Dilatrate-SR

You should not use isosorbide dinitrate if:

• you are allergic to isosorbide dinitrate, isosorbide mononitrate, or nitroglycerin; or

• you have early signs of a heart attack (chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating).

You should not take erectile dysfunction medicine (Viagra, Cialis, Levitra, Stendra, Staxyn, sildenafil, avanafil, tadalafil, vardenafil) while you are taking isosorbide dinitrate. Taking these medicines together can cause a sudden and serious decrease in blood pressure.

To make sure isosorbide dinitrate is safe for you, tell your doctor if you have:

• congestive heart failure;

• kidney disease; or

• low blood pressure.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether isosorbide dinitrate passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Before using isosorbide dinitrate to treat a sudden angina attack, your doctor may want you to first use a nitroglycerin sublingual tablet. Follow your doctor's instructions about what medications to use during an attack and how much time to allow between doses.

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended. If you use too much isosorbide dinitrate, it might stop working as well in controlling your condition.

Try to rest or stay seated when you take this medicine (may cause dizziness or fainting).

To prevent angina attacks, isosorbide dinitrate is usually taken at regular intervals.

To treat an angina attack that has already begun, use the medicine at the first sign of chest pain. Place the tablet under your tongue and allow it to dissolve slowly. Do not chew or swallow it.

You may use the sublingual tablet within 15 minutes before an activity you think might cause chest pain. Follow your doctor's instructions.

Do not crush, chew, break, or open an extended-release capsule or tablet. Swallow it whole.

Follow your doctor's dosing instructions very carefully. If your doctor changes your brand, strength, or type of isosorbide dinitrate, your dosage needs may change. Ask your pharmacist if you have any questions about the new kind of isosorbide dinitrate you receive at the pharmacy.

Seek emergency medical attention if your chest pain gets worse or lasts longer than 5 minutes, especially if you have trouble breathing or feel weak, dizzy, or nauseated, or lightheaded.

You may have very low blood pressure while taking this medicine. Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. Prolonged illness can lead to a serious electrolyte imbalance, making it dangerous for you to use isosorbide dinitrate.

If you take isosorbide dinitrate on a regular schedule to prevent angina, do not stop taking it suddenly or you could have a severe attack of angina. Keep this medicine on hand at all times. Get your prescription refilled before you run out of medicine completely.

Store at room temperature, away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Since isosorbide dinitrate is sometimes used only when needed, you may not be on a dosing schedule. If you are on a schedule, take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 2 hours away.

If you are using the extended-release capsule or tablet and your next dose is less than 6 hours away, skip the missed dose and use the medicine at your next regularly scheduled time.

Do not use extra medicine to make up a missed dose.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of isosorbide dinitrate in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of isosorbide dinitrate in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving isosorbide dinitrate.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Avanafil
• Riociguat
• Sildenafil
• Tadalafil
• Vardenafil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Congestive heart failure or
• Heart attack, recent or
• Hypertrophic cardiomyopathy (a heart disease) or
• Hypotension (low blood pressure) or
• Hypovolemia (low amount of blood)—Use with caution. May make these conditions worse.

If you will be taking this medicine for a long time, it is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Do not take avanafil (Stendra®), riociguat (Adempas®), sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®) while you are using this medicine. Using these medicines together may cause blurred vision, dizziness, lightheadedness, or fainting. If you are taking these medicines and you experience an angina attack, you must go to the hospital right away.

This medicine may cause headaches. These headaches are a sign that the medicine is working. Do not stop using the medicine or change the time you use it in order to avoid the headaches. If you have severe pain, talk with your doctor.

Dizziness, lightheadedness, or faintness may occur, especially when you get up quickly from a lying or sitting position. Getting up slowly may help.

Dizziness, lightheadedness, or fainting is also more likely to occur if you drink alcohol, stand for long periods of time, exercise, or if the weather is hot. While you are taking this medicine, be careful to limit the amount of alcohol you drink. Also, use extra care during exercise or hot weather or if you must stand for long periods of time.

Do not stop using this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bluish-colored lips, fingernails, or palms
• dark urine
• difficulty with breathing
• dizziness or lightheadedness
• fever
• headache
• pale skin
• rapid heart rate
• sore throat
• unusual bleeding or bruising
• unusual tiredness or weakness

• Arm, back, or jaw pain
• blurred vision
• chest pain or discomfort
• chest tightness or heaviness
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast or irregular heartbeat
• sweating

Get emergency help immediately if any of the following symptoms of overdose occur:

• Blurred or loss of vision
• bulging soft spot on the head of an infant
• change in consciousness
• change in the ability to see colors, especially blue or yellow
• cold, clammy skin
• convulsions
• disturbed color perception
• double vision
• fast, irregular, pounding, or racing heartbeat or pulse
• feeling of constant movement of self or surroundings
• halos around lights
• headache, severe and throbbing
• increased sweating
• loss of appetite
• loss of consciousness
• nausea
• night blindness
• overbright appearance of lights
• paralysis
• sensation of spinning
• slow heartbeat
• tunnel vision
• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

dilatrate®-SR sustained release capsules are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of controlled-release oral isosorbide dinitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.

