act in the brain to lower blood pressure. It works by relaxing blood vessels so blood can flow more easily.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat painful menstrual periods, hot flashes that occur with menopause, attention deficit hyperactivity disorder (ADHD), and withdrawal symptoms from dependence on narcotics, alcohol, or nicotine (smoking).

HOW TO USE: Take this medication by mouth with or without food, usually twice daily (in the morning and at bedtime) or as directed by your doctor.

The dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

Do not stop taking this medication without first consulting your doctor. Withdrawal reactions (e.g., nervousness, agitation, shaking, headache) and a rapid rise in blood pressure may occur when the drug is abruptly stopped. The risk is greater if you have used this drug for a long time or in high doses, or if you are also taking a beta blocker (e.g., atenolol). There have also been rare reports of severe (possibly fatal) reactions from stopping this drug too quickly (e.g., stroke). Therefore, it is important that you do not run out of clonidine or miss any doses. Tell your doctor or pharmacist immediately if you are unable to take the medication (e.g., due to vomiting). If you must stop taking this drug, your dose should be gradually decreased over several days as directed by your doctor.

When used for a long time, this medication may not work as well and may require different dosing or an additional medication. Talk with your doctor if this medication stops working well (e.g., your routine blood pressure readings increase).

SIDE EFFECTS: Dizziness, lightheadedness, drowsiness, dry mouth, or constipation may occur as your body adjusts to the medication. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fast/slow/irregular heartbeat, mental/mood changes (e.g., depression), cold hands/feet.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking clonidine, tell your doctor or pharmacist if you are allergic to it; or if you developed a rash during treatment with clonidine in the patch form; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, heart disease (e.g., severe coronary artery disease, irregular heart rhythm, recent heart attack), depression, blood circulation disorders (e.g., Raynaud's disease, stroke).

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Older adults may be more sensitive to the effects of this product, especially dizziness.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: cyclobenzaprine, other drugs that can slow the heart rate (e.g., digoxin, calcium channel blockers such as diltiazem, beta blockers such as metoprolol), MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine), tricyclic antidepressants (e.g., amitriptyline, desipramine).

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine, phenobarbital), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs such as ibuprofen for pain/fever reduction) because they may contain ingredients that could increase your blood pressure. Many cough-and-cold products may also contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: fainting, fast/slow/irregular heartbeat, slow/shallow breathing, seizures.

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise, and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Check your blood pressure regularly while taking this medication. Learn how to monitor your own blood pressure at home, and share the results with your doctor.

MISSED DOSE: See also How to Use section.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up. If you miss 2 or more doses in a row, contact your doctor immediately.

STORAGE: Store at room temperature (77 degrees F or 25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.