IMDUR
Clinical safety rating
cautionComprehensive clinical and safety monograph for IMDUR (IMDUR).
Isosorbide mononitrate is a nitrate vasodilator that relaxes vascular smooth muscle via conversion to nitric oxide (NO), which activates guanylate cyclase, increasing cGMP levels, leading to vasodilation. It primarily dilates veins (venodilation) with lesser effects on arteries, reducing preload and afterload, thereby decreasing myocardial oxygen demand.
| Metabolism | Primarily hepatic metabolism via denitration and glucuronidation; isosorbide mononitrate is the active metabolite of isosorbide dinitrate and does not undergo significant first-pass metabolism. |
| Excretion | Isosorbide dinitrate (IMDUR active metabolite? Actually IMDUR is isosorbide mononitrate, the active metabolite of isosorbide dinitrate. For isosorbide mononitrate: renal excretion is approximately 96% as metabolites, with about 2% unchanged; biliary/fecal excretion is minimal, <2%. |
| Half-life | Terminal elimination half-life of isosorbide mononitrate is approximately 5 hours. This supports once-daily dosing for IMDUR (extended-release formulation) due to prolonged absorption phase. |
| Protein binding | Less than 5%, primarily to albumin. Very low protein binding, which contributes to high free fraction. |
| Volume of Distribution | Volume of distribution is approximately 0.6-0.7 L/kg for isosorbide mononitrate. This moderate Vd indicates distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability is nearly 100% for isosorbide mononitrate due to lack of first-pass metabolism (unlike isosorbide dinitrate). For IMDUR extended-release, relative bioavailability is comparable to immediate-release, with controlled release properties. |
| Onset of Action | Oral immediate-release: approximately 30-60 minutes. Extended-release (IMDUR): onset is slower, typically within 1-2 hours due to controlled release. |
| Duration of Action | IMDUR extended-release: duration of antianginal effect is approximately 12-14 hours with once-daily dosing. Tolerance may develop with sustained use, requiring a nitrate-free interval (typically 10-12 hours) to maintain efficacy. |
| Molecular Weight | 236.27 |
Initial: 30-60 mg orally once daily; titrate to 120 mg once daily as tolerated. Maximum: 240 mg once daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No dosage adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, use with caution; consider starting at 30 mg once daily and titrate slowly. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%; start at 30 mg once daily. Child-Pugh Class C: Contraindicated or use with extreme caution; start at 30 mg once daily with careful monitoring. |
| Pediatric use | Not approved for pediatric use. Limited data: 0.5-2 mg/kg orally once daily, not to exceed 120 mg once daily. |
| Geriatric use | Start at 30 mg once daily; titrate slowly due to increased sensitivity and risk of hypotension. |
| 1st trimester | Limited human data; animal studies show increased fetal mortality and reduced fetal growth at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Avoid use in second trimester due to potential for reduced placental blood flow and fetal hypoxia. |
| 3rd trimester | Avoid use in third trimester as it may cause uterine relaxation and delay labor; also may lead to fetal bradycardia and hypotension. |
Clinical note
Comprehensive clinical and safety monograph for IMDUR (IMDUR).
| Placental transfer | Crosses placenta readily with fetal concentrations similar to maternal. |
| Breastfeeding | Excreted into breast milk in small amounts; unlikely to cause adverse effects in infant. Use with caution, especially in preterm or ill infants. |
| Lactation Rating | L2 - Safer |
| Teratogenic Risk | FDA Pregnancy Category C. In animal studies, isosorbide mononitrate (IMDUR) caused embryotoxicity and fetotoxicity at high doses. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. First trimester: No specific malformation pattern identified. Second and third trimesters: Potential risk of fetal hypotension and reduced placental perfusion due to maternal vasodilation. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate for hypotension. Assess fetal heart rate and uterine activity if used near term. Monitor for signs of maternal hypovolemia or syncope. |
| Fertility Effects | No human data on fertility effects. Animal studies showed no impairment of fertility at therapeutic doses. |
■ FDA Black Box Warning
Not recommended for use in patients with acute myocardial infarction (MI) or congestive heart failure (CHF) requiring rapid hemodynamic monitoring; use only under close clinical observation.
| 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 nitratesConcomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil)Severe hypotension (systolic BP <90 mmHg)Cardiac tamponadeConstrictive pericarditis
| Precautions | Hypotension: may cause severe hypotension, especially with upright posture, Tolerance: continuous use may lead to tolerance and cross-tolerance to other nitrates; use with a daily nitrate-free interval, Headache: often occurs but may diminish with continued use, Glaucoma: controversial; generally considered safe, Volume depletion: increased risk of hypotension |
| Food/Dietary | Avoid high-fat meals as they may delay absorption. No specific food interactions; alcohol may increase hypotensive effects. |
| Clinical Pearls | Imdur (isosorbide mononitrate) is an extended-release nitrate used for angina prophylaxis. Avoid concomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil) due to risk of severe hypotension. Tachyphylaxis can occur with continuous use; maintain a daily nitrate-free interval (typically 10-12 hours) to preserve efficacy. Do not crush or chew extended-release tablets. Monitor blood pressure and heart rate during initiation. Use with caution in patients with hypertrophic obstructive cardiomyopathy, aortic stenosis, or volume depletion. |
| Patient Advice | Take Imdur exactly as prescribed, usually once daily in the morning to maintain a nitrate-free interval. · Do not crush, chew, or cut the tablet; swallow it whole with a glass of water. · Avoid taking erectile dysfunction medications (e.g., Viagra, Cialis, Levitra) while on Imdur, as this can cause a dangerous drop in blood pressure. · If you experience headache, it may indicate the drug is working; acetaminophen can help. Inform your doctor if headaches persist. · Store at room temperature, away from moisture and heat. |
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