Perindopril

Cardiovascular Drug

Drug class: Angiotensin Converting Enzyme Inhibitors, ACEI

Perindopril (ACERTIL)（中文：培哚普利）

Pronunciation

Perindopril 4mg (ACERTIL 4mg)

Common Strengths of Perindopril

Perindopril is available in the following strengths:

• 2 mg
• 4 mg
• 5 mg
• 10 mg

Drug Trade Names of Perindopril

The brand names for prindopril include:

• Acertil
• Acertil AR
• Acertil Plus

Mechanism of Action

Perindopril is an inhibitor of Angiotensin Converting Enzyme (ACE inhibitor).

The beneficial effects of ACE inhibitors appear to result primarily from the suppression of the plasma renin-angiotensin-aldosterone (RAA) system.

Renin is an enzyme synthesized by the kidneys and released into the circulation where it converts angiotensinogen to angiotensin-I. Angiotensin-I is then converted by angiotensin converting enzyme (ACE) to angiotensin-II. Angiotensin-II is a potent vasoconstrictor responsible for arterial vasoconstriction and increased blood pressure as well as for stimulation of the adrenal gland to secrete aldosterone.

Inhibition of ACE results in decreased plasma angiotensin-II level, which leads to decreased vasopressor activity and to reduced aldosterone secretion. The latter decrease results in an increase in serum potassium concentration.

Perindopril is used in the treatment of hypertension and heart failure. Perindopril helps to reduce the risk of future strokes and heart attacks. It also improves your survival if you are taking it following a heart attack or heart surgery.

It works by widening your blood vessels and making it easier for your heart to pump blood around your body. This can improve the symptoms of heart failure.

Perindopril can be used alone or in combination with other antihypertensive agents such as indapamide.

Route of Administration

Perindopril is administered orally in a single daily dose

Dosages

• Dose for Perindopril Tertbutylamine
  • Hypertension: 4 mg once a day (the maximum dose is 8 mg once daily)
  • Heart failure: 4 mg once a day
  • After a heart attack: 8 mg once a day

• Dose for Perindopril Arginine
  • Hypertension: 5 mg once a day (the maximum dose is 10 mg once daily)
  • Heart failure: 5 mg once a day
  • After a heart attack: 10 mg once a day

When will I feel better?

• Perindopril starts to work within a few hours to reduce high blood pressure, but it may take up to a month to achieve its full effects.
• If you are taking perindopril for heart failure, it may take weeks, even months, before you feel better.

Side Effects

Frequency	Adverse reactions
Common (≥1/100 to <1/10)	Dizziness
	Headache
	Vertigo
	Dry
	Tickly (non-productive) cough
	Dyspnoea
	Visual disturbances
	Tinnitus
	Itching
	Rash
	Nausea
	Vomiting
	Diarrhoea
	Abdominal pain
	Dyspepsia
	Constipation
	Hypotension
	Muscle cramps
Uncommon (≥1/1,000 to <1/100)	Confusion
	Oedema of the face, extremities, lips, tongue, glottis, and/or larynx
	Dry mouth
	Palpitations
	Tachycardia
	Vasculitis
Rare (≥1/10,000 to <1/1,000)	Flushing
Very rare (<1/10,000)	Glossitis
	Pancreatitis

Pharmacokinetics

• Perindopril acts through its active metabolite, perindoprilat.
• After oral administration, the absorption of perindopril is rapid, and the peak concentration is reached within 1 hour.
• The plasma half-life of perindopril is about 1 hour.
• Perindopril is a pro-drug. About 27 % of the total quantity of perindopril absorbed is converted into perindoprilat, the active metabolite.
• The peak plasma concentration of perindoprilat is achieved within 3 to 4 hours.
• As ingestion of food decreases conversion to perindoprilat, hence bioavailability, perindopril should be administered orally in a single daily dose in the morning before breakfast.

Elimination

Perindopril is eliminated in the urine and the half-life of the unbound fraction is approximately 17 hours, resulting in steady state within 4 days.

Special population

Elimination of perindoprilat is decreased in the elderly, and also in patients with heart or renal failure. Dosage adjustment in renal insufficiency is desirable depending on the degree of impairment (creatinine clearance).

Drug Management

Safety

Your very first dose may make you feel dizzy, so it is best to take it at bedtime. After the first dose, if you do not feel dizzy, you can take perindopril in the morning.

Pregnancy

Perindopril should be avoided in pregnancy.

Breast Feeding

Perindopril is not recommended.

Hepatic Impairment

Perindopril is a prodrug, and its use requires close monitoring in patients with hepatic impairment.

Renal Impairment

For perindopril tertbutylamine

• If eGFR 31-60 mL/minute/1.73 m²
  • Max. initial dose 2mg once

• If eGFR 15-30 mL/minute/1.73 m²
  • 2 mg once daily on alternate days

Monitoring Requirements

Renal function and electrolytes should be checked before starting ACE inhibitors (or increasing the dose) and monitored during treatment (more frequently if side effects mentioned are present).

Drug Interaction

• Diuretics
  • Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with Perindopril.
• Potassium sparing diuretics (triamterene, amiloride and spironolactone) or potassium supplement
  • May cause significant increase in serum potassium levels, resulting in hyperkalaemia.
• Co-trimoxazole (trimethoprim/sulfamethoxazole)
  • Taking concomitant co-trimoxazole may be at increased risk for hyperkalaemia

Caution

• Concomitant diuretics
  • First dose hypotension (especially in patients taking high doses of diuretics, on a low-sodium diet, on dialysis, dehydrated , or with heart failure)
• Use with care in those with a history of angioedema
• Use with care in patients with severe or symptomatic aortic stenosis (risk of hypotension)
• Use with care in patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney (risk of acute renal failure)

FAQs

How should I take the tablet?

• You will usually take perindopril once a day.
• Swallow perindopril tablet whole with a drink of water.
• Your doctor may suggest that you take your first dose before bedtime because it can make you feel dizzy. After the very first dose and if you do not feel dizzy, take perindopril in the morning, ideally 30 to 60 minutes before breakfast.

What should I avoid while taking?

Should avoid potassium rich foods: perindopril has the capacity to increase potassium level in the blood. High levels of potassium can lead to irregular heartbeat. It is better to avoid potassium-rich foods like bananas.

What happens if I miss a dose?

If you forget to take a dose:

• Once a day: Take it as soon as you remember unless it is less than 12 hours until your next dose. In this case leave out the missed dose and take your next dose at the usual time.

Never take 2 doses to make up for a forgotten dose.