CORGARD (nadolol) is a synthetic nonselective beta-adrenergic receptor blocking agent designated chemically as 1-(tert-butylamino)-3-[(5,6,7,8-tetrahydro-cis-6,7-dihydroxy-1- naphthyl)oxy]-2-propanol. Structural formula:

C₁₇H₂₇NO₄                 MW 309.40

Nadolol is a white crystalline powder. It is freely soluble in ethanol, soluble in hydrochloric acid, slightly soluble in water and in chloroform, and very slightly soluble in sodium hydroxide.

CORGARD (nadolol) is available for oral administration as 20 mg, 40 mg, and 80 mg tablets. Inactive ingredients: microcrystalline cellulose, colorant (FD&C Blue No. 2), corn starch, magnesium stearate, povidone (except 20 mg and 40 mg), and other ingredients.

Angina Pectoris

CORGARD (nadolol) is indicated for the long-term management of patients with angina pectoris.

Hypertension

CORGARD (nadolol) is indicated in the management of hypertension; it may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

DOSAGE MUST BE INDIVIDUALIZED. CORGARD (NADOLOL) MAY BE ADMINISTERED WITHOUT REGARD TO MEALS.

Angina Pectoris

The usual initial dose is 40 mg CORGARD (nadolol) once daily. Dosage may be gradually increased in 40 to 80 mg increments at 3 to 7 day intervals until optimum clinical response is obtained or there is pronounced slowing of the heart rate. The usual maintenance dose is 40 or 80 mg administered once daily. Doses up to 160 or 240 mg administered once daily may be needed.

The usefulness and safety in angina pectoris of dosage exceeding 240 mg per day have not been established. If treatment is to be discontinued, reduce the dosage gradually over a period of one to two weeks (see WARNINGS).

Hypertension

The usual initial dose is 40 mg CORGARD (nadolol) once daily, whether it is used alone or in addition to diuretic therapy. Dosage may be gradually increased in 40 to 80 mg increments until optimum blood pressure reduction is achieved. The usual maintenance dose is 40 or 80 mg administered once daily. Doses up to 240 or 320 mg administered once daily may be needed.

Dosage Adjustment in Renal Failure

Absorbed nadolol is excreted principally by the kidneys and, although nonrenal elimination does occur, dosage adjustments are necessary in patients with renal impairment. The following dose intervals are recommended:

Creatinine Clearance

CORGARD Tablets (Nadolol Tablets USP)

20 mg tablets in bottles of 100 (NDC 60793-800-01), 40 mg tablets in bottles of 100 (NDC 60793-801-01) and 80 mg tablets in bottles of 100 (NDC 60793-802-01).

All tablets are scored (bisect bar) and easy to break. Tablet identification numbers: 20 mg, 232; 40 mg, 207; and 80 mg, 241.

Storage

Store at room temperature; avoid excessive heat. Protect from light. Keep bottle tightly closed.

Prescribing Information as of July 2007. Manufactured and Distributed by: King Pharmaceuticals, Inc., Bristol, TN 37620. FDA Rev date: 2/4/2008

Most adverse effects have been mild and transient and have rarely required withdrawal of therapy.

Cardiovascular

Bradycardia with heart rates of less than 60 beats per minute occurs commonly, and heart rates below 40 beats per minute and/or symptomatic bradycardia were seen in about 2 of 100 patients. Symptoms of peripheral vascular insufficiency, usually of the Raynaud type, have occurred in approximately 2 of 100 patients. Cardiac failure, hypotension, and rhythm/conduction disturbances have each occurred in about 1 of 100 patients. Single instances of first degree and third degree heart block have been reported; intensification of AV block is a known effect of beta-blockers (see also CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS).

Central Nervous System

Dizziness or fatigue has been reported in approximately 2 of 100 patients; paresthesias, sedation, and change in behavior have each been reported in approximately 6 of 1000 patients.

Respiratory

Bronchospasm has been reported in approximately 1 of 1000 patients (see CONTRAINDICATIONS and WARNINGS).

