Usage
Perindopril erbumine is prescribed for:
- Hypertension: Managing high blood pressure.
- Heart Failure: Treating mild to moderate heart failure, often in conjunction with other medications like diuretics and digoxin.
- Stable Coronary Artery Disease: Reducing the risk of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, and cardiac arrest) in patients with hypertension or post-myocardial infarction and stable coronary artery disease.
Pharmacological Classification:
Perindopril is an 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, thereby lowering blood pressure.
Alternate Names
Perindopril is sometimes referred to as perindopril tert-butylamine. A related salt is perindopril arginine. Brand names include Aceon, Coversyl, and Prestarium among others. These brand names can vary regionally.
How It Works
Pharmacodynamics: Perindopril’s primary effect is to lower blood pressure by reducing peripheral vascular resistance. It also decreases afterload and preload on the heart, improving cardiac output in heart failure patients.
Pharmacokinetics:
- Absorption: Perindopril is absorbed orally, and its absorption is reduced by food.
- Metabolism: Perindopril is a prodrug metabolized in the liver to its active form, perindoprilat.
- Elimination: Perindoprilat is primarily excreted by the kidneys. Elimination is reduced in patients with renal impairment.
Mode of Action: Perindopril competitively inhibits ACE, the enzyme responsible for converting angiotensin I to angiotensin II. This inhibition reduces the levels of angiotensin II, decreasing vasoconstriction and aldosterone secretion.
Receptor Binding/Enzyme Inhibition: Perindopril specifically targets and inhibits ACE.
Elimination Pathways: Perindoprilat is primarily eliminated via renal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 4 mg once daily, which may be increased to 8 mg after 2 weeks if needed. The maximum dose is 8mg daily for high blood pressure.
- Heart Failure: Initial dose is 2 mg once daily, titrated up to 4 mg as tolerated.
- Stable Coronary Artery Disease: Initial dose is 4 mg once daily, increasing to 8 mg daily after 2 weeks if tolerated.
Children: Use in children is not recommended due to limited safety and efficacy data.
Special Cases:
- Elderly Patients: Initial dose of 2 mg daily, titrated cautiously based on renal function and tolerance.
- Patients with Renal Impairment: Dose adjustment is necessary based on creatinine clearance (CrCl). Consult dosage guidelines in the prescribing information. Not recommended for those with severe impairment (CrCl < 30 mL/min).
- Patients with Hepatic Dysfunction: No specific dosage adjustment recommended, but caution is advised.
- Patients with Comorbid Conditions: Consider individual patient factors such as diabetes or cardiovascular disease when adjusting dosage.
Clinical Use Cases
Perindopril’s dosage in specialized clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations should be determined on a case-by-case basis, taking into account the patient’s hemodynamic status and overall clinical condition. It is not indicated for emergency use in situations such as cardiac arrest or status epilepticus.
Dosage Adjustments
Dosage adjustments may be required based on patient-specific factors including renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms affecting drug metabolism. Careful titration and monitoring are essential.
Side Effects
Common Side Effects:
Cough, dizziness, headache, weakness, fatigue, gastrointestinal disturbances (nausea, vomiting, diarrhea, abdominal pain), and low blood pressure.
Rare but Serious Side Effects:
Angioedema (swelling of face, lips, tongue, or throat), severe hypotension, renal failure, liver dysfunction, blood disorders (decreased white blood cells, red blood cells, or platelets), hyperkalemia, and allergic reactions.
Long-Term Effects:
Chronic kidney disease and electrolyte imbalances can potentially occur with long-term use.
Adverse Drug Reactions (ADR):
Angioedema, anaphylaxis, and severe hypotension are serious ADRs that necessitate immediate intervention.
Contraindications
- Hypersensitivity to perindopril, any ACE inhibitor, or any component of the formulation.
- History of angioedema related to previous ACE inhibitor therapy.
- Hereditary or idiopathic angioedema.
- Pregnancy (second and third trimesters; use during the first trimester is not recommended).
- Concomitant use with sacubitril/valsartan (neprilysin inhibitor) or aliskiren in patients with diabetes.
- Bilateral or unilateral renal artery stenosis.
Drug Interactions
Perindopril can interact with various medications, including:
- Diuretics: Can increase the risk of hypotension.
- Potassium supplements or potassium-sparing diuretics: Can lead to hyperkalemia.
