Usage
Perindopril arginine is prescribed for:
- Hypertension: Managing high blood pressure.
- Heart Failure: Treating symptomatic heart failure.
- Stable Coronary Artery Disease: Reducing the risk of cardiovascular events (e.g., heart attack, stroke, cardiac arrest) in patients with stable coronary artery disease or a history of myocardial infarction.
Pharmacological Classification: Angiotensin-Converting Enzyme (ACE) inhibitor.
Mechanism of Action: Perindopril inhibits the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced aldosterone secretion, and decreased sodium and water retention, ultimately lowering blood pressure and reducing cardiac workload.
Alternate Names
- Perindopril tert-butylamine (erbumine salt) - Another form of perindopril, with different dosing.
Coversyl Arginine, Coversum are brand names under which perindopril arginine is marketed. Aceon is a brand name for perindopril erbumine.
How It Works
Pharmacodynamics: Perindopril’s primary effect is vasodilation, reducing peripheral vascular resistance and blood pressure. It also decreases cardiac preload and afterload, improving cardiac output in heart failure. It reduces aldosterone secretion, leading to decreased sodium and water retention.
Pharmacokinetics:
- Absorption: Perindopril is rapidly absorbed after oral administration, and is a prodrug that is hydrolyzed in the liver to its active metabolite, perindoprilat. Food may slightly reduce hepatic conversion to perindoprilat.
- Metabolism: Perindopril is extensively metabolized in the liver, primarily to perindoprilat.
- Elimination: Perindoprilat is primarily excreted by the kidneys. Elimination is reduced in patients with renal impairment and elderly patients.
Mode of Action: Perindopril competitively inhibits ACE, preventing the conversion of angiotensin I to angiotensin II.
Receptor Binding/Enzyme Inhibition: Perindopril and its active metabolite, perindoprilat, bind to and inhibit ACE.
Elimination Pathways: Primarily renal excretion of perindoprilat.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 5 mg once daily, taken in the morning. The dose may be increased to 10 mg once daily after 1-2 weeks as needed based on blood pressure control.
- Heart Failure: Initial dose is 2.5 mg once daily, which may be increased to 5 mg once daily after 1-2 weeks if tolerated.
- Stable Coronary Artery Disease: Initial dose is 5 mg once daily for two weeks, then increased to 10 mg once daily, as tolerated.
Children: Not recommended for use in children.
Special Cases:
- Elderly Patients: Initial dose is 2.5 mg once daily, then titrated up as tolerated.
- Patients with Renal Impairment: Dosage adjustment is necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: Minor dosage adjustments may be required.
- Patients with Comorbid Conditions: Close monitoring and dosage adjustments may be necessary.
Clinical Use Cases
Perindopril is not typically used in clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations at the initial stages. It is primarily used for long-term management of hypertension, heart failure, and stable coronary artery disease.
Dosage Adjustments
Dosage adjustments are based on renal function, hepatic function, concomitant medications, and therapeutic response.
Side Effects
Common Side Effects:
- Dry cough
- Dizziness
- Headache
- Fatigue
- Hypotension (low blood pressure)
Rare but Serious Side Effects:
- Angioedema (swelling of face, lips, tongue, or throat)
- Acute renal failure
- Pancreatitis
- Hyperkalemia
- Neutropenia/agranulocytosis
- Hepatic dysfunction
Long-Term Effects:
- Renal impairment (with prolonged use)
Adverse Drug Reactions (ADR):
- Angioedema requiring urgent medical attention
Contraindications
- Hypersensitivity to perindopril or other ACE inhibitors.
- History of angioedema related to ACE inhibitor therapy.
- Pregnancy (especially second and third trimesters).
- Breastfeeding.
- Bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney.
- Concomitant use of sacubitril/valsartan or aliskiren (especially in patients with diabetes or renal impairment).
Drug Interactions
- Diuretics: Increased risk of hypotension.
- Potassium-sparing diuretics, potassium supplements: Increased risk of hyperkalemia.
- Lithium: Increased lithium levels.
- NSAIDs: Reduced antihypertensive effect and increased risk of renal impairment.