Gastrointestinal

Nausea, diarrhea, abdominal discomfort, constipation, vomiting, indigestion, anorexia, bloating, and flatulence have been reported in 1 to 5 of 1000 patients.

Miscellaneous

Each of the following has been reported in 1 to 5 of 1000 patients: rash; pruritus; headache; dry mouth, eyes, or skin; impotence or decreased libido; facial swelling; weight gain; slurred speech; cough; nasal stuffiness; sweating; tinnitus; blurred vision. Reversible alopecia has been reported infrequently.

The following adverse reactions have been reported in patients taking nadolol and/or other beta-adrenergic blocking agents, but no causal relationship to nadolol has been established.

Central Nervous System

Reversible mental depression progressing to catatonia; visual disturbances; hallucinations; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability with slightly clouded sensorium, and decreased performance on neuropsychometrics.

Gastrointestinal

Mesenteric arterial thrombosis; ischemic colitis; elevated liver enzymes.

Hematologic

Agranulocytosis; thrombocytopenic or nonthrombocytopenic purpura.

Allergic

Fever combined with aching and sore throat; laryngospasm; respiratory distress.

Miscellaneous

Pemphigoid rash; hypertensive reaction in patients with pheochromocytoma; sleep disturbances; Peyronie's disease.

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with nadolol.

When administered concurrently, the following drugs may interact with beta-adrenergic receptor blocking agents:

Anesthetics, general-exaggeration of the hypotension induced by general anesthetics (see WARNINGS, Major Surgery).

Antidiabetic drugs (oral agents and insulin)-hypoglycemia or hyperglycemia; adjust dosage of antidiabetic drug accordingly (see WARNINGS, Diabetes and Hypoglycemia).

Catecholamine-depleting drugs (e.g., reserpine)-additive effect; monitor closely for evidence of hypotension and/or excessive bradycardia (e.g., vertigo, syncope, postural hypotension).

Digitalis glycosides-Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Response to Treatment for Anaphylactic Reaction-While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Cardiac Failure

Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta-blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, if necessary, they can be used with caution in patients with a history of failure who are well-compensated, usually with digitalis and diuretics. Beta-adrenergic blocking agents do not abolish the inotropic action of digitalis on heart muscle.

IN PATIENTS WITHOUT A HISTORY OF HEART FAILURE, continued use of beta- blockers can, in some cases, lead to cardiac failure. Therefore, at the first sign or symptom of heart failure, the patient should be digitalized and/or treated with diuretics, and the response observed closely, or nadolol should be discontinued (gradually, if possible).

Nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema)

PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD IN GENERAL NOT RECEIVE BETA-BLOCKERS. Nadolol should be administered with caution since it may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta2 receptors.

Major Surgery

Because beta-blockade impairs the ability of the heart to respond to reflex stimuli and may increase the risks of general anesthesia and surgical procedures, resulting in protracted hypotension or low cardiac output, it has generally been suggested that such therapy should be withdrawn several days prior to surgery. Recognition of the increased sensitivity to catecholamines of patients recently withdrawn from beta-blocker therapy, however, has made this recommendation controversial. If possible, beta-blockers should be withdrawn well before surgery takes place. In the event of emergency surgery, the anesthesiologist should be informed that the patient is on beta-blocker therapy. The effects of nadolol can be reversed by administration of beta-receptor agonists such as isoproterenol, dopamine, dobutamine, or levarterenol. Difficulty in restarting and maintaining the heart beat has also been reported with beta-adrenergic receptor blocking agents.

Diabetes and Hypoglycemia

Beta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia and blood pressure changes) of acute hypoglycemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycemia; therefore, it may be necessary to adjust the dose of antidiabetic drugs.

Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blockade which might precipitate a thyroid storm.

Impaired Renal Function

Nadolol should be used with caution in patients with impaired renal function (see DOSAGE AND ADMINISTRATION).

