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Isosorbide Dinitrate


Pronunciation: EYE-sos-ORE-bide die-NYE-trate
Class: Vasodilator, Nitrate

Trade Names

- Capsules, sustained-release 40 mg

- Tablets, sustained-release 40 mg

Isosorbide dinitrate
- Tablets, sublingual 2.5 mg
- Tablets, sublingual 5 mg

Isordil Titradose
- Tablets 5 mg
- Tablets 10 mg
- Tablets 40 mg

Apo-ISDN (Canada)


Relaxes vascular smooth muscle and dilation of peripheral arteries and veins.

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Absorption after oral administration nearly complete but absolute bioavailability variable (immediate-release tablets average 25%; range, 10% to 90%; sublingual 40% to 50%).


Vd is 2 to 4 L/kg.


Denitration to active metabolites 2-monohydrate (15% to 25%) and 5-mononitrate (75% to 85%).


The t ½ of isosorbide dinitrate is about 1 h; t ½ of 2-monohydrate and 5-mononitrate is about 2 h and 5 h, respectively.

Indications and Usage

Extended-release tablets, immediate-release tablets, sustained-release capsules

Prevention of angina pectoris caused by coronary artery disease.

Sublingual tablets

Prevention and treatment of angina pectoris caused by coronary artery disease.

Unlabeled Uses

In combination with hydralazine to increase survival among black patients with advanced heart failure; for the treatment of acute angle-closure glaucoma in emergency situations; achalasia.


Allergy to organic nitrates.

Dosage and Administration

Angina Pectoris (Treatment)

Sublingual 2.5 to 5 mg. Titrate upward until angina relieved or adverse reactions limit dose.

Angina Pectoris (Acute Prophylaxis)

Sublingual 2.5 to 5 mg 15 min before activity likely to cause angina.

Angina Pectoris (Prevention)

Sublingual 2.5 to 5 mg 3 or 4 times daily; titrate upward until angina is relieved or adverse reactions limit dose. PO (immediate release) Initial : 5 to 20 mg 3 or 4 times daily. Maintenance : 10 to 40 mg 3 or 4 times daily. PO (extended-release tablets and capsules) Initial : 40 mg twice daily (6 h apart). Do not exceed 160 mg/day.

General Advice

  • To minimize development of tolerance, ensure daily dose-free interval is provided: at least 14 h for sublingual and oral tablets; at least 18 h for extended-release tablets and capsules.
  • Caution patients not to chew or crush sublingual tablets or extended-release tablets or capsules.


Store oral tablets at room temperature (approximately 77°F). Protect from light. Store sublingual tablets and extended-release tablets and capsules at controlled room temperature (59° to 86°F). Protect sublingual tablets from light and moisture.

Drug Interactions


Severe hypotension and CV collapse.


Increased nitrate concentration and actions.


Increased systolic BP and decreased antianginal effects.

Phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil, vardenafil)

Because the hypotensive effects of nitrates may be potentiated, concomitant use of any form of organic nitrates is contraindicated in patients receiving phosphodiesterase type 5 inhibitors.

Laboratory Test Interactions

May cause false report of reduced serum cholesterol with Zlatkis-Zak color reaction.

Adverse Reactions


Crescendo angina; hypotension; rebound hypertension; syncope.


Headache; light-headedness.





Category C .




Safety and efficacy not established.


Dose selection should be cautious, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and comorbidity.

Acute MI/CHF

Benefits of immediate- and extended-release isosorbide dinitrate not established; use in these settings not recommended because effects of isosorbide dinitrate are difficult to terminate rapidly.

Angina acute treatment

Although sublingual isosorbide dinitrate is indicated for the treatment of acute angina, the onset of action of sublingual isosorbide is significantly slower than that of sublingual nitroglycerin; sublingual isosorbide dinitrate is not the drug of first choice for abortion of an acute anginal episode.


May aggravate angina caused by hypertrophic cardiomyopathy.


High doses may produce methemoglobinemia, especially in patients with methemoglobin reductase deficiency.

Severe hypotension

May occur even with small doses, particularly with upright posture; use with caution in patients who are hypotensive or volume depleted; alcohol accentuates this reaction.


May develop with repeated use for prolonged periods of time; minimize tolerance by ensuring daily isosorbide dinitrate-free intervals.



Air hunger, bloody diarrhea, colic, coma, confusion, death, diaphoresis with flushed or cold and clammy skin, dyspnea followed later by reduced ventilatory effort, heart block and bradycardia, increased intracranial pressure, methemoglobinemia, moderate fever, nausea, palpitations, paralysis, seizures, syncope, throbbing headache, vertigo, visual disturbances, vomiting.

Patient Information

  • Advise patient to review the patient information leaflet carefully before starting therapy and to read and check for new information each time the medication is refilled.
  • Review with patient and family the signs and symptoms of angina (eg, acute onset of pressure-like chest pain that may radiate down the left arm and/or into the neck or jaw, often associated with sweating and shortness of breath or difficulty breathing).
  • Instruct patient not to change from one brand of medicine to another without consulting health care provider. Products manufactured by different companies may not be equally effective.
  • Instruct patient using sublingual isosorbide for acute treatment of angina symptoms in proper use of drug: place tablet under the tongue and allow to dissolve; caution patient not to chew or crush sublingual tablets.
  • Instruct patient using extended-release tablets or capsules to swallow whole and not to crush, chew, break, or open.
  • Ensure patient using oral forms of isosorbide dinitrate has sublingual nitroglycerin available at all times. Ensure patient knows when and how to use sublingual nitroglycerin and what to do if angina pain worsens or fails to respond to sublingual nitroglycerin.
  • Caution patient that antianginal effectiveness of isosorbide is strongly related to the dosing regimen and not to change the dose or frequency of administration, or stop taking, unless advised by health care provider.
  • Advise patient that headaches are a common adverse reaction of therapy and are also a marker of antianginal effectiveness. Advise patient that acetaminophen can be used to relieve headache without reducing the medication's antianginal effectiveness. Caution patient not to reduce the dose or change the frequency of administration of isosorbide to avoid medication-induced headache.
  • Advise patient to notify health care provider if angina symptoms increase in frequency or severity, or if there is a sudden increase in the frequency of use of SL nitroglycerin.
  • Caution patient that medication may cause dizziness, light-headedness, or fainting, especially if used while standing or following consumption of alcohol.
  • Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patient to notify health care provider if any of the following occur: frequent episodes of dizziness or light-headedness; fainting; intolerable headache; episodes of sweating, nausea, and/or vomiting; any unusual or unexplained feeling or sensation.

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