Managing Patients With Chronic Angina

Managing Patients With Chronic Angina: Emerging Therapeutic Options for Improving Clinical Efficacy and Outcomes Paul P. Dobesh, PharmD, FCCP, BCPS,Edith A. Nutescu, PharmD John S. Rumsfeld, MD, PhD, FACC Toby C. Trujillo, PharmD, BCPS Supplement October 2006 Vol. 12, No. 8 Continuing EducationThis article is based on a presentation given by the author at a symposium titled “Emerging Therapies for Management of Patients with Stable Angina

http://www.medicinenet.com/nitroglycerin-sublingual/article.htmGENERIC NAME: NITROGLYCERIN - SUBLINGUAL (nye-troh-GLISS-er-in) BRAND NAME(S): Nitrostat Medication Uses | How To Use | Side Effects | Precautions | Drug Interactions | Overdose | Notes | Missed Dose | Storage | Medical Alert

USES: This medication is a nitrate used to relieve and prevent chest pain (angina). Nitroglycerin relaxes blood vessels allowing more blood to flow through. This reduces the workload on the heart and improves blood flow to the heart.

HOW TO USE: At the first sign of chest pain, sit down and place one tablet under the tongue or between your cheek and gum allowing it to dissolve. The drug is absorbed directly through the lining of the mouth. Do not chew or swallow the tablet. Do not eat, drink or smoke while the nitroglycerin is in your mouth. Relief of symptoms should begin in 1 to 3 minutes. If after 5 minutes there is no relief of chest pain, use another tablet. If after an additional 5 minutes there is no relief, use a third tablet. If after another 5 minutes there is no relief, go to a hospital emergency room immediately. To prevent an angina attack, take one tablet 5-10 minutes before activities that you feel may cause an angina attack, such as exercise or sexual intercourse; or as directed by your doctor. Carry this medication with you at all times. SIDE EFFECTS: Burning or tingling under the tongue, headache, dizziness, flushing, or restlessness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. To minimize dizziness and lightheadedness, get up slowly when rising from a seated or lying position. Tell your doctor immediately if any of these serious side effects occur: blurred vision, dry mouth, nausea, pale skin, rapid heartbeat. Headache is often a sign the medication is working. Treat headaches with an aspirin or non-aspirin pain reliever as recommended by your doctor. If the headaches continue or become severe, notify your doctor. A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, severe dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist.

NITROGLYCERIN-SUBLINGUAL (cont.) PRECAUTIONS: Before taking nitroglycerin, tell your doctor or pharmacist if you are allergic to it; or to other nitrates; or if you have any other allergies. Before using this medication, tell your doctor or pharmacist your medical history, especially of: anemia, glaucoma, head injury or surgery, heart problems, severe kidney disease, liver problems, thyroid conditions. This drug may make you dizzy; use caution engaging in activities requiring alertness such as driving or using machinery. Avoid alcoholic beverages while using this medication. Alcoholic beverages may increase the risk of fainting or dizziness. 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: This drug should not be used with the following medications because very serious (possibly fatal) interactions may occur: drugs to treat impotence (e.g., sildenafil, vardenafil, tadalafil). 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: alteplase, aspirin, drugs for high blood pressure (e.g., ACE inhibitors such as fosinopril or lisinopril, alpha blockers such as prazosin or doxazosin, beta-blockers such as propranolol), certain migraine drugs (ergot alkaloids such as ergotamine). This product can affect the results of certain lab tests. Make sure laboratory personnel and your doctors know you use this drug. Do not start or stop any medicine without doctor or pharmacist approval.

NITROGLYCERIN-SUBLINGUAL (cont.) 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 1-800222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include a persistent, throbbing headache; severe dizziness; confusion; weakness; sweating; changes in heart rate; changes in vision; flushing; severe nausea and vomiting. NOTES: Do not share this medication with others. Some persons may develop a tolerance to the effects of this medication over time. Notify your doctor if the medication appears to be losing its effectiveness or if the chest pain continues while taking this drug. Always have this medication readily available. Do not keep it in your pants or shirt pockets.

Your body heat may decrease the effectiveness of this medication. Keep the bottle loose and away from you body in a jacket pocket, tote bag, or purse. MISSED DOSE: This medication is used only at the onset of an attack of chest pain or 10 to 15 minutes before engaging in an activity that may cause chest pain. This medication is not for routine use. STORAGE: If the bottle of tablets contains cotton, remove it and throw the cotton away. Replacing the cotton in the bottle may cause the medication to lose its effectiveness. Store this medication at room temperature away from heat, moisture and sunlight. Keep it in the original screw-cap glass bottle with the cap tightly closed. Otherwise, this drug will not be as effective and may not work as well. Once you have opened the bottle, the expiration date may not apply. Ask your pharmacist for specific storage instructions and about your brand's open bottle expiration date. Do not store in the bathroom. Keep all medicines away from children and pets. 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).

