Nitroglycerin-transdermal

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 peel off the protective clear liner as directed. Usually, you will wear the patch on the upper arm or chest. However, you can wear it anywhere on the body below the neck and above the knees or elbows. Apply the patch to a clean, dry, and hairless area. Hair in the area may be clipped, but not shaved. Avoid areas with cuts or irritation. Do not apply the patch immediately after bathing or showering. Wait until your skin is completely dry. However, you may bathe, shower, and swim while wearing the patch. Press the patch firmly in place with the palm of your hand. Wash your hands after applying the patch.You will usually use 1 patch a day and wear it for 12 to 14 hours or as directed by your doctor. The dosage is based on your medical condition and response to treatment.To reduce skin irritation, apply each new patch to a different area of skin. After removing the old patch, fold it in half with the sticky sides together, and discard out of reach of children and pets.Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time each day.Do not suddenly stop using this medication without consulting your doctor. Some conditions may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.Although unlikely, when this medication is used for a long time, it may not work as well and may require different dosing. Tell your doctor if this medication stops working well (for example, you have worsening chest pain or it occurs more often).

You should not use this medicine if you are allergic to any type of adhesive on a bandage or other transdermal skin patch, or if you are using medicine to treat pulmonary arterial hypertension (PAH), such as riociguat, (Adempas), sildenafil (Revatio), or tadalafil (Adcirca).

Do not take erectile dysfunction medicine (Viagra, Cialis, and others) while you are using nitroglycerin transdermal, or you could have a sudden and serious decrease in blood pressure.

Apply a patch as soon as you remember, and keep it on for the rest of your wearing time without changing your patch removal schedule. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra patches to make up the missed dose.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• worsening chest pain, slow heart rate;

• a light-headed feeling, like you might pass out; or

• pale or blue colored appearance in your fingers or toes.

Nitroglycerin can cause severe headaches, especially when you first start using it. These headaches may gradually become less severe as you continue to use the medicine. Do not stop using this medicine to avoid headaches. Ask your doctor before using any headache pain medication.

Common side effects may include:

• headache; or

• mild dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Angina Pectoris:

INTRAVENOUS SOLUTION:
5 mcg/min continuous IV infusion via non-absorptive tubing; increase by 5 mcg/min every 3 to 5 minutes as needed up to 20 mcg/min, then by 10 or 20 mcg/min if needed

Comments:
-Starting doses of 25 mcg/min or higher have been used with polyvinyl chloride (PVC) tubing.
-Lower concentrations increase potential dosing precision and volume to be delivered; consider patient fluid requirements and expected infusion duration when selecting an appropriate dilution.

Use: Treatment of angina pectoris in patients who have not responded to sublingual nitroglycerin and beta-blockers.


LINGUAL SPRAY:
1 to 2 sprays (0.4 to 0.8 mg) on or under tongue every 5 minutes as needed, up to 3 sprays in 15 minutes; if pain persists after maximum dose, prompt medical attention is recommended

Comments:
-Administer while sitting due to rapid onset.
-Advise patient not to inhale or swallow this medication.

Use: Acute relief of an anginal attack.


SUBLINGUAL TABLET:
0.3 to 0.6 mg sublingually or in the buccal pouch every 5 minutes as needed, up to 3 doses in 15 minutes; if pain persists after maximum dose, prompt medical attention is recommended

Comments:
-Administer while sitting down due to rapid onset.
-Advise patient not to chew or swallow this medication.

Use: Acute relief of an anginal attack.

Usual Adult Dose for Angina Pectoris Prophylaxis:

LINGUAL SPRAY:
1 to 2 sprays (0.4 to 0.8 mg) on or under tongue 5 to 10 minutes prior to activity that might precipitate an acute attack

Comments:
-Administer while sitting due to rapid onset.
-Advise patient not to inhale or swallow this medication.


SUBLINGUAL TABLET:
0.3 to 0.6 mg sublingually or in the buccal pouch 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack

Comments:
-Administer while sitting due to rapid onset.
-Advise patient not to chew or swallow this medication.


TOPICAL OINTMENT:
1/2 inch (7.5 mg) topically upon rising and 1/2 inch (7.5 mg) 6 hours later; titrate as needed and tolerated

Comments:
-Clinical trial doses have ranged from 1/2 to 2 inches (7.5 to 30 mg) applied to 36 square inches of truncal skin.
-Ointment should be applied to a dry and hairless area of the trunk.


TRANSDERMAL PATCH:
0.2 to 0.4 mg/hr patch applied topically once a day for 12 to 14 hours per day; titrate as needed and tolerated up to 0.8 mg/hr

Comments:
-Patch should be applied to a dry and hairless area of the upper arm or body; rotate application sites to avoid skin irritation.
-Doses between 0.4 and 0.8 mg/hr have shown continued effectiveness for 10 to 12 hours daily for at least 1 month of intermittent administration.


EXTENDED RELEASE CAPSULE:
2.5 to 6 mg orally 3 to 4 times a day; titrate as needed and tolerated

Comments:
-Subjects were titrated up to 26 mg four times a day in one clinical trial.

Usual Adult Dose for Myocardial Infarction:

INTRAVENOUS SOLUTION:
5 mcg/min continuous IV infusion via non-absorptive tubing; increase by 5 mcg/min every 3 to 5 minutes as needed up to 20 mcg/min, then by 10 or 20 mcg/min if needed

Comments:
-Starting doses of 25 mcg/min or higher have been used with polyvinyl chloride (PVC) tubing.
-Lower concentrations increase potential dosing precision and volume to be delivered; consider patient fluid requirements and expected infusion duration when selecting an appropriate dilution.

