Complete SPL Sections
DESCRIPTION
DESCRIPTION SECTION
Nitroglycerin is 1,2,3-propanetriol, trinitrate, an organic nitrate whose structural formula is: and whose molecular weight is 227.09. The organic nitrates are vasodilators, active on both arteries and veins. The Nitroglycerin Transdermal System is a flat unit designed to provide continuous controlled release of nitroglycerin through intact skin. The rate of release of nitroglycerin is linearly dependent upon the area of the applied system; each cm 2 of applied system delivers approximately 0.03 mg of nitroglycerin per hour. Thus, the 7-, 14-, and 21-cm 2 systems deliver approximately 0.2, 0.4, and 0.6 mg of nitroglycerin per hour, respectively. The remainder of the nitroglycerin in each system serves as a reservoir and is not delivered in normal use. After 12 hours, for example, each system has delivered approximately 6% of its original content of nitroglycerin. The Nitroglycerin Transdermal System comprises 3 layers as shown below. Proceeding from the visible surface towards the surface attached to the skin, these layers are: 1) a transparent outer backing layer composed of a composite plastic film and is printed with the name of the drug and strength; 2) nitroglycerin in acrylic-based polymer adhesive with a cross-linking agent; 3) a protective white, translucent peelable silicone treated polystyrene release liner which covers the second layer and must be removed-prior to use. The inactive ingredients are: multilayer plastic film (polyolefin/EVA/PVDC), silicone coated polystyrene film, acrylic adhesive with a cross-linking agent and blue ink. Cross section of the system: OUTER BACKING (impermeable) SECOND LAYER (nitroglycerin in acrylic-based adhesive) PROTECTIVE PEELABLE LINER (release liner)
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
The principal pharmacological action of nitroglycerin is relaxation of 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 had been absent from the body for several hours was their antianginal efficacy restored.
INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Transdermal nitroglycerin is indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of transdermal nitroglycerin is not sufficiently rapid for this product to be useful in aborting an acute attack.
CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
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. Do not use Nitroglycerin Transdermal Systems in patients who are taking phosphodiesterase inhibitors (such as sildenafil, tadalafil, or vardenafil) for erectile dysfunction or pulmonary arterial hypertension. Concomitant use can cause severe drops in blood pressure. Do not use Nitroglycerin Transdermal Systems in patients who are taking the soluble guanylate cyclase stimulator riociguat. Concomitant use can cause hypotension.
WARNINGS
WARNINGS SECTION
Amplification of the vasodilatory effects of Nitroglycerin Transdermal System by phosphodiesterase inhibitors, e.g., sildenafil may result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion. The benefits of transdermal nitroglycerin in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use nitroglycerin in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia. A cardioverter/defibrillator should not be discharged through a paddle electrode that overlies a nitroglycerin transdermal patch. The arcing that may be seen in this situation is harmless in itself, but it may be associated with local current concentration that can cause damage to the paddles and burns to the patient.
PRECAUTIONS
PRECAUTIONS SECTION
ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
Adverse reactions to nitroglycerin are generally dose-related, and almost all of these reactions are the result of nitroglycerin's activity as a vasodilator. Headache, which may be severe, is the most commonly reported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon. Allergic reactions to nitroglycerin are also uncommon, and the great majority of those reported have been cases of contact dermatitis or fixed drug eruptions in patients receiving nitroglycerin in ointments or patches. There have been a few reports of genuine anaphylactoid reactions, and these reactions can probably occur in patients receiving nitroglycerin by any route. Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients. Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred (see OVERDOSAGE ). Application-site irritation may occur but is rarely severe. In two placebo-controlled trials of intermittent therapy with nitroglycerin patches at 0.2 to 0.8 mg/hr, the most frequent adverse reactions among 307 subjects were as follows: Placebo Patch Headache 18% 63% Lightheadedness 4% 6% Hypotension and/or syncope 0% 4% Increased angina 2% 2%
OVERDOSAGE
OVERDOSAGE SECTION
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
The suggested starting dose is between 0.2 mg/hr and 0.4 mg/hr. Doses between 0.4 mg/hr and 0.8 mg/hr have shown continued effectiveness for 10-12 hours daily for at least one month (the longest period studied) of intermittent administration. Although the minimum nitrate-free interval has not been defined, data show that a nitrate-free interval of 10-12 hours is sufficient (see CLINICAL PHARMACOLOGY ). Thus, an appropriate dosing schedule for nitroglycerin patches would include a daily patch-on period of 12-14 hours and a daily patch-off period of 10-12 hours. Although some well-controlled clinical trials using exercise tolerance testing have shown maintenance of effectiveness when patches are worn continuously, the large majority of such controlled trials have shown the development of tolerance (i.e., complete loss of effect) within the first 24 hours after therapy was initiated. Dose adjustment, even to levels much higher than generally used, did not restore efficacy.
PATIENT INSTRUCTIONS FOR APPLICATION OF SYSTEM
INFORMATION FOR PATIENTS SECTION
A patient information leaflet is supplied with each carton.