Last Editorial Review: 3/2/2005

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Medline ® Abstract for Reference 52 of 'Nitrates in the management of stable angina pectoris'

Acute and chronic antianginal efficacy of continuous twenty-four-hour TI application of transdermal nitroglycerin. Steering Committee, Transdermal Nitroglycerin Cooperative Study. AU SO Am J Cardiol 1991 Nov 15;68(13):1263-73. To resolve the controversies surrounding the antianginal use of chronic, continuous 24-hour transdermal nitroglycerin therapy, a double-blind, placebo-controlled, randomized, parallel-group study was designed. Eligible patients had chronic angina pectoris with symptom-limited, reproducible treadmill tests and were responsive to sublingual nitroglycerin (n = 562). Patients were randomly assigned to placebo or 1 of 7 doses of active treatment (15, 30, 45, 60, 75, 90 and 105 mg/24 hours). In the active drug groups, treatment was initiated with 15 mg/24 hours during the first week of doubleblind dosing with subsequent weekly increases until the assigned dose was reached, after which the dose was held constant. Treadmill tests were performed 0, 4 and 24 hours after the initial double-blind patches were

applied, after each titration step and after 8 weeks. At the end of double-blind therapy, a sublingual nitroglycerin exercise challenge was repeated. Exercise tolerance in patients using the active patch increased 34 seconds (p less than 0.05) over patients taking placebo 4 hours after the initial application of double-blind therapy, but there was no statistically significant difference in exercise time between placebo and active drug groups by 24 hours after the first application or for the remaining 8 weeks of the trial. Increasing the dose did not overcome the loss of effect. A partial attenuation of the response to a sublingual nitroglycerin challenge seen on exercise tolerance testing also occurred, with patients who received the highest dose showing the greatest attenuation. There were no differences in angina frequency among the groups, although in a post hoc analysis, patients with greater than 7 attacks per week had a reduction in anginal frequency of 6 to 7 attacks per week with active treatment versus 2 attacks per week with placebo. The study showed that (1) tolerance to the exercise effects of continuous transdermal nitroglycerin develops within 24 hours after application; and (2) increasing the dose does not overcome this tolerance. The observation that symptomatic improvement may occur in the absence of increases in exercise tolerance seems deserving of further study. http://www.uptodate.com/patients/content/abstract.do? topicKey=~tiij_ElHm&refNum=52

Transdermal nitroglycerinhttp://www.drugs.com/cdi/nitroglycerin-patch.html

How to use Nitroglycerin Patch: Use Nitroglycerin Patch as directed by your doctor. Check the label on the medicine for exact dosing instructions.

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An extra patient leaflet is available with Nitroglycerin Patch. Talk to your pharmacist if you have questions about this information.

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Nitroglycerin Patch is for external use only.

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Apply the patch at the same time every day.

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Wash your hands thoroughly before and after applying the patch.

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Apply the patch to a non-hairy area of the chest, inner side of the upper arm, back, or shoulder.

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Clean and completely dry the skin before applying the patch. If necessary, hair should be removed by clipping or lightly shaving.

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Remove the patch from the package. Apply with a firm pressure to the skin. To avoid skin irritation, change the treatment site daily. Do not apply to irritated or damaged skin.

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If the patch becomes loose, remove it and apply a new patch at a different site.

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After removing the used patch, fold it in half with the sticky sides together. Discard the patch out of the reach of children and away from pets.

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This patch should only be worn for up to 12 to 14 hours a day, or as directed by your doctor, so that you will have a 10 to 12 hour "nitratefree" period each day. Do not use more of Nitroglycerin Patch than prescribed. It is important to have a "nitrate-free" period of time each day for Nitroglycerin Patch to continue to work well and to decrease the risk of physical dependence.

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If you miss a dose of Nitroglycerin Patch, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Nitroglycerin Patch.

Important safety information: •

Nitroglycerin Patch may cause dizziness, lightheadedness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Nitroglycerin Patch with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

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Check with your doctor before you drink alcohol while you are taking Nitroglycerin Patch. Drinking alcohol may increase the risk of low blood pressure with Nitroglycerin Patch.

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Nitroglycerin Patch may cause dizziness, lightheadedness, or fainting. Sit down while taking Nitroglycerin Patch to avoid falling caused by lightheadedness or dizziness.

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Contact your doctor right away if you develop slow heartbeat or new or worsening chest pain after you take Nitroglycerin Patch.

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Tell your doctor or dentist that you take Nitroglycerin Patch before you receive any medical or dental care, emergency care, or surgery.

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Nitroglycerin Patch may give you daily headaches. This should become less noticeable with time.

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Other dosage forms of Nitroglycerin Patch (eg, sublingual, or under the tongue, tablets) may not work as well while you are taking Nitroglycerin Patch.

