Isosorbide dinitrate

Organic nitrate, nitric oxide donor

ATC code: C01DA08 (Isosorbide dinitrate)

Brand names

Isordil, Dilatrate-SR

Mechanism of action

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.

Indications

Coronary artery disease

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

Drug–drug interactions

2 pairs found. Sorted from critical to minor.

Critical

Sildenafil

Phosphodiesterase type 5 inhibitors (PDE5)

Mechanism

Sildenafil and isosorbide dinitrate via cGMP – synergistic hypotension.

Symptoms

Fatal hypotension.

Management

Combination contraindicated.

Sources

AEMPS: Ficha tecnica de Iso-Mack (isosorbida dinitrato) (2023)

Pair details →

Critical

Tadalafil

Phosphodiesterase type 5 (PDE-5) inhibitor

Mechanism

Synergistic systemic vasodilation.

Symptoms

Fatal hypotension.

Management

Combination contraindicated.

Sources

AEMPS: Ficha tecnica de Cialis (tadalafilo) (2024)

Pair details →

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Safety

Contraindications

PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) – fatal hypotension
Riociguat
Acute inferior MI with right ventricular involvement
Hypovolemia, shock
Severe anaemia
Closed-angle glaucoma

Serious adverse effects

Severe hypotension with syncope
Methaemoglobinaemia (rare)
Tolerance with continuous use

Common adverse effects

Headache (often resolves within 1–2 weeks)
Facial flushing
Dizziness
Orthostatic hypotension

PregnancyFDA C

Pregnancy experience limited. For severe angina in pregnancy, cardiology decision balancing expected benefit.

Breastfeeding

Limited milk data. Breastfeeding possible with infant monitoring for hypotension.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Isosorbide dinitrate used for?

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.

What are the side effects of Isosorbide dinitrate?

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.

Is Isosorbide dinitrate safe during pregnancy?

FDA category C. Pregnancy experience limited. For severe angina in pregnancy, cardiology decision balancing expected benefit.

Is Isosorbide dinitrate compatible with breastfeeding?

Limited milk data. Breastfeeding possible with infant monitoring for hypotension.

Who should not take Isosorbide dinitrate?

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.

Mechanism of action

Drug–drug interactions

2 pairs found. Sorted from critical to minor.

Critical

Sildenafil

Phosphodiesterase type 5 inhibitors (PDE5)

Mechanism

Sildenafil and isosorbide dinitrate via cGMP – synergistic hypotension.

Symptoms

Fatal hypotension.

Management

Combination contraindicated.

Sources

AEMPS: Ficha tecnica de Iso-Mack (isosorbida dinitrato) (2023)

Pair details →

Critical

Tadalafil

Phosphodiesterase type 5 (PDE-5) inhibitor

Mechanism

Synergistic systemic vasodilation.

Symptoms

Fatal hypotension.

Management

Combination contraindicated.

Sources

AEMPS: Ficha tecnica de Cialis (tadalafilo) (2024)

Pair details →

Safety

Contraindications

PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) – fatal hypotension
Riociguat
Acute inferior MI with right ventricular involvement
Hypovolemia, shock
Severe anaemia
Closed-angle glaucoma

Serious adverse effects

Severe hypotension with syncope
Methaemoglobinaemia (rare)
Tolerance with continuous use

Common adverse effects

Headache (often resolves within 1–2 weeks)
Facial flushing
Dizziness
Orthostatic hypotension

PregnancyFDA C

Pregnancy experience limited. For severe angina in pregnancy, cardiology decision balancing expected benefit.

Breastfeeding

Limited milk data. Breastfeeding possible with infant monitoring for hypotension.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Isosorbide dinitrate used for?

What are the side effects of Isosorbide dinitrate?

Is Isosorbide dinitrate safe during pregnancy?

FDA category C. Pregnancy experience limited. For severe angina in pregnancy, cardiology decision balancing expected benefit.

Is Isosorbide dinitrate compatible with breastfeeding?

Limited milk data. Breastfeeding possible with infant monitoring for hypotension.

Who should not take Isosorbide dinitrate?