- Aliskiren: Increased risk of hypotension, hyperkalemia, and renal impairment, especially in patients with diabetes or renal impairment.
- Sacubitril/valsartan: Increased risk of angioedema.
- Immunosuppressants (e.g., everolimus, sirolimus): Increased risk of angioedema.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category D (first trimester) and Category X (second and third trimesters). ACE inhibitors are contraindicated during pregnancy and should be discontinued as soon as pregnancy is detected.
- Breastfeeding: Perindopril is excreted in breast milk. Breastfeeding is not recommended while taking perindopril.
Drug Profile Summary
- Mechanism of Action: Inhibits ACE, leading to vasodilation and reduced aldosterone secretion.
- Side Effects: Dry cough, dizziness, headache, fatigue, hypotension, angioedema (rare but serious).
- Contraindications: Hypersensitivity, history of angioedema, pregnancy, breastfeeding, bilateral renal artery stenosis.
- Drug Interactions: Diuretics, potassium supplements, lithium, NSAIDs, aliskiren, sacubitril/valsartan.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Hypertension: 5-10 mg once daily; Heart Failure: 2.5-5 mg once daily; Stable CAD: 5-10 mg once daily.
- Monitoring Parameters: Blood pressure, renal function (creatinine, potassium), signs of angioedema.
Popular Combinations
- Perindopril + Indapamide: Combines an ACE inhibitor with a diuretic for enhanced blood pressure control in patients whose hypertension is not controlled by perindopril alone.
- Perindopril + Amlodipine: For patients whose blood pressure is not adequately controlled by perindopril alone. Perindopril + Amlodipine is now available as a fixed dose combination tablet. However, therapy should not be initiated with this combination.
Precautions
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General Precautions: Monitor renal function and electrolytes, especially in patients with renal impairment, heart failure, or taking diuretics or potassium supplements. Assess for signs of angioedema.
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Specific Populations: As above for pregnant women, breastfeeding mothers, children, and the elderly.
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Lifestyle Considerations: Encourage lifestyle modifications such as diet, exercise, and smoking cessation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Perindopril Arginine?
A: Standard adult dosages: 5-10mg for hypertension and stable coronary artery disease and 2.5-5mg for heart failure. Pediatric use is not recommended. Elderly and patients with renal impairment require dosage adjustments.
Q2: What is the most common side effect of Perindopril?
A: A dry, persistent cough is the most commonly reported side effect.
Q3: What should be done if angioedema occurs?
A: Angioedema is a serious side effect. Discontinue perindopril immediately and provide appropriate medical care, which may include airway management, antihistamines, corticosteroids, and/or epinephrine.
Q4: Can Perindopril be used during pregnancy?
A: No, perindopril is contraindicated during pregnancy, especially in the second and third trimesters, due to the risk of fetal harm.
Q5: How does Perindopril interact with potassium-sparing diuretics?
A: Co-administration with potassium-sparing diuretics can increase the risk of hyperkalemia. Closely monitor potassium levels.
Q6: Is it safe to take Perindopril with NSAIDs?
A: NSAIDs can reduce the antihypertensive effect of perindopril and increase the risk of renal impairment. Co-administration should be done cautiously with monitoring of renal function.
Q7: What are the signs of perindopril overdose?
A: Severe hypotension is the primary sign of overdose. Management includes supportive care and measures to raise blood pressure.
Q8: Should perindopril be taken with food?
A: Although food can slightly decrease bioavailability of the active metabolite, perindoprilat, it can be taken with or without food. However, it is often recommended to take it before a meal for consistency.
Q9: Can a patient switch from perindopril arginine to perindopril erbumine (or vice-versa)?
A: Yes, but with a dosage adjustment as perindopril erbumine is dosed differently than perindopril arginine. Both are therapeutically equivalent.
Q10: What is the role of monitoring renal function while a patient is on perindopril?
A: Monitoring renal function (creatinine and potassium levels) is essential, especially at initiation and dosage adjustments, to detect potential renal impairment, especially in high-risk patients (e.g. elderly, those with pre-existing renal disease, or those on concomitant nephrotoxic medications).
