Irbesartan

Overview

Irbesartan is an angiotensin-II receptor blocker (ARB) that may be useful in dogs and cats for the treatment of hypertension associated with renal disease. Veterinary experience with this drug remains limited.

In dogs, irbesartan may also be considered for the management of proteinuria associated with glomerular disease in combination with an ACE inhibitor. It has been suggested as an adjunctive option for heart failure in dogs that cannot tolerate ACE inhibitors, although documentation supporting this use is lacking.

Mechanism of Action (MOA): Irbesartan selectively blocks angiotensin-II AT1 receptors, reducing aldosterone synthesis and secretion. This results in vasodilation, decreased potassium excretion, and increased sodium excretion. Unlike losartan, irbesartan does not require conversion to an active metabolite.

Indications

Irbesartan is used extra-label in dogs and cats primarily for the management of hypertension associated with renal disease. Veterinary experience remains limited.

• Hypertension: Management of hypertension associated with renal insufficiency.
• Proteinuria: Reduction of proteinuria associated with glomerular disease, in combination with an ACE inhibitor.
• Heart failure: May be considered as adjunctive therapy in dogs unable to tolerate ACE inhibitors, although supporting documentation is lacking.

Dosage (Reference)

Dogs

The following dosages have been published for extra-label use in dogs; the lower dosage has been recommended anecdotally.

Warnings and Precautions

• Correct volume depletion or sodium depletion before initiating irbesartan therapy.
• Do not use in patients with hypotension.
• Contraindicated in patients with a known hypersensitivity to irbesartan.
• Do not use during pregnancy.

Drug Interactions

• ACE inhibitors (e.g., benazepril, enalapril): Increased risk of hypotension, hyperkalemia, and changes in renal function. Increased monitoring may be warranted. Combination is not recommended in humans.
• NSAIDs (e.g., carprofen, meloxicam) and aspirin: May reduce the antihypertensive effect of irbesartan and increase the risk of renal impairment. Increased monitoring may be warranted.
• Potassium preparations, potassium-sparing diuretics (e.g., spironolactone), and low-molecular-weight heparins (e.g., dalteparin, enoxaparin): Increased risk of hyperkalemia. Monitor serum potassium as appropriate.
• Antihypertensive or hypotensive agents (e.g., baclofen, benzodiazepines, buspirone, cabergoline, dexmedetomidine, diazoxide, dichlorphenamide, diphenhydramine, doxepin, opioids): Concurrent use may produce additive hypotensive effects or increase the risk of hypotension.
• Corticosteroids (e.g., betamethasone, dexamethasone): May decrease the antihypertensive effects of angiotensin-II receptor blockers.
• Digoxin: May increase digoxin concentrations. Closely monitor digoxin concentrations and therapeutic effects.
• Fluconazole: May increase irbesartan concentrations. Other azole antifungals (e.g., itraconazole, ketoconazole) do not appear to have this effect.
• Insulin: May increase the risk of hypoglycemia.
• Lithium: May increase the risk of lithium toxicity.
• Yohimbine: May decrease the efficacy of angiotensin-II receptor blockers.

Side Effects and Overdose

Side Effects

• The adverse effect profile in dogs and cats has not been established because of limited veterinary experience.
• Reported adverse effects in humans include:
  • Diarrhea
  • Dyspepsia
  • Fatigue
  • Orthostatic dizziness
  • Hypotension

Overdose

• Expected overdose effects include hypotension with either bradycardia or tachycardia.
• Treatment is supportive.

Key Notes

• Unlike losartan, irbesartan does not require conversion to an active metabolite.
• The drug may be administered with or without food. If gastrointestinal upset occurs when given on an empty stomach, administer future doses with food or a small treat.
• Veterinary clinical experience with irbesartan remains limited; patients should be monitored carefully for unexpected adverse effects during therapy.
• Irbesartan tablets should be stored at room temperature (15°C–30°C [59°F–86°F]).
• Monitor blood pressure and heart rate, with baseline and periodic serum electrolytes, BUN and creatinine.