Isosorbide dinitrate

Oral
Angina pectoris
Adult: Prophylaxis and treatment: As conventional tab: 20-120 mg daily in divided doses based on individual requirements. Gradually increase dose to minimise risk of nitrate headache and/or tolerance. Max: 240 mg daily in divided doses. Alternative dosage regimen for prophylaxis: Initially, 5-20 mg bid or tid; maintenance: 10-40 mg bid or tid; daily dose-free interval of at least 14 hours is recommended between the evening and morning dose. As prolonged-release tab: 20 mg bid (administer the 2nd dose 6-8 hours after the 1st dose of the day). Dose may be increased to 20 mg tid (ensure at least 12 hours of treatment free interval every 24 hours).
Elderly: Dose reduction may be required.

Oral
Congestive heart failure
Adult: As conventional tab: 40-160 mg daily in divided doses based on individual requirements. Max: 240 mg daily in divided doses.
Elderly: Dose reduction may be required.

Sublingual
Congestive heart failure
Adult: In acute and chronic (as initial treatment) cases: 5-10 mg 2 hourly or as necessary.
Incompatibility: Avoid use of PVC containers as significant losses of the active ingredient by adsorption may occur.

Sublingual
Angina pectoris
Adult: Prophylaxis of acute angina: 5-10 mg 2-3 hourly. Supplement doses of 5-10 mg may be given prior to activities or stressful situations that may provoke an angina attack.

Intravenous
Left ventricular failure
Adult: For the treatment of unresponsive cases secondary to acute MI or of various aetiology: 2-12 mg per hour, may be titrated up to 20 mg per hour according to patient response.
Reconstitution: Prior to administration, concentrated solution (1 mg/mL) must be diluted to a Max concentration of 0.5 mg/mL.
Incompatibility: Avoid use of polyvinyl chloride (PVC) or polyurethane (PU) giving sets and containers as adsorption of the drug may occur.

Intracoronary
Percutaneous transluminal coronary angioplasty
Adult: To facilitate prolongation of balloon inflation and for prophylaxis or relief of coronary spasm: 1 mg via bolus inj prior to balloon inflation, may give additional doses up to a Max of 5 mg within a 30-minute period.
Reconstitution: Prior to administration, concentrated solution (1 mg/mL) must be diluted to a Max concentration of 0.5 mg/mL
Incompatibility: Avoid use of polyvinyl chloride (PVC) or polyurethane (PU) giving sets and containers as adsorption of the drug may occur.

Intravenous
Angina pectoris
Adult: For the treatment of severe or unstable cases: 2-12 mg per hour, may be titrated up to 20 mg per hour according to patient response.
Reconstitution: Prior to administration, concentrated solution (1 mg/mL) must be diluted to a Max concentration of 0.5 mg/mL.
Incompatibility: Avoid use of polyvinyl chloride (PVC) or polyurethane (PU) giving sets and containers as adsorption of the drug may occur.

Should be taken on an empty stomach. Take 30 min before meals.

Acute circulatory failure (e.g. shock, vascular collapse), hypertrophic obstructive cardiomyopathy; acute MI with low filling pressures, severe hypotension, low cardiac filling pressures, cardiac tamponade, constrictive pericarditis, aortic or mitral valve stenosis, diseases associated with raised intracranial pressure (e.g. following a head trauma, cerebral haemorrhage), marked anaemia, hypovolaemia, cor pulmonale. Concomitant use with phosphodiesterase 5 (PDE5) inhibitors (e.g. sildenafil, vardenafil, tadalafil) and riociguat.

Patient with closed-angle glaucoma, malnutrition, hypothyroidism, hypothermia, hypoxaemia, ventilation or perfusion imbalance due to lung disease or ischaemic heart failure, orthostatic syndrome. Avoid abrupt withdrawal. Severe renal and hepatic impairment. Elderly. Pregnancy and lactation. Monitoring Parameters Monitor blood pressure and heart rate. Evaluate closely for volume depletion, hypotension, and right ventricular infarction.

Significant: Orthostatic or severe hypotension, syncope, tolerance and cross-tolerance to other nitrates; may precipitate haemolysis (in patients with G6PD deficiency); increased intracranial pressure; headache (during initial treatment). Cardiac disorders: Palpitations, tachycardia, aggravated angina pectoris. Gastrointestinal disorders: Rarely, nausea, vomiting. General disorders and administration site conditions: Peripheral oedema (oral), asthenia. Nervous system disorders: Dizziness, somnolence, cerebral ischaemia. Skin and subcutaneous tissue disorders: Rarely, allergic skin reactions (e.g. rash). Vascular disorders: Cutaneous vasodilation (including flushing), circulatory collapse (occasionally accompanied by syncope and bradyarrhythmia).

