Nitroglycerin is 1,2,3-propanetriol, trinitrate, an organic nitrate whose structural formula is

and whose molecular weight is 227.09. The organic nitrates are vasodilators, active on both arteries and veins.

The Transderm-Nitro (nitroglycerin) transdermal system is a flat unit designed to provide continuous controlled release of nitroglycerin through intact skin.

The rate of release of nitroglycerin is linearly dependent upon the area of the applied system; each cm² of applied system delivers approximately 0.02 mg of nitroglycerin per hour. Thus, the 5-, 10-, 20-, and 30-cm² systems deliver approximately 0.1, 0.2, 0.4, and 0.6 mg of nitroglycerin per hour, respectively.

The remainder of the nitroglycerin in each system serves as a reservoir and is not delivered in normal use. After 12 hours, for example, each system has delivered 10% of its original content of nitroglycerin.

The Transderm-Nitro system comprises four layers as shown below. Proceeding from the visible surface towards the surface attached to the skin, these layers are: 1) a tan-colored backing layer (aluminized plastic) that is impermeable to nitroglycerin; 2) a drug reservoir containing nitroglycerin adsorbed on lactose, colloidal silicon dioxide, and silicone medical fluid; 3) an ethylene-vinyl acetate copolymer membrane that is permeable to nitroglycerin; and 4) a layer of hypoallergenic silicone adhesive. Prior to use, a protective peel strip is removed from the adhesive surface.

Cross section of the system

Last updated on RxList: 3/30/2009

Transdermal nitroglycerin is indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of transdermal nitroglycerin is not sufficiently rapid for this product to be useful in aborting an acute attack.

The suggested starting dose is between 0.2 mg/hr*, and 0.4 mg/hr*. Doses between 0.4 mg/hr* and 0.8 mg/hr* have shown continued effectiveness for 10-12 hours daily for at least one month (the longest period studied) of intermittent administration. Although the minimum nitrate-free interval has not been defined, data show that a nitrate-free interval of 10-12 hours is sufficient (see CLINICAL PHARMACOLOGY). Thus, an appropriate dosing schedule for nitroglycerin patches would include a daily patch-on period of 12-14 hours and a daily patchoff period of 10-12 hours.

Although some well-controlled clinical trials using exercise tolerance testing have shown maintenance of effectiveness when patches are worn continuously, the large majority of such controlled trials have shown the development of tolerance (i.e., complete loss of effect) within the first 24 hours after therapy was initiated. Dose adjustment, even to levels much higher than generally used, did not restore efficacy.

Patient Instructions for Application of System

A patient leaflet is supplied with each carton.

Nitroglycerin Transdermal System 0.1 mg/hr-tan, round (imprinted Transderm-Nitro 0.1 mg/hr), supplied in a foil-lined pouch

30 Systems.........................................NDC 0078-0332-85

Nitroglycerin Transdermal System 0.2 mg/hr-tan, oblong (imprinted Transderm-Nitro 0.2 mg/hr), supplied in a foil-lined pouch

30 Systems.........................................NDC 0078-0333-85

Nitroglycerin Transdermal System 0.4 mg/hr-tan, oblong (imprinted Transderm-Nitro 0.4 mg/hr), supplied in a foil-lined pouch

30 Systems.........................................NDC 0078-0334-85

Nitroglycerin Transdermal System 0.6 mg/hr-tan, oblong (imprinted Transderm-Nitro 0.6 mg/hr), supplied in a foil-lined pouch

30 Systems.........................................NDC 0078-0335-85

*Rated release in vivo. Release rates were formerly described in terms of drug delivered per 24 hours. In these terms, the supplied Transderm-Nitro systems would be rated at 2.5 mg/24 hr (0.1 mg/hr), 5 mg/24 hr (0.2 mg/hr), 10 mg/24 hr (0.4 mg/hr), 15 mg/24 hr (0.6 mg/hr), and 20 mg/24 hr (0.8 mg/hr).

Do not store above 30°C (86°F).

Do not store unpouched. Apply immediately upon removal from the pouch.

REV: June 2000. Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936.

Last updated on RxList: 3/30/2009

Adverse reactions to nitroglycerin are generally dose-related, and almost all of these reactions are the result of nitroglycerin.s activity as a vasodilator. Headache, which may be severe, is the most commonly reported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon.

Allergic reactions to nitroglycerin are also uncommon, and the great majority of those reported have been cases of contact dermatitis or fixed drug eruptions in patients receiving nitroglycerin in ointments or patches. There have been a few reports of genuine anaphylactoid reactions, and these reactions can probably occur in patients receiving nitroglycerin by any route.

Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients. Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred (see OVERDOSAGE).

Application-site irritation may occur but is rarely severe.

In two placebo-controlled trials of intermittent therapy with nitroglycerin patches at 0.2 to 0.8 mg/hr, the most frequent adverse reactions among 307 subjects were as follows:

	Placebo	Patch
Headache	18%	63%
Lightheadedness	4%	6%
Hypotension, and/or syncope	0%	4%
Increased angina	2%	2%

The vasodilating effects of nitroglycerin may be additive with those of other vasodilators. Alcohol, in particular, has been found to exhibit additive effects of this variety.

Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination. Dose adjustments of either class of agents may be necessary.

Last updated on RxList: 3/30/2009

Amplification of the vasodilatory effects of Transderm-Nitro by sildenafil may result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion.

The benefits of transdermal nitroglycerin in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use nitroglycerin in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.

A cardioverter/defibrillator should not be discharged through a paddle electrode that overlies a Transderm-Nitro patch. The arcing that may be seen in this situation is harmless in itself, but it may be associated with local current concentration that can cause damage to the paddles and burns to the patient.

General

Severe hypotension, particularly with upright posture, may occur with even small doses of nitroglycerin. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

As tolerance to other forms of nitroglycerin develops, the effect of sublingual nitroglycerin on exercise tolerance, although still observable, is somewhat blunted.

In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating the existence of true physical dependence.

Several clinical trials in patients with angina pectoris have evaluated nitroglycerin regimens which incorporated a 10-12 hour nitrate-free interval. In some of these trials, an increase in the frequency of anginal attacks during the nitrate-free interval was observed in a small number of patients. In one trial, patients demonstrated decreased exercise tolerance at the end of the nitrate-free interval. Hemodynamic rebound has been observed only rarely; on the other hand, few studies were so designed that rebound, if it had occurred, would have been detected. The importance of these observations to the routine, clinical use of transdermal nitroglycerin is unknown.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal carcinogenesis studies with topically applied nitroglycerin have not been performed.

Rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes. At high dose, the incidences of hepatocellular carcinomas in both sexes were 52% vs. 0% in controls, and incidences of testicular tumors were 52% vs. 8% in controls. Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in mice.

Nitroglycerin was weakly mutagenic in Ames tests performed in two different laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with doses up to about 363 mg/kg/day, p.o., or in in vitro cytogenetic tests in rat and dog tissues.

In a three-generation reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for six months prior to mating of the F0 generation with treatment continuing through successive F1 and F2 generations. The high dose was associated with decreased feed intake and body weight gain in both sexes at all matings. No specific effect on the fertility of the F0 generation was seen. Infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the highdose males. In this three-generation study there was no clear evidence of teratogenicity.

Pregnancy Category C

Animal teratology studies have not been conducted with nitroglycerin transdermal systems. Teratology studies in rats and rabbits, however, were conducted with topically applied nitroglycerin ointment at doses up to 80 mg/kg/day and 240 mg/kg/day, respectively. No toxic effects on dams or fetuses were seen at any dose tested. There are no adequate and wellcontrolled studies in pregnant women. Nitroglycerin should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitroglycerin is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of transdermal nitroglycerin did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last updated on RxList: 3/30/2009

Hemodynamic Effects

The ill effects of nitroglycerin overdose are generally the result of nitroglycerin.s capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death.

Laboratory determinations of serum levels of nitroglycerin and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of nitroglycerin overdose.

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of nitroglycerin and its active metabolites. Similarly, it is not known which, if any, of these substances can usefully be removed from the body by hemodialysis.

No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the hypotension associated with nitroglycerin overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward an increase in central fluid volume. Passive elevation of the patient.s legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.

The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do more harm than good.

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia

Nitrate ions liberated during metabolism of nitroglycerin can oxidize hemoglobin into methemoglobin. Even in patients totally without cytochrome b5 reductase activity, however, and even assuming that the nitrate moieties of nitroglycerin are quantitatively applied to oxidation of hemoglobin, about 1 mg/kg of nitroglycerin should be required before any of these patients manifests clinically significant ( ≥ 10%) methemoglobinemia. In patients with normal reductase function, significant production of methemoglobin should require even larger doses of nitroglycerin. In one study in which 36 patients received 2-4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr, the average methemoglobin level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo.

