Isosorbide Dinitrate / Isosorbide Mononitrate
1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate / 1,4:3,6-dianhydro-D-glucitol 5-nitrate
Also known as: Isordil · Ismo · Imdur · Isochron · Dilatrate-SR · Monoket · Titradose · ISDN · EV-151 · sorbide nitrate · AHR-4698 · BM-22145 · IS5-MN · isosorbide-5-mononitrate
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Refractory heart failure or in combination with hydralazine or amlodipine in patients unable to tolerate ACE inhibitors | Isosorbide dinitrate at 0.5-2 mg/kg PO twice daily OR isosorbide mononitrate at 0.25-2 mg/kg PO twice daily | PO | twice daily | — | 🌎 NA |
- Refractory heart failure or in combination with hydralazine or amlodipine in patients unable to tolerate ACE inhibitors: Efficacy is unknown. It is unknown if nitrate-free periods are required to prevent nitrate tolerance.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive treatment of heart failure associated with thyroid storm | Isosorbide dinitrate at 0.5-2 mg/kg PO q8-12h | PO | q8-12h | — | 🌎 NA |
| Refractory heart failure or in combination with hydralazine or amlodipine in patients unable to tolerate ACE inhibitors | Isosorbide dinitrate at 0.5-2 mg/kg PO twice daily OR isosorbide mononitrate at 0.25-2 mg/kg PO twice daily | PO | twice daily | — | 🌎 NA |
- Adjunctive treatment of heart failure associated with thyroid storm: Start at lowest level and titrate upward.
- Refractory heart failure or in combination with hydralazine or amlodipine in patients unable to tolerate ACE inhibitors: Efficacy is unknown.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Isosorbide dinitrate (ISDN) and isosorbide mononitrate (ISMN) are organic nitrates that act as potent venodilators, primarily used to reduce cardiac preload.
- Veterinary Use: While widely used in human medicine for angina and congestive heart failure (CHF), clinical experience and proven efficacy in small animal medicine remain limited. They are occasionally utilized as adjunctive therapy for refractory heart failure or in patients unable to tolerate ACE inhibitors.
- Pharmacological Nuances: Dogs appear to require significantly higher dosages of isosorbide to achieve therapeutic hemodynamic effects compared to humans.
- Clinical Pearl: Like other organic nitrates (e.g., nitroglycerin), continuous use of isosorbide nitrates can lead to nitrate tolerance (tachyphylaxis), where the vasodilatory effects diminish over time. In human medicine, a "nitrate-free" interval (usually 10-12 hours daily) is required to maintain efficacy, though the exact requirement for this in veterinary patients is unknown.
Mechanism of action
Organic nitrates act as prodrugs that donate nitric oxide (NO) to vascular smooth muscle, leading to profound vasodilation (predominantly venous, with some arterial effects at higher doses).
Mechanism Pathway: Organic Nitrate → converted to free radical Nitric Oxide (NO) → activates soluble guanylate cyclase (sGC) → increases intracellular cyclic GMP (cGMP) → activates Protein Kinase G (PKG) → decreases intracellular calcium and dephosphorylates myosin light chain → Vascular Smooth Muscle Relaxation.
- Hemodynamic Effects: By dilating the venous capacitance vessels, nitrates significantly decrease venous return to the heart (reduced preload), which lowers ventricular filling pressures and helps alleviate pulmonary edema in CHF.
- Additional Effects: Nitrates functionally antagonize acetylcholine, norepinephrine, and histamine. They also relax non-vascular smooth muscle, including biliary, bronchial, gastrointestinal, ureteral, and uterine tissues.
Safety & warnings
Contraindications
- Cardiogenic or hypovolemic shock
- Severe hypotension
- Hypovolemia
- Use as a sole agent for treating heart failure
- Concurrent use with selective phosphodiesterase inhibitors (e.g., sildenafil)
Adverse effects
- Postural hypotension
- Reflex tachycardia
- Lethargy or weakness (secondary to hypotension)
- Gastrointestinal upset
- Restlessness
- Headache (well-documented in humans, difficult to assess in animals)
- Hypersensitivity reactions (rare)
Precautions
Hemodynamic Warning: Use with extreme caution in patients with low blood pressure or uncorrected hypovolemia.
