Imidapril

Warnings & Precautions

Imidapril should be used cautiously in patients at increased risk of hypotension or impaired renal function. Careful monitoring is recommended, particularly during the initiation of therapy.

• Contraindications: Do not use in dogs with hypersensitivity to ACE inhibitors, hypotension, acute renal insufficiency, congenital heart disease, obstructive hypertrophic cardiomyopathy, or hemodynamically significant stenoses (aortic stenosis, mitral valve stenosis, or pulmonic stenosis).
• Hypovolemia or dehydration: Use ACE inhibitors with caution in patients with hypovolemia or dehydration because of the increased risk of hypotension; one reference lists hypovolemia as a contraindication.
• Electrolyte disorders: Use cautiously in dogs with hyponatremia or sodium depletion.
• Cardiovascular disease: Use with caution in patients with coronary or cerebrovascular insufficiency.
• Hematologic or immune-mediated disorders: Use cautiously in patients with pre-existing hematologic abnormalities or collagen vascular diseases (e.g., systemic lupus erythematosus).
• Severe congestive heart failure: Dogs with severe CHF should be monitored closely when treatment is initiated.
• Renal impairment: Dose reduction may be required in patients with renal insufficiency.
• Dogs under 4 kg: The safety of imidapril has not been established in dogs weighing less than 4 kg.
• Pregnancy and breeding: Do not use in pregnant or lactating bitches or in breeding dogs, as safety has not been established.

Drug Interactions

The following interactions have been reported or are considered theoretically possible with ACE inhibitors, including imidapril. Concurrent use is not necessarily contraindicated but may require dose adjustment or additional monitoring.

• Anesthetic agents (e.g., alfaxalone, etomidate, isoflurane, propofol): May increase the risk of hypotension.
• Aluminum-, calcium-, or magnesium-containing antacids: May reduce the oral absorption of ACE inhibitors. Separate administration by at least 2 hours.
• Angiotensin receptor blockers (ARBs; e.g., telmisartan): May increase the risk of hyperkalemia, hypotension, syncope, and acute kidney injury.
• Antihypertensive agents and vasodilators (e.g., amlodipine, hydralazine, prazosin, sildenafil): May increase the risk of hypotension and other adverse effects.
• Baclofen, buspirone, cabergoline, diphenhydramine, doxepin, oral glycerin, and opioids (e.g., butorphanol, hydrocodone, morphine): May increase the risk of hypotension.
• Cimetidine: Concurrent use with ACE inhibitors has been associated with neurologic dysfunction in human patients.
• Corticosteroids (e.g., dexamethasone, fludrocortisone, prednisolone): May reduce the antihypertensive effects of ACE inhibitors.
• Darbepoetin alfa and epoetin alfa: ACE inhibitors may interfere with erythropoiesis.
• Digoxin: Serum digoxin concentrations may increase by approximately 15–30%. Monitor serum digoxin concentrations; routine dose reduction is not recommended.
• Disopyramide: May enhance hypoglycemic effects.
• Diuretics (e.g., furosemide, torsemide): May increase the risk of hypotension. Titrate dosages carefully.
• Low molecular weight heparins (e.g., dalteparin, enoxaparin): May increase the risk of hyperkalemia.
• Nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., carprofen, meloxicam, robenacoxib): May reduce the antihypertensive efficacy of ACE inhibitors; there may also be an increased risk of nephrotoxicity.
• Potassium supplements or potassium-sparing diuretics (e.g., spironolactone): May increase the risk of hyperkalemia.
• Probenecid: May decrease the renal excretion of ACE inhibitors and enhance their clinical and toxic effects.
• Negative inotropes (e.g., beta-blockers): There is a risk of hypotension with concurrent use.

Side Effects & Overdose

Side Effects

Imidapril is generally well tolerated, although adverse effects are primarily related to the gastrointestinal, cardiovascular, and renal systems.

• Gastrointestinal effects: Diarrhea, vomiting, anorexia, and other gastrointestinal disturbances may occur.
• Cardiovascular effects: Hypotension may occur and can be accompanied by fatigue, dizziness, or apathy; the dosage should be reduced if signs such as weakness or disorientation develop.
• Renal effects: Dogs with hypovolemia or dehydration are at increased risk of acute hypotension, and treatment should be suspended until fluid and electrolyte balance is restored.
• Electrolyte abnormalities: Hyperkalemia is a potential adverse effect.
• Rare immune-mediated effects: Although less likely than with captopril, rashes, neutropenia, and agranulocytosis have been reported in humans receiving other ACE inhibitors.
• Cats: No signs of toxicity were reported in cats receiving 0.5 mg/kg PO once daily for 3 months.

Overdose

Healthy dogs have tolerated oral doses up to 5 mg/kg (approximately 20 times the labeled dose). Clinical signs of overdose are primarily related to excessive hypotension.

• Clinical signs: Hypotension, apathy, and ataxia.
• Management: Treatment is symptomatic.

Key Notes

Practical clinical points for the use of imidapril in dogs and cats:

• Administration with food: Oral bioavailability is reduced by food; administer on an empty stomach whenever possible.
• Protein-losing nephropathy: In addition to its cardiovascular effects, imidapril may help reduce proteinuria and preserve renal function in dogs with glomerular disease.
• RAAS modulation: Imidapril partially blocks amlodipine-induced activation of the renin-angiotensin-aldosterone system (RAAS) in dogs.
• Monitoring: Regular evaluation of serum electrolytes, creatinine, BUN, urine protein:creatinine ratio, CBC with differential, and blood pressure is recommended during treatment.
• Treatment adherence: Do not discontinue or reduce the dosage without veterinary guidance.