HOW SUPPLIED
HOW SUPPLIED SECTION
Nitroglycerin Transdermal System 0.2 mg/hr is a white, translucent round patch (registered imprint 'Nitroglycerin 0.2 mg/hr'), supplied in a foil-lined pouch 30 Systems………………………...…..... NDC 68382-309-30 Nitroglycerin Transdermal System 0.4 mg/hr is a white, translucent round patch (registered imprint 'Nitroglycerin 0.4 mg/hr'), supplied in a foil-lined pouch 30 Systems………………………...…..... NDC 68382-310-30 Nitroglycerin Transdermal System 0.6 mg/hr is a white, translucent round patch (registered imprint 'Nitroglycerin 0.6 mg/hr'), supplied in a foil-lined pouch 30 Systems………………………...…..... NDC 68382-311-30 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Do not store unpouched. Apply immediately upon removal from the pouch. Manufactured by: Hercon Pharmaceuticals, LLC Emigsville, PA 17318 Distributed by: Zydus Pharmaceuticals (USA) Inc. Pennington, NJ 08534 1000084 Rev : 07/18
Information for the Patient
SPL PATIENT PACKAGE INSERT SECTION
Please read this instruction sheet carefully before using Nitroglycerin Transdermal System Nitroglycerin Transdermal System for the prevention of angina Nitroglycerin Transdermal System How to Use Nitroglycerin Transdermal System is easy to use-- it has a transparent outer backing with a special adhesive that keeps the system in place and a white, translucent protective peelable liner. Where to place Nitroglycerin Transdermal System Select any area of skin on the body, EXCEPT the ex tremities below the knee or elbow. The chest is the pre ferred site. The area should be clean, dry, and hairless. If hair is likely to interfere with system adhesion or removal, it can be clipped but not shaved. Take care to avoid areas with cuts or irritations. Do NOT apply the system immediately after showering or bathing. It is best to wait until you are certain the skin is completely dry. How to apply Nitroglycerin Transdermal System Each Nitroglycerin Transdermal System is individually sealed in a protective pouch. Application • Wash hands before applying. • Tear or cut pouch along dotted line. Remove patch from the pouch. • Hold patch with the printed side away from you, with the score line in an up-and-down position. • Bend sides of patch toward you then away from you. Repeat as necessary until the liner snaps down the middle. • Peel off the larger part of the liner. • Hold patch by the smaller part of the liner (which is still in place) to avoid touching the sticky side of the patch • Apply the sticky side of the patch to your skin. Smooth down. • Fold back the smaller part of the patch so that you can easily remove the remaining piece of the liner. • Press the entire patch firmly in place. Then wash your hands with soap and water to remove any drug residue. When Nitroglycerin Transdermal System is applied to your body, the nitroglycerin contained in the system begins to flow onto your skin so that it is released and available for absorption through your skin at a uniform rate. At the time recommended by your doctor, remove and discard the system. Removal • Press down on the center of the system to raise its outer edge away from the skin. • Grasp the edge gently, and slowly peel the unit away from your skin. Wash skin area with soap and water. Towel dry. Wash hands. You should use a different application site every day. Place a new system on a different skin site, following the steps for application, according to your doctor's instructions. Please note Contact with water, as in bathing, swimming, or showering will not affect the system. In the unlikely event that a system falls off, discard it and put a new one on a different skin site. Precautions The most common side effect is headache, which often decreases as therapy is continued, but may require treatment with a mild analgesic. Although uncommon, faintness, flushing, and dizziness may occur, especially when suddenly rising from the recumbent (lying horizontal) position. If these symptoms occur, remove the system and notify your physician. Skin irritation may occur. If it persists, consult your physician. Keep these systems and all drugs out of the reach of children. Important Your doctor may decide to increase or decrease the size of the system, or prescribe a combination of systems, to suit your particular needs. The dose may vary depending on your individual response to the system. This system is to be used for preventing angina, not for treating an acute attack. Usual Dosage Each 24 hour period should include a patch-on period of 12 to 14 hours, followed by a patch-free interval. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Do not store unpouched. Apply immediately upon removal from the protective pouch. "Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. " Manufactured by: Hercon Pharmaceuticals, LLC Emigsville, PA 17318 Distributed by: Zydus Pharmaceuticals (USA) Inc. Pennington, NJ 08534 1000085 Rev.: 07/18
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 68382- 309 -30 Nitroglycerin Transdermal System 0.2 mg/hr For Transdermal Use Only. Approximate rated release in vivo 0.2 mg/hr. Each 7 cm 2 system contains 37.3 mg of nitroglycerin in acrylic-based polymer adhesive with a cross-linking agent. 30 Systems Rx only zydus pharmaceuticals NDC 68382- 310 -30 Nitroglycerin Transdermal System 0.4 mg/hr For Transdermal Use Only. Approximate rated release in vivo 0.4 mg/hr. Each 14 cm 2 system contains 74.6 mg of nitroglycerin in acrylic-based polymer adhesive with a cross-linking agent. 30 Systems Rx only zydus pharmaceuticals NDC 68382- 311 -30 Nitroglycerin Transdermal System 0.6 mg/hr For Transdermal Use Only. Approximate rated release in vivo 0.6 mg/hr. Each 21 cm 2 system contains 111.9 mg of nitroglycerin in acrylic-based polymer adhesive with a cross-linking agent. 30 Systems Rx only zydus pharmaceuticals