ISMO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ISMO (ISMO).
Isosorbide mononitrate is a nitrate that dilates coronary arteries and peripheral veins. It acts by releasing nitric oxide, which activates guanylate cyclase, increasing cGMP levels, leading to smooth muscle relaxation and vasodilation.
| Metabolism | Primarily metabolized in the liver by denitration; minor metabolism via glucuronidation. Metabolites are inactive. |
| Excretion | Primarily renal; 80-90% of the dose is excreted as inactive metabolites (isosorbide mononitrate and isosorbide dinitrate) in urine. Less than 1% is excreted unchanged. Fecal excretion is minimal. |
| Half-life | Terminal elimination half-life is approximately 5-6 hours. In elderly patients or those with hepatic impairment, half-life may be prolonged (up to 8-10 hours), warranting dose adjustment. |
| Protein binding | Approximately 30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd is 0.6-0.9 L/kg, indicating distribution into total body water. Higher Vd may be observed in patients with heart failure. |
| Bioavailability | Oral: 90-100% (sustained-release formulations). Sublingual: high but variable; generally effective due to extensive absorption. |
| Onset of Action | Sublingual: 3-5 minutes; Oral: 30-60 minutes. |
| Duration of Action | Sublingual: 1-2 hours; Oral (sustained-release): 6-8 hours. Clinical duration correlates with hemodynamic effects and is used for prophylaxis of angina. |
20 mg orally twice daily, 7 hours apart (e.g., 8 AM and 3 PM) to minimize nitrate tolerance.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, consider reducing dose to 10 mg twice daily due to potential accumulation of active metabolite. |
| Liver impairment | No dose adjustment in Child-Pugh A or B. For Child-Pugh C, reduce dose to 10 mg twice daily and monitor for hypotension. |
| Pediatric use | Safety and efficacy not established; no standard dosing recommendations. |
| Geriatric use | Start at 10 mg twice daily with gradual titration based on tolerance and renal function. Monitor for hypotension and dizziness. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ISMO (ISMO).
| Breastfeeding | Excretion into human milk is unknown. Due to risk of infant methemoglobinemia and hypotension, caution is advised. M/P ratio: Not available. American Academy of Pediatrics considers nitrate derivatives compatible with breastfeeding, but monitor infant for cyanosis and lethargy. |
| Teratogenic Risk | ISMO (isosorbide mononitrate) is categorized as FDA Pregnancy Category C. In animal studies, reduced fetal survival and growth retardation were observed at high doses. No adequate human studies exist. Use only if potential benefit justifies risk. First trimester: Theoretical risk of hemodynamic effects; avoid unless necessary. Second/third trimester: May cause fetal hypoxia due to maternal hypotension; monitor fetal heart rate. Peripartum: May exacerbate uterine relaxation and postpartum hemorrhage if used near delivery. |
■ FDA Black Box Warning
Do not use with phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) due to risk of severe hypotension.
| Common Effects | Headache Flushing sense of warmth in the face ears neck and trunk Upper respiratory tract infection Abdominal pain Allergic reaction Chest pain Diarrhea |
| Serious Effects |
["Concurrent use of PDE-5 inhibitors","Severe anemia","Closed-angle glaucoma","Hypersensitivity to isosorbide mononitrate or nitrates","Acute myocardial infarction with low filling pressures"]
| Precautions | ["Hypotension and reflex tachycardia may occur","Caution in patients with volume depletion or hypotension","May cause headaches; tolerance may develop with prolonged use","Abrupt withdrawal may increase angina frequency"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and symptoms of hypotension. Assess fetal heart rate during labor. In high-risk pregnancies, consider fetal ultrasound for growth and amniotic fluid index. Long-term use requires periodic liver function tests (rare hepatic effects). |
| Fertility Effects | No human data. Animal studies show no significant effects on fertility at therapeutic doses. Potential indirect effects via altered hormone metabolism (e.g., decreased LH) have not been reported. Use is not likely to impair fertility. |