- NSAIDs: Can reduce the antihypertensive effect and increase the risk of renal impairment.
- Lithium: Can increase lithium levels.
- Other antihypertensive medications: Can have additive hypotensive effects.
- Sacubitril/valsartan: Increases the risk of angioedema.
- Aliskiren (in patients with diabetes): Increases the risk of hypotension, hyperkalemia, and renal impairment.
- mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus): Increased risk of angioedema.
- Racecadotril: Increased risk of angioedema
- Gold: Can cause nitritoid reactions.
- Thrombolytics: Caution advised.
It is essential to consider interactions with OTC drugs, supplements (e.g., potassium-containing salt substitutes), and lifestyle factors like alcohol consumption. Grapefruit juice can increase the risk of side effects and should be avoided.
Pregnancy and Breastfeeding
Pregnancy: Perindopril is contraindicated during the second and third trimesters of pregnancy and not recommended during the first trimester due to the risk of fetal harm or death.
Breastfeeding: Perindopril is excreted in breast milk and is generally not recommended during breastfeeding. The risks and benefits should be assessed individually. If used, monitor the infant closely for hypotension.
Drug Profile Summary
- Mechanism of Action: ACE inhibitor, reducing angiotensin II and aldosterone levels.
- Side Effects: Cough, dizziness, headache, hypotension, angioedema, hyperkalemia, renal impairment.
- Contraindications: Hypersensitivity, angioedema history, pregnancy, sacubitril/valsartan, aliskiren (with diabetes), bilateral renal artery stenosis.
- Drug Interactions: Diuretics, potassium supplements, NSAIDs, lithium, other antihypertensives.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy (2nd/3rd trimesters), not recommended during breastfeeding.
- Dosage: 4 mg/day (hypertension), 2 mg/day (heart failure), initial doses lower in elderly and renal impairment.
- Monitoring Parameters: Blood pressure, renal function, serum potassium, and white blood cell counts.
Popular Combinations
Perindopril is often combined with other antihypertensives like thiazide diuretics (e.g., hydrochlorothiazide) or calcium channel blockers (e.g., amlodipine) for synergistic blood pressure control. It may also be used with beta-blockers (in heart failure or after a heart attack) and with a statin, anti-platelets and/or nitrates (for reducing cardiovascular risk).
Precautions
- General Precautions: Screen for allergies, renal and hepatic function, electrolyte imbalances, and history of angioedema.
- Specific Populations: Monitor closely as described above.
- Lifestyle Considerations: Advise patients about potential dizziness and limit alcohol intake. Caution regarding operating machinery or driving.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Perindopril erbumine?
A: The recommended dosage depends on the indication and patient-specific factors. For hypertension, it is usually 4 mg once daily, which may be increased to 8 mg if needed. For heart failure and stable coronary artery disease, the initial dose is usually lower. Dose adjustments are necessary in elderly patients and patients with renal impairment.
Q2: What is the most common side effect of perindopril?
A: A persistent dry cough is the most common side effect.
Q3: What are the serious side effects of perindopril?
A: Angioedema, severe hypotension, kidney problems, liver dysfunction, and blood disorders.
Q4: When should perindopril be avoided?
A: In patients with a history of angioedema related to ACE inhibitor use, during pregnancy (especially the 2nd and 3rd trimesters), and in those with hypersensitivity to perindopril or any ACE inhibitor.
Q5: Can perindopril be used with other blood pressure medications?
A: Yes, perindopril can often be combined with other antihypertensive drugs, like diuretics or calcium channel blockers for a synergistic effect but needs careful monitoring. Consult the drug interaction section for specific interactions.
Q6: What should I monitor in patients taking perindopril?
A: Blood pressure, renal function (creatinine and electrolytes, especially potassium), and signs of angioedema. White blood cell counts might be needed in some patients.
Q7: How does perindopril affect pregnancy?
A: Perindopril can cause severe harm or death to the developing fetus, especially in the second and third trimesters. It should be avoided during pregnancy.
Q8: Is perindopril safe during breastfeeding?
A: Perindopril can pass into breast milk. It’s generally not recommended, but the benefits and risks should be weighed on a case-by-case basis, considering infant age and maternal condition.
A: It’s a prodrug converted in the liver to its active form, perindoprilat.
Q10: How is perindopril excreted?
A: Primarily by the kidneys. Dose adjustment is needed in renal impairment.
