Cilazapril is a competitive inhibitor of the angiotensin-converting enzyme. It blocks the conversion of angiotensin I to angiotensin II, inhibiting the renin-angiotensin-aldosterone pathway. Since Angiotensin II has strong vasoconstrictive properties, its inhibition causes vasodilation. Thus, it is indicated in the treatment of Hypertension and Heart failure.

Off-Label uses of cilazapril in Adults include:

• ST-elevation & Non–ST-elevation ACS (acute coronary syndrome)
• Patients with a stable coronary artery disease.

Cilazapril dose in Adults

Cilazapril dose in heart failure:

• 0.5 mg once a day. Increase the dose incrementally to the maximum dose of 2.5 mg once a day.

Cilazapril dose in Hypertension:

• 2.5 mg once a day. Increase the dose incrementally at two weeks intervals to the maximum dose of 10 mg per day. (The usual dose is 2.5 - 5 mg per day).

Cilazapril dose in combination therapy with a diuretic:

• 0.5 mg once a day.

Cilazapril Dose in Childrens

The manufacturer has not recommended any dose in the pediatric age group.

Pregnancy Risk Factor X

• [Canadian Boxed Warn]
  • It is not recommended during pregnancy because it could cause injury or death to the developing foetus.
  • When pregnancy is confirmed, it should be stopped immediately
  • Patients on ACE-I or ARBs treatment and planning to conceive should be switched to alternative therapies prior to conception.
  • Due to decreased fetal renal function and skeletal malformations, drugs that affect the renin/angiotensin systems are associated with oligohydramnios.

Use of Cilazapril while breastfeeding

• It is unknown if it is excreted into breastmilk. It is recommended that you avoid breastfeeding while it is active.

Dose adjustment in Renal Disease:

• For the treatment of heart failure:
  • Patients with CrCl of more than 40 mL/minute:
    • 0.5 mg once a day to a maximum dose of  2.5 mg once a day.
  • CrCl of 10 - 40 mL/minute:
    • 0.25 -  0.5 mg once a day to a maximum dose of 2.5 mg once a day.
  • CrCl of less than 10 mL/minute:
    • Not recommended

• For the treatment of hypertension:
  • CrCl of more than 40 mL/minute:
    • 1 mg once a day to a maximum dose of 5 mg once a day.
  • CrCl 10 - 40 mL/minute:
    • 0.5 mg once a day to a maximum dose of 2.5 mg once a day.
  • CrCl of less than 10 mL/minute:
    • Not recommended.

Dose adjustment in Liver disease:

• For Hypertension in patients with compensated cirrhosis:
  • 0.5 mg or less once a day with caution.

Common Side Effects of Cilazapril:

• Cardiovascular:
  • Orthostatic hypotension
  • Palpitations
  • Symptomatic hypotension
• Central nervous system:
  • Dizziness
  • Headache
  • Fatigue
• Gastrointestinal:
  • Nausea
• Neuromuscular & skeletal:
  • Weakness
• Renal:
  • Increased serum creatinine
• Respiratory:
  • Cough

Contraindication to Cilazapril include:

• Allergy reactions to cilazapril or another ACE inhibitor or any component of this formulation
• Angioedema history to an ACE inhibitor
• Angioedema idiopathic or hereditary
• Ascites
• Anuria
• Concomitant use with the direct renin inhibitor - aliskiren
• Moderate-to-severe kidney impairment, with a GFR of 60mL/minute/1.73m2
• Pregnancy
• Breastfeeding
• Galactose intolerance or Glucose–galactose malabsorption are all possible. Lapp lactase deficiency is also possible.

Warnings and Precautions

• Angioedema:
  • It is possible to get angioedema in the neck and head that could compromise the airway.
  • Patients at highest risk for ACE-I associated angioedema include patients with a prior history of angioedema, black-skinned patients of African descent, and the concomitant use of mTOR inhibitors like everolimus.
  • Long-term monitoring may be necessary for patients with angioedema. Aggressive management is important.
• Cholestatic jaundice
  • It is possible for cholestatic jaundice to progress to fulminant liver failure. 
  • If liver enzymes show marked elevations, ACE-Inhibitors must be stopped immediately.

• Cough:
  • It is possible for patients to develop a dry, hacking and nonproductive cough after the drug has been used.
  • This usually disappears once the drug is stopped, but it can sometimes take several months.
  • Other causes of cough should also be considered, including pulmonary congestion caused by heart failure.

• Hyperkalemia:
  • Hyperkalemia is a risk for patients who are taking potassium-sparing diuretics, potassium supplement, or direct renin inhibitors.
  • Patients with diabetes mellitus or underlying renal dysfunction are also at risk for hyperkalemia.

• Hypersensitivity reactions
  • ACE-Inhibitors have been linked to severe allergic reactions, including anaphylaxis.
  • Patients who receive hemodialysis with high flow dialysis membranes (example: AN69) and occasionally with dextran-sulfate-cellulose use during low density lipoprotein apheresis are often subject to allergic reactions.

• Hypotension and syncope:
  • Hypotension is most common after the first dose. This is most common in patients with low volume.

• Neutropenia & agranulocytosis:
  • Rarely, it can cause severe cytopenias, including neutropenia, angranulocytosis and aplasia.

• Renal function deterioration:
  • Patients with heart disease and renal artery stenosis are at greater risk for deteriorating renal function. 
  • Oliguria, progressive and severe azotemia, as well as acute renal failure, may occur.

• Aortic stenosis
  • Patients with severe aortic stenosis must use ACE inhibitors with caution due to the possibility of reduced coronary perfusion.

• Ascites:
  • Ascites patients should be warned to avoid the drug.

• Collagen vascular disease:
  • Hematologic toxicities can be caused by collagen vascular disease.

• Hypertrophic cardiomyopathy with outflow tract obstruction (HCM):
  • Reducing afterload can worsen the symptoms and signs of HOCM.

• Renal artery stenosis:
  • Avoid bilateral renal artery narrowing. Use caution in unilateral renal artery narrowing.

• Renal impairment:
  • Preexisting renal impairments should be avoided. Avoid rapid dose increases. Adjusting the dose may be necessary.

Cilazapril (United States: Not available): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

• Blood pressure
• BUN, Serum Creatinine, & Serum electrolytes.
• Liver function tests at baseline and periodically thereafter especially in patients with pre-existing liver dysfunction
• CBC with differential count (especially in patients with a pre-existing renal dysfunction and/ or collagen vascular disease.
• Plasma glucose in patients with diabetes.

How to take Cilazapril?

It may be administered as oral medicine with or without regard to meals.

Mechanism of action of Cilazapril:

• Cilazapril, when converted to its active metabolite cilazaprilat, inhibits angiotensin-converting enzyme (ACE).
• It prevents angiotensin I from angiotensin 2, which is a powerful vasoconstrictor.

The Onset of action of cilazapril is 1 - 2 hours and the peak antihypertensive effect is seen in 3 - 7 hours, reduction in the systemic vascular resistance and pulmonary capillary wedge pressure takes 2 - 4 hours. It isRapidly absorbedTheIts durationIt can last up to 24 hours. ThebioavailabilityThe oral intake is approximately 57%, and the half-life of the active (terminal) drug is between 36 and 49 hours. It is mostly excreted as an unchanged drug through urine.

International Brands of Cilazapril: (Not approved in the US)

• APO-Cilazapril
• CO Cilazapril
• Inhibace
• MYLAN-Cilazapril
• PHL-Cilazapril
• PMS-Cilazapril
• TEVA-Cilazapril
• Abapril
• Cilaril
• Cilazil
• Dynorm
• Inhibace
• Inocar
• Justor
• Kemicilaz
• Pipredo
• Prilatop
• Vascace
• Zapril
• Zapritens

Cilazapril Brands in Pakistan:

No brands available in Pakistan