When pregnancy is detected, discontinue lisinopril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Acute coronary syndrome:
Non-ST-elevation acute coronary syndrome (off-label use):
Note: Initiate in stable patients prior to hospital discharge as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue indefinitely for patients with concurrent diabetes, left ventricular ejection fraction ≤40%, hypertension, or stable chronic kidney disease (AHA/ACC [Amsterdam 2014]). Dosing recommendations based on general dosing range in manufacturer's labeling.
Oral: Initial: 2.5 to 10 mg once daily (depending on initial blood pressure); titrate slowly based on tolerability and response up to 40 mg/day.
ST-elevation myocardial infarction:
Note: In hemodynamically stable patients with large anterior ST-elevation myocardial infarction, consider starting within 24 hours of presentation as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue therapy indefinitely (ACCF/AHA [O'Gara 2013]). Dosing recommendations based on general dosing range in manufacturer's labeling.
Oral: Initial: 2.5 to 5 mg once daily initiated within 24 hours of presentation; titrate slowly up to 10 mg/day or higher as tolerated under close monitoring to avoid hypotension; maximum: 40 mg/day (ACCF/AHA [O'Gara 2013]; GISSI-3 1994; Reeder 2018).
Heart failure with reduced ejection fraction:
Note: If tolerated, an angiotensin II receptor-neprilysin inhibitor is generally preferred over an angiotensin-converting enzyme inhibitor (ACC [Maddox 2021]).
Oral: Initial: 2.5 to 5 mg once daily; as tolerated, may increase dose (eg, double but by no more than 10 mg increments) every ≥2 weeks to a target dose of 40 mg once daily (ACC [Maddox 2021]; ACCF/AHA [Yancy 2013]; ACC/AHA [Yancy 2017]). In closely monitored hospitalized patients, may titrate more rapidly as tolerated (Meyer 2021).
Hypertension, chronic:
Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (ACC/AHA [Whelton 2018]).
Oral: Initial: 5 to 10 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose (eg, increase the daily dose by doubling) as needed, up to 40 mg once daily; if additional blood pressure control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (ACC/AHA [Whelton 2018]; Mann 2021).
Posttransplant erythrocytosis (renal transplant recipients) (off-label use):
Note: For patients with a hemoglobin concentration >17 g/dL (Vlahakos 2021).
Oral: Initial: 2.5 or 5 mg once daily; if inadequate response seen within 4 weeks, may titrate up to 40 mg/day based on hemoglobin and blood pressure response; if hemoglobin remains >17 g/dL after an additional 4 weeks, consider additional therapy (eg, phlebotomy) (Glicklich 2001; MacGregor 1996; Sauron 1993; Vlahakos 2021).
Proteinuric chronic kidney disease (diabetic or nondiabetic) (off-label use): Dosing recommendations based on expert opinion and general dosing range in manufacturer's labeling:
Oral: Initial: 2.5 to 10 mg once daily depending on blood pressure; titrate slowly based on tolerability and response up to 40 mg/day. Target to an appropriate blood pressure goal and a proteinuria goal of <1 g/day (KDIGO 2013; Mann 2020).
IgA nephropathy: In addition to an appropriate BP goal, a proteinuria goal of <1 g/day is also generally recommended (KDIGO 2012). Some experts treat to a proteinuria goal of <500 mg/day. If proteinuria goal is not met with monotherapy at the maximum tolerated dose, consider adding other modalities and/or agents (Cattran 2022).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
Note: Small, transient increases in serum creatinine are expected following initiation of therapy. Therapy discontinuation is recommended if serum creatinine increases ≥30% in the first 2 months of therapy or if hyperkalemia develops anytime during therapy (Bakris 2000).
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl 10 to <30 mL/minute: Initial: 2.5 mg once daily (may consider beginning 5 mg once daily in some patients [eg, hypertension]); titrate slowly based on tolerability and response with close monitoring, not to exceed usual maximum dose of up to 40 mg/day (manufacturer's labeling).
CrCl <10 mL/minute: Consider alternative therapy; risk of adverse effects or complications (eg, hyperkalemia, kidney failure) are increased (expert opinion). If necessary, begin 2.5 mg once daily; titrate slowly based on tolerability and response with close monitoring, not to exceed usual maximum dose of up to 40 mg/day (manufacturer's labeling).
Hemodialysis, intermittent (thrice weekly): Dialyzable (50%) (Winnicki 2012):
Daily dosing: Initial: 2.5 mg once daily; when scheduled dose falls on a dialysis day, administer post hemodialysis. Titrate slowly based on tolerability and response with close monitoring (manufacturer's labeling), not to exceed usual maximum dose of up to 40 mg/day (expert opinion).
