Version May 2024
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 (Ref). 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 (Ref). 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 (Ref).
Heart failure with reduced ejection fraction:
Note: If tolerated, an angiotensin II receptor-neprilysin inhibitor is generally preferred over an angiotensin-converting enzyme inhibitor (Ref).
Oral: Initial: 2.5 to 5 mg once daily; increase dose (eg, double but by no more than 10 mg increments) as tolerated every ≥1 to 2 weeks to a target dose of 20 to 40 mg once daily (Ref). In hospitalized patients, may titrate more rapidly as tolerated (Ref).
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) (Ref).
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 (Ref).
Migraine, prevention (alternative agent) (off-label use):
Note: Among second-line agents for migraine prevention, consider use in patients with comorbid hypertension (Ref). An adequate trial for assessment of effect is considered to be at least 2 to 3 months at a therapeutic dose (Ref).
Oral: Initial: 10 mg once daily; may increase dose after 1 week to 20 mg daily based on response and tolerability (Ref).
Posttransplant erythrocytosis, kidney transplant recipients (off-label use):
Note: For patients with a hemoglobin concentration >17 g/dL (Ref).
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) (Ref).
Proteinuric chronic kidney disease, diabetic or nondiabetic (off-label use):
Oral: Initial: 2.5 to 10 mg once daily depending on baseline BP. Titrate gradually (eg, by doubling the dose every 2 to 4 weeks) up to the maximally tolerated dose, not to exceed 40 mg/day. If proteinuria target is not met despite optimized dosage, consider additional therapies (eg, sodium-glucose cotransporter-2 inhibitor) (Ref).
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 A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Kidney impairment prior to treatment initiation:
Altered kidney function:
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 (Ref).
CrCl <10 mL/minute: Consider alternative therapy; risk of adverse effects or complications (eg, hyperkalemia, kidney failure) are increased (Ref). 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 (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (50%) (Ref):
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 (Ref), not to exceed usual maximum dose of up to 40 mg/day (Ref).
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 (Ref).
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 (Ref).
Alterations in kidney function during treatment: Small, transient increases in serum creatinine are likely to occur within 4 weeks following initiation of therapy or an increase in dose. If serum creatinine increases by >30%, review for possible etiologies (eg, acute kidney injury, volume depletion, concomitant medications, renal artery stenosis) before determining if dose reduction or discontinuation of lisinopril therapy should be considered (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution, particularly in patients with ascites due to cirrhosis (Ref).
Hyperkalemia: Assess for alternative or contributing factors (eg, diet, concomitant medications) of increased potassium before determining if dose reduction or discontinuation of lisinopril therapy should be considered (Ref).
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 (Ref).
(For additional information see "Lisinopril: Pediatric drug information")
Dosage guidance:
Safety: 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:
Children <6 years: Limited data available: Oral: Initial: 0.07 mg/kg/dose once daily; maximum initial daily dose: 5 mg/day; titrate dose based on response; maximum daily dose: 0.6 mg/kg/day not to exceed 40 mg/day (Ref).
Children ≥6 years and Adolescents: Oral: Initial: 0.07 mg/kg/dose once daily; titrate dose based on response; maximum initial daily dose: 5 mg/day; maximum daily dose: 0.61 mg/kg/day not to exceed 40 mg/day (Ref).
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 (Ref); 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) (Ref). 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) (Ref).
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: No dosage adjustment needed.
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.
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 (5% 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, 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, asthenia, fatigue, paresthesia, vertigo
Neuromuscular & skeletal: Arthralgia, arthritis, gout, 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 (4%; literature suggests incidence may be as high as 20%) (Bangalore 2010; Israili 1992; Yusuf 2008) (table 1)
|
Drug (Lisinopril) |
Placebo |
Dosage Form |
Indication |
|---|---|---|---|
|
4% |
1% |
Oral tablets |
Hypertension |
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).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 kidney 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 kidney impairment (GFR <60 mL/minute/1.73 m2).
Concerns related to adverse effects:
• Hematologic effects: Patients with kidney impairment are at high risk of developing neutropenia. Patients with both kidney 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: Generally, 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 BP and kidney function carefully to avoid rapid development of kidney failure (AASLD [Biggins 2021]; AASLD [Runyon 2013]).
