8289421/0715OS
id: 737606a9-7193-4394-a43e-1f02d515a972
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5
Rx only
DESCRIPTION:
id: 3ccb73d4-4067-40d0-8c58-569c2dee210e
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Isosorbide dinitrate (ISDN) is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate, an organic nitrate whose structural formula is:
The organic nitrates are vasodilators, active on both arteries and veins.
Isosorbide dinitrate is a white, crystalline, odorless compound which is stable in air and in solution, has a melting point of 70°C and has an optical rotation of +134° (c=1, alcohol, 20°C). Isosorbide dinitrate is freely soluble in organic solvents such as acetone, alcohol, and ether, but is only sparingly soluble in water.
Isosorbide dinitrate is available as 5 mg, 10 mg, and 20 mg tablets for oral administration. Inactive ingredients: lactose (monohydrate), magnesium stearate, microcrystalline cellulose. The 5 mg also contains FD & C Red #40 Aluminum Lake. The 20 mg also contains D & C Yellow #10 Aluminum Lake, FD & C Blue #1 Aluminum Lake, and FD & C Yellow #6 Aluminum Lake.
CLINICAL PHARMACOLOGY:
id: 92e62cc3-97f8-44e7-b3f2-308df59b5f1f
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
The principal pharmacological action of isosorbide dinitrate 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 anti-anginal efficacy of continuously-delivered nitrates. In the large majority of these trials, active agents were no more effective than 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 anti-anginal efficacy been restored.
INDICATIONS AND USAGE:
id: abd08fa7-d70e-4df1-b835-6206053d65ca
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Isosorbide dinitrate tablets are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of immediate-release oral isosorbide dinitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.
CONTRAINDICATIONS:
id: 5a11f7f4-b359-4386-8eef-524e404fa0ba
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Isosorbide dinitrate tablets are contraindicated in patients who are allergic to isosorbide dinitrate or any of its ingredients.
Do not use isosorbide dinitrate tablets in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil. Concomitant use can cause severe hypotension, syncope, or myocardial ischemia.
Do not use isosorbide dinitrate tablets in patients who are taking the soluble guanylate cyclase stimulator riociguat. Concomitant use can cause hypotension.
WARNINGS:
id: 3ef06a4f-80f1-46d0-82d9-29084bf521d4
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
Amplification of the vasodilatory effects of isosorbide dinitrate by sildenafil can 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 immediate release oral isosorbide dinitrate in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use isosorbide dinitrate in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia. Because the effects of oral isosorbide dinitrate are so difficult to terminate rapidly, this formulation is not recommended in these settings.
ADVERSE REACTIONS:
id: faf903e9-2dad-4d15-9d5d-f39311351fe2
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Adverse reactions to isosorbide dinitrate are generally dose-related, and almost all of these reactions are the result of isosorbide dinitrate’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.
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
).
Data are not available to allow estimation of the frequency of adverse reactions during treatment with isosorbide dinitrate tablets.
DOSAGE AND ADMINISTRATION:
id: 729c7360-59c2-4f10-bbe1-aed7cfe633ff
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
As noted under
CLINICAL PHARMACOLOGY
, multiple-dose studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for isosorbide dinitrate tablets must provide a daily dose-free interval to minimize the development of this tolerance. With immediate-release ISDN, it appears that one daily dose-free interval must be at least 14 hours long.
As also noted under
CLINICAL PHARMACOLOGY
, the effects of the second and later doses have been smaller and shorter-lasting than the effects of the first.
Large controlled studies with other nitrates suggest that no dosing regimen with isosorbide dinitrate tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.
As with all titratable drugs, it is important to administer the minimum dose which produces the desired clinical effect. The usual starting dose of isosorbide dinitrate is 5 mg to 20 mg, two or three times daily. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended. Some patients may require higher doses. A daily dose-free interval of at least 14 hours is advisable to minimize tolerance. The optimal interval will vary with the individual patient, dose and regimen.
HOW SUPPLIED:
id: b9fd7200-92ca-444f-832d-3d50d39b142c
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Isosorbide dinitrate tablets, USP are supplied as:
5 mg: Round, pink, scored tablets, debossed GG 259 on one side and plain on the reverse side, and supplied as:
Unit dose packages of 30 (5 x 6) NDC 68084-894-25
PACKAGING INFORMATION
id: 440e577d-0f2a-44ae-96c3-0b6f191d140c
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5
American Health Packaging unit dose blisters (see How Supplied section) contain drug product from BluePoint Laboratories as follows:
(5 mg / 30 UD) NDC 68084-894-25 packaged from NDC 68001-223
Distributed by:
American Health Packaging
Columbus, OH 43217
8289421/0715OS
Principle Display Panel
id: 1f759e9f-8c9b-4ac2-80b3-d04c323abf37
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
NDC 68084-894-25
Isosorbide Dinitrate
Tablets, USP
ORAL
5 mg
30 Tablets (5 x 6)
Each Tablet Contains:
Isosorbide Dinitrate…………………………….5 mg
Usual Dosage: See package insert for full
prescribing information.
Store at 20° to 25°C (68° to 77°F); excursions
permitted between 15° to 30°C (59° to 86°F) [see
USP Controlled Room Temperature]. Protect from
moisture.
Keep this and all drugs out of reach of children.
FOR YOUR PROTECTION: Do not use if blister is
torn or broken.
Rx Only
The drug product contained in this package is from
NDC # 68001-223, BluePoint Laboratories.
Distributed by:
American Health Packaging
Columbus, OH 43217
089425
Rev. 07/2015OS