Three times weekly (post dialysis) dosing (hypertension only): Initial: 10 mg 3 times weekly administered post hemodialysis on dialysis days; titrate slowly based on tolerability and response with close monitoring to a maximum of 40 mg 3 times weekly administered post hemodialysis on dialysis days (Agarwal 2001; Agarwal 2014; Georgianos 2016).
Peritoneal dialysis: Initial: 2.5 mg once daily; titrate slowly based on tolerability and response with close monitoring, not to exceed usual maximum dose of up to 40 mg/day (expert opinion).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
(For additional information see "Lisinopril: Pediatric drug information")
Note : Compounded and commercially available oral solutions have multiple concentrations; precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as mg.
Hypertension: Note: Use lower listed initial dose in patients with hyponatremia, hypovolemia, severe CHF, decreased renal function, or in those receiving diuretics. Titrate dose according to patient's response.
Children <6 years: Limited data available: Oral: Initial: 0.07 mg/kg/dose once daily; maximum initial daily dose: 5 mg/day; maximum daily dose: 0.6 mg/kg/day or 40 mg/day (Flynn 2006)
Children ≥6 years and Adolescents: Oral: Initial: 0.07 mg/kg/dose once daily; maximum initial daily dose: 5 mg/day; maximum daily dose: 0.6 mg/kg/day or 40 mg/day
Proteinuria (eg, mild IgA nephropathy, focal segmental glomerulosclerosis [FSGS]): Limited data available: Children ≥2 years and Adolescents: Oral: Initial: 0.1 to 0.2 mg/kg/dose once daily; increase at 1- to 2-week intervals to target dose of 0.4 mg/kg/dose once daily (Gipson 2011; Nakanishi 2009); maximum dose: 40 mg/day. Dosing based on a prospective study (total patients: n=138; pediatric patients: n=93, age range: 2 to 17 years) in patients with steroid-resistant FSGS comparing mycophenolate to cyclosporine in which most patients received lisinopril (n=118) for protein sparing effects. Lisinopril was initiated at 0.1 mg/kg/dose and increased every 2 weeks to target dose of 0.4 mg/kg/dose (maximum dose: 40 mg/dose) (Gipson 2011). In pediatric patients with mild IgA nephropathy (n=40, mean age: 11.4 years; range: 4.4 to 15.4 years), a similar protocol was used, with an initial dose of 0.2 mg/kg/dose increased after 7 days to 0.4 mg/kg/dose (maximum dose: 20 mg/dose) (Nakanishi 2009).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents: CrCl <30 mL/minute/1.73 m2: Use is not recommended
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Refer to adult dosing. In the management of hypertension, consider lower initial doses (eg, 2.5 to 5 mg once daily) and titrate to response (Aronow 2011).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Oral:
Qbrelis: 1 mg/mL (150 mL) [contains sodium benzoate]
Tablet, Oral:
Prinivil: 5 mg [DSC], 10 mg [DSC], 20 mg [DSC] [scored]
Zestril: 2.5 mg
Zestril: 5 mg [scored]
Zestril: 10 mg, 20 mg, 30 mg, 40 mg
Generic: 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Prinivil: 10 mg [DSC], 20 mg [DSC]
Zestril: 5 mg, 10 mg, 20 mg [contains corn starch]
Generic: 5 mg, 10 mg, 20 mg, 40 mg [DSC]
Oral: Administer as a single daily dose and without regard to meals.
Oral: May be administered without regard to food
Heart failure with reduced ejection fraction: Adjunctive therapy to reduce signs and symptoms of systolic heart failure.
Hypertension, chronic: Management of hypertension in adult and pediatric patients ≥6 years of age.
ST-elevation myocardial infarction: Treatment of acute MI within 24 hours in hemodynamically stable patients to improve survival.
Non-ST-elevation acute coronary syndrome; Posttransplant erythrocytosis (renal transplant recipients); Proteinuric chronic kidney disease (diabetic or nondiabetic); Stable coronary artery disease
Lisinopril may be confused with fosinopril, Lioresal, Lipitor, RisperDAL
Prinivil may be confused with Plendil, Pravachol, Prevacid, PriLOSEC, Proventil
Zestril may be confused with Desyrel, Restoril, Vistaril, Zegerid, Zerit, Zetia, Zostrix, ZyPREXA
Acepril [Malaysia] may be confused with Accupril which is a brand name for quinapril [US]
Acepril: Brand name for lisinopril [Malaysia], but also the brand name for captopril [Great Britain]; enalapril [Hungary, Switzerland]
Use may be associated with increased blood urea nitrogen and increased serum creatinine, resulting in oliguria and acute kidney injury (AKI). Increases in serum creatinine are expected and usually stabilize within 20% to 30% of baseline; higher increases may indicate high efferent tone (such as with hypovolemia, congestive heart failure, or renal artery stenosis) (Ref).
