PRINDO -4

Indications

• Hypertension
• Heart failure
• Secondary prevention of cardiovascular events in coronary artery disease

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric populations.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated.

Mechanism of action

Perindopril exerts its pharmacological effects by inhibiting the enzyme ACE, which is responsible for converting angiotensin I to angiotensin II. This leads to decreased levels of angiotensin II, resulting in vasodilation, reduced secretion of aldosterone, and lower blood pressure. The inhibition of ACE also results in increased levels of bradykinin, a peptide that promotes vasodilation, further contributing to the antihypertensive effects.

Pharmacodynamics

The antihypertensive effects of perindopril are dose-dependent and may take several weeks to fully manifest. The drug reduces systemic vascular resistance and afterload on the heart, improving cardiac output. Additionally, perindopril has been shown to have cardioprotective effects, reducing the risk of myocardial infarction and stroke in high-risk patients.

Pharmacokinetics

Perindopril is administered orally and is well absorbed from the gastrointestinal tract. It is converted to its active metabolite, perindoprilat, which has a longer half-life. The drug is primarily eliminated through the kidneys, and its clearance may be reduced in patients with renal impairment. The peak plasma concentration occurs approximately 1 hour after administration, with effects lasting up to 24 hours.

Contra-indications

• History of hypersensitivity to perindopril or any of its components
• History of angioedema related to previous treatment with an ACE inhibitor
• Severe renal impairment
• Pregnancy
• Concomitant use with aliskiren in patients with diabetes

Adverse effects

• Cough
• Angioedema
• Hypotension
• Dizziness
• Fatigue
• Hyperkalemia
• Renal impairment

Interactions

• Potassium-sparing diuretics may increase the risk of hyperkalemia
• NSAIDs may reduce the antihypertensive effect of ACE inhibitors
• Lithium levels may increase when used with ACE inhibitors
• Other antihypertensive agents may enhance the hypotensive effect

Precautions

• Monitor renal function before and during treatment
• Caution in patients with aortic stenosis or heart failure
• Use with caution in patients with a history of angioedema
• Discontinue in case of severe hypotension

Pregnancy

Perindopril is contraindicated during pregnancy due to the risk of fetal harm.

Breast-feeding

There is insufficient data on the excretion of perindopril in human milk. Caution is advised.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets: 2 mg, 4 mg, 8 mg