ISORDIL
Clinical safety rating
cautionComprehensive clinical and safety monograph for ISORDIL (ISORDIL).
Isosorbide dinitrate is converted to nitric oxide (NO) in vascular smooth muscle, activating guanylate cyclase, increasing cGMP, leading to vasodilation of veins (greater effect) and arteries. Reduces preload and afterload, decreasing myocardial oxygen demand.
| Metabolism | Primarily hepatic via glutathione-organic nitrate reductase; also undergoes denitration to active metabolites (isosorbide-2-mononitrate and isosorbide-5-mononitrate). |
| Excretion | Renal: 80% as inactive metabolites; biliary/fecal: 20% as conjugates. |
| Half-life | Terminal half-life: 1–4 hours (isosorbide dinitrate); clinical context: short duration requires frequent dosing or sustained-release formulations. |
| Protein binding | ~28% bound to albumin. |
| Volume of Distribution | 2–4 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Sublingual: ~40–60% (first-pass bypassed); oral: <30% due to extensive first-pass hepatic metabolism. |
| Onset of Action | Sublingual: 2–5 minutes; oral immediate-release: 15–30 minutes; oral sustained-release: 30–60 minutes. |
| Duration of Action | Sublingual: 1–2 hours; oral immediate-release: 4–6 hours; oral sustained-release: up to 12 hours (tolerance may develop with continuous use). |
| Molecular Weight | 236.14 |
Isosorbide dinitrate: initial 5-20 mg orally 2-3 times daily, maintenance 10-40 mg orally 2-3 times daily. Sublingual: 2.5-5 mg every 15 minutes for up to 3 doses for acute angina. Extended-release: 40 mg orally once daily, increased to 80 mg once daily as tolerated.
| Dosage form | TABLET |
| Renal impairment | No specific GFR-based dose adjustments are recommended; however, caution is advised in severe renal impairment due to potential accumulation of metabolites. |
| Liver impairment | In Child-Pugh class A: no adjustment. Child-Pugh class B and C: reduce dose by 50% and monitor for hypotension. |
| Pediatric use | Isosorbide dinitrate: not recommended for use in children due to lack of safety and efficacy data; no established pediatric dosing guidelines. |
| Geriatric use | Elderly patients may have increased sensitivity to hypotension. Initiate with lowest doses (e.g., 5 mg orally twice daily) and titrate slowly. Monitor blood pressure and orthostatic changes. |
| 1st trimester | Use only if clearly needed. No well-controlled studies in pregnant women. Potential risk of fetal hypotension and hypoxia. |
| 2nd trimester | Use only if clearly needed. Monitor for maternal hypotension and fetal heart rate changes. |
| 3rd trimester | Use only if clearly needed. May cause uterine relaxation and potential for preterm labor. Avoid near term due to risk of maternal hypotension and fetal distress. |
Clinical note
Comprehensive clinical and safety monograph for ISORDIL (ISORDIL).
| Placental transfer | Isosorbide dinitrate and its metabolites cross the placenta; degree of transfer is not well quantified but is presumed significant based on molecular weight and lipid solubility. |
| Breastfeeding | Excretion into breast milk is unknown. Use with caution due to potential for adverse effects in infants (e.g., hypotension, methemoglobinemia). Monitor infant for signs of vasodilation. |
| Lactation Rating | L3 - Limited Data |
| Teratogenic Risk | Isosorbide dinitrate (ISORDIL) is an organic nitrate vasodilator. Animal studies have not demonstrated teratogenic effects, but adequate human studies in pregnant women are lacking. It should be used during pregnancy only if clearly needed. Potential fetal risks include hypotension and reduced uteroplacental perfusion, particularly in the first trimester. Second and third trimester risks are theoretical due to maternal hemodynamic changes. Avoid use near term due to risk of neonatal methemoglobinemia. FDA pregnancy category C. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of hypotension. Assess fetal heart rate and uterine activity if used during labor. Monitor for maternal headache, dizziness, and syncope. In neonates, observe for signs of methemoglobinemia (e.g., cyanosis, respiratory distress). |
| Fertility Effects | No human data on fertility effects. Animal studies have not shown impaired fertility. Theoretical concerns from vasodilation affecting reproductive organ blood flow; however, no specific adverse effects on fertility are reported. |
■ FDA Black Box Warning
Do not use in patients with erectile dysfunction medications (PDE-5 inhibitors) due to risk of severe hypotension.
| Common Effects | Headache |
| Serious Effects |
Hypersensitivity to isosorbide dinitrate or any componentConcurrent use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil)Severe anemiaIncreased intracranial pressureAcute myocardial infarction with low filling pressuresCardiac tamponadeConstrictive pericarditis
| Precautions | Hypotension (especially with volume depletion or alcohol), Tolerance with prolonged use (intermittent dosing recommended), Exacerbation of angina upon abrupt withdrawal, Use cautiously in hypertrophic cardiomyopathy |
| Food/Dietary | Avoid excessive alcohol consumption. No specific food interactions; however, high-fat meals may delay absorption of oral formulations. Maintain consistent dietary habits to minimize variations in drug effects. |
| Clinical Pearls | Isordil (isosorbide dinitrate) is a nitrate vasodilator used for angina prophylaxis. Sublingual formulation provides rapid onset for acute attacks; oral sustained-release is for chronic prophylaxis. Tolerance develops with continuous exposure; use a daily nitrate-free interval of 10-12 hours. Avoid use with PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) due to severe hypotension. Monitor for headache, hypotension, and reflex tachycardia. |
| Patient Advice | Take sublingual isordil at the first sign of an angina attack; sit down before using to avoid dizziness. · For chronic prophylaxis, take as prescribed; do not skip doses to maintain the nitrate-free interval. · Avoid alcohol as it can increase the risk of hypotension and dizziness. · Report any severe headaches, worsening chest pain, or fainting to your healthcare provider immediately. · Never take erectile dysfunction medications (e.g., Viagra, Cialis, Levitra) while on isordil. |
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