Mechanism: Related to pharmacologic action; inhibits efferent arteriolar vasoconstriction, lowering glomerular filtration pressure, which can lead to a reduction in glomerular filtration rate (GFR). Kidney hypoperfusion from hypotension may also occur (Ref).
Onset: Intermediate; increases in serum creatinine generally occur within 2 weeks of initiation and stabilize within 2 to 4 weeks (Ref). However, more immediate increases may occur in patients with other risk factors for AKI (Ref).
Risk factors:
• Patients with low renal blood flow whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II (Ref):
- Low effective circulating volume (sodium or volume depletion)
- Congestive heart failure
- Hypotension or shock
- Renal artery stenosis
• High-dose initiation (especially with concomitant diuretic use) (Ref)
• Older patients (Ref)
• Preexisting kidney impairment (Ref)
• Concurrent diuretic and/or nonsteroidal anti-inflammatory drug use (Ref)
Angioedema may occur rarely; edema may manifest in the head and neck (potentially compromising the airway) or the intestine (presenting with abdominal pain). Use is contraindicated in patients with idiopathic or hereditary angioedema or previous angioedema associated with any angiotensin-converting enzyme inhibitors or neprilysin inhibitors (Ref).
Mechanism: Related to pharmacologic action (ie, increased bradykinin and Substance P, vascular permeability, and vasodilation) (Ref).
Onset: Varied; may occur at any time during treatment. Most cases occur within the first week of therapy but may also occur after years of therapy (Ref).
Risk factors:
• Black patients (estimated 4- to 5-fold higher risk); the mechanism for this is not completely understood but may be related to genetic variants (Ref)
• Females (Ref)
• Smoking history (Ref)
• Previous history of angioedema (Ref)
• Age >65 years (Ref)
• Seasonal allergies (Ref)
• Concurrent use of mechanistic target of rapamycin (mTOR) inhibitors (eg, everolimus) (Ref)
• Concurrent use of neprilysin inhibitor (contraindicated)
A dry, hacking, nonproductive cough that is typically associated with tickling or scratching in the throat may occur with angiotensin converting enzyme inhibitors (ACEI), including lisinopril in adult and pediatric patients (Ref). Recurrence is likely with rechallenge (Ref). Resolution of cough typically occurs 1 to 4 weeks after ACEI discontinuation but may persist for up to 3 months (Ref).
Mechanism: Various proposed mechanisms. May be related to the pharmacologic action (ie, increased bradykinin and substance P, resulting in accumulation in the lungs and bronchoconstriction) (Ref).
Onset: Variable; within hours to 4 weeks after initiation but can be delayed for up to 6 months (Ref).
Risk factors:
• Females (Ref)
• Possibly certain genetic variants (some of which may be independent of the bradykinin pathway) (Ref)
Hyperkalemia (elevated serum potassium) may occur with angiotensin converting enzyme inhibitors (ACEI), including lisinopril.
Mechanism: Related to pharmacologic action; inhibits formation of circulating angiotensin II, which leads to efferent arteriole vasodilation and subsequent lowering of GFR, which lowers potassium elimination. Additionally, interferes with generation and release of aldosterone from the adrenal cortex, leading to an impairment of potassium excretion from the kidney (Ref).