General

Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide dinitrate. 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 isosorbide dinitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

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

Some clinical trials in angina patients have provided nitroglycerin for about 12 continuous hours of every 24-hour day. During the interdosing intervals in some of these trials, anginal attacks have been more easily provoked than before treatment and patients have demonstrated hemodynamic rebound and decreased exercise tolerance. The importance of these observations to the routine, clinical use of controlled-release oral isosorbide dinitrate is not known.

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.

Information for Patients

Patients should be told that the antianginal efficacy of isosorbide dinitrate is strongly related to its dosing regimen, so the prescribed schedule of dosing should be followed carefully. In particular, daily headaches sometimes accompany treatment with isosorbide dinitrate. In patients who get these headaches, the headaches are a marker of the activity of the drug. Patients should resist the temptation to avoid headaches by altering the schedule of their treatment with isosorbide dinitrate, since loss of headache may be associated with simultaneous loss of antianginal efficacy. Aspirin and/or acetaminophen, on the other hand, often successfully relieve isosorbide dinitrate-induced headaches with no deleterious effect on isosorbide dinitrate's antianginal efficacy.

Treatment with isosorbide dinitrate 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.

Drug Interactions

Concomitant use of dilatrate®-SR with phosphodiesterase inhibitors in any form is contraindicated (see CONTRAINDICATIONS).

Concomitant use of dilatrate®-SR with riociguat, a soluble guanylate cyclase stimulator, is contraindicated (see CONTRAINDICATIONS).

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

Carcinogenesis, Mutagenesis and Impairment of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of isosorbide dinitrate. In a modified two-litter reproduction study, there was no remarkable gross pathology and no altered fertility or gestation among rats fed isosorbide dinitrate at 25 or 100 mg/kg/day.

Pregnancy Category C

At oral doses 35 and 150 times the daily Maximum Recommended Human Dose (MRHD), isosorbide dinitrate has been shown to cause a dose related increase in embryotoxicity (increase in mummified pups) in rabbits. There are no adequate, well-controlled studies in pregnant women. Isosorbide dinitrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of dilatrate®-SR did not include sufficient numbers of subjects aged 65 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.

Applies to isosorbide dinitrate: oral capsule extended release, oral tablet, oral tablet chewable, oral tablet extended release, sublingual tablet

General

The most common side effect was headache.[Ref]

Nervous system

Frequency not reported: Headache, dizziness, syncope, lightheadedness[Ref]

Cardiovascular

Common (1% to 10%): Decrease in blood pressure and/or orthostatic hypotension with reflex tachycardia and symptoms/signs of cerebral ischemia (including drowsiness and dizziness and weakness) with first time use and when the dose is increased
Uncommon (0.1% to 1%): Marked decreases in blood pressure with an aggravation of symptomatic angina pectoris, collapse associated with bradycardia and cardiac rhythm disturbances
Frequency not reported: Pallor, crescendo angina, rebound hypertension, hypotension[Ref]

Other

Common (1% to 10%): Peripheral edema in patients treated for left ventricular failure[Ref]

Dermatologic

Uncommon (0.1% to 1%): Allergic skin reactions
Very rare (less than 0.01%): Exfoliative dermatitis/Stevens-Johnson Syndrome or angioedema
Frequency not reported: Cutaneous vasodilation with flushing, excessive perspiration, rash[Ref]

Gastrointestinal

Uncommon (0.1% to 1%): Nausea and vomiting
Frequency not reported: Heartburn[Ref]

Endocrine

Very rare (less than 0.01%): Pituitary apoplexy in patients with undiagnosed pituitary tumors[Ref]

Ocular

Very rare (less than 0.01%): Angle closure glaucoma[Ref]

Respiratory

Very rare (less than 0.01%): Alveolar hypoventilation with consequent hypoxemia and the risk of developing a myocardial infarction in patients with coronary heart disease[Ref]

Hematologic

Frequency not reported: Methemoglobinemia, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase-deficient syndrome[Ref]

Psychiatric

Frequency not reported: Restlessness[Ref]

Some side effects of Dilatrate-SR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.