Isosorbide Dinitrate

Mechanism-of-action classes: Guanylate Cyclase Activators; Nitric Oxide Donors; Phosphodiesterase 5 Inhibitors.

• 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.ICD-10: I20.9

• Isosorbide dinitrate is contraindicated in patients who are allergic to isosorbide dinitrate or any of its other ingredients. Do not use isosorbide dinitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil.contraindicated

As noted under " CLINICAL PHARMACOLOGY ," multiple-dose studies with isosorbide dinitrate 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 isosorbide dinitrate, 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.

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 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. To report SUSPECTED ADVERSE REACTIONS contact AvKARE at 1-855-361-3993; email drugsafety@avkare.com ; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Pregnancy Category C At oral doses 35 and 150 times the maximum recommended human daily dose, isosorbide dinitrate has been shown to cause a dose-related increase in embryotoxicity (increase in mummified pups) in rabbits. There are no adequate, well-controlled studies in pregnant women. Isosorbide dinitrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Metabolism

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 hour after ingestion.

Hemodynamic Effects The ill effects of isosorbide dinitrate overdose are generally the results of isosorbide dinitrate's capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; 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 dinitrate overdose. 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 (LD 50 ) was found to be 1100 mg/kg.

• Nov 9, 1959NDANDA012093Bausch
• Mar 12, 1987ANDAANDA086925Ph Health
• Mar 12, 1987ANDAANDA086923Ph Health
• Mar 12, 1987ANDAANDA087946Ph Health
• Oct 2, 1987ANDAANDA087537Ph Health
• Nov 2, 1987ANDAANDA088088Hikma Intl Pharms
• Jan 7, 1988ANDAANDA086221Sandoz
• Jun 23, 2005NDANDA020727Azurity

1. 1Dyspnoea1,6618.5%
2. 2Nausea1,3576.9%
3. 3Fatigue1,3396.8%
4. 4Dizziness1,2986.6%
5. 5Diarrhoea1,2896.6%
6. 6Myocardial Infarction1,1926.1%
7. 7Chest Pain1,1355.8%
8. 8Pain1,0565.4%
9. 9Headache1,0115.2%
10. 10Vomiting9905.0%
11. 11Malaise8894.5%
12. 12Off Label Use8314.2%
13. 13Asthenia8214.2%
14. 14Death8194.2%
15. 15Renal Failure8044.1%

Recent PubMed references pinned to Isosorbide Dinitrate as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Vasodilation, loop diuretics, or their combination in acute heart failure: Rationale and design of the randomized placebo-controlled DECONGEST-AHF trial.
  American heart journal · 2026 · Olesen ASO, Lukoschewitz JD, Taraldsen IA, et al.
  PMID 42044762DOI 10.1016/j.ahj.2026.107461
• Significant Antispastic Effect of Combined Fasudil and Isosorbide Dinitrate on Internal Mammary Artery in Coronary Artery Bypass Grafting.
  Basic & clinical pharmacology & toxicology · 2026 · Zhang YF, Hou HT, Yang Q, et al.
  PMID 41339615DOI 10.1111/bcpt.70148
• Empagliflozin and hydralazine-isosorbide dinitrate combination therapy improves outcomes in Black patients with heart failure.
  International journal of clinical pharmacology and therapeutics · 2025 · Baskaran P, Aldhaeefi M, Asaadi A, et al.
  PMID 40888214DOI 10.5414/CP204854
• Drug repurposing: isosorbide mononitrate enhances tumor accumulation to augment sonodynamic therapy for hepatocellular carcinoma.
  Journal of nanobiotechnology · 2025 · Peng Y, Li Z, Zhou L, et al.
  PMID 40855307DOI 10.1186/s12951-025-03674-7
• Pharmacokinetics and Safety with Bioequivalence of Isosorbide Mononitrate Sustained-Release Tablets in Chinese Healthy Volunteers: Bioequivalence Study.
  Drug design, development and therapy · 2025 · Wu B, Wang W, Zhang Q, et al.
  PMID 40687901DOI 10.2147/DDDT.S508202
• Erythropoietin-isosorbide dinitrate-loaded nanocomplex cryogel scaffold: a multifunctional smart dressing for diabetic wound healing.
  Life sciences · 2025 · Abdelrahman TA, Motawea A, El-Dahhan MS, et al.
  PMID 40645403DOI 10.1016/j.lfs.2025.123850
• κ-Carrageenan and hyaluronic acid composite injectable hydrogel-containing isosorbide mononitrate-loaded liposomes for treatment of myocardial infarction.
  Biomedical physics & engineering express · 2025 · Hua Y, Zeng J, He S, et al.
  PMID 40441164DOI 10.1088/2057-1976/adde67
• Effects of Nicorandil, Isosorbide Mononitrate, or Diltiazem on Radial Artery Grafts After CABG: The Randomized ASRAB-Pilot Trial.
  Circulation. Cardiovascular interventions · 2025 · Zhu Y, Zhang W, Qin K, et al.
  PMID 40123490DOI 10.1161/CIRCINTERVENTIONS.124.014542

The 10 most recently updated of 103 ClinicalTrials.gov registrations naming Isosorbide Dinitrate as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• DANHEART (H-HeFT and Met-HeFT)
  Completed · Phase 4 · Interventional · 1,100 enrolled · Henrik Wiggers
  NCT03514108updated 2026-06-11
• Vasodilator Therapy With Isosorbide Mononitrate or Diltiazem to Reduce Vasotoxicity in Patients With Gastrointestinal Cancer Receiving Fluoropyrimidine Therapy
  Recruiting · Phase 1 · Phase 2 · Interventional · 60 enrolled · Mayo Clinic
  NCT07456852updated 2026-06-02
• Optimized Treatment of Pulmonary Edema or Congestion
  Recruiting · Phase 4 · Interventional · 1,104 enrolled · Rigshospitalet, Denmark
  NCT05276219updated 2026-04-22
• Different Anti-Spastic Therapy Strategies After CABG Using Radial Artery Grafts
  Active not recruiting · Phase 4 · Interventional · 150 enrolled · Ruijin Hospital
  NCT04310995updated 2026-04-03
• Baroreflex Activation Therapy for Heart Failure
  Completed · Interventional · 1,090 enrolled · CVRx, Inc.
  NCT02627196updated 2026-03-10
• Reduction of Cesareans by Nitric Oxide (NO) Donors in Post Term Pregnancies
  Completed · Phase 3 · Interventional · 1,409 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT00930618updated 2025-12-01
• Isosorbide Mononitrate and Butylphthalide to Reduce the Risk of Disability in Patients With Acute Lacunar Stroke (IMPACT)
  Not yet recruiting · Phase 3 · Interventional · 3,156 enrolled · Beijing Tiantan Hospital
  NCT07252544updated 2025-11-26
• Treatment of Orthostatic Intolerance
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 150 enrolled · Satish R. Raj
  NCT00262470updated 2025-10-08
• Effect of Oral Isosorbide Mononitrate Plus Amlodipine Antispasm Therapy on Outcomes of Radial Artery Grafts After CABG
  Withdrawn · Phase 4 · Interventional · 0 enrolled · Ruijin Hospital
  NCT06730945updated 2025-09-17
• Cervical Ripening With Misoprostol vs Isosorbide Mononitrate ; A Parallel -Arm Randomized Controlled Trial
  Active not recruiting · Interventional · 80 enrolled · Raid M. Al-Ani
  NCT07121634updated 2025-08-13

Frequently asked questions

How does Isosorbide Dinitrate work?

Mechanism-of-action classes: Guanylate Cyclase Activators; Nitric Oxide Donors; Phosphodiesterase 5 Inhibitors.

What is Isosorbide Dinitrate used for?

According to FDA labeling, Isosorbide Dinitrate carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Isosorbide Dinitrate?

Isosorbide Dinitrate is classified as Muscle relaxants, Organic nitrates, Nitrate Vasodilator, Guanylate Cyclase Activators, Nitric Oxide Donors, Phosphodiesterase 5 Inhibitors, Arterial Vasodilation, Decreased Blood Pressure, Decreased Vascular Smooth Muscle Tone, Increased Nitric Oxide Activity, Vasodilation, Venous Vasodilation.

What are the brand names for Isosorbide Dinitrate?

Isosorbide Dinitrate is marketed under brand names including Bidil, IsoDitrate, Isochron, Isordil.

What are the contraindications for Isosorbide Dinitrate?

Isosorbide Dinitrate labeling lists contraindications including: Isosorbide dinitrate is contraindicated in patients who are allergic to isosorbide dinitrate or any of its other ingredients. Do not use isosorbide dinitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil.. Always consult the full prescribing information and a clinician.