Carcinogenesis, Mutagenesis, Impairment of Fertility

In chronic oral toxicologic studies (one to two years) in mice, rats, and dogs, nadolol did not produce any significant toxic effects. In two-year oral carcinogenic studies in rats and mice, nadolol did not produce any neoplastic, preneoplastic, or non-neoplastic pathologic lesions. In fertility and general reproductive performance studies in rats, nadolol caused no adverse effects.

Pregnancy

Category C

In animal reproduction studies with nadolol, evidence of embryo- and fetotoxicity was found in rabbits, but not in rats or hamsters, at doses 5 to 10 times greater (on a mg/kg basis) than the maximum indicated human dose. No teratogenic potential was observed in any of these species.

There are no adequate and well-controlled studies in pregnant women. Nadolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates whose mothers are receiving nadolol at parturition have exhibited bradycardia, hypoglycemia, and associated symptoms.

Nursing Mothers

Nadolol is excreted in human milk. Because of the potential for adverse effects in nursing infants, a decision should be made whether to discontinue nursing or to discontinue therapy taking into account the importance of CORGARD (nadolol) to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Nadolol can be removed from the general circulation by hemodialysis.

In addition to gastric lavage, the following measures should be employed, as appropriate. In determining the duration of corrective therapy, note must be taken of the long duration of the effect of nadolol.

Excessive Bradycardia

Administer atropine (0.25 to 1.0 mg). If there is no response to vagal blockade, administer isoproterenol cautiously.

Cardiac Failure

Administer a digitalis glycoside and diuretic. It has been reported that glucagon may also be useful in this situation.

Hypotension

Administer vasopressors, e.g., epinephrine or levarterenol. (There is evidence that epinephrine may be the drug of choice.)

Bronchospasm

Administer a beta2-stimulating agent and/or a theophylline derivative.

Nadolol is contraindicated in bronchial asthma, sinus bradycardia and greater than first degree conduction block, cardiogenic shock, and overt cardiac failure (see WARNINGS).

CORGARD (nadolol) is a nonselective beta-adrenergic receptor blocking agent. Clinical pharmacology studies have demonstrated beta-blocking activity by showing (1) reduction in heart rate and cardiac output at rest and on exercise, (2) reduction of systolic and diastolic blood pressure at rest and on exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia.

CORGARD (nadolol) specifically competes with beta-adrenergic receptor agonists for available beta receptor sites; it inhibits both the beta1 receptors located chiefly in cardiac muscle and the beta2 receptors located chiefly in the bronchial and vascular musculature, inhibiting the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation proportionately. CORGARD has no intrinsic sympathomimetic activity and, unlike some other beta-adrenergic blocking agents, nadolol has little direct myocardial depressant activity and does not have an anesthetic-like membrane- stabilizing action. Animal and human studies show that CORGARD slows the sinus rate and depresses AV conduction. In dogs, only minimal amounts of nadolol were detected in the brain relative to amounts in blood and other organs and tissues. CORGARD has low lipophilicity as determined by octanol/water partition coefficient, a characteristic of certain beta-blocking agents that has been correlated with the limited extent to which these agents cross the blood-brain barrier, their low concentration in the brain, and low incidence of CNS-related side effects.

In controlled clinical studies, CORGARD (nadolol) at doses of 40 to 320 mg/day has been shown to decrease both standing and supine blood pressure, the effect persisting for approximately 24 hours after dosing.

The mechanism of the antihypertensive effects of beta-adrenergic receptor blocking agents has not been established; however, factors that may be involved include (1) competitive antagonism of catecholamines at peripheral (non-CNS) adrenergic neuron sites (especially cardiac) leading to decreased cardiac output, (2) a central effect leading to reduced tonic- sympathetic nerve outflow to the periphery, and (3) suppression of renin secretion by blockade of the beta-adrenergic receptors responsible for renin release from the kidneys.

While cardiac output and arterial pressure are reduced by nadolol therapy, renal hemodynamics are stable, with preservation of renal blood flow and glomerular filtration rate.

