Isosorbide dinitrate

Isosorbide dinitrate
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

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Overview

Isosorbide dinitrate is an anti-anginal nitrate that is FDA approved for the {{{indicationType}}} of angina pectoris due to coronary artery disease. Common adverse reactions include hypotension, lightheadedness, and headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Prophylaxis of Angina Pectoris

• Isosorbide dinitrate 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.
• 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.
• 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 Isordil Titradose 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.
• 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 Isordil Titradose tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.

• Dosing Information

• Initial Dosage

• 5–20 mg PO bid–tid

• Maintenance Dosage

• 10–40 mg PO bid–tid

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Ischemic Symptoms of Unstable Angina

• Developed by: ACCF/AHA

• Class of Recommendation: Class I

• Strength of Evidence: Level C

• Dosing Information

• 5–80 mg, 2 or 3 times daily

Non–Guideline-Supported Use

Cardiac Syndrome X

• Dosing Information

• 5 mg sublingual

Congestive Heart Failure

• Dosing Information

• Hydralazine-isosorbide dinitrate (H-ID) 37.5/20 mg 3 times daily, titrated to 75/40 mg 3 times daily
• Addition of isosorbide dinitrate 40 mg four times daily and hydralazine 300 mg daily to a digoxin/diuretic combination

Myocardial Infarction

• Dosing Information

• Initial dose was 2 mg/hour, titrated every 10 minutes until systolic blood pressure decreased 10% or a maximum infusion rate of 10 mg/hour.

Pulmonary Edema

• Dosing Information

• Repeated boluses of IV isosorbide dinitrate 4 mg every 4 min, until oxygen saturation increased above 96% or systolic blood pressure fell below 110 mm Hg or 30% below baseline.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• Safety and effectiveness in pediatric patients have not been established.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Isosorbide dinitrate in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Isosorbide dinitrate in pediatric patients.

Contraindications

• Hypersensitivity

• Allergic reactions to organic nitrates are extremely rare, but they do occur. Isordil is contraindicated in patients who are allergic to isosorbide dinitrate or any of its other ingredients.

Warnings

• Amplification of the vasodilatory effects of Isordil 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 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.

Precautions

• 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 whatever reason, are already hypotensive. Hypotension induced by isosorbide dinitrate may be accompanied by paradoxical 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 easily provoked than before treatment, and patients have demonstrated hemodynamic rebound and decreased exercise tolerance. The importance of these observations to the routine, clinical use of immediate-release oral isosorbide dinitrate is not known.

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

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Isosorbide dinitrate in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Isosorbide dinitrate in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Isosorbide dinitrate in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Isosorbide dinitrate during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Isosorbide dinitrate with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Isosorbide dinitrate with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Isosorbide dinitrate with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Isosorbide dinitrate with respect to specific gender populations.

Race

There is no FDA guidance on the use of Isosorbide dinitrate with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Isosorbide dinitrate in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Isosorbide dinitrate in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Isosorbide dinitrate in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Isosorbide dinitrate in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

There is limited information regarding Monitoring of Isosorbide dinitrate in the drug label.

Condition1

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Isosorbide dinitrate in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Isosorbide dinitrate in the drug label.

Pharmacology

Isosorbide dinitrate
Systematic (IUPAC) name
1,4:3,6-dianhydro-2,5-di-O-nitro-D-glucitol
Identifiers
CAS number	87-33-2
ATC code	C01DA08 C05AE02 (WHO)
PubChem	6883
DrugBank	DB00883
Chemical data
Formula	Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox
Mol. mass	236.136 g/mol
SMILES	eMolecules & PubChem
Synonyms	(3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furan-3,6-diyl dinitrate
Pharmacokinetic data
Bioavailability	10–90%, average 25%
Metabolism	Hepatic
Half life	1 hour
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C(US)
Legal status	Template:Unicode Prescription only
Routes	Oral

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Isosorbide dinitrate in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Isosorbide dinitrate in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Isosorbide dinitrate in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Isosorbide dinitrate in the drug label.

Condition1

• Description

How Supplied

• Isordil® (isosorbide dinitrate) Oral Titradose™ Tablets are available as follows:

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

NDC 64455-152-01, bottles of 100.

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

NDC 64455-192-01, bottles of 100.

• Store at controlled room temperature, 25°C (77°F); excursions permitted to 15 -30° (59-86°F)

• Protect from light.

• Keep bottles tightly closed.

• Dispense in a light-resistant, tight container.

Storage

There is limited information regarding Isosorbide dinitrate Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

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

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

Precautions with Alcohol

• Alcohol-Isosorbide dinitrate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• Isordil®

Look-Alike Drug Names

• Isordil® — Plendil®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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