Lisinopril

-1.01

log Kow = -1.22

97000

97 mg/mL

189.7 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

194.29 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；189.62 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；189.37 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；191.72 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

White to off-white, odorless , crystalline powder. Crystals from methanol:ethyl acetate, mp 159-160 °C. pKa1 = 2.5; pKa2 = 4.0; pKa3 = 6.7; pKa4 = 10.1 at (25 °C). log P (n-octanol/0.1M ph 7 phosphate buffer): 10.5; Approximate UV max (0.1N NaOH): 246, 254, 258, 261, 267 nm (A 1%(cm) 4.0, 4.5, 5.1, 3.7): (0.1 N HCl): 246, 253, 258, 264, 267 nm (A 1%(cm) 3.2, 3.9, 4.5, 3.0, 2.8). Specific optical rotation: -23.3 deg at 26 °C/D (c = 1.0 in CH3-OH); -120 deg at 25 °C/405 ( c = 1 in 0.25M pH 6.4 zinc aceate); -96 deg at 25 °C/436 ( c = 1 in 0.25M pH 6.4 zinc acetate). Soluble in water; sparingly solluble in methanol. Practically insoluble in ethano,a cetone, acetonitrile, chlorform, DMF. /Lisinopril dihyrate/

Like benazepril, enalapril, fosinopril, quinapril, and ramipril but unlike captopril, lisinopril does not contain a sulfhydryl group.

This chemical does not meet GHS hazard criteria for 1.9% (2 of 106) of reports.

Danger

H360 (89.6%): May damage fertility or the unborn child [Danger Reproductive toxicity]；H361 (55.7%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]；H373 (86.8%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P203, P260, P280, P318, P319, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 106 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 2 of 106 reports by companies.；There are 12 notifications provided by 104 of 106 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including lisinopril, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Skin Irrit. 2 (28.6%)；Eye Irrit. 2 (71.4%)；Repr. 1A (42.9%)；Repr. 1A (14.3%)；Repr. 2 (28.6%)；Lact. (28.6%)；STOT RE 2 (42.9%)

Repr. 1A (89.6%)；Repr. 2 (55.7%)；STOT RE 2 (86.8%)

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non Combustible Solids.

Store at controlled room temperature, 15-30 °C (59-86 °F), and protect from moisture.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: No special environmental precautions required. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: No special environmental precautions required.

Precautions for safe handling: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: General industrial hygiene practice.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.

Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Potential pharmacologic interaction (additive hyperkalemic effect). Includes potassium-sparing diuretics, potassium supplements, and other drugs that can increase serum potassium. The manufacturer states that lisinopril should be used cautiously (with frequent monitoring of serum potassium), if at all, with potassium supplements or salt substitutes containing potassium.

Potential pharmacologic interaction (increased hypoglycemic effect), especially during initial weeks of combined treatment /of lisinopril and antidiabetic agents/ and in patients with renal impairment.

Potential pharmacologic interaction (additive hyperkalemic effect). Includes potassium-sparing diuretics, potassium supplements, and other drugs that can increase serum potassium. The manufacturer states that lisinopril should be used cautiously (with frequent monitoring of serum potassium), if at all, with potassium supplements or salt substitutes containing potassium.

Potential pharmacologic interaction (decreased antihypertensive effect) when lisinopril is used concomitantly concurrently with nonsteroidal anti-inflammatory agents (NSAIAs). Potential pharmacologic interaction (decreased renal function) when lisinopril is used concomitantly with NSAIAs in patients with impaired renal function.

For more Interactions (Complete) data for LISINOPRIL (14 total), please visit the HSDB record page.

