DESCRIPTION
id: dce14438-070a-458b-a818-331d0eb19d57
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:
and whose molecular weight is 236.14. The organic nitrates are vasodilators, active on both arteries and veins.
ISDN 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=1.0, alcohol. 20°C). ISDN is freely soluble in organic solvents such as acetone, alcohol, and ether, but is only sparingly soluble in water.
Each isosorbide dinitrate sublingual tablet contains 2.5 mg or 5 mg of ISDN.
Inactive ingredients are as follows:
2.5 mg Sublingual: Ammonium phosphate dibasic, anhydrous lactose, colloidal silicon dioxide, corn starch, D&C Yellow No. 10 Lake, FD&C Yellow No. 6 Lake, magnesium stearate, microcrystalline cellulose, sodium starch glycolate.
5 mg Sublingual: Ammonium phosphate dibasic, anhydrous lactose, colloidal silicon dioxide, corn starch, magnesium stearate, microcrystalline cellulose.
CLINICAL PHARMACOLOGY
id: 32af6207-be00-4b34-8261-c71b808af0ff
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
The principal pharmacological action of ISDN 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 lesistance, 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: 5f1d4f1b-68eb-4b02-af68-4393ec299c77
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Isosorbide dinitrate sublingual tablets are indicated for the prevention and treatment of angina pectoris due to coronary artery disease. However, because the onset of action of sublingual ISDN is significantly slower than that of sublingual nitroglycerin, sublingual ISDN is not the drug of first choice for abortion of an acute anginal episode.
CONTRAINDICATIONS
id: 9153b97e-d36b-4f74-bf01-508a3ad4850a
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Allergic reactions to organic nitrates are extremely rare, but they do occur. The isosorbide dinitrate sublingual tablet is contraindicated in patients who are allergic to ISDN or any of its other ingredients.
WARNINGS
id: b8d47393-35f8-4568-adc1-d0f65888dfe1
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 sublingual ISDN in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use ISDN in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.
ADVERSE REACTIONS
id: c173103e-332e-4c7c-bad6-efe409a58af1
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Adverse reactions to ISDN are generally dose-related, and almost all of these reactions are the result of ISDN’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 of isosorbide dinitrate sublingual tablets.
DOSAGE AND ADMINISTRATION
id: b0d30c7f-299c-4ed2-b525-2b3a134a90de
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
As noted under
CLINICAL PHARMACOLOGY
, multiple studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for ISDN must provide a daily dose-free interval to minimize the development of this tolerance. In the case of sublingual tablets, it is probably true that one of the daily dose-free intervals must be somewhat longer than 14 hours.
As also noted under
CLINICAL PHARMACOLOGY
, the efficacy of daily doses after the first has never been demonstrated.
Large controlled studies with other nitrates suggest that no dosing regimen with Isosorbide Dinitrate Sublingual Tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.
A patient anticipating activity likely to cause angina should take one isosorbide dinitrate sublingual tablet (2.5 to 5 mg) about 15 minutes before the activity is expected to begin. Isosorbide dinitrate sublingual tablets may be used to abort an acute anginal episode, but its use is recommended only in patients who fail to respond to sublingual nitroglycerin.
HOW SUPPLIED
id: 2c77caa9-535a-4bec-84df-76a1d41d1e95
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Isosorbide Dinitrate Sublingual Tablets USP 2.5 mg: Yellow, round, compressed tablet imprinted “W1”.
- Bottles of 100 tablets.
- Bottles of 1000 tablets.
- Unit Dose Boxes of 100 tablets.
Isosorbide Dinitrate Sublingual Tablets USP 5 mg: White, round, compressed tablet engraved with “W3”.
- Bottles of 100 tablets.
- Bottles of 1000 tablets.
- Unit Dose Boxes of 100 tablets.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.
Also available: Isosorbide Dinitrate Oral Tablets in the following dosage strengths:
5 mg; in bottles of 100, 500, 1000 or unit dose boxes of 100 tablets.
10 mg; in bottles of 100, 500, 1000 or unit dose boxes of 100 tablets.
20 mg; in bottles of 100, 1000 or unit dose boxes of 100 tablets.
Manufactured by:
West-ward Pharmaceutical Corp.
Eatontown, NJ 07724
Revised November 2007
PRINCIPAL DISPLAY PANEL
id: 4c9dbe95-04d7-4d36-a057-be6c16326422
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Isosorbide Dinitrate Sublingual Tablets, USP
NDC 0143-1765-01
2.5 mg/100 Tablets
PRINCIPAL DISPLAY PANEL
id: 7f5f6f47-d630-484d-878f-4de7e1478b90
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Isosorbide Dinitrate Subligual Tablets, USP
NDC 0143-1767-01
5 mg/100 Tablets
