Minitran

• Graceway Pharmaceuticals, LLC.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• any medicines that are used to treat angina, heart failure, or an irregular heartbeat.
• any medicines that reduce blood pressure.
• any diuretics (water pills).
• medications to treat depression or psychiatric illness.
• ergotamine or similar drugs for migraine headaches.
• aspirin.
• the blood thinner medicine heparin.
• any medicines for erectile dysfunction.

Do not consume alcohol while taking Minitran, as this can lower your blood pressure.

This is not a complete list of Minitran drug interactions. Ask your doctor or pharmacist for more information.

Nitroglycerin ointment or skin patch is used to prevent angina (chest pain) caused by coronary artery disease. It does not work fast enough to relieve the pain of an angina attack that has already started.

Nitroglycerin belongs to the group of medicines called nitrates. It works by relaxing the blood vessels and increasing the supply of blood and oxygen to the heart while reducing its work load. When used regularly on a long-term basis, this helps prevent angina attacks from occurring.

This medicine is available only with your doctor's prescription.

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 nitroglycerin transdermal 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 nitroglycerin transdermal in the elderly. However, elderly patients are more likely to have low blood pressure and age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving nitroglycerin transdermal.

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

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alteplase, Recombinant

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetylcysteine
• Aspirin
• Dihydroergotamine
• Pancuronium

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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

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:

• Cardioversion (medical heart procedure) or
• Defibrillation (medical heart procedure)—Use with caution. The patch should be removed before having these procedures.

• 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.

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:

• Lightheadedness

• 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
• nausea
• sweating
• unusual tiredness or weakness

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

• Blistering, burning, crusting, dryness, or flaking of the skin
• cough
• difficulty with swallowing
• hives or rash
• itching, scaling, severe redness, soreness, or swelling of the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

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
• disturbed color perception
• double vision
• feeling of constant movement of self or surroundings
• halos around lights
• headache, severe and throbbing
• loss of consciousness
• night blindness
• overbright appearance of lights
• paralysis
• sensation of spinning
• tunnel vision

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Burning, itching, redness, skin rash, swelling, or soreness at the application site

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.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Skin irritation.
• You may have headaches when you start taking this medicine. Most of the time it gets better with time. Do not change how you use Minitran to avoid these headaches. Talk with your doctor for ways to lessen this side effect.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Throw away all patches in a sealed container away from children and pets.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

The principal pharmacological action of nitroglycerin is relaxation of the 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 have been absent from the body for several hours has 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 (non vasoactive) mononitrates and, ultimately, to glycerol and carbon dioxide.

To avoid development of tolerance to nitroglycerin, drug-free intervals of 10 to 12 hours are known to be sufficient; shorter intervals have not been well studied. In one well-controlled 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 2 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 to 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.

NDC 99207-171-05

Minitran™
(nitroglycerin)

TRANSDERMAL DELIVERY SYSTEM

0.2 mg/hr
30 systems

Each 6.7 cm2 system contains 18 mg of
nitroglycerin in an acrylate-based
hypoallergenic adhesive.

Manufactured for:
Medicis, The Dermatology Company
Scottsdale, AZ 85256
by: 3M Drug Delivery Systems
Northridge, CA 91324

MEDICIS®