Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 7/25/2022

Drug Summary

What Is Isordil?

Isordil (isosorbide dinitrate) is a nitrate indicated for the prevention of angina due to coronary artery disease and congestive heart failure. Isordil is available in generic form.

What Are Side Effects of Isordil?

Common side effects of Isordil include:

  • headache,
  • weakness,
  • mild dizziness, and
  • skin changes such as redness, tingling, or warmth.

Serious side effects of Isordil include:

  • heart rate changes,
  • increased chest pain (angina),
  • fainting or near-fainting,
  • nausea and vomiting,
  • sweating,
  • pale skin,
  • blurry vision, and
  • shortness of breath.

Isordil may cause serious side effects including:

  • lightheadedness,
  • worsening chest pain,
  • fast or slow heart rate,
  • pounding heartbeats,
  • fluttering in your chest,
  • hives,
  • difficulty breathing, and
  • swelling of your face, lips, tongue or throat

Get medical help right away, if you have any of the symptoms listed above.

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Isordil

Isordil (isosorbide dinitrate) tablets come in strengths of 5 or 40 mg of isosorbide dinitrate. The usual starting dose of Isordil Titradose 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.

What Drugs, Substances, or Supplements Interact with Isordil?

Isordil may interact with blood pressure medications, dihydroergotamine or ergotamine, erectile dysfunction medications, beta-blockers, or calcium channel blockers. Tell your doctor all medications and supplements you use.

Isordil During Pregnancy and Breastfeeding

It is not known if Isordil affects the fetus in pregnant women or if it occurs in breast milk. Tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding before using Isordil. Safety and effectiveness of Isordil in pediatric patients have not been established.

Additional Information

Our Isordil Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

Drug Description


Isosorbide dinitrate (ISDN) is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate, an organic nitrate whose structural formula is

Isordil® Titradose® (isosorbide dinitrate) Structural Formula Illustration

and whose molecular weight is 236.14. 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=1.0, alcohol, 20°C). Isosorbide dinitrate is freely soluble in organic solvents such as acetone, alcohol, and ether, but is only sparingly soluble in water.

Each Isordil® Titradose® tablet contains 5 or 40 mg of isosorbide dinitrate. The inactive ingredients in each tablet are lactose, cellulose, and magnesium stearate. The 5 mg and 40 mg dosage strengths also contain the following: 5 mg . FD&C Red 40; 40 mg . D&C Yellow 10, FD&C Blue 1, and FD&C Yellow 6.

Indications & Dosage


Isordil (isosorbide dinitrate) Titradose tablets are indicated for the prevention of angina pectoris due to coronaryartery disease. The onset of action of immediate-release oral isosorbide dinitrate is not sufficiently rapid for thisproduct to be useful in aborting an acute anginal episode.


As noted under CLINICAL PHARMACOLOGY, multiple-dose studies with ISDN and other nitrates haveshown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosingregimen for Isordil Titradose tablets must provide a daily dose-free interval to minimize the development of thistolerance. With immediate-release ISDN, it appears that one daily dose-free interval must be at least 14 hourslong.

As also noted under CLINICAL PHARMACOLOGY, the effects of the second and later doses have beensmaller and shorter-lasting than the effects of the first.

Large controlled studies with other nitrates suggest that no dosing regimen with Isordil Titradose tablets shouldbe 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 clinicaleffect. The usual starting dose of Isordil Titradose is 5 mg to 20 mg two or three times daily. For maintenancetherapy, 10 mg to 40 mg two or three times daily is recommended. Some patients may require higher doses. Adaily dose-free interval of at least 14 hours is advisable to minimize tolerance. The optimal interval will varywith the individual patient, dose and regimen.


Storage And Handling

Isordil Titradose (isosorbide dinitrate) tablets are available as follows:

5 mg, round, pink tablets imprinted "BPI 152" on one side and deeply scored on reverse side:

NDC 0187-0152-01, bottles of 100.