Use: Control of congestive heart failure in the setting of acute myocardial infarction.

Usual Adult Dose for Hypertension:

INTRAVENOUS SOLUTION:
5 mcg/min continuous IV infusion via non-absorptive tubing; increase by 5 mcg/min every 3 to 5 minutes as needed up to 20 mcg/min, then by 10 or 20 mcg/min if needed

Comments:
-Starting doses of 25 mcg/min or higher have been used with polyvinyl chloride (PVC) tubing.
-Lower concentrations increase potential dosing precision and volume to be delivered; consider patient fluid requirements and expected infusion duration when selecting an appropriate dilution.

Uses:
-Treatment of perioperative hypertension.
-Induction of intraoperative hypotension.

Usual Adult Dose for Anal Fissure and Fistula:

RECTAL OINTMENT:
1 inch of ointment (375 mg of ointment equivalent to 1.5 mg of nitroglycerin) intra-anally every 12 hours for up to 3 weeks

Comments:
-A finger covering such as plastic wrap, a disposable surgical glove, or a finger cot should be placed on the finger to apply ointment.
-Insert finger no further than first finger joint and apply around side of anal canal; if unable to insert finger due to pain, apply directly to outside of anus.

Use: Treatment of moderate to severe pain associated with chronic anal fissure.

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

Do not use nitroglycerin if you take riociguat (Adempas®), sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®). Using one of these medicines while treated with nitroglycerin may cause severe drops in blood pressure, 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.

nitroglycerin 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. Ask you doctor if you can take aspirin or acetaminophen to treat the headache.

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 using nitroglycerin, 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 nitroglycerin without checking with your doctor first. Your doctor may want you to gradually reduce the amount you are using before stopping it completely.

Tell the doctor in charge that you are using nitroglycerin before having a magnetic resonance imaging (MRI) scan. Skin burns may occur at the site where the patch is worn during this procedure. Ask your doctor if the patch should be removed before having an MRI scan. You might need to put on a new patch after the procedure.

Use of Nitroglycerin Transdermal system is contraindicated in patients using sildenafil because sildenafil may amplify the vasodilatory effects of Nitroglycerin Transdermal systems 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.

Hemodynamic Effects

The ill effects of nitroglycerin overdose are generally the results 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 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 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.

Nitroglycerin Transdermal System 0.2 mg/hr

NDC 68382-309-30

Rx only

Contains 30 systems

ZYDUS

Nitroglycerin Transdermal System 0.4 mg/hr

NDC 68382-310-30

Rx only

Contains 30 systems

ZYDUS

Nitroglycerin Transdermal System 0.6 mg/hr

NDC 68382-311-30

Rx only

Contains 30 systems

ZYDUS

Nitroglycerin Transdermal SYSTEM  Nitroglycerin Transdermal system patch, extended release

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68382-309 Route of Administration TRANSDERMAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength NITROGLYCERIN (NITROGLYCERIN) NITROGLYCERIN 0.2 mg  in 1 h

Inactive Ingredients Ingredient Name Strength METHYL ACRYLATE   ACRYLIC ACID   GLYCIDYL METHACRYLATE

Packaging # Item Code Package Description 1 NDC:68382-309-30 30 POUCH in 1 CARTON 1 NDC:68382-309-01 1 PATCH in 1 POUCH 1 14 h in 1 PATCH

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA089884 02/15/2017

Nitroglycerin Transdermal SYSTEM  Nitroglycerin Transdermal system patch, extended release

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68382-310 Route of Administration TRANSDERMAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength NITROGLYCERIN (NITROGLYCERIN) NITROGLYCERIN 0.4 mg  in 1 h

Inactive Ingredients Ingredient Name Strength METHYL ACRYLATE   ACRYLIC ACID   GLYCIDYL METHACRYLATE

Packaging # Item Code Package Description 1 NDC:68382-310-30 30 POUCH in 1 CARTON 1 NDC:68382-310-01 1 PATCH in 1 POUCH 1 14 h in 1 PATCH

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA089885 02/15/2017

Nitroglycerin Transdermal SYSTEM  Nitroglycerin Transdermal system patch, extended release

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68382-311 Route of Administration TRANSDERMAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength NITROGLYCERIN (NITROGLYCERIN) NITROGLYCERIN 0.6 mg  in 1 h

Inactive Ingredients Ingredient Name Strength METHYL ACRYLATE   ACRYLIC ACID   GLYCIDYL METHACRYLATE

Packaging # Item Code Package Description 1 NDC:68382-311-30 30 POUCH in 1 CARTON 1 NDC:68382-311-01 1 PATCH in 1 POUCH 1 14 h in 1 PATCH

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA089886 02/15/2017

Labeler - Zydus Pharmaceuticals (USA) Inc. (156861945)

Registrant - Hercon Pharmaceuticals LLC (078710593)

Revised: 01/2017   Zydus Pharmaceuticals (USA) Inc.

Headache, dizziness, lightheadedness, nausea, and flushing may occur as your body adjusts to this medication. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Headache is often a sign that this medication is working. Your doctor may recommend treating headaches with an over-the-counter pain reliever (such as acetaminophen, aspirin). If the headaches continue or become severe, tell your doctor promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

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 right away if any of these unlikely but serious side effects occur: fainting, fast/irregular/pounding heartbeat.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), 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.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

List Nitroglycerin PATCH Patch, Transdermal 24 Hours side effects by likelihood and severity.