Notwithstanding these observations, there are case reports of significant methemoglobinemia in association with moderate overdoses of organic nitrates. None of the affected patients had been thought to be unusually susceptible.

Methemoglobin levels are available from most clinical laboratories. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1-2 mg/kg intravenously.

Use of Transderm-Nitro (nitroglycerin) transdermal system is contraindicated in patients using Viagra® (sildenafil) because sildenafil may amplify the vasodilatory effects of Transderm-Nitro resulting in severe hypotension.

Allergic reactions to organic nitrates are extremely rare, but they do occur. Nitroglycerin is contraindicated in patients who are allergic to it. Allergy to the adhesives used in nitroglycerin patches has also been reported, and it similarly constitutes a contraindication to the use of this product.

Last updated on RxList: 3/30/2009

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle, and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilatation of the coronary arteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilatation remains undefined.

Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continuously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates. Several well-controlled clinical trials have used exercise testing to assess the antianginal efficacy of continuously-delivered nitrates. In the large majority of these trials, active agents were indistinguishable from placebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates had been absent from the body for several hours was their antianginal efficacy restored.

Pharmacokinetics

The volume of distribution of nitroglycerin is about 3 L/kg, and nitroglycerin is cleared from this volume at extremely rapid rates, with a resulting serum half-life of about 3 minutes. The observed clearance rates (close to 1 L/kg/min) greatly exceed hepatic blood flow. Known sites of extrahepatic metabolism include red blood cells and vascular walls.

The first products in the metabolism of nitroglycerin are inorganic nitrate and the 1, 2-and 1, 3-dinitroglycerols. The dinitrates are less effective vasodilators than nitroglycerin but they are longer-lived in the serum, and their net contribution to the overall effect of chronic nitroglycerin regimens is not known. The dinitrates are further metabolized to (nonvasoactive) mononitrates and, ultimately, to glycerol and carbon dioxide.

To avoid development of tolerance to nitroglycerin, drug-free intervals of 10-12 hours are known to be sufficient; shorter intervals have not been well studied. In one wellcontrolled clinical trial, subjects receiving nitroglycerin appeared to exhibit a rebound or withdrawal effect, so that their exercise tolerance at the end of the daily drug-free interval was less than that exhibited by the parallel group receiving placebo.

In healthy volunteers, steady-state plasma concentrations of nitroglycerin are reached by about two hours after application of a patch and are maintained for the duration of wearing the system (observations have been limited to 24 hours). Upon removal of the patch, the plasma concentration declines with a half-life of about an hour.

Clinical Trials

Regimens in which nitroglycerin patches were worn for 12 hours daily have been studied in well-controlled trials up to 4 weeks in duration. Starting about 2 hours after application and continuing until 10-12 hours after application, patches that deliver at least 0.4 mg of nitroglycerin per hour have consistently demonstrated greater antianginal activity than placebo. Lower-dose patches have not been as well studied, but in one large, well-controlled trial in which higher-dose patches were also studied, patches delivering 0.2 mg/hr had significantly less antianginal activity than placebo.

It is reasonable to believe that the rate of nitroglycerin absorption from patches may vary with the site of application, but this relationship has not been adequately studied.

The onset of action of transdermal nitroglycerin is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.

Last updated on RxList: 3/30/2009

Daily headaches sometimes accompany treatment with nitroglycerin. In patients who get these headaches, the headaches may be a marker of the activity of the drug. Patients should resist the temptation to avoid headaches by altering the schedule of their treatment with nitroglycerin, since loss of headache may be associated with simultaneous loss of antianginal efficacy.

Treatment with nitroglycerin may be associated with lightheadedness on standing, especially just after rising from a recumbent or seated position. This effect may be more frequent in patients who have also consumed alcohol.

After normal use, there is enough residual nitroglycerin in discarded patches that they are a potential hazard to children and pets.

A patient leaflet is supplied with the systems.

Last updated on RxList: 3/30/2009

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.

NITROGLYCERIN PATCH - TRANSDERMAL

(nye-troh-GLISS-er-in)

COMMON BRAND NAME(S): Nitro-Dur, Nitrodisc, Transderm-Nitro

USES: Nitroglycerin transdermal patch is used to prevent chest pain (angina). When used regularly, nitroglycerin can decrease the number and severity of attacks of chest pain from angina and improve your ability to exercise. This medication is called a nitrate. It works by relaxing blood vessels and allowing more blood to flow to the heart. Increasing blood flow to the heart can relieve chest pain due to angina.

