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 1-800-

222-1222. 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

Top of Form

Bottom of Form
 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 double-
blind 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.

• An extra patient leaflet is available with Nitroglycerin Patch. Talk to

your pharmacist if you have questions about this information.
• Nitroglycerin Patch is for external use only.
• Apply the patch at the same time every day.
• Wash your hands thoroughly before and after applying the patch.
• Apply the patch to a non-hairy area of the chest, inner side of the
upper arm, back, or shoulder.
• Clean and completely dry the skin before applying the patch. If
necessary, hair should be removed by clipping or lightly shaving.
• 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.
• If the patch becomes loose, remove it and apply a new patch at a
different site.
• 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.
• 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 "nitrate-
free" 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.
• 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.
• 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.
• Nitroglycerin Patch may cause dizziness, lightheadedness, or fainting.
Sit down while taking Nitroglycerin Patch to avoid falling caused by
lightheadedness or dizziness.
• Contact your doctor right away if you develop slow heartbeat or new or
worsening chest pain after you take Nitroglycerin Patch.
• Tell your doctor or dentist that you take Nitroglycerin Patch before you
receive any medical or dental care, emergency care, or surgery.
• Nitroglycerin Patch may give you daily headaches. This should become
less noticeable with time.
• Other dosage forms of Nitroglycerin Patch (eg, sublingual, or under the
tongue, tablets) may not work as well while you are taking
Nitroglycerin Patch.
• Nitroglycerin Patch takes about 1 to 2 hours to start working and
should not be used for a sudden chest pain attack.
• 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.
• Use Nitroglycerin Patch with caution in the ELDERLY; they may be
more sensitive to its effects.
• Nitroglycerin Patch is not recommended for use in CHILDREN; safety
and effectiveness in children have not been confirmed.
• 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 breast-
feeding 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.
• Nitroglycerin Patch is to be used only by the patient for whom it is
prescribed. Do not share it with other people.
• 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

• you are allergic to the adhesive that makes the patch stick to your skin
• you have increased pressure in or severe injury to the head
• you have severe anemia
• 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:
 • if you are pregnant, planning to become pregnant, or are breast-
feeding
• if you are taking any prescription or nonprescription medicine, herbal
preparation, or dietary supplement
• if you have allergies to medicines, foods, or other substances
• if you drink alcoholic beverages
• 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
• 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:

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