40 mg, round, light green tablets imprinted "BPI 192" on one side and deeply scored on reverse side:

NDC 0187-0192-01, bottles of 100.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP ControlledRoom Temperature].

Protect from light.

Keep bottles tightly closed.

Dispense in a light-resistant, tight container.

Keep out of reach of children

Manufactured by: Bausch Health Companies Inc. Steinbach, MB R5G 1Z7, Canada. Revised: Aug 2019.

Side Effects & Drug Interactions


Adverse reactions to isosorbide dinitrate are generally dose-related, and almost all of these reactions are theresult of isosorbide dinitrate's activity as a vasodilator. Headache, which may be severe, is the most commonlyreported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transientepisodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Hypotensionoccurs 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-seemingpatients. Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis andtreatment is deferred (see OVERDOSE).

Data are not available to allow estimation of the frequency of adverse reactions during treatment with IsordilTitradose tablets.

To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 orFDA at 1-800-FDA-1088 or


The vasodilating effects of isosorbide dinitrate may be additive with those of other vasodilators. Alcohol, inparticular, has been found to exhibit additive effects of this variety.

Concomitant use of Isordil Titradose with phosphodiesterase inhibitors in any form is contraindicated (see CONTRAINDICATIONS).

Concomitant use of Isordil Titradose with riociguat, a soluble guanylate cyclase stimulator, is contraindicated (see CONTRAINDICATIONS).

Warnings & Precautions


Amplification of the vasodilatory effects of Isordil by sildenafil can result in severe hypotension. The timecourse and dose dependence of this interaction have not been studied. Appropriate supportive care hasnot been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of theextremities and with central volume expansion.

The benefits of immediate-release oral isosorbide dinitrate in patients with acute myocardial infarction orcongestive 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 notrecommended in these settings.



Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide dinitrate.This drug should therefore be used with caution in patients who may be volume depleted or who, for whateverreason, are already hypotensive. Hypotension induced by isosorbide dinitrate may be accompanied byparadoxical bradycardia and increased angina pectoris.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

As tolerance to isosorbide dinitrate develops, the effect of sublingual nitroglycerin on exercise tolerance,although still observable, is somewhat blunted.

Some clinical trials in angina patients have provided nitroglycerin for about 12 continuous hours of every 24-hour day. During the daily dose-free interval in some of these trials, anginal attacks have been more easilyprovoked than before treatment, and patients have demonstrated hemodynamic rebound and decreased exercisetolerance. The importance of these observations to the routine, clinical use of immediate-release oral isosorbidedinitrate is not known.

In industrial workers who have had long-term exposure to unknown (presumably high) doses of organicnitrates, tolerance clearly occurs. Chest pain, acute myocardial infarction, and even sudden death have occurredduring temporary withdrawal of nitrates from these workers, demonstrating the existence of true physicaldependence.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of isosorbidedinitrate. In a modified two-litter reproduction study, there was no remarkable gross pathology and no alteredfertility or gestation among rats fed isosorbide dinitrate at 25 or 100 mg/kg/day.


At oral doses 35 and 150 times the maximum recommended human daily dose, isosorbide dinitrate has beenshown to cause a dose-related increase in embryotoxicity (increase in mummified pups) in rabbits. There are noadequate, well-controlled studies in pregnant women. Isosorbide dinitrate should be used during pregnancy onlyif the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether isosorbide dinitrate is excreted in human milk. Because many drugs are excreted inhuman milk, caution should be exercised when isosorbide dinitrate is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Isordil (isosorbide dinitrate) Titradose did not include sufficient numbers of subjects aged 65and over to determine whether they respond differently from younger subjects. Other reported clinicalexperience has not identified differences in responses between the elderly and younger patients. In general, doseselection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflectingthe greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drugtherapy.