Symptoms: Paleness, sweating, fall in blood pressure (≤90 mmHg), weak pulse, tachycardia, light-headedness on standing, persistent throbbing headache, weakness, dizziness, nausea, vomiting, increased intracranial pressure with confusion and moderate fever; vertigo, visual disturbances, palpitations; heart block, paralysis, coma, seizures, and death; methaemoglobinaemia and cyanosis with subsequent tachypnoea, anxiety, loss of consciousness, and cardiac arrest may also occur. Management: Supportive and symptomatic treatment. Perform gastric lavage in conscious patients if recent ingestion (within 4 hours). In case of hypotension, supply oxygen and expand plasma volume (e.g. IV fluids). Patient must be kept in a horizontal position with legs raised and head lowered. In patients who do not respond to adequate fluid resuscitation, vasopressors may be used. For the treatment of methaemoglobinaemia, initiate artificial ventilation and administration of oxygen and initiation of haemodialysis may be done if necessary; administer reduction therapy with either vitamin C, methylene blue, or toluidine blue.

May act as a physiological antagonist to norepinephrine, acetylcholine, histamine, and other agents. May potentiate hypotensive effects with antihypertensive agents (e.g. Ca channel blockers, β-blockers, angiotensin II receptor blockers). May cause orthostatic hypotension with phenothiazines, MAOIs, and TCAs. Concomitant use in patients already receiving ACE inhibitors may cause symptoms of circulatory collapse.
Potentially Fatal: Risk of severe hypotension, myocardial ischaemia, or syncope with PDE5 inhibitors (e.g. sildenafil, vardenafil, tadalafil). Increased risk of hypotension with riociguat.

Alcohol may potentiate the vasodilating and hypotensive effects of isosorbide dinitrate; avoid concomitant use.

Isosorbide dinitrate is an organic nitrate vasodilator that forms free radical nitric oxide which stimulates the guanylate cyclase that increases guanosine 3'5' monophosphate (cGMP), thus relaxing the vascular smooth muscles and consequently dilating peripheral arteries and veins. This action promotes peripheral pooling of blood and reduces venous return to the heart, therefore decreasing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). It may also modestly reduce systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload).
Onset: Anti-anginal: Approx 2-5 minutes (sublingual); approx 1 hour (oral).
Duration: Anti-anginal: 1-2 hours (sublingual); 4-6 hours (oral).
Absorption: Readily absorbed from the oral mucosa (sublingual) and from the gastrointestinal tract (oral). Bioavailability: 10-90% (highly variable; increases with chronic therapy). Time to peak plasma concentration: 0.5-1 hour.
Distribution: : Widely distributed. Volume of distribution: 2-4 L/kg. Plasma protein binding: <1%.
Metabolism: Undergoes extensive first-pass metabolism, primarily in the liver, into isosorbide 2-mononitrate and isosorbide 5-mononitrate (major active metabolites).
Excretion: Elimination half-life: Approx 1 hour (isosorbide dinitrate); approx 5 hours (isosorbide 5-mononitrate); approx 2 hours (isosorbide 2-mononitrate).

Intracoronary: Store below 30°C. Once opened or diluted, use immediately or may store between 2-8°C for 24 hours. Storage recommendations may vary among countries and individual products. Refer to detailed product guidelines. Intravenous: Store below 30°C. Once opened or diluted, use immediately or may store between 2-8°C for 24 hours. Storage recommendations may vary among countries and individual products. Refer to detailed product guidelines. Oral: Store between 20-25°C. Storage recommendations may vary among countries and individual products. Refer to detailed product guidelines. Sublingual: Store between 20-25°C. Storage recommendations may vary among countries and individual products. Refer to detailed product guidelines.

Anti-Anginal Drugs

C01DA08 - isosorbide dinitrate ; Belongs to the class of organic nitrate vasodilators. Used in the treatment of cardiac disease.
C05AE02 - isosorbide dinitrate ; Belongs to the class of muscle relaxants. Used in the topical treatment for the treatment of hemorrhoids and anal fissures.