By blocking catecholamine-induced increases in heart rate, velocity and extent of myocardial contraction, and blood pressure, CORGARD (nadolol) generally reduces the oxygen requirements of the heart at any given level of effort, making it useful for many patients in the long-term management of angina pectoris. On the other hand, nadolol can increase oxygen requirements by increasing left ventricular fiber length and end diastolic pressure, particularly in patients with heart failure.

Although beta-adrenergic receptor blockade is useful in treatment of angina and hypertension, there are also situations in which sympathetic stimulation is vital. For example, in patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. Beta-adrenergic blockade may worsen AV block by preventing the necessary facilitating effects of sympathetic activity on conduction. Beta2- adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients.

Absorption of nadolol after oral dosing is variable, averaging about 30 percent. Peak serum concentrations of nadolol usually occur in three to four hours after oral administration and the presence of food in the gastrointestinal tract does not affect the rate or extent of nadolol absorption. Approximately 30 percent of the nadolol present in serum is reversibly bound to plasma protein.

Unlike many other beta-adrenergic blocking agents, nadolol is not metabolized by the liver and is excreted unchanged, principally by the kidneys.

The half-life of therapeutic doses of nadolol is about 20 to 24 hours, permitting once-daily dosage. Because nadolol is excreted predominantly in the urine, its half-life increases in renal failure (see PRECAUTIONS and DOSAGE AND ADMINISTRATION). Steady-state serum concentrations of nadolol are attained in six to nine days with once-daily dosage in persons with normal renal function. Because of variable absorption and different individual responsiveness, the proper dosage must be determined by titration.

Exacerbation of angina and, in some cases, myocardial infarction and ventricular dysrhythmias have been reported after abrupt discontinuation of therapy with beta- adrenergic blocking agents in patients with coronary artery disease. Abrupt withdrawal of these agents in patients without coronary artery disease has resulted in transient symptoms, including tremulousness, sweating, palpitation, headache, and malaise. Several mechanisms have been proposed to explain these phenomena, among them increased sensitivity to catecholamines because of increased numbers of beta receptors.

Patients, especially those with evidence of coronary artery insufficiency, should be warned against interruption or discontinuation of nadolol therapy without the physician's advice. Although cardiac failure rarely occurs in properly selected patients, patients being treated with beta-adrenergic blocking agents should be advised to consult the physician at the first sign or symptom of impending failure. The patient should also be advised of a proper course in the event of an inadvertently missed dose.

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.

NADOLOL - ORAL

(nay-DOE-lole)

WARNING: If you have chest pain (angina) or heart disease (e.g., coronary artery disease, ischemic heart disease, high blood pressure), do not stop using this drug without first consulting your doctor. Your condition may become worse when the drug is suddenly stopped. If your doctor decides you should no longer use this drug, you must gradually decrease your dose according to your doctor's instructions.

When gradually stopping this medication, it is recommended that you temporarily limit physical activity to decrease work for the heart. Seek immediate medical attention if you develop worsening chest pain, tightness/pressure in the chest, chest pain spreading to the jaw/neck/arm, sweating, trouble breathing, or fast/irregular heartbeat.

USES: Nadolol is used alone or with other medications to treat high blood pressure (hypertension) and to prevent chest pain (angina). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. In the management of chest pain, nadolol may also help to reduce the frequency of chest pain episodes and improve your ability to exercise.

Nadolol belongs to a class of medications called beta blockers. It works by blocking the action of certain natural substances such as adrenaline (epinephrine) on the heart and blood vessels. This results in a lowering of heart rate, blood pressure, and strain on the heart.

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 protect the heart after a heart attack, treat irregular heartbeat (e.g., atrial fibrillation, atrial flutter), and prevent migraine headaches. Your doctor may also use this medication to treat other conditions.

HOW TO USE: See also the Warning section.

Take this medication by mouth with or without food, usually once daily or as directed by your doctor. Your dosage is based on your medical condition and response to therapy.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day. This medication treats, but does not cure, high blood pressure. 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 consulting your doctor. Your condition may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.

Inform your doctor if your condition persists or worsens (e.g., routine blood pressure readings increase).

SIDE EFFECTS: Dizziness, drowsiness, weakness, and cough may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

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.