Overdose & Contraindications


Hemodynamic Effects

The ill effects of isosorbide dinitrate overdose are generally the results of isosorbide dinitrate's capacity toinduce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changesmay have protean manifestations, including increased intracranial pressure, with any or all of persistentthrobbing headache, confusion, and moderate fever; vertigo; palpitations; visual disturbances; nausea andvomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hungerand dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold andclammy; heart block and bradycardia; paralysis; coma; seizures; and death.

Laboratory determinations of serum levels of isosorbide dinitrate and its metabolites are not widely available,and such determinations have, in any event, no established role in the management of isosorbide dinitrateoverdose.

There are no data suggesting what dose of isosorbide dinitrate is likely to be life-threatening in humans. In rats,the median acute lethal dose (LD50 ) was found to be 1100 mg/kg.

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) thatmight accelerate elimination of isosorbide dinitrate and its active metabolites. Similarly, it is not known which,if any, of these substances can usefully be removed from the body by hemodialysis.

No specific antagonist to the vasodilator effects of isosorbide dinitrate is known, and no intervention has beensubject to controlled studies as a therapy for isosorbide dinitrate overdose. Because the hypotension associatedwith isosorbide dinitrate overdose is the result of venodilatation and arterial hypovolemia, prudent therapy inthis situation should be directed toward increase in central fluid volume. Passive elevation of the patient's legsmay be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.

The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do more harm than good.

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is notwithout hazard. Treatment of isosorbide dinitrate overdose in these patients may be subtle and difficult, andinvasive monitoring may be required.


Nitrate ions liberated during metabolism of isosorbide dinitrate can oxidize hemoglobin into methemoglobin.Even in patients totally without cytochrome b reductase activity, however, and even assuming that the nitratemoieties of isosorbide dinitrate are quantitatively applied to oxidation of hemoglobin, about 1 mg/kg ofisosorbide dinitrate should be required before any of these patients manifests clinically significant (≥10%)methemoglobinemia. In patients with normal reductase function, significant production of methemoglobinshould require even larger doses of isosorbide dinitrate. In one study in which 36 patients received 2 to 4 weeksof continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr (equivalent, in total administered dose of nitrate ions, to4.8 to 6.9 mg of bioavailable isosorbide dinitrate per hour), the average methemoglobin level measured was0.2%; this was comparable to that observed in parallel patients who received placebo.

Notwithstanding these observations, there are case reports of significant methemoglobinemia in associationwith moderate overdoses of organic nitrates. None of the affected patients had been thought to be unusuallysusceptible.

Methemoglobin levels are available from most clinical laboratories. The diagnosis should be suspected inpatients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposureto air.

When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.


Isordil Titradose is contraindicated in patients who are allergic to isosorbide dinitrate or any of its ingredients.

Do not use Isordil Titradose in patients who are taking certain drugs for erectile dysfunction (phosphodiesteraseinhibitors), such as sildenafil, tadalafil, or vardenafil. Concomitant use can cause severe hypotension, syncope,or myocardial ischemia.

Do not use Isordil Titradose in patients who are taking the soluble guanylate cyclase stimulator riociguat.Concomitant use can cause hypotension.

Clinical Pharmacology


The principal pharmacological action of isosorbide dinitrate is relaxation of vascular smooth muscle andconsequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotesperipheral 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 systemicvascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilatation of the coronaryarteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilatationremains undefined.

Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that arecontinuously 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 ofcontinuously delivered nitrates. In the large majority of these trials, active agents were no more effective thanplacebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate tolerance by doseescalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates havebeen absent from the body for several hours has their anti-anginal efficacy been restored.


Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable(10% to 90%), with extensive first-pass metabolism in the liver. Serum levels reach their maxima about an hourafter ingestion. The average bioavailability of ISDN is about 25%; most studies have observed progressiveincreases in bioavailability during chronic therapy.