Risk factors:
• Disease states associated with hyperkalemia (congestive heart failure, diabetes mellitus, chronic kidney disease) (Ref)
• Concurrent use of medications which cause hyperkalemia (ACEI, ARBs, spironolactone, NSAIDs, beta blockers, heparin, tacrolimus, cyclosporine) (Ref)
• Acute kidney injury (elevated BUN/serum creatinine) (Ref)
• High dietary intake of potassium or concurrent use of potassium supplements (including potassium-containing salt substitutes) (Ref)
• Baseline elevated potassium (≥5 mmol/L) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypotension (4% to 11%)
Nervous system: Dizziness (4% to 19%)
1% to 10%:
Cardiovascular: Flushing, orthostatic hypotension, syncope (5% to 7%), vasculitis
Dermatologic: Alopecia, diaphoresis, erythema of skin, pruritus, skin photosensitivity, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Diabetes mellitus, gout, hyperkalemia (2% to 6%; incidence varies in literature and may be impacted by comorbidities) (Reardon 1998; Weir 2010; Yusuf 2008), SIADH
Gastrointestinal: Constipation, diarrhea, dysgeusia, flatulence, pancreatitis, xerostomia
Genitourinary: Impotence
Hematologic & oncologic: Bone marrow depression, eosinophilia, hemolytic anemia, increased erythrocyte sedimentation rate, leukocytosis, leukopenia, neutropenia, positive ANA titer, pseudolymphoma (cutaneous), thrombocytopenia
Nervous system: Altered sense of smell, fatigue, paresthesia, vertigo
Neuromuscular & skeletal: Arthralgia, arthritis, asthenia, myalgia
Ophthalmic: Blurred vision, diplopia, photophobia, vision loss
Otic: Tinnitus
Renal: Increased blood urea nitrogen (≤2%; transient), increased serum creatinine (≤10%; transient), renal insufficiency (in patients with acute myocardial infarction: 1% to 2%)
Respiratory: Cough (3% to 4%; literature suggests incidence may be as high as 20% [placebo: 1%]) (Bangalore 2010; Israili 1992; Yusuf 2008)
Miscellaneous: Fever
Postmarketing:
Dermatologic: Psoriasis (White 2001)
Endocrine & metabolic: Hyponatremia (Jenks 2016; Jiang 2020)
Hematologic & oncologic: Aplastic anemia (Schratzlseer 1994), pancytopenia (Schratzlseer 1994)
Hepatic: Cholestatic hepatitis (Singh 2014), fulminant hepatitis (Larrey 1990), hepatocellular hepatitis (Zalawadya 2010)
Hypersensitivity: Angioedema (Vleeming 1998)
Nervous system: Confusion, mood changes (including depressive symptoms), visual hallucination (Doane 2013)
Renal: Acute kidney injury (Wang 1996)
Hypersensitivity to lisinopril, other ACE inhibitors, or any component of the formulation; angioedema related to previous treatment with an ACE inhibitor; idiopathic or hereditary angioedema; concomitant use with aliskiren in patients with diabetes mellitus; coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).
Canadian labeling: Additional contraindications (not in US labeling): Women who are pregnant, intend to become pregnant, or of childbearing potential and not using adequate contraception; breastfeeding; concomitant use with aliskiren, angiotensin receptor blockers (ARBs), or other ACE inhibitors in patients with moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2), hyperkalemia (>5 mmol/L), or with heart failure who are hypotensive; concomitant use with ARBs or other ACE inhibitors in diabetic patients with end organ damage; pediatric patients <6 years; pediatric patients 6 to 16 years of age with severe renal impairment (GFR <60 mL/minute/1.73 m2).
Concerns related to adverse effects:
• Hematologic effects: Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Periodically monitor CBC with differential in these patients.
• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with angiotensin-converting enzyme (ACE) inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses). Effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation. Close monitoring of patients is required especially within the first few weeks of initial dosing and with dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation. Avoid use in hemodynamically unstable patients after acute myocardial infarction (MI).
Disease-related concerns:
• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• Ascites: Avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor blood pressure and renal function carefully to avoid rapid development of renal failure (AASLD [Runyon 2012]).
• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs. In a retrospective cohort study of elderly patients (≥65 years of age) with MI and impaired left ventricular function, administration of an ACE inhibitor was associated with a survival benefit, including patients with serum creatinine concentrations >3 mg/dL (265 micromol/L) (Frances 2000).
• Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity.
• Hepatic impairment: Use with caution in patients with hepatic impairment; consider baseline LFTs prior to initiating therapy.
• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2020]).
• Renal impairment: Use with caution in preexisting renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation, which may lead to further renal impairment.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Oral solution: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982). Some data suggest that benzoate displaces bilirubin from protein-binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
Special populations:
• Race/Ethnicity: In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2017).
• Surgical patients: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Based on current research and clinical guidelines in patients undergoing noncardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).
