ACE inhibitors
Brand names: Zestril, Prinivil, Lisinopril Normon, Lisinopril Cinfa
Updated · Methodology
First line
First-line for hypertension per 2023 and Spanish SEH-LELHA 2022. Starting dose 10 mg once daily, target 20–40 mg. Effective in patients with heart failure, post-MI, diabetic nephropathy. In Afro-Caribbean patients monotherapy is less effective than CCB or thiazide – ESC 2023 recommends combination.
Sources
ICD-10: I10 · ICD-11: BA00
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Lisinopril is a long-acting once-daily ACE inhibitor. It is prescribed for hypertension, heart failure, and after myocardial infarction ( 2023, SEH-LELHA). In anti-aging regimens, lisinopril is given to healthy normotensives with promises of vessel protection and rejuvenation. In people with normal blood pressure, no clinical studies of prophylactic use exist. The drug causes a dry cough (10–20% of patients), hyperkalemia, angioedema in predisposed people, and teratogenicity. If lisinopril was prescribed to a person with normal blood pressure, consider seeking a second opinion.
Competitive ACE inhibitor. Blocks conversion of angiotensin I to active vasopressor angiotensin II, reduces aldosterone, slows bradykinin breakdown. Antihypertensive effect develops within 6 hours, peaks at 6 hours, lasts 24 hours – suitable for once-daily dosing. Unlike enalapril and ramipril, lisinopril is not a prodrug and does not require hepatic activation – convenient in liver disease. Minimal plasma protein binding, excreted unchanged by the kidneys.
AEMPS summary of product characteristics (section 4.6): ACE inhibitors are not recommended in the first trimester and are contraindicated in the second and third trimesters. Epidemiological evidence on teratogenicity after first-trimester exposure is inconclusive, but a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning a pregnancy should switch to an antihypertensive with an established safety profile in pregnancy; once pregnancy is confirmed, lisinopril is stopped immediately and, if appropriate, alternative therapy is started. Second- and third-trimester exposure causes fetal toxicity (reduced renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). After second-trimester exposure, an ultrasound check of renal function and the skull is advised, and infants of mothers who took ACE inhibitors are closely watched for hypotension.
Milk levels are low. Acceptable in lactation for term infants with maternal BP and infant monitoring.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Verbatim lines from the interaction sections, in the language of the label
«Bloqueo dual del sistema renina-angiotensina-aldosterona (SRAA): No se deben utilizar de forma concomitante los inhibidores de la enzima convertidora de angiotensina y los antagonistas de los…»AEMPS, section 4.4 · Open on CIMA
«Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension…»FDA, section 7 · Open on DailyMed
«Diuréticos: Los factores de riesgo para el desarrollo de hipercalemia son: insuficiencia renal, diabetes mellitus y el uso concomitante de diuréticos ahorradores de potasio (ej. espironolactona…»AEMPS, section 4.5 · Open on CIMA
«Diuréticos: Los factores de riesgo para el desarrollo de hipercalemia son: insuficiencia renal, diabetes mellitus y el uso concomitante de diuréticos ahorradores de potasio (ej. espironolactona…»AEMPS, section 4.5 · Open on CIMA
«Diuretics: Initiation of lisinopril in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with lisinopril can be minimized by either…»FDA, section 7 · Open on DailyMed
«Diuréticos: Los factores de riesgo para el desarrollo de hipercalemia son: insuficiencia renal, diabetes mellitus y el uso concomitante de diuréticos ahorradores de potasio (ej. espironolactona…»AEMPS, section 4.5 · Open on CIMA
«Litio: Durante la administración simultánea de litio e inhibidores de la ECA se han comunicado aumentos reversibles de las concentraciones séricas de litio y toxicidad. La utilización simultánea de…»AEMPS, section 4.5 · Open on CIMA
«Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension…»FDA, section 7 · Open on DailyMed
«Diuretics: Initiation of lisinopril in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with lisinopril can be minimized by either…»FDA, section 7 · Open on DailyMed
«Diuréticos: Los factores de riesgo para el desarrollo de hipercalemia son: insuficiencia renal, diabetes mellitus y el uso concomitante de diuréticos ahorradores de potasio (ej. espironolactona…»AEMPS, section 4.5 · Open on CIMA
«Diuretics: Initiation of lisinopril in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with lisinopril can be minimized by either…»FDA, section 7 · Open on DailyMed
«Diuréticos: Los factores de riesgo para el desarrollo de hipercalemia son: insuficiencia renal, diabetes mellitus y el uso concomitante de diuréticos ahorradores de potasio (ej. espironolactona…»AEMPS, section 4.5 · Open on CIMA
«Diuretics: Initiation of lisinopril in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with lisinopril can be minimized by either…»FDA, section 7 · Open on DailyMed
«Diuréticos: Los factores de riesgo para el desarrollo de hipercalemia son: insuficiencia renal, diabetes mellitus y el uso concomitante de diuréticos ahorradores de potasio (ej. espironolactona…»AEMPS, section 4.5 · Open on CIMA
«Diuretics: Initiation of lisinopril in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with lisinopril can be minimized by either…»FDA, section 7 · Open on DailyMed
«La coadministración de los AINEs (incluyendo los inhibidores de la COX-2) y los inhibidores de la ECA tiene un efecto adicional sobre el incremento del potasio sérico y pueden provocar un deterioro…»AEMPS, section 4.5 · Open on CIMA