Once absorbed, the volume of distribution of isosorbide dinitrate is 2 to 4 L/kg, and this volume is cleared at therate of 2 to 4 L/min, so ISDN's half-life in serum is about an hour. Since the clearance exceeds hepatic bloodflow, considerable extra hepatic metabolism must also occur. Clearance is affected primarily by denitration tothe 2-mononitrate (15% to 25%) and the 5-mononitrate (75% to 85%).

Both metabolites have biological activity, especially the 5-mononitrate. With an overall half-life of about 5hours, the 5-mononitrate is cleared from the serum by denitration to isosorbide, glucuronidation to the 5-mononitrate glucuronide, and denitration/hydration to sorbitol. The 2-mononitrate has been less well studied,but it appears to participate in the same metabolic pathways, with a half-life of about 2 hours.

The daily dose-free interval sufficient to avoid tolerance to organic nitrates has not been well defined. Studies ofnitroglycerin (an organic nitrate with a very short half-life) have shown that daily dose-free intervals of 10 to 12hours are usually sufficient to minimize tolerance. Daily dose-free intervals that have succeeded in avoidingtolerance during trials of moderate doses (e.g., 30 mg) of immediate-release ISDN have generally beensomewhat longer (at least 14 hours), but this is consistent with the longer half-lives of ISDN and its activemetabolites.

Few well-controlled clinical trials of organic nitrates have been designed to detect rebound or withdrawaleffects. In one such trial, however, subjects receiving nitroglycerin had less exercise tolerance at the end of thedaily dose-free interval than the parallel group receiving placebo. The incidence, magnitude, and clinicalsignificance of similar phenomena in patients receiving ISDN have not been studied.

Clinical Trials

In clinical trials, immediate-release oral isosorbide dinitrate has been administered in a variety of regimens,with total daily doses ranging from 30 mg to 480 mg. Controlled trials of single oral doses of isosorbidedinitrate have demonstrated effective reductions in exercise-related angina for up to 8 hours. Anti-anginalactivity is present about 1 hour after dosing.

Most controlled trials of multiple-dose oral ISDN taken every 12 hours (or more frequently) for several weekshave shown statistically significant anti-anginal efficacy for only 2 hours after dosing. Once-daily regimens, andregimens with one daily dose-free interval of at least 14 hours (e.g., a regimen providing doses at 8 am, 2 pm,and 6 pm), have shown efficacy after the first dose of each day that was similar to that shown in the single-dosestudies cited above. The effects of the second and later doses have been smaller and shorter-lasting than theeffect of the first.

From large, well-controlled studies of other nitrates, it is reasonable to believe that the maximal achievabledaily duration of anti-anginal effect from isosorbide dinitrate is about 12 hours. No dosing regimen forisosorbide dinitrate, however, has ever actually been shown to achieve this duration of effect. One study of 8patients, who were administered a pretitrated dose (average 27.5 mg) of immediate-release ISDN at 8 am, 1 pm,and 6 pm for 2 weeks, revealed that significant anti-anginal effectiveness was discontinuous and totaled about 6hours in a 24-hour period.

Medication Guide


Patients should be told that the anti-anginal efficacy of isosorbide dinitrate is strongly related to its dosingregimen, so the prescribed schedule of dosing should be followed carefully. In particular, daily headachessometimes accompany treatment with isosorbide dinitrate. In patients who get these headaches, the headachesare a marker of the activity of the drug. Patients should resist the temptation to avoid headaches by altering theschedule of their treatment with isosorbide dinitrate, since loss of headache may be associated withsimultaneous loss of anti-anginal efficacy. Aspirin and/or acetaminophen, on the other hand, often successfullyrelieve isosorbide dinitrate-induced headaches with no deleterious effect on isosorbide dinitrate's anti-anginalefficacy.

Treatment with isosorbide dinitrate may be associated with lightheadedness on standing, especially just afterrising from a recumbent or seated position. This effect may be more frequent in patients who have alsoconsumed alcohol.

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