None known.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification
Allopurinol: Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy
Alteplase: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Everolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy
Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor therapy
Finerenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor therapy
Gold Sodium Thiomalate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. This combination may increase the risk of developing a nitritoid reaction. Risk C: Monitor therapy
Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk X: Avoid combination
Green Tea: May decrease the serum concentration of Lisinopril. Risk C: Monitor therapy
Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Management: Follow iron dextran recommendations closely regarding both having resuscitation equipment and trained personnel on-hand prior to iron dextran administration and the use of a test dose prior to the first therapeutic dose. Risk D: Consider therapy modification
Lanthanum: May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Octreotide: May increase the serum concentration of Lisinopril. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Pregabalin: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Racecadotril: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor therapy
Ranolazine: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Sacubitril: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid combination
Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Sirolimus Products: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy
Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ACEIs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification
Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Temsirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
TiZANidine: May enhance the hypotensive effect of Lisinopril. Risk C: Monitor therapy
Tolvaptan: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Urapidil: May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider therapy modification
Urokinase: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Avoid use of angiotensin-converting enzyme (ACE) inhibitor therapy in patients who may become pregnant and who are not using effective contraception (ADA 2021).
ACE inhibitors should generally be avoided for the treatment of hypertension in patients planning to become pregnant; use should only be considered for cases of hypertension refractory to other medications (ACOG 203 2019).
Lisinopril crosses the placenta (Bhatt-Mehta 1993; Filler 2003).
Exposure to an angiotensin-converting enzyme (ACE) inhibitor during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]); however, outcomes observed may also be influenced by maternal disease (ACC/AHA [Whelton 2017]).
Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
Drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. The use of these drugs in pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Infants exposed to an ACE inhibitor in utero should be monitored for hyperkalemia, hypotension, and oliguria. Oligohydramnios may not appear until after irreversible fetal injury has occurred. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function, although data related to the effectiveness in neonates is limited.
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, pre-eclampsia, delivery complications, stroke and myocardial infarction (ACOG 203 2019).
When treatment of hypertension in pregnancy is indicated, ACE inhibitors should generally be avoided due to their adverse fetal events; use in pregnant women should only be considered for cases of hypertension refractory to other medications (ACOG 203 2019). ACE inhibitors are not recommended for the treatment of heart failure in pregnancy (Regitz-Zagrosek [ESC 2018]).
It is not known if lisinopril is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue lisinopril.
Use potassium-containing salt substitutes cautiously in patients with diabetes, patients with renal impairment, or those maintained on potassium supplements or potassium-sparing diuretics.
BP, heart rate; BUN, serum creatinine, and potassium (especially in patients on concomitant potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts); consider baseline LFTs (if preexisting hepatic impairment); monitor for jaundice or signs of hepatic failure; if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential. If angioedema is suspected, assess risk of airway obstruction (eg, involvement of tongue, glottis, larynx, and/or history of airway surgery).
Heart failure: Within 1 to 2 weeks after initiation and periodically thereafter, reassess renal function and serum potassium especially in patients with preexisting hypotension, hyponatremia, diabetes mellitus, azotemia, or those taking potassium supplements (ACCF/AHA [Yancy 2013]).
BP goals: May vary depending on clinical condition, different clinical practice guidelines, and expert opinion. Refer to "Clinical Practice Guidelines" for specific treatment goals.
Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion; a CNS mechanism may also be involved in hypotensive effect as angiotensin II increases adrenergic outflow from CNS; vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure
Onset of action: 1 hour; Peak effect: Hypotensive: Oral: ~6 hours
Duration: 24 hours
Metabolism: Not metabolized
Bioavailability:
Pediatric patients:
2 to 15 years: 20% to 36% (Hogg 2007)
6 to 16 years: ~28%
Adults: ~25% (range: 6% to 60%); decreased to 16% with NYHA Class II-IV heart failure
Half-life elimination: 12 hours
Time to peak:
Pediatric patients 6 months to 15 years: Median (range): 5 to 6 hours (Hogg 2007)
Adults: ~7 hours
Excretion: Primarily urine (as unchanged drug)
Renal function impairment: Decreased elimination when glomerular filtration rate is <30 mL/minute. With greater impairment, peak and trough lisinopril levels increase, time to peak concentration increases, and time to attain steady state is prolonged.
Solution (Qbrelis Oral)
1 mg/mL (per mL): $4.32
Tablets (Lisinopril Oral)
2.5 mg (per each): $0.01 - $0.65
5 mg (per each): $0.02 - $0.97
10 mg (per each): $0.02 - $1.00
20 mg (per each): $0.03 - $1.08
30 mg (per each): $0.04 - $1.51
40 mg (per each): $0.04 - $1.57
Tablets (Zestril Oral)
2.5 mg (per each): $15.95
5 mg (per each): $15.95
10 mg (per each): $15.95
20 mg (per each): $15.95
30 mg (per each): $15.95
40 mg (per each): $15.95
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