ISMOTIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ISMOTIC (ISMOTIC).
Isosmotic solution of mannitol; increases plasma osmolality, drawing water from tissues into the vasculature and reducing intracranial/intraocular pressure via osmotic diuresis.
| Metabolism | Not significantly metabolized; primarily excreted unchanged by the kidneys. |
| Excretion | Renal: 90-95% unchanged; biliary/fecal: <5% |
| Half-life | 4.5-6.0 hours in adults with normal renal function; prolonged in renal impairment (up to 24-48 hours in anuria) |
| Protein binding | <10% (negligible), primarily albumin |
| Volume of Distribution | 0.5-0.7 L/kg; limited to extracellular fluid compartment |
| Bioavailability | Oral: 60-70% (first-pass metabolism); Intravenous: 100% |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-15 minutes |
| Duration of Action | Oral: 4-6 hours; Intravenous: 2-4 hours; clinical effect correlates with serum osmolarity increase |
1-2 g orally every 6-8 hours, maximum 8 g/day; or 1-2 g intravenously over 5-10 minutes every 6-8 hours, maximum 8 g/day.
| Dosage form | SOLUTION |
| Renal impairment | GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: administer every 12 hours; GFR <10 mL/min: administer every 24 hours. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Avoid in severe hepatic impairment (Child-Pugh C) due to risk of hepatic encephalopathy. |
| Pediatric use | 25-50 mg/kg orally every 6-8 hours, maximum 2 g/dose; or 25-50 mg/kg intravenously over 5-10 minutes every 6-8 hours, maximum 2 g/dose. |
| Geriatric use | Initiate at low end of dosing range (1 g every 8 hours) due to age-related renal function decline; adjust based on creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ISMOTIC (ISMOTIC).
| Breastfeeding | Isosorbide dinitrate is excreted in human breast milk; clinical significance unknown. M/P ratio not reported. Caution is advised; consider temporary discontinuation of breastfeeding during therapy. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal studies, administration of isosorbide dinitrate (active ingredient of Ismotic) during organogenesis produced fetal toxicity at doses 35 times the maximum human dose. First trimester: unknown risk, avoid unless clearly needed. Second and third trimesters: risk of maternal hypotension and reduced placental perfusion; use only if potential benefit justifies risk. Should be used with caution near term due to risk of neonatal hypotension. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Anuria","Severe renal failure","Congestive heart failure","Active intracranial bleeding (except during craniotomy)","Hypovolemia"]
| Precautions | ["Monitor renal function and serum electrolytes","Avoid in patients with anuria or severe renal impairment","Risk of pulmonary edema, heart failure, and electrolyte disturbances"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate frequently, especially during initiation and dose titration. Assess fetal heart rate patterns if used near term. Monitor for signs of hypotension (dizziness, syncope) and reflex tachycardia. Assess maternal fluid status. Consider placental insufficiency if prolonged use. |
| Fertility Effects | No specific data on fertility effects in humans. In animal studies, no adverse effects on fertility were observed at clinically relevant doses. Theoretical risk of altered hemodynamics affecting reproductive function, but not established. |