What is Cilazapril?
Cilazapril is an orally active angiotensin converting enzyme (ACE) inhibitor used primarily for treating hypertension and congestive heart failure, administered once daily at doses of 2.5-5 mg. 1
Mechanism of Action
- Cilazapril is a prodrug that is hydrolyzed after absorption to its active metabolite cilazaprilat, which is one of the most potent ACE inhibitors available with an IC50 of 1.9 nM. 2
- The active metabolite has a long terminal elimination half-life of 30-50 hours, permitting once-daily dosing. 1, 3
- It lowers peripheral vascular resistance without significantly affecting heart rate through reversible ACE inhibition. 1, 3
- Cilazaprilat increases cyclic adenosine monophosphate (cAMP) levels, providing vasodilatory effects. 2
Clinical Indications
Hypertension:
- Effective for mild to moderate essential and renal hypertension at doses of 2.5-5 mg once daily. 1
- Reduces sitting diastolic blood pressure by approximately 9 mm Hg after 4 weeks of treatment. 4
- Achieves responder rates of 50-60% as monotherapy, increasing to 71% when combined with hydrochlorothiazide 12.5 mg/day. 4
- Demonstrates comparable efficacy to captopril, enalapril, propranolol, nitrendipine, and hydrochlorothiazide at usual therapeutic dosages. 1, 4
Heart Failure:
- Produces sustained beneficial hemodynamic effects in patients with congestive heart failure, though data remain preliminary. 1
Pharmacokinetics
- Exceptionally well absorbed orally (98% absorption in animal studies). 2
- Peak plasma concentrations occur at 2 hours after dosing. 2
- More than 90% plasma ACE inhibition is required to achieve blood pressure reduction. 3
- The plasma concentration causing 50% ACE inhibition is approximately 1 ng/ml. 3
- Approximately 43% of the dose is recovered unchanged in urine. 5
Dosing Considerations
- Standard effective dose is 2.5-5 mg once daily, with 5 mg identified as the dose producing maximal effect. 3, 4
- In elderly patients (65-83 years), peak plasma concentrations are higher and clearance is lower compared to younger patients, though ACE inhibition differs by less than 10% between age groups. 5
- Dose reduction or less frequent dosing is recommended in patients with severe chronic renal impairment or hepatic failure due to prolonged ACE inhibition. 3
Drug Interactions
- No clinically relevant interaction with food or furosemide. 3
- Hydrochlorothiazide effects on sodium and chloride excretion are potentiated by cilazapril. 3
- Additive blood pressure lowering effects occur with propranolol and nitrendipine. 3
- Nonsteroidal anti-inflammatory drugs may reduce the antihypertensive effect. 3
Safety Profile
- Well tolerated with adverse effects typical of the ACE inhibitor class. 1
- Most common side effects include headache, dizziness, fatigue, nausea, cough, and chest pain, typically occurring within the first 8-16 weeks of treatment. 4
- Non-life-threatening angioedema and facial edema occur in ≤0.2% of patients. 4
- Orthostatic hypotension reported in 2% of patients. 4
- No detrimental effects on glucose or lipid metabolism. 1
- Abnormal laboratory values are rarely observed. 4
Renal Considerations
- Slightly increases effective renal plasma flow while glomerular filtration rate remains unaltered. 3
- As with all ACE inhibitors, can cause functional renal insufficiency when renal perfusion pressure cannot be sustained or when GFR is highly angiotensin II-dependent. 6
- Should be used with caution in patients with bilateral renal artery stenosis or stenosis of a single kidney. 6
Relationship to Current Guidelines
- ACE inhibitors (including cilazapril) are recommended as first-line treatments for hypertension alongside ARBs, dihydropyridine calcium channel blockers, and thiazide diuretics. 6
- ACE inhibitors have compelling indications for heart failure, left ventricular dysfunction post-myocardial infarction, diabetic nephropathy, and chronic kidney disease. 6
- Contraindicated in pregnancy and should be used with caution in renal impairment and renovascular disease. 6