This drug may reduce blood flow to your hands and feet, causing them to feel cold. Smoking may worsen this effect. Dress warmly and avoid tobacco use.

Tell your doctor immediately if any of the following unlikely but serious side effects occur: bluish color of the fingers/toes/nails, hair loss (reversible), mental/mood changes (e.g., depression, confusion, memory problems), numbness/tingling, decreased sexual ability, swelling of the ankles/feet, severe tiredness, vision changes, wheezing, unexplained/sudden weight gain.

Seek immediate medical attention if any of these unlikely but very serious side effects occur: chest pain, jaw/left arm pain, slow/irregular/fast heartbeat, severe dizziness/fainting.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, 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 nadolol, tell your doctor or pharmacist if you are allergic to it; or to other beta blockers (e.g., atenolol, propranolol); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: very slow heartbeat (e.g., sinus bradycardia, second- or third-degree atrioventricular block), a certain serious heart condition (cardiogenic shock), uncontrolled severe heart failure, asthma.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: severe allergic reactions (e.g., anaphylaxis), breathing problems (e.g., COPD, emphysema), blood circulation problems (e.g., Raynaud's disease), low blood flow to the heart/brain (coronary artery disease, stroke, transient ischemic attack), diabetes, heart problems (e.g., heart failure, heart attack, valve problems), kidney disease, mental/mood disorders (e.g., depression), muscle problems (e.g., myasthenia gravis), certain skin conditions (atopy, psoriasis), overactive thyroid (hyperthyroidism), certain types of tumor (pheochromocytoma).

This drug may make you dizzy or drowsy; use caution while engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

To minimize dizziness, get up slowly when rising from a seated or lying position.

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

This drug may infrequently make your blood sugar level rise, causing or worsening diabetes. Tell your doctor immediately if you develop symptoms of high blood sugar such as increased thirst or urination.

If you already have diabetes, be sure to check your blood sugar regularly. This medication may mask the fast/pounding heartbeat, nervousness and shakiness you would usually feel when your blood sugar falls too low (hypoglycemia). Other symptoms of low blood sugar such as hunger, dizziness and sweating are unaffected by this drug.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at a greater risk for side effects such as dizziness while using this drug.

This medication should be used only when clearly needed during pregnancy. If used near the time of delivery, the newborn may have problems such as slow heart rate or low blood sugar. Tell your doctor immediately if you notice a slow heart rate or signs of low blood sugar (e.g., shakiness, sweating) in your newborn. Discuss the risks and benefits with your doctor.

Nadolol passes into breast milk and may have undesirable effects on a nursing infant. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

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

This drug should not be used with the following medication because a very serious interaction may occur: arbutamine.

If you are currently using this medication, tell your doctor or pharmacist before starting nadolol.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: alpha blockers (e.g., prazosin), other beta blockers (e.g., atenolol), bronchodilators (e.g., albuterol, theophylline), calcium channel blockers (e.g., diltiazem, verapamil), clonidine, drugs for diabetes (e.g., glyburide, insulin), epinephrine, fenoldopam, methyldopa, nasal decongestants (e.g., phenylephrine, pseudoephedrine), nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen, naproxen), neuromuscular blocking agents (e.g., tubocurarine), reserpine, "water pills" (e.g., diuretics such as furosemide).

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), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, amitriptyline, trazodone).

Check the labels on all your medications (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs for pain/fever reduction) because they may contain ingredients that could cause drowsiness or increase your heart rate or blood pressure. Ask your doctor or pharmacist about the safe use of those products.

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. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: very slow heartbeat, severe dizziness/fainting, loss of consciousness, severe weakness, shortness of breath.

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.

Laboratory and/or medical tests (e.g., blood pressure, kidney function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Have your blood pressure and pulse checked regularly while taking this medication. It may be best to learn how to monitor your own blood pressure and pulse.

MISSED DOSE: 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.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. 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 enrollment information call MedicAlert at 1-800-854- 1166 (USA) or 1-800-668-1507 (Canada).

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