This medication should not be used to treat angina when it occurs. Use other medications (e.g., sublingual nitroglycerin) to relieve an angina attack as directed by your doctor. Consult your doctor or pharmacist for details.

HOW TO USE: Read the Patient Information Leaflet available from your pharmacist. Consult your doctor or pharmacist if you have any questions.

Remove the patch from its pouch and remove the clear liner as directed. Apply the patch to a clean, dry, hairless area anywhere on the body except on the legs or arms below the knee or elbow. Generally, the patch is worn on the upper arm or upper chest. To make sure your skin is completely dry, it is best to avoid applying the patch immediately after bathing or showering. Avoid areas with cuts, calluses or irritation. Hair may be clipped if necessary. Do not shave hair because this may cause skin irritation. After applying the patch, wash your hands. You may bathe, shower, and swim while wearing the patch.

Generally, the patch is worn for 12-14 hours, then removed for the last 10-12 hours of the day. Follow your doctor's instructions. The dosage and the time the patch is left on the skin are based on your medical condition and response to therapy.

To decrease skin irritation, apply each new patch to a different area of skin. After removing the old patch, fold it together so that the adhesive sticks to itself and discard out of reach of children and pets.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time each day. It is important to continue using this medication even if you feel well.

When this medication is used for a long time, it may not work as well. Different dosing may be required. Follow your doctor's instructions on how to use this product to decrease the risk that the medication will become less effective over time. Talk with your doctor if this medication stops working well.

Do not suddenly stop using 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 worsens (e.g., the number of angina attacks increases).

SIDE EFFECTS: Headache, lightheadedness, flushing, dizziness, nervousness, nausea, and vomiting may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Headache generally means that the medication is working. Treat headaches with an over-the-counter pain reliever (e.g., acetaminophen) as directed by your doctor. If the headaches continue or become severe, notify your doctor.

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: severe dizziness, fainting, fast/pounding heartbeat with headaches, paleness, sweating, blurred vision, dry mouth.

Tell your doctor immediately if any of these rare but very serious side effects occur: dark urine, bluish lips/skin/nails, unusual tiredness, severe weakness, irregular heartbeat, seizures.

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 using this medication, tell your doctor or pharmacist if you are allergic to it; or to any other nitrates; or if you have any other allergies.

This medication should not be used if you have a certain medical condition. Before using this medicine, consult your doctor or pharmacist if you have: severe anemia.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, a severe loss of body water (dehydration), certain heart problems (e.g., recent heart attack, chronic heart failure, cardiomyopathy), increased pressure in the brain (e.g., due to head trauma, cerebral hemorrhage), exposure to nitrates while on the job.

This drug may make you dizzy or drowsy or cause temporary blurred vision; use caution engaging in activities requiring alertness and clear vision such as driving or using machinery. Limit alcoholic beverages.

To minimize dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

If you are going to have an MRI test, notify testing personnel that you are using this patch. Serious burns may occur during MRI tests because of the aluminum contained in some brands of these patches. Check with your pharmacist or testing personnel whether your specific brand of patch should be removed just before the MRI test or consult your doctor for specific instructions.

Caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug, especially dizziness, increased risk of falling, and worsening chest pain.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. 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 medications because very serious (possibly fatal) interactions may occur: drugs used to treat sexual problems (e.g., sildenafil, tadalafil, vardenafil).

If you are currently using any of these medications, tell your doctor or pharmacist before starting nitroglycerin.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: alcohol, alteplase, migraine drugs (e.g., ergotamine), water pills/diuretics (e.g., furosemide, hydrochlorothiazide), other drugs for high blood pressure (e.g., beta blockers, calcium channel blockers, ACE inhibitors).

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs for pain/fever reduction) because they may contain ingredients that could increase your blood pressure, cause a fast heartbeat, or increase chest pain (e.g., pseudoephedrine, phenylephrine, chlorpheniramine, diphenhydramine, clemastine, ibuprofen, naproxen). Ask your 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: This patch may be harmful if swallowed. If overdose or swallowing is suspected, remove the patch from the skin or mouth. 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: persistent throbbing headache, fainting, confusion, fever, slow/irregular heartbeat, vision changes, severe nausea/vomiting, sweating, shortness of breath, cold/clammy skin, seizures.

NOTES: Do not share this medication with others.

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

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

Avoid situations that may lead to chest pain (e.g., vigorous exercise, cold air, heavy meals). Discuss with your doctor.

MISSED DOSE: If you miss a dose, use 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 between 59-86 degrees F (15-30 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 (See How to Use section).

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.