Meta Information
ID:ace-inhibitors
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-25T02:52:39.753058+00:00
Model
wave7-launch-claude-sonnet-4.6
Interactions
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lisinopril can cause significant injury and even death to a developing fetus, particularly during the second and third trimesters. This is a boxed warning from the FDA.
Actionable advice:
Lisinopril is absolutely contraindicated during pregnancy; stop taking it immediately and contact your doctor if you become pregnant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
When pregnancy is detected, discontinue Lisinopril as soon as possible [see Warnings and Precautions (5.1) ]. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) ].
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/condition/history-of-angioedema
Target name:
History of Angioedema
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Patients with a history of angioedema (hereditary, idiopathic, or related to previous ACE inhibitor use) are at a very high risk of a recurrence, which can be life-threatening.
Actionable advice:
Lisinopril should not be taken with any history of angioedema.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Lisinopril is contraindicated in patients with: • a history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme inhibitor • hereditary or idiopathic angioedema Do not co-administer aliskiren with Lisinopril in patients with diabetes [see Drug Interactions (7.4) ] • Angioed
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/intervention/sacubitril-valsartan
Target name:
Sacubitril/Valsartan (Entresto)
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
36
Hours after target:
36
Description:
Taking lisinopril and sacubitril (a neprilysin inhibitor) close together dramatically increases the risk of angioedema, a serious and potentially fatal swelling of the face, lips, and airway.
Actionable advice:
Lisinopril should not be taken within 36 hours (before or after) of taking sacubitril/valsartan.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
History of angioedema related to previous ACEi or ARB therapy
Label source:
FDA label: Sacubitril/Valsartan (Entresto) — Contraindications (4) (target-side evidence)
Action type:
separate
Target id:
/class/potassium-sparing-diuretics
Target name:
Potassium-Sparing Diuretics
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both lisinopril and potassium-sparing diuretics (e.g., spironolactone, amiloride) reduce the body's excretion of potassium, leading to a high risk of dangerous hyperkalemia (excessively high blood potassium).
Actionable advice:
These medications should not be used together unless under strict medical supervision with frequent potassium monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(5.3) • Hypotension: Patients with other heart or renal diseases have increased risk, monitor blood pressure after initiation (5.4) • Hyperkalemia: Monitor serum potassium periodically (5.5) • Cholestatic jaundice and hepatic failure: Monitor for jaundice or signs of liver failure (5.6) Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trime
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/intervention/potassium
Target name:
Potassium Supplements
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lisinopril causes the body to retain potassium. Taking potassium supplements at the same time can easily lead to dangerously high potassium levels (hyperkalemia), which can affect heart rhythm.
Actionable advice:
All potassium supplements should be avoided unless specifically prescribed and closely monitored by a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(5.3) • Hypotension: Patients with other heart or renal diseases have increased risk, monitor blood pressure after initiation (5.4) • Hyperkalemia: Monitor serum potassium periodically (5.5) • Cholestatic jaundice and hepatic failure: Monitor for jaundice or signs of liver failure (5.6) Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trime
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/dietary/potassium-salt-substitutes
Target name:
Potassium-Containing Salt Substitutes
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Many salt substitutes replace sodium with potassium chloride. Using these products while taking lisinopril can cause dangerously high blood potassium levels (hyperkalemia).
Actionable advice:
Salt substitutes that contain potassium should not be used; the ingredient label is worth checking carefully.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(5.3) • Hypotension: Patients with other heart or renal diseases have increased risk, monitor blood pressure after initiation (5.4) • Hyperkalemia: Monitor serum potassium periodically (5.5) • Cholestatic jaundice and hepatic failure: Monitor for jaundice or signs of liver failure (5.6) Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trime
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/class/arbs
Target name:
Angiotensin II Receptor Blockers (ARBs)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining an ACE inhibitor (lisinopril) with an ARB (e.g., telmisartan, losartan) is known as dual RAAS blockade. This combination significantly increases the risk of low blood pressure, high potassium, and kidney failure without providing additional benefits.
Actionable advice:
Lisinopril should never be taken together with an ARB.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end state renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/intervention/aliskiren
Target name:
Aliskiren
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The combination of lisinopril and aliskiren (a direct renin inhibitor) is contraindicated in patients with diabetes or renal impairment due to a high risk of hypotension, hyperkalemia, and acute kidney injury.