- Nitrate Tolerance: Continuous exposure may lead to tolerance. Consider dosing strategies that allow for a nitrate-free interval if chronic use is intended.
- Laboratory Interference: Serum cholesterol levels may be falsely decreased by nitrates when using the Zlatkis-Zak color reaction method.
- Pregnancy: FDA Category C. Use only if the potential benefit justifies the potential risk to the fetus.
Drug interactions
Possible additive hypotensive effects; monitor blood pressure closely.
Possible additive hypotensive effects due to alpha-adrenergic blockade.
Concurrent use with sildenafil can cause profound, life-threatening hypotension and is strictly contraindicated. Use with pimobendan (a PDE3 inhibitor) is common in vet med but requires monitoring for excessive vasodilation.
Monitoring
- Clinical efficacy (improvement in respiratory rate/effort, resolution of pulmonary edema)
- Systemic blood pressure (monitor for hypotension)
- Heart rate (monitor for reflex tachycardia)
- Renal values and electrolytes (if used concurrently with diuretics and ACE inhibitors)
Pharmacokinetics
Half-life
Absorption
Dogs: Isosorbide mononitrate oral bioavailability is approximately 70%. Oral doses >2 mg/kg yield peak plasma levels >100 ng/mL (believed to be the minimum required for hemodynamic effects). Humans: Both ISDN and ISMN are well absorbed orally; food may delay the rate but not the extent of absorption.
Distribution
Widely distributed. Hemodynamic effects require minimum serum concentrations of approximately 100 ng/mL, though some canine studies showed no hemodynamic changes even at much higher peak levels.
Metabolism
Isosorbide dinitrate undergoes extensive first-pass hepatic metabolism primarily to isosorbide mononitrate. Isosorbide mononitrate is metabolized primarily in the liver but does not undergo first-pass metabolism.
Elimination
Metabolites do not appear to have pharmacologic activity and are principally excreted in the urine.
Overdose
Toxicity Profile: Isosorbide mononitrate caused significant lethality in rats and mice at massive dosages (2000 mg/kg and 3000 mg/kg, respectively).
Clinical Signs of Overdose:
- Profound venous pooling
- Decreased cardiac output
- Severe hypotension
- Reflex tachycardia
- Collapse or syncope
Treatment:
- Treatment is primarily supportive.
- Avoid Epinephrine: Drug therapies with agents such as epinephrine are NOT recommended as they may exacerbate the cardiovascular collapse.
- Fluid Therapy: Increasing central fluid volume may be useful to counteract venous pooling, but in patients with pre-existing congestive heart failure (CHF), IV fluids must be administered with extreme caution to avoid precipitating fulminant pulmonary edema.
Available products
Formulations
- Oral tablets
- Sublingual tablets
- Extended-release tablets
- Sustained-release capsules
Human-labeled
- Isosorbide Dinitrate Oral Tablets: 5 mg, 10 mg, 20 mg, 30 mg, & 40 mg
- Isosorbide Dinitrate Sublingual Oral Tablets: 2.5 mg, & 5 mg
- Isosorbide Dinitrate Extended-Release Oral Tablets: 40 mg
- Isosorbide Dinitrate Sustained-Release Oral Capsules: 40 mg
- Isosorbide Mononitrate Tablets: 10 mg, & 20 mg
- Isosorbide Mononitrate Extended-Release Tablets: 30 mg, 60 mg, & 120 mg
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Isosorbide dinitrate and standard isosorbide mononitrate tablets should be stored in well-closed/tight containers below 40°C (preferably between 15°-30°C). Isosorbide mononitrate extended-release tablets should be stored between 2°-30°C. Heat and moisture accelerate the loss of potency.
Client information
- Experimental Nature: There is limited experience using this medication in veterinary medicine; it is typically reserved for advanced or difficult-to-treat heart conditions.
- Administration: May be given with or without meals. Follow your veterinarian's dosing schedule exactly, as specific timing may be needed to prevent the body from building a tolerance to the drug.
- What to Watch For: Because this drug lowers blood pressure, watch your pet closely for signs of weakness, lethargy, stumbling, or fainting. If these occur, contact your veterinarian immediately.
- Storage: Keep the medication tightly closed in its original container, protected from heat and moisture, as these can cause the drug to lose its potency.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.