«Neutropenia/AEMPS, section 4.4 · Open on CIMA
«Antidiabéticos: En pacientes diabéticos tratados con agentes antidiabéticos orales o insulina, deberá vigilarse estrechamente el control glucémico por casos de hipoglucemia, especialmente durante el…»AEMPS, section 4.5 · Open on CIMA
«Antidiabéticos: En pacientes diabéticos tratados con agentes antidiabéticos orales o insulina, deberá vigilarse estrechamente el control glucémico por casos de hipoglucemia, especialmente durante el…»AEMPS, section 4.5 · Open on CIMA
«Ciclosporina: Se puede producir hiperpotasemia durante el uso concomitante de IECA con ciclosporina. Se recomienda controlar con frecuencia el potasio en sangre.»AEMPS, section 4.5 · Open on CIMA
«Hipotensión sintomática: Raramente se ha observado hipotensión sintomática en pacientes hipertensos no complicados. En pacientes hipertensos tratados con lisinopril , la hipotensión es más probable…»AEMPS, section 4.4 · Open on CIMA
«Hipersensibilidad/AEMPS, section 4.4 · Open on CIMA
«Neutropenia/AEMPS, section 4.4 · Open on CIMA
«Antidiabéticos: En pacientes diabéticos tratados con agentes antidiabéticos orales o insulina, deberá vigilarse estrechamente el control glucémico por casos de hipoglucemia, especialmente durante el…»AEMPS, section 4.5 · Open on CIMA
«Antidiabéticos: En pacientes diabéticos tratados con agentes antidiabéticos orales o insulina, deberá vigilarse estrechamente el control glucémico por casos de hipoglucemia, especialmente durante el…»AEMPS, section 4.5 · Open on CIMA
«Lithium: Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs, which cause elimination of sodium, including ACE inhibitors. Lithium toxicity was usually…»FDA, section 7 · Open on DailyMed
«Antidiabetics: In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2…»FDA, section 7 · Open on DailyMed
«Hipersensibilidad/AEMPS, section 4.4 · Open on CIMA
«Hipersensibilidad/AEMPS, section 4.4 · Open on CIMA
«Ácido acetilsalicílico, trombolíticos, betabloqueadores, nitratos: Lisinopril puede utilizarse concomitantemente con ácido acetilsalicílico (con dosis cardiológicas), trombolíticos, beta-bloqueantes…»AEMPS, section 4.5 · Open on CIMA
«Antidepresivos tricíclicos/AEMPS, section 4.5 · Open on CIMA
«Antidepresivos tricíclicos/AEMPS, section 4.5 · Open on CIMA
«Ácido acetilsalicílico, trombolíticos, betabloqueadores, nitratos: Lisinopril puede utilizarse concomitantemente con ácido acetilsalicílico (con dosis cardiológicas), trombolíticos, beta-bloqueantes…»AEMPS, section 4.5 · Open on CIMA
«mTOR Inhibitors: Patients taking concomitant mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema. [see Warnings and Precautions (5.2) ]»FDA, section 7 · Open on DailyMed
«Antidiabetics: Concomitant administration of lisinopril and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia.»FDA, section 7 · Open on DailyMed
«Otros agentes antihipertensivos: El uso concomitante de estos agentes puede aumentar los efectos hipotensores de lisinopril. El uso concomitante con nitroglicerina y otros nitratos u otros…»AEMPS, section 4.5 · Open on CIMA
«Otros agentes antihipertensivos: El uso concomitante de estos agentes puede aumentar los efectos hipotensores de lisinopril. El uso concomitante con nitroglicerina y otros nitratos u otros…»AEMPS, section 4.5 · Open on CIMA
«Simpaticomiméticos: Los simpaticomiméticos pueden reducir los efectos antihipertensivos de los inhibidores de la ECA.»AEMPS, section 4.5 · Open on CIMA
«Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension…»FDA, section 7 · Open on DailyMed
«Lisinopril: La administración de una única dosis de 20 mg de lisinopril con liraglutida mostró una reducción en la AUC de lisinopril de un 15%; la C max disminuyó un 27%. Se produjo un retraso en el…»AEMPS, section 4.5 · Open on CIMA
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Lisinopril is evaluated for the following indications with varying evidence strength: Hypertension (evidence tier A), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Lisinopril (≥ 1 in 100): Dry cough (10–15%), Dizziness, Fatigue, Hyperkalemia, Creatinine elevation. See the Safety section for uncommon and serious reactions.
AEMPS summary of product characteristics (section 4.6): ACE inhibitors are not recommended in the first trimester and are contraindicated in the second and third trimesters. Epidemiological evidence on teratogenicity after first-trimester exposure is inconclusive, but a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning a pregnancy should switch to an antihypertensive with an established safety profile in pregnancy; once pregnancy is confirmed, lisinopril is stopped immediately and, if appropriate, alternative therapy is started. Second- and third-trimester exposure causes fetal toxicity (reduced renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). After second-trimester exposure, an ultrasound check of renal function and the skull is advised, and infants of mothers who took ACE inhibitors are closely watched for hypotension.
Milk levels are low. Acceptable in lactation for term infants with maternal BP and infant monitoring.
Lisinopril is contraindicated in: ACE-I hypersensitivity; Prior ACE-I angioedema; Pregnancy (all trimesters – teratogenic); Bilateral renal artery stenosis; Aliskiren combination in diabetes or CKD. Full list in the Safety section.
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Losartan, Losartan + Hydrochlorothiazide, Olmesartan medoxomil, Olmesartan + Hydrochlorothiazide, Perindopril + Indapamide, Valsartan, Amlodipine + Valsartan + Hydrochlorothiazide, Candesartan + Hydrochlorothiazide