Actionable advice:
Lisinopril should not be taken with aliskiren, especially in diabetes or kidney disease.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
rsensitivity related to previous treatment with an angiotensin converting enzyme inhibitor • hereditary or idiopathic angioedema Do not co-administer aliskiren with Lisinopril in patients with diabetes [see Drug Interactions (7.4) ] • Angioedema or a history of hereditary or idiopathic angioedema (4) • Hypersensitivity (4) • Co-administration of aliskiren with Lisinopril in patients with diabetes
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/intervention/lithium
Target name:
Lithium
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lisinopril reduces the kidneys' ability to clear lithium from the body. This can lead to a toxic buildup of lithium, causing serious side effects.
Actionable advice:
This combination should be avoided; if it is medically necessary, lithium levels must be monitored extremely closely.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(7.3) • Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia (7.4) • Lithium: Symptoms of lithium toxicity (7.5) • Gold: Nitritoid reactions have been reported (7.6) Initiation of Lisinopril in patients on diuretics may result in excessive reduction of blood pressure.
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/biomarker/serum-potassium
Target name:
Serum Potassium Level
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Because lisinopril can cause potassium retention, it is essential to monitor blood potassium levels to prevent hyperkalemia, which can lead to serious cardiac arrhythmias.
Actionable advice:
Serum potassium should be checked before starting and periodically during therapy as directed by a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(5.3) • Hypotension: Patients with other heart or renal diseases have increased risk, monitor blood pressure after initiation (5.4) • Hyperkalemia: Monitor serum potassium periodically (5.5) • Cholestatic jaundice and hepatic failure: Monitor for jaundice or signs of liver failure (5.6) Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trime
Label source:
FDA label: Lisinopril
Action type:
monitor
Target id:
/biomarker/creatinine
Target name:
Serum Creatinine
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lisinopril can affect kidney function, particularly when starting therapy or in at-risk individuals. Monitoring creatinine (and eGFR) is crucial to ensure renal safety.
Actionable advice:
Kidney function should be checked before starting and periodically during therapy as directed by a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
ncidence of renal dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration).
Label source:
FDA label: Lisinopril
Action type:
monitor
Target id:
/class/nsaids
Target name:
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NSAIDs (e.g., ibuprofen, naproxen) can reduce the blood pressure-lowering effect of lisinopril and, when used together, increase the risk of kidney damage, especially in the elderly or dehydrated individuals.
Actionable advice:
Chronic use of NSAIDs is best avoided; for occasional pain relief, acetaminophen may be a safer alternative.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Diuretics: Excessive drop in blood pressure (7.1) • NSAIDS: Increased risk of renal impairment and loss of antihypertensive efficacy (7.3) • Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia (7.4) • Lithium: Symptoms of lithium toxicity (7.5) •
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/class/diuretics
Target name:
Diuretics (Water Pills)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Initiating lisinopril in a patient already taking a diuretic can cause a sharp, excessive drop in blood pressure (first-dose hypotension), leading to significant dizziness or fainting.
Actionable advice:
Your doctor may advise stopping the diuretic for a few days before starting lisinopril or initiating it at a very low dose.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology.
Label source:
FDA label: Lisinopril
Action type:
informational_none
Target id:
/class/mtor-inhibitors
Target name:
mTOR Inhibitors (e.g., Rapamycin/Sirolimus)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking an ACE inhibitor like lisinopril with an mTOR inhibitor may increase the risk of developing angioedema, a serious swelling reaction.
Actionable advice:
This combination is best used with caution, and it is worth being vigilant for signs of angioedema (swelling of the face, lips, or tongue).
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Permanently discontinue everolimus tablets for oral suspension for the development of clinically significant hypersensitivity. 5.4 Angioedema with Concomitant Use of Angiotensin-Converting Enzyme (ACE) Inhibitors Patients taking concomitant ACE inhibitors with everolimus tablets for
Label source:
FDA label: Everolimus (target-side evidence)
Action type:
monitor
Target id:
/class/dpp4-inhibitors
Target name:
DPP-4 Inhibitors (e.g., Sitagliptin)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concomitant use of a DPP-4 inhibitor (a type of diabetes medication) with an ACE inhibitor may increase the risk of developing angioedema.
Actionable advice:
If taking these together, be aware of the signs of angioedema (swelling of the face, lips, or tongue) and seek medical help if they occur.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Significant interaction signals were observed for sitagliptin/irbesartan, sitagliptin/valsartan, linagliptin/valsartan and alogliptin/lisinopril combinations
Label source:
Sridharan & Sivaramakrishnan, Diabetol Metab Syndr 2025: DPP-4i × RAAS angioedema pharmacovigilance
Action type:
monitor
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications (e.g., Insulin, Metformin)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lisinopril can improve insulin sensitivity, which may enhance the glucose-lowering effect of diabetes medications and increase the risk of hypoglycemia (low blood sugar).