• 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 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 kidney 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]).
• Kidney impairment: Use with caution in preexisting kidney insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation, which may lead to further kidney 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 2018).
• 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]).
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]
Prinivil: 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
Solution (Qbrelis Oral)
1 mg/mL (per mL): $5.01
Tablets (Lisinopril Oral)
2.5 mg (per each): $0.01 - $0.65
5 mg (per each): $0.02 - $0.97
10 mg (per each): $0.01 - $1.00
20 mg (per each): $0.02 - $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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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
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.
Migraine, prevention; Non-ST-elevation acute coronary syndrome; Posttransplant erythrocytosis, kidney 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]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. 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
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
Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. 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. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme (ACE) inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. 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
Polyethylene Glycol-Electrolyte Solution: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. 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
Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. 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
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. Risk C: Monitor therapy
Sparsentan: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk X: Avoid combination
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. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. 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
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 2023).
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. Angiotensin-converting enzyme (ACE) inhibitors are fetotoxic. Transition patients prior to conception to an agent preferred for use during pregnancy unless treatment with an ACE inhibitor is absolutely necessary (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
When ACE inhibitors are used for the treatment of proteinuric chronic kidney disease in patients who could become pregnant, discontinue use at the first positive pregnancy test (ADA 2023; Fakhouri 2023).
ACE inhibitors are not recommended for the treatment of heart failure in patients planning to become pregnant (AHA/ACC/HFSA [Heidenreich 2022]).
Lisinopril may be effective for prevention of migraines. In general, preventive treatment for migraine in patients trying to become pregnant should be avoided. Options for patients planning a pregnancy should be considered as part of a shared decision-making process. Nonpharmacologic interventions should be considered initially. When needed, preventive treatment should be individualized considering the available safety data and needs of the patient should pregnancy occur. A gradual discontinuation of preventive medications is generally preferred when the decision is made to stop treatment prior to conception (ACOG 2022; AHS [Ailani 2021]). When lisinopril is used for migraine prevention, treatment should be discontinued prior to attempting to conceive (ACOG 2022).
Lisinopril crosses the placenta (Bhatt-Mehta 1993; Filler 2003).
Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. 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 2019; ESC [Regitz-Zagrosek 2018]). Following exposure during the second or third trimesters, 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. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. ACE inhibitor use during pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Monitor infants exposed to an ACE inhibitor in utero for hyperkalemia, hypotension, and oliguria. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function.
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 the 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 2019).
Discontinue ACE inhibitors as soon as possible once pregnancy is detected. Agents other than ACE inhibitors are recommended for the treatment of chronic hypertension during pregnancy (ACOG 2019; ESC [Cífková 2020]; SOGC [Magee 2022]). Consider the use of ACE inhibitors only for pregnant patients with hypertension refractory to other medications (ACOG 2019). Closely monitor pregnant patients on ACE inhibitors with serial ultrasounds.
ACE inhibitors are not recommended for the treatment of heart failure or proteinuric chronic kidney disease during pregnancy (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Regitz-Zagrosek 2018]; Fakhouri 2023).
In general, preventive treatment for migraine should be avoided during pregnancy. Options for pregnant patients should be considered as part of a shared decision-making process. Nonpharmacologic interventions should be considered initially. When needed, preventive treatment should be individualized considering the available safety data, the potential for adverse maternal and fetal events, and needs of the patient (ACOG 2022; AHS [Ailani 2021]). Lisinopril is not recommended for migraine prevention during pregnancy (ACOG 2022).
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.
In general, preventive treatment for migraine in lactating patients should be avoided. When needed, therapy should be individualized considering the available safety data and needs of the patient (AHS [Ailani 2021]). When postpartum treatment with an ACE inhibitor is needed, consider use of an agent other than lisinopril (ESC [Cífková 2020]). Avoid breastfeeding if high maternal doses of an ACE inhibitor are needed (ACOG 2019).
Use potassium-containing salt substitutes cautiously in patients with diabetes, patients with kidney impairment, or those maintained on potassium supplements or potassium-sparing diuretics.
Blood pressure; BUN; serum creatinine; electrolytes (eg, 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 kidney 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).
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)
Altered kidney function: 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.
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