Organic nitrate, nitric oxide donor
Brand names: Isordil, Dilatrate-SR
Updated · Methodology
Second line
Isosorbide dinitrate is used for prophylaxis and treatment of angina attacks in coronary artery disease. and SEC place nitrates as second-line antianginal therapy after beta-blockers and calcium antagonists. The drug does not reduce mortality in stable angina but relieves symptoms. For sublingual use in acute attack nitroglycerin is preferred (faster onset).
Sources
ICD-10: I25 · ICD-11: BA5Z
Tissue-metabolised to isosorbide-5-mononitrate and isosorbide-2-mononitrate, which release nitric oxide. NO activates soluble guanylate cyclase, raising cGMP in vascular smooth muscle and producing venous (predominant) and arterial vasodilation. Reduces preload and myocardial oxygen demand. Half-life is 1 hour; an 8–12 hour nitrate-free interval is required to prevent tolerance.
Pregnancy experience limited. For severe angina in pregnancy, cardiology decision balancing expected benefit.
Limited milk data. Breastfeeding possible with infant monitoring for hypotension.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
3 pairs found. Sorted from critical to minor.
Mechanism
Sildenafil and isosorbide dinitrate via cGMP – synergistic hypotension.
Symptoms
Fatal hypotension.
Management
Combination contraindicated.
Sources
Mechanism
Synergistic systemic vasodilation.
Symptoms
Fatal hypotension.
Management
Combination contraindicated.
Sources
Mechanism
Vardenafil and isosorbide dinitrate drive the same NO–cGMP signalling pathway from opposite ends. The dinitrate releases nitric oxide in the body and boosts cGMP synthesis in vascular smooth muscle; vardenafil blocks phosphodiesterase-5 and slows the breakdown of that same cGMP. Cyclic GMP accumulates from both directions at once, vascular tone collapses, and additive vasodilation progresses up to refractory hypotension that responds poorly to fluids and vasopressors while both drugs remain active. Unlike sublingual nitroglycerin with its minutes of action, isosorbide dinitrate works for hours and its extended-release forms for most of the day, so the window of danger is stretched out. The Levitra SmPC lists nitrates and other nitric oxide donors as absolute contraindications.
Symptoms
A sharp drop in blood pressure: dizziness, visual greying, reflex tachycardia, cold sweat, syncope. In patients with ischaemic heart disease the collapse of coronary perfusion pressure threatens myocardial infarction. Because the dinitrate is long-acting, hypotension can be prolonged and return in waves as the extended-release form keeps releasing nitrate.
Management
The combination is not prescribed in any form. In a patient on maintenance isosorbide dinitrate, extended-release forms included, vardenafil is contraindicated; the labels give no safe interval for that scenario, and after stopping an extended-release form the nitrate keeps working for hours. After the last dose of vardenafil, wait at least 24 hours before any nitrate, the same as for sildenafil and half the 48 hours required for tadalafil. If angina strikes before that window closes, withhold the dinitrate: use morphine, oxygen and urgent angiography, with furosemide an option for preload reduction. When choosing an alternative, remember vardenafil's second quirk, QT prolongation: it is not combined with class IA and III antiarrhythmics (quinidine, procainamide, amiodarone, sotalol).
Sources
Verbatim lines from the interaction sections, in the language of the label
«CONTRAINDICATIONS: Do not use isosorbide dinitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Do not use isosorbide dinitrate in patients who are taking the soluble guanylate cyclase stimulator riociguat. Concomitant use can cause hypotension.»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Do not use isosorbide dinitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Do not use isosorbide dinitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Do not use isosorbide dinitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil…»FDA, section 4 · Open on DailyMed
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Isosorbide dinitrate is evaluated for the following indications with varying evidence strength: Coronary artery disease (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Isosorbide dinitrate (≥ 1 in 100): Headache (often resolves within 1–2 weeks), Facial flushing, Dizziness, Orthostatic hypotension. See the Safety section for uncommon and serious reactions.
Pregnancy experience limited. For severe angina in pregnancy, cardiology decision balancing expected benefit.
Limited milk data. Breastfeeding possible with infant monitoring for hypotension.
Isosorbide dinitrate is contraindicated in: PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) – fatal hypotension; Riociguat; Acute inferior MI with right ventricular involvement; Hypovolemia, shock; Severe anaemia. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Isosorbide mononitrate, Ivabradine, Lidocaine, Meldonium, Propafenone, Ubidecarenone (coenzyme Q10), Dofetilide, Nitroglycerin