SORBITRATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SORBITRATE (SORBITRATE).
Sorbitrate (isosorbide dinitrate) is a nitrate that relaxes vascular smooth muscle by converting to nitric oxide (NO), which activates guanylate cyclase, increasing cGMP levels, leading to vasodilation. It primarily dilates coronary arteries and peripheral veins (venodilation > arteriodilation), reducing preload and afterload, thereby decreasing myocardial oxygen demand.
| Metabolism | Isosorbide dinitrate undergoes extensive first-pass metabolism in the liver via glutathione-dependent organic nitrate reductase (likely mediated by mitochondrial aldehyde dehydrogenase, ALDH2) to active metabolites isosorbide-2-mononitrate and isosorbide-5-mononitrate, with the latter being the major active metabolite. These metabolites are further glucuronidated and excreted renally. |
| Excretion | Renal: ~20% unchanged; remainder as metabolites (isosorbide-2-mononitrate, isosorbide-5-mononitrate). Biliary/fecal: negligible. |
| Half-life | Terminal elimination half-life: 5–6 hours. Clinical context: supports dosing every 6–8 hours; requires nitrate-free interval to prevent tolerance. |
| Protein binding | ~28% bound to albumin. |
| Volume of Distribution | Vd: 1.5–3.5 L/kg. Clinical meaning: extensive tissue distribution, high uptake in vascular smooth muscle. |
| Bioavailability | Sublingual: ~40–60% (bypasses first-pass metabolism). Oral: ~10–20% (extensive first-pass hepatic metabolism). |
| Onset of Action | Sublingual: 2–5 minutes; Oral: 15–40 minutes. |
| Duration of Action | Sublingual: 1–2 hours; Oral (immediate-release): 4–6 hours. Clinical notes: tolerance may develop with continuous exposure; sustained-release forms may last 8–12 hours. |
Sublingual: 2.5-5 mg as needed for acute angina, up to 10 mg per episode. Oral (sustained-release): 40-80 mg twice daily (immediate-release: 10-20 mg three times daily).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required. GFR <10 mL/min: limited data, consider reduced dose. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: reduce dose by 50% or extend dosing interval. |
| Pediatric use | Not recommended for children <18 years due to lack of safety data. |
| Geriatric use | Start at lower end of dosing range (e.g., sublingual 2.5 mg, oral 10 mg twice daily) due to increased sensitivity and risk of hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SORBITRATE (SORBITRATE).
| Breastfeeding | It is not known if isosorbide dinitrate is excreted in human milk. The M/P ratio is unknown. Because many drugs are excreted in milk, caution should be exercised when administered to a nursing woman. |
| Teratogenic Risk | Isosorbide dinitrate (Sorbitrate) has no well-controlled studies in pregnant women. Animal studies have not shown teratogenic effects. Due to vasodilatory effects, there is a potential risk of fetal hypoxia, especially during the second and third trimesters. Use only if clearly needed. |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Headache |
| Serious Effects |
["Hypersensitivity to isosorbide dinitrate or any component of the formulation","Concomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to risk of severe hypotension","Severe hypotension (systolic BP < 90 mmHg)","Cardiogenic shock (unless used to maintain coronary perfusion pressure with inotropic support)","Obstructive cardiomyopathy (relative contraindication)","Increased intracranial pressure (relative contraindication)"]
| Precautions | ["Hypotension: May cause severe hypotension, especially upon standing (orthostatic hypotension). Correct hypovolemia before use.","Tolerance: Continuous use may lead to development of tolerance; a daily nitrate-free interval (10-12 hours) is recommended to maintain efficacy.","Headache: Common, often dose-limiting; may be severe initially but decreases with continued use.","Worsening angina: Abrupt discontinuation may precipitate angina; taper gradually.","Hypertrophic cardiomyopathy: Use with caution in patients with hypertrophic obstructive cardiomyopathy as vasodilation may worsen outflow obstruction.","Increased intracranial pressure: Use with caution in patients with increased intracranial pressure (e.g., head trauma, cerebral hemorrhage)."] |
Loading safety data…
| Fetal Monitoring |
| Monitor maternal blood pressure and heart rate for hypotension and reflex tachycardia. Monitor fetal heart rate for bradycardia or signs of distress. Assess for signs of maternal dizziness or syncope. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies have not shown impaired fertility. |