Perindopril
Regulatory sources consulted
- openfda-label-spl_id:46f1c769-2a77-4526-8303-0abc4a78d53e
- AEMPS Ficha Técnica · 72240
- ANSM RCP · 69945011
- PubMed PMID:37417783 ↗
- PubMed PMID:34533690 ↗
- PubMed PMID:37432701 ↗
- PubMed PMID:38771738 ↗
- PubMed PMID:38228033 ↗
- OpenFDA · C09AA04
- RxNorm rxcui 54552 ↗
Approved indications
- Treatment of essential hypertension. May be used alone or in combination with other classes of antihypertensives, especially thiazide diuretics.
- Treatment of stable coronary artery disease to reduce the risk of cardiovascular mortality or nonfatal myocardial infarction.
Contraindications
Absolute
- Hypersensitivity to perindopril or any other ACE inhibitor. History of angioedema (hereditary, idiopathic, or associated with previous ACE inhibitor therapy).
- Concomitant use with aliskiren in patients with diabetes or renal impairment (GFR < 60 ml/min/1.73m²).
- Concomitant use with sacubitril/valsartan. Do not start perindopril until 36 hours after the last dose of sacubitril/valsartan.
- Second and third trimesters of pregnancy.
- Bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney.
Clinical warnings
- Boxed warning · Fetal Toxicity: When pregnancy is detected, discontinue perindopril as soon as possible. Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. — FDA
- Major warning · Angioedema: Head and neck, and intestinal angioedema have been reported. The risk is higher in Black patients and with concomitant use of mTOR or neprilysin inhibitors. — FDA
- Major warning · Hypotension: Symptomatic hypotension may occur, especially in volume-depleted or heart failure patients. — FDA
- Hyperkalemia: Risk of increased serum potassium, especially in patients with renal insufficiency, diabetes, or on concomitant therapy with drugs that increase potassium. — EMA SPC
Drug interactions
- HighSacubitril/ValsartanC09DX04
Mechanism: Concomitant use increases the risk of angioedema due to inhibition of neprilysin (sacubitril) and ACE inhibition (perindopril).
Recommendation: Contraindicated. Do not administer perindopril within 36 hours of switching to or from sacubitril/valsartan.
FDA labelEMA SPC
- HighAliskirenC09XA02
Mechanism: Dual blockade of the renin-angiotensin-aldosterone system (RAAS), which increases the risk of hypotension, hyperkalemia, and renal function deterioration.
Recommendation: Contraindicated in patients with diabetes or renal impairment (GFR < 60 ml/min). Not recommended in other patients.
FDA labelEMA SPC
- ModeratePotassium-sparing diureticsC03D
Mechanism: Additive effects increasing the risk of hyperkalemia, as ACE inhibitors can decrease aldosterone production.
Recommendation: If concomitant use is indicated, use with caution and monitor serum potassium frequently.
FDA label
- ModerateLithiumN05AN01
Mechanism: ACE inhibitors can reduce the renal clearance of lithium, leading to increased serum levels and risk of lithium toxicity.
Recommendation: Combination is not recommended. If necessary, frequent monitoring of serum lithium levels is required.
FDA labelEMA SPC
Adverse events
Common (≥1%)
cough · dizziness · back pain · headache · asthenia
Rare but serious
angioedema · hyperkalemia · acute renal failure · neutropenia · agranulocytosis · severe hypotension · pancreatitis · hepatitis
Pregnancy and lactation
FDA category: D
Contraindicated in the second and third trimesters of pregnancy due to the risk of fetal (renal failure, oligohydramnios, skull ossification retardation) and neonatal (renal failure, hypotension, hyperkalemia) toxicity. Discontinue as soon as pregnancy is detected.
Recent literature (PubMed)
Revisión sistemática y metaanálisis en red de 135 ECA (45,420 pacientes) que evalúa el riesgo de tos inducida por IECA. El riesgo relativo (RR) de tos para los IECA vs. placebo fue de 2.21. Perindopril se clasificó en el rango medio (SUCRA 54.1%) en cuanto a la inducción de tos entre los IECA, siendo menor que ramipril pero mayor que captopril.
Revisión que examina la evidencia para la combinación de betabloqueantes e IECA, utilizando datos de ensayos con bisoprolol y perindopril como evidencia de apoyo. Se destaca el fundamento de sus acciones complementarias sobre el SRAA y el sistema nervioso simpático para mejorar los resultados cardiovasculares y lograr los objetivos de presión arterial más rápidamente.
Metaanálisis en red de 32 ECA (16,273 pacientes) que evalúa la eficacia de combinaciones a dosis fija (SPC). La combinación perindopril/amlodipino fue una de las 11 SPC incluidas. El estudio concluye que las combinaciones ARB/CCB pueden tener ventajas sobre otras SPC, aunque los datos para algunas combinaciones son limitados.
Artículo de revisión de The Medical Letter que resume las opciones de tratamiento farmacológico para la hipertensión, posicionando a los IECA como una de las clases de primera línea.
Revisión sobre los efectos de telmisartán en el síndrome metabólico. Perindopril se menciona brevemente en una comparación, indicando que telmisartán tiene una eficacia superior en el control de la presión arterial, especialmente hacia el final del intervalo de dosificación.