Actionable advice:
Blood glucose levels should be monitored closely, especially during the first few weeks of taking lisinopril.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Concomitant administration of Lisinopril and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia.
Label source:
FDA label: Lisinopril
Action type:
monitor
Target id:
/condition/renal-impairment
Target name:
Renal Impairment (Kidney Disease)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Since lisinopril is cleared by the kidneys, impaired renal function increases the risk of drug accumulation, hyperkalemia, and further kidney damage. Lower starting doses are required.
Actionable advice:
Your dose must be adjusted based on your kidney function; close monitoring is essential.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Angioedema: Discontinue Lisinopril, provide appropriate therapy and monitor until resolved (5.2) • Renal impairment: Monitor renal function periodically (5.3) • Hypotension: Patients with other heart or renal diseases have increased risk, monitor blood pressure after initiation (5.4) • Hyperkalemia: Monitor serum potassium periodically (5.5) • Cholestatic jaundic
Label source:
FDA label: Lisinopril
Action type:
adjust_with_prescriber
Target id:
/condition/dehydration
Target name:
Dehydration
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Being dehydrated (e.g., from vomiting, diarrhea, or excessive sweating) significantly increases the risk of a severe drop in blood pressure (hypotension) and acute kidney injury when taking lisinopril.
Actionable advice:
It is a good idea to maintain adequate fluid intake, and it is important to consult a doctor if severe dehydration occurs.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
excessive perspiration and dehydration may lead to an excessive fall in blood pressure
Label source:
FDA label: Lisinopril — Patient Counseling Information (dehydration/volume depletion)
Action type:
informational_none
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Alcohol can potentiate the blood pressure-lowering effects of lisinopril, leading to increased dizziness, lightheadedness, or fainting.
Actionable advice:
Alcohol intake is best limited, and caution is warranted when rising from a sitting or lying position.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Source url:
Exact phrase from label:
Label source:
Anecdotal: GoodRx
Action type:
informational_none
Target id:
/class/antihypertensives
Target name:
Other Antihypertensive Medications
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Using lisinopril with other blood pressure-lowering drugs (e.g., beta-blockers, calcium channel blockers) has an additive effect. This is often intentional but requires monitoring to avoid hypotension.
Actionable advice:
Blood pressure should be monitored regularly, especially when adding a new medication, and any symptoms of dizziness are worth reporting.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Renal impairment: Monitor renal function periodically (5.3) • Hypotension: Patients with other heart or renal diseases have increased risk, monitor blood pressure after initiation (5.4) • Hyperkalemia: Monitor serum potassium periodically (5.5) • Cholestatic jaundice and hepatic failure: Monitor for jaundice or signs of liver failure (5.6) Pregnancy Category D Use of drugs that act on the renin-an
Label source:
FDA label: Lisinopril
Action type:
monitor
Target id:
/intervention/trimethoprim
Target name:
Trimethoprim (Antibiotic)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The antibiotic trimethoprim can increase serum potassium levels, and its use with lisinopril significantly elevates the risk of developing hyperkalemia.
Actionable advice:
If this combination is necessary, use with caution and ensure potassium levels are monitored.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Case reports of hyperkalemia in elderly patients receiving trimethoprim-sulfamethoxazole have been published
Label source:
FDA label: Trimethoprim — Hyperkalemia (target-side evidence)
Action type:
monitor
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not definitively known if lisinopril is excreted in human milk. Due to the potential for serious adverse reactions in a nursing infant, a decision should be made whether to discontinue nursing or the drug.
Actionable advice:
It is important to talk to a doctor about treatment options, as an alternative medication may be preferred while breastfeeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ACE inhibitors, a decision should be made whether to discontinue nursing or discontinue Lisinopril, taking into account the importance of the drug to the mother.
Label source:
FDA label: Lisinopril
Action type:
informational_none
Target id:
/dietary/potassium-rich-foods
Target name:
High-Potassium Foods
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While normal dietary intake is generally safe, excessive consumption of high-potassium foods (e.g., bananas, oranges, potatoes, spinach) can contribute to elevated potassium levels, especially in those with kidney disease.
Actionable advice:
Consume high-potassium foods in moderation and avoid excessive, consistent intake.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
fit compared to monotherapy for the combined endpoint of decline in GFR, end state renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group.
Label source:
FDA label: Lisinopril
Action type:
avoid
Target id:
/intervention/gold-sodium-thiomalate
Target name:
Injectable Gold (for Arthritis)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Rarely, patients on ACE inhibitors have experienced nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) during or shortly after injections of gold.
Actionable advice:
This potential reaction is worth keeping in mind for those receiving injectable gold therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Lisinopril.
Label source:
FDA label: Lisinopril
Action type:
informational_none