ISMO
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 191.14 |
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 | No adequate studies in humans; animal studies show fetal toxicity at high doses; use only if clearly needed. |
| 2nd trimester | Use only if potential benefit justifies potential risk to fetus; may cause fetal hypoxia due to maternal hypotension. |
| 3rd trimester | May cause fetal distress, hypotension, and uterine relaxation; avoid near term if possible. |
Clinical note
Comprehensive clinical and safety monograph for ISMO (ISMO).
| Placental transfer | Likely crosses placenta based on molecular weight and lipid solubility; no specific data for isosorbide mononitrate. |
| Breastfeeding | Excretion into breast milk is unknown; due to potential for serious adverse reactions in nursing infants, consider discontinuing nursing or drug. |
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
■ 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 |
Hypersensitivity to isosorbide mononitrate or any componentConcurrent use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil)Severe hypotension (systolic BP < 90 mmHg)Cardiogenic shockAcute myocardial infarction with low filling pressuresSevere anemiaIncreased intracranial pressureConstrictive pericarditisPericardial tamponade
| 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 |
| Food/Dietary | Alcohol may enhance hypotension risk. Avoid high-fat meals if extended-release formulation, as they may affect absorption. No other significant food interactions. |
| Clinical Pearls | ISMO (isosorbide mononitrate) is a nitrate used for angina prophylaxis, not for acute attacks. Tolerance develops with sustained use; maintain a 10-12 hour nitrate-free interval to prevent tolerance. Do not use with phosphodiesterase-5 inhibitors (e.g., sildenafil) due to risk of profound hypotension. Contraindicated in severe anemia, increased intracranial pressure, or hypertrophic obstructive cardiomyopathy. Discontinue if blurred vision or dry mouth occurs. |
| Patient Advice | Take as prescribed to prevent angina; do not use for acute attacks. · May cause headache, dizziness, or hypotension; rise slowly from sitting. · Avoid taking erectile dysfunction drugs (e.g., sildenafil, tadalafil) as severe blood pressure drop can occur. · Do not stop abruptly to avoid rebound angina. · Store in original container away from light and moisture. |
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