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Nitroglycerin Patch takes about 1 to 2 hours to start working and should not be used for a sudden chest pain attack.

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Lab tests, including heart function, blood pressure, and blood electrolyte levels, may be performed while you use Nitroglycerin Patch. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

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Use Nitroglycerin Patch with caution in the ELDERLY; they may be more sensitive to its effects.

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Nitroglycerin Patch is not recommended for use in CHILDREN; safety and effectiveness in children have not been confirmed.

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PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Nitroglycerin Patch while you are pregnant. It is not known if Nitroglycerin Patch is found in breast milk. If you are or will be breastfeeding while you are using Nitroglycerin Patch, check with your doctor. Discuss any possible risks to your baby.

When used for long periods of time without a break, Nitroglycerin Patch may not work as well. This is known as TOLERANCE. Increasing the dose is not effective in managing tolerance to Nitroglycerin Patch. Tolerance to other nitrates or nitrites may also occur. Be sure to have a "nitrate-free" period of time each day to help

prevent this tolerance. Talk with your doctor if Nitroglycerin Patch stops working well. Do not take more than prescribed. Some people who use Nitroglycerin Patch for a long time without a break may develop a physical need to continue taking it. This is known as physical DEPENDENCE. If you use Nitroglycerin Patch without a break and then suddenly stop using it, you may get WITHDRAWAL symptoms. These may include chest pain, heart attack, or possibly sudden death. Be sure to have a "nitrate-free" period of time each day; this may help prevent dependence and withdrawal problems. Possible side effects of Nitroglycerin Patch: All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome: Dizziness, lightheadedness, or fainting when sitting up or standing; flushing of face and neck; headache; irritation at site of patch; nausea; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision; dry mouth; fainting; flushing; heavy sweating; irregular heartbeat; new or worsening chest pain; pale skin; pounding in the chest; rapid heartbeat; severe dizziness or headache; severe or persistent nausea or vomiting; shortness of breath; slow heartbeat; swelling of the hands, ankles, or feet; unusual weakness. This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If OVERDOSE is suspected: Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center (http://www.aapcc.org), or emergency room immediately. Symptoms may include cold

or blue skin; confusion; diarrhea; excessive sweating; fainting; fast, slow, or irregular heartbeat; persistent throbbing headache; seizures; trouble breathing; vision problems.

Proper storage of Nitroglycerin Patch: Store Nitroglycerin Patch at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Nitroglycerin Patch out of the reach of children and away from pets.

General information: •

If you have any questions about Nitroglycerin Patch, please talk with your doctor, pharmacist, or other health care provider.

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Nitroglycerin Patch is to be used only by the patient for whom it is prescribed. Do not share it with other people.

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If your symptoms do not improve or if they become worse, check with your doctor.

This information is a summary only. It does not contain all information about Nitroglycerin Patch. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Nitroglycerin Patch is used for:

Preventing chronic chest pain caused by heart disease. It also may be used for other conditions as determined by your doctor. Nitroglycerin Patch is a nitrate. It works by relaxing (widening) blood vessels. Chest pain occurs when the heart needs more oxygen than it can get. Relaxing blood vessels allows blood to flow more easily. This reduces the heart's workload and the amount of oxygen needed by the heart.

Do NOT use Nitroglycerin Patch if: •

you are allergic to any ingredient in Nitroglycerin Patch

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you are allergic to the adhesive that makes the patch stick to your skin

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you have increased pressure in or severe injury to the head

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you have severe anemia

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you are taking a phosphodiesterase type 5 inhibitor (eg, sildenafil)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Nitroglycerin Patch: Some medical conditions may interact with Nitroglycerin Patch. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

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if you are pregnant, planning to become pregnant, or are breastfeeding

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if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

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if you have allergies to medicines, foods, or other substances

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if you drink alcoholic beverages

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if you have a history of other heart problems (eg, heart failure, enlarged heart, heart attack), overactive thyroid, stroke or other bleeding in the brain, or recent head injury

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if you have anemia, low blood pressure, dehydration, or low blood volume

Some MEDICINES MAY INTERACT with Nitroglycerin Patch. Tell your health care provider if you are taking any other medicines, especially any of the following:

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Beta-blockers (eg, propranolol), calcium channel blockers (eg, diltiazem), diuretics (eg, furosemide, hydrochlorothiazide), medicines for high blood pressure, phenothiazines (eg, thioridazine), or phosphodiesterase type 5 inhibitors (eg, sildenafil) because the risk of low blood pressure and dizziness on standing may be increased

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Salicylates (eg, aspirin) because they may increase the risk of Nitroglycerin Patch's side effects

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Alteplase because the effectiveness of Nitroglycerin Patch may be decreased

This may not be a complete list of all interactions that may occur. Ask your health care provider if Nitroglycerin Patch may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.