Cilazapril

Question 1

What is cilazapril?

Answer 1

a pro-drug ACE inhibitor used for HT and is hydrolysed to its main metabolite, cilazaprilat

Question 2

What class of drugs does cilazapril belong to?

Answer 2

ACE inhibitor which suppresses RAAS system.

Antihypertensive agent

Question 3

What are other drugs belonging to the same class as cilazapril?

Answer 3

quinapril HCl
Enalapril maleate
Nifedipine
Amlodipine
Captopril
Diltiazem
Doxazosin

Question 4

What is cilazapril indicated for?

Answer 4

hypertension
renovascular hypertension
CHF

Question 5

What is the dose of cilazapril given for hypertension?

Answer 5

initially 1mg OD (reduce to 500ug OD if concomitant admin with diuretic, or in severe hypertension, volume depletion, elderly or renally impaired patients)

then adjust according to response.

NB: usual maintenace dose = 2.5-5mg OD, MAX 5mg OD

Question 6

What is the dose of cilazapril given for renovascular HT?

Answer 6

250-500ug OD adjusted according to response MAX 5mg OD

Question 7

What is the dose of cilazapril given for heart failure?

Answer 7

initially 500ug OD under close medical supervision. Increase @ fortnightly intervals if tolerated to a target dose of 5mg OD

Aim for target dose or highest tolerated dose. Dose can be approx doubled every 2 weeks if tolerated.

Question 8

What is the mechanism of action of cilazapril?

Answer 8

ACE inhibitor which competes with angiotensin I for binding. Suppresses RAAS and the conversion of inactive angiotensin I to II.
Thus preventing vasoconstriction and lowering blood presure.

Question 9

What are the relevant PK or PD parameters with cilazapril?

Answer 9

PK:
efficiently absorbed, rapidly converted to active compound

not therapeutically affected by ingestion of food.

Bioavailability ~60%

Half life: 9 hours

PD: decreases vascular resistance and BP

Question 10

What are the precautions associated with cilazapril use?

Answer 10

patients currently on diuretics as first doses can cause hypotension.
peripheral vascular disease or generalised atherosclerosis
collagen vascular disease
severe/symptomatic aortic stenoisis disease
idiopathic or hereditary angiodema
Pregnancy class D: avoid at all stages
Breastfeeding not recommended due to no data.

Question 11

What are the contraindications with cilazapril use?

Answer 11

hypersensitivty to ACE inhibitors (including angiodema)
pregnancy
anaphylactoid reactions (avoid in dialysis with high-flux polyacrylonitrctile membranes
Withheld before desnsitatisation with wasp or bee venom.

Question 12

What are the adverse effects with cilazapril use?

Answer 12

GI disturbance, hypotension, persistent dry cough, headache, dizziness, fatigue, renal impairment, hyperkalaemia

less common: dry mouth & taste disturbance, elevated LFTs, angina, tachycardia, palpitation, flushing, dyspnoea, angiodema, URT problems, fever, excessive sweating, decreased appetite, impotence

Question 13

What are the interactions with cilazapril use?

Answer 13

avoid concomitant use with aliskiren
increased risk of hyperkalaemia when given with angiotensin II receptor antagonists, ciclosporin, diuretics, potassium sparing diuretics and aldosterone antagonists, potassium salts,
flushing and hypotension reported with sodium aurothiomalate

reduce the excretion of lithium

Question 14

What are the alarm bells associated with cilazapril?

Answer 14

Renal function and electrolytes should be checked before starting (particularly in patients with prexisting renovascular disease)

blood counts are recommended

LFTs as if jaundice or marked elevation of hepatic enzymes occur, may indicate risk of hepatic necrosis

check blood pressure, serum potassium and renal function prior to each increase.