Isosorbide
Unchecked
Isosorbide (dinitrate, mononitrate)
Imdur (mononitrate ER), Isordil (dinitrate); generics; with hydralazine as BiDil for HFrEF in self-identified Black patients
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Summary
Classes
Common uses
Stable angina (prophylaxis)0, Heart failure with reduced ejection fraction (with hydralazine)0, Esophageal spasm (off-label)0
Pharmacy
Starting dose
Isosorbide mononitrate ER: 30-60 mg PO once daily in the morning, titrate to 120-240 mg/d; isosorbide dinitrate IR: 5-20 mg PO TID with a 12-14 hour nitrate-free interval to prevent tolerance
Preparations
Mononitrate 10, 20 mg IR; 30, 60, 120 mg ER; dinitrate 5, 10, 20, 30, 40 mg IR and ER
US FDA Max
240 mg/d (mononitrate ER); 160 mg/d (dinitrate)
Pharmacology
Routes
Oral, sublingual (dinitrate)
Onset
SL: 2-5 minutes; PO mononitrate: 30-60 minutes
Duration
Mononitrate ER: 12-24 hours; dinitrate IR: 4-6 hours
Half-life
Mononitrate ~5 hours; dinitrate ~1 hour[1]
Bioavailability
Mononitrate ~100% (no first-pass; the principal advantage over dinitrate); dinitrate ~20%[1]
Pregnancy
Limited data.[citation needed]
Legal status
Rx-only in US
Purported mechanism
Isosorbide nitrates are enzymatically denitrated (largely by mitochondrial aldehyde dehydrogenase, ALDH2) to release nitric oxide (NO), which activates soluble guanylyl cyclase, raises cGMP, and relaxes vascular smooth muscle predominantly in the venous capacitance bed (preload reduction) at typical doses, with arterial vasodilation at higher doses.0 Phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil) catastrophically potentiate nitrate-induced hypotension — concurrent use is absolutely contraindicated. Daily nitrate-free intervals (12-14 hours) restore responsiveness and limit tolerance development; this is why mononitrate ER is dosed once-daily in the morning rather than continuously[1].
References
[edit | edit source]- ↑ 1.0 1.1 1.2 FDA Prescribing Information, Imdur (isosorbide mononitrate ER), AstraZeneca, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019091s039lbl.pdf