ISOSORBIDE MONONITRATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Isosorbide mononitrate is an organic nitrate that acts as a vasodilator. It is metabolized to nitric oxide (NO), which activates guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells. This leads to dephosphorylation of myosin light chains and relaxation of smooth muscle, resulting in dilation of peripheral arteries and veins. Venodilation reduces preload, while arterial dilation reduces afterload, decreasing myocardial oxygen demand.
| Metabolism | Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate. It is not subject to first-pass metabolism. Metabolism occurs via denitration and glucuronidation in the liver. The primary metabolic pathways are reduction of nitrate groups and conjugation with glucuronic acid. |
| Excretion | Renal: ~93% (as metabolites, primarily isosorbide and glucuronides); fecal: ~2%; biliary: negligible. |
| Half-life | Terminal half-life: 4–5 hours; clinical context: allows twice-daily dosing for sustained antianginal effect. |
| Protein binding | <5%; binding proteins: albumin (minimal). |
| Volume of Distribution | 0.6–0.7 L/kg; clinical meaning: distributes primarily into total body water. |
| Bioavailability | Oral: bioavailability 90–100% (no significant first-pass metabolism). |
| Onset of Action | Oral immediate-release: 30–60 minutes; oral extended-release: 1–2 hours. |
| Duration of Action | Immediate-release: 6–8 hours; extended-release: 12–24 hours; note: tolerance develops with frequent dosing; use asymmetric dosing or nitrate-free interval. |
20 mg orally twice daily, with the two doses given 7 hours apart to maintain low nitrate-free interval.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (eGFR < 30 mL/min), use with caution due to potential for accumulation of inactive metabolites; no specific dose adjustment guidelines. |
| Liver impairment | No specific dose adjustment for Child-Pugh class A or B. For Child-Pugh class C, consider dose reduction (e.g., initial 10 mg twice daily) due to reduced clearance and increased risk of hypotension. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no standard dosing recommendations. |
| Geriatric use | Initiate at lower dose (e.g., 20 mg once daily) and titrate cautiously due to increased sensitivity to hypotensive effects and potential for altered pharmacokinetics. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Phosphodiesterase inhibitors (eg sildenafil) can cause severe hypotension Can cause tolerance with continuous use and severe headaches.
| Breastfeeding | Isosorbide mononitrate is excreted into human breast milk in low amounts. M/P ratio is unknown. Based on limited data, exposure to the infant via milk is expected to be low and unlikely to cause adverse effects. However, use with caution in nursing mothers, monitoring infant for hypotension. |
| Teratogenic Risk | Isosorbide mononitrate is an organic nitrate vasodilator. Human data are limited. Animal studies have not shown teratogenic effects. However, due to hemodynamic effects, use in first trimester is generally avoided unless clearly needed. In second and third trimesters, risk of maternal hypotension and decreased placental perfusion may cause fetal bradycardia and distress. No specific malformations are linked to first trimester exposure. |
■ FDA Black Box Warning
None
| Common Effects | Headache |
| Serious Effects |
Hypersensitivity to isosorbide mononitrate or other nitrates. Concurrent use with phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to risk of severe hypotension. Severe hypotension (systolic blood pressure <90 mmHg). Cardiogenic shock. Constrictive pericarditis. Pericardial tamponade. Acute myocardial infarction with low left ventricular filling pressure. Severe anemia. Closed-angle glaucoma (relative contraindication).
| Precautions | Hypotension: Can cause severe hypotension, especially in volume-depleted patients or with alcohol use. Tolerance: Continuous exposure may lead to tolerance and cross-tolerance to other nitrates; use with a daily nitrate-free interval (e.g., dosing twice daily with 7-hour interval) is recommended. Withdrawal: Abrupt discontinuation may precipitate angina. Headache: Common side effect, may require dose adjustment. Increased intracranial pressure: Use cautiously in patients with elevated intracranial pressure (e.g., head trauma, cerebral hemorrhage). |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate; fetal heart rate monitoring during prolonged use or high doses; assess for signs of maternal hypotension or fetal distress. |
| Fertility Effects | No data on effects on human fertility. Animal studies have not shown impairment of fertility. |
| Food/Dietary | Avoid high-fat meals with immediate-release formulations as they may delay absorption. No specific food restrictions for extended-release formulation. Minimize alcohol consumption due to additive hypotensive effects. |
| Clinical Pearls | Isosorbide mononitrate is an active metabolite of isosorbide dinitrate with 100% oral bioavailability and no first-pass metabolism. The extended-release formulation should be administered once daily in the morning to maintain a nitrate-free interval of 10-12 hours to prevent tolerance. Do not use for acute angina attacks. Monitor for hypotension, especially with PDE-5 inhibitors (e.g., sildenafil) which are contraindicated within 24 hours. Abrupt discontinuation may cause rebound angina. |
| Patient Advice | Take the extended-release tablet once daily in the morning exactly as prescribed, with or without food. · Do not crush or chew the extended-release tablet; swallow it whole. · If you miss a dose, skip it and resume the next day; do not double the dose. · Common side effects include headache, dizziness, and flushing; headaches may improve with continued use. · Avoid alcohol as it can increase the risk of low blood pressure and dizziness. · Seek immediate medical help if you experience vision changes, severe chest pain, or fainting. · Inform all healthcare providers you are taking this medication, especially before surgery or dental procedures. |