The primary adverse reactions associated with ACE inhibitors include hyperkalemia, dry cough, angioedema, hypotension, dizziness, headache, and renal insufficiency. These effects may be more common in patients with renal, autoimmune, or collagen vascular diseases. The AHA/ACCF recommends caution when prescribing lisinopril for patients with cardiomyopathy with outflow obstruction, as the drug may exacerbate symptoms. Historically, ACE inhibitors have been associated with increased morbidity and mortality in patients with aortic stenosis. However, recent studies suggest that ACE inhibitors may be safer than originally thought and even provide some benefits in certain patients.；ACE inhibitor-induced cough is a dry, nonproductive, hacking cough that usually begins within months of initiating therapy and resolves within 1 to 4 weeks after discontinuing. Deteriorating renal function can occur in patients whose glomerular function depends on event arteriolar vasoconstriction by angiotensin II. A benign increase in serum creatinine may occur at the beginning of therapy, but medication should only be discontinued if there is a progressive or significant elevation of BUN/creatinine.；Angioedema is asymmetric swelling of subcutaneous tissue without itching or urticaria involving the face, mouth, and upper airway. ACE inhibitor-induced angioedema can occur anytime during therapy but most commonly occurs within the first 3 months of treatment. This adverse reaction is secondary to elevated bradykinin levels by inhibiting ACE, causing vasodilatation and extravasation of plasma into the submucosal tissue, leading to angioedema. The most crucial step in management is to discontinue the ACE inhibitors and note ACE inhibitors under the patient's allergies. Immediate symptomatic treatment and airway protection may be necessary.；Drug Interactions；Diuretics: When initiating lisinopril therapy, diuretics may further reduce blood pressure and lead to hypotension. When coadministered with thiazide-type diuretics or potassium-sparing diuretics (eg, amiloride, spironolactone, triamterene), lisinopril may increase the risk of hyperkalemia. Therefore, if coadministration of these diuretics is necessary, the patient’s serum potassium should be monitored frequently.；Antidiabetics: Concomitant administration of antidiabetic medicines (eg, insulins, oral hypoglycemic agents) and lisinopril can increase the risk of hypoglycemia.；NSAIDs: Non-steroidal anti-inflammatory agents can reduce the antihypertensive effect of ACE inhibitors. However, coadministration of NSAIDs and lisinopril in patients who are older, volume-depleted (including those on diuretic therapy), or renally impaired may worsen renal function and possibly cause acute renal injury (AKI). This is usually reversible, but renal function should be monitored periodically in patients receiving lisinopril and NSAID therapy.；Renin-angiotensin system blockers: Dual blockade of the renin-angiotensin with ACE inhibitors, angiotensin receptor blockers, or aliskiren is associated with higher risks of hyperkalemia, hypotension, and changes in renal function, including AKI, compared to monotherapy. Clinicians should closely monitor blood pressure, electrolytes, and renal function in these patients.；Lithium: Lithium toxicity has been reported in patients taking ACE inhibitors and lithium and is usually reversible. Clinicians should monitor serum lithium levels in these patients.；Rapamycin inhibitors: Patients using concomitant mechanistic targets of rapamycin inhibitors (eg, sirolimus, temsirolimus, everolimus) are at increased risk for angioedema.

IDENTIFICATION AND USE: Lisinopril is angiotensin-converting enzyme (ACE) inhibitor, antihypertensive and cardiotonic agent. HUMAN EXPOSURE AND TOXICITY: The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Marked hypotension may occur in patients with congestive heart failure-potential for myocardial infarction or stroke in those with acute myocardial infarction or ischemic cardiovascular or cerebrovascular disease. Rare ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice or hepatitis; may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including lisinopril, who develop jaundice or marked elevations in hepatic enzymes should discontinue the drug and receive appropriate monitoring. Hyperkalemia can develop, especially in those with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration. Sensitivity reactions, including anaphylactoid reactions and angioedema (including laryngeal edema, tongue edema), are potentially fatal. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. ANIMAL STUDIES: There was no evidence of a tumorigenic effect when lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg per kg per day or for 92 weeks to male and female mice at doses up to 135 mg per kg per day. Lisinopril treatment in male rats resulted in a marked decrease in sperm density, sperm motility and zona pellucida penetration. Acrosome reaction by spermatozoa obtained from drug-treated animals was significantly lower when compared with spermatozoa from normal animals. The developmental toxicity of lisinopri have been tested in mice and rabbits. In mice, the incidence of reso

As lisinopril metabolism depends on renal excretion, overdose management consists of general supportive care. However, gastric emptying strategies, intravenous fluids, vasopressors, and hemodialysis may also be considered when appropriate. Maintaining optimal blood pressure using fluids is critical for hypotensive patients. Some reports suggest using angiotensin II administration as an alternative supportive treatment for the treatment of ACE inhibitor overdose. There is no antidote available for lisinopril.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /Lisinopril dihydrate was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of October 28, 2016: http://actor.epa.gov/dashboard/]

/HUMAN EXPOSURE STUDIES/ To examine the effect of chronic administration of angiotensin I-converting enzyme (ACE) inhibitor on circulating angiotensin II (AII) concentration, 20 mg of lisinopril was administered once daily for 7 consecutive days to eight healthy volunteers. Plasma ACE activity was inhibited to less than approximately 30% of the pretreatment level during the repeated administration. Mean arterial pressure (MAP) was slightly but significantly reduced during the administration period. Plasma AII concentration measured by an established method using high performance liquid chromatography combined with a radioimmunoassay, however, was maintained at approximately the pretreatment level when it was measured at 24 hr intervals after each administration of lisinopril. With the gradual recovery of ACE activity following discontinuation of administration, the plasma AII concentration correlated with AI concentration (r = 0.46), and also with the product of AI and ACE activity (AI x ACE; r = 0.80), corresponding to the formula obtained from the kinetics of ACE activity. No correlation was observed between MAP and AII levels throughout the study period. /Data suggest/ that in normal subjects repeatedly administered with ACE inhibitor, the AII level in the circulation is still determined by an elevated level of AI and any remaining ACE activity, thus maintaining AII at pretreatment levels. /Data confirm/ that it is not necessary to achieve a decrease in plasma AII concentration through the chronic administration of ACE inhibitor in order to effectively lower blood pressure.

/SIGNS AND SYMPTOMS/ Hyperkalemia can develop, especially in those with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes). Hyperkalemia can result in serious, potentially fatal, cardiac arrhythmias.

/SIGNS AND SYