Cilazapril for Hypertension & Heart Failure

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

Risk Factor C (Monitor therapy).

Alfuzosin Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Amphetamines May decrease the antihypertensive effects of Antihypertensive Drugs.
Angiotensin II Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II.
Antipsychotic Agents, Second Generation (Atypical) Blood Pressure Lowering Agents can increase the hypotensive effects of Antipsychotic Agents (Second Gen [Atypical]).
Aprotinin May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors.
AzaTHIOprine Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine.
Barbiturates Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Benperidol Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Brigatinib May decrease the antihypertensive effects of Antihypertensive Drugs. Brigatinib could increase the bradycardic effects of Antihypertensive Drugs.
Brimonidine (Topical) Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Dapoxetine May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors.
Dexmethylphenidate Antihypertensive agents may have a less therapeutic effect.
Diazoxide Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Dipeptidyl Peptidase-IV Inhibitors May enhance the adverse/toxic effect of AngiotensinConverting Enzyme Inhibitors. In particular, angioedema risk may be increased.
Drospirenone Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Drospirenone.
DULoxetine DULoxetine may increase hypotension by lowering blood pressure.
Eplerenone May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.
Everolimus May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. In particular, angioedema risk may be increased.
Ferric Gluconate Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate.
Complex of Ferric Hydroxide Polymaltose Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. In particular, there may be an increase in the risk of allergic reactions or angioedema.
Gelatin (Succinylated). Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). In particular, there may be a greater risk of hypotensive reactions paradoxical to Gelatin (Succinylated).
Gold Sodium Thiomalate Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. It has been noted that there is a higher risk of developing nitritoid reactions.
Heparin May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.
Heparins (Low Molecular Weight) May enhance the hyperkalemic effect of AngiotensinConverting Enzyme Inhibitors.
Herbs (Hypertensive Properties) May decrease the antihypertensive effects of Antihypertensive Drugs.
Herbs (Hypotensive properties) Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Hypotension-Associated Agents Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Icatibant May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors.
Levodopa-Containing Products Blood Pressure Lowering Agents can increase the hypotensive effects of Levodopa -Containing Products.
Loop Diuretics May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors.
Lormetazepam Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Methylphenidate May decrease the antihypertensive effects of Antihypertensive Drugs.
Molsidomine Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Naftopidil Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Nicergoline Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Nicorandil May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.
Nicorandil Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Nitroprusside The hypotensive effects of Nitroprusside may be enhanced by blood pressure lowering agents.
Nonsteroidal Anti-Inflammatory Drugs Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. The combination could result in a significant decrease of renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors.
Pentoxifylline Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Pholcodine Pholcodine may increase hypotensive effects by lowering blood pressure.
Phosphodiesterase 5 Inhibitors Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Potassium Salts May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.
Potassium-Sparing Diuretics May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.
Pregabalin Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Angioedema risk may increase.
Prostacyclin Analogues Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Quinagolide Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Racecadotril May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. This combination may increase the risk of angioedema.
Ranolazine May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors.
Salicylates May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors.
Sirolimus May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors.
Tacrolimus (Systemic) Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic).
Temsirolimus May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors.
Thiazide and Thiazide -Like Diuretics May enhance the hypotensive effect of AngiotensinConverting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors.
TiZANidine May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors.
Tolvaptan May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.
Trimethoprim May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.
Yohimbine May decrease the antihypertensive effects of Antihypertensive Drugs.

Risk Factor D (Regard therapy modification)

 
Aliskiren May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated.Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. Monitor potassium, creatinine and blood pressure carefully if combined.
Allopurinol Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol.
Amifostine Amifostine's hypotensive effects may be enhanced by blood pressure lowering agents. Treatment: Blood pressure lowering drugs should be stopped 24 hours before amifostine administration. Amifostine should be avoided if blood pressure lowering medication cannot be withheld.
Angiotensin II Receptor Blockers May enhance the adverse/toxic effect of AngiotensinConverting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Telmisartan/ramipril are not recommended for US labeling. It is unclear if any other combination of ACE inhibitors and ARBs would be safer. If possible, consider alternatives to the combination.
Grass Pollen Allergen Extract (5 Grass Extract) Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors could increase the risk for severe allergic reactions to Grass Pollen Allergen extract (5 Grass).
Iron Dextran Complex Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Patients who are taking an ACE inhibitor could be more susceptible to anaphylactic-type reactions. Management: Carefully follow iron dextran guidelines regarding the preparation of equipment for resuscitation and training personnel prior to administering iron dextran and the use a test dose before the first therapeutic dose.
Lanthanum May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum.
Lithium Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. After adding an ACE inhibitor, it is likely that you will need to reduce your lithium dosage. Follow up on patients' reactions to lithium after discontinuing or adding concurrent ACE inhibitor therapy.
Obinutuzumab This may increase the hypotensive effects of Blood Pressure Lowering Agents. Management: You may temporarily withhold blood pressure lowering medication beginning 12 hours before obinutuzumab injection and continuing for 1 hour after infusion.
Sodium Phosphates Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. In particular, acute phosphate-nephropathy risk may be increased. Management: You can avoid this combination by temporarily stopping treatment with ACEIs or looking for alternatives to oral sodium phosphate bowel prep. Maintain adequate hydration, and closely monitor your renal function if the combination is not possible.
Urapidil May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors.

Risk Factor X (Avoid Combination)

 
Bromperidol Bromperidol's hypotensive effects may be enhanced by Blood Pressure Lowering agents. Bromperidol could decrease the hypotensive effects of Blood Pressure Lowering agents.
Sacubitril Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. This combination may increase the risk of angioedema.

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

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