Isosorbide dinitrate


Generic Medicine Info
Indications and Dosage
Intracoronary
Percutaneous transluminal coronary angioplasty
Adult: 1 mg as a bolus inj before balloon inflation, may give additional doses at a Max of 5 mg over 30 min.

Intravenous
Unstable angina, Heart failure
Adult: 2-12 mg/hr titrated according to patient's response. Doses up to 20 mg/hr may be given as necessary.

Oral
Heart failure
Adult: 30-160 mg daily in divided doses. Max: 240 mg daily.

Oral
Angina pectoris
Adult: 20-120 mg daily in divided doses. Gradually increase according to patient's response. Max: 240 mg daily.

Sublingual
Acute angina
Adult: 2.5-10 mg placed under the tongue.

Sublingual
Heart failure
Adult: 5-10 mg every 2 hours as needed.
Administration
Should be taken on an empty stomach. Take 30 min before meals.
Incompatibility
Avoid use of PVC containers as significant losses of the active ingredient by adsorption may occur.
Contraindications
Aortic or mitral stenosis, marked anaemia, cardiac tamponade, hypertrophic cardiomyopathy, hypotension, hypovolaemia, raised intracranial pressure. Concomitant use of a phosphodiesterase 5 (PDE5) inhibitors and riociguat.
Special Precautions
Patients w/ susceptibility to angle-closure glaucoma, hypothermia, hypothyroidism, hypoxaemia, malnutrition, MI, toxic pulmonary oedema, constrictive pericarditis, ventilation and perfusion abnormalities. Severe renal and hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Postural hypotension.
Nervous: Dizziness, headache, syncope.
CV: Tachycardia, rebound hypertension, severe hypotension, rebound angina, paradoxical bradycardia, palpitation, peripheral oedema.
GI: Heartburn, nausea, vomiting.
Haematologic: Hypoxaemia, haemolysis; methaemoglobinaemia (IV).
Ophthalmologic: Angle-closure glaucoma.
Immunologic: Hypersensitivity.
Others: Flushing; restlessness.
Potentially Fatal: Severe hypotension and bradycardia.
Patient Counseling Information
This drug may cause dizziness on standing, sit or lie down before use and get up gradually to minimise this effect.
MonitoringParameters
Monitor BP and heart rate closely during IV admin.
Overdosage
Symptoms: Increased intracranial pressure (manifested by throbbing headache, confusion, and moderate fever), vertigo, palpitations, visual disturbances, nausea, vomiting, syncope, dyspnoea, diaphoresis, heart block, bradycardia, paralysis, coma, seizures, methaemoglobinaemia. Management: Passive elevation of the patient’s legs may be sufficient but IV infusion of normal saline or similar fluid may also be necessary. Methaemoglobinaemia may be treated w/ IV methylene blue 1-2 mg/kg.
Drug Interactions
Reduced effect w/ disopyramide (sublingual). Additive hypotensive effects w/ antihypertensive drugs or phenothiazines.
Potentially Fatal: Risk of severe hypotension, myocardial ischaemia, or syncope w/ PDE5 inhibitors (e.g. sildenafil). Increased risk of hypotension w/ riociguat.
Food Interaction
Enhanced vasodilatory effect w/ alcohol.
Action
Description: Isosorbide dinitrate, a nitro vasodilator, is a source of nitric oxide which stimulates cyclic guanosine 3’,5’monophosphate (cGMP), thereby relaxing the vascular smooth muscles. It decreases left ventricular pressure (preload) and arterial resistance (afterload).
Onset: 2-5 min (sublingual); approx 1 hr (oral).
Duration: 1-2 hr (sublingual); ≤8 hr (oral).
Pharmacokinetics:
Absorption: Readily absorbed from the oral mucosa (sublingual) and from the GI tract (oral). Bioavailability: Highly variable (10-90%).
Distribution: Widely distributed. Volume of distribution: 2-4 L/kg. Plasma protein binding: Approx 28%.
Metabolism: Undergoes extensive hepatic first-pass metabolism; converted to active isosorbide 2-mononitrate and 5-mononitrate.  Also metabolised via denitration and glucuronidation.
Excretion: Via urine (80-100%, as metabolites). Elimination half-life: Approx 1 hr (isosorbide dinitrate); 5 hr (isosorbide 5-mononitrate); 2 hr (isosorbide 2-mononitrate).
Chemical Structure

Chemical Structure Image
Isosorbide dinitrate

Source: National Center for Biotechnology Information. PubChem Database. Isosorbide dinitrate, CID=6883, https://pubchem.ncbi.nlm.nih.gov/compound/Isosorbide-dinitrate (accessed on Jan. 21, 2020)

Storage
Store between 20-25°C. Protect from light.
MIMS Class
ATC Classification
C01DA08 - isosorbide dinitrate ; Belongs to the class of organic nitrate vasodilators. Used in the treatment of cardiac disease.
References
Anon. Isosorbide Dinitrate. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/07/2017.

Anon. Isosorbide Dinitrate/Mononitrate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/07/2017.

Buckingham R (ed). Isosorbide Dinitrate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/07/2017.

Isosorbide Dinitrate Tablets (Carilion Materials Management). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 06/07/2017.

Joint Formulary Committee. Isosorbide Dinitrate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/07/2017.

Disclaimer: This information is independently developed by MIMS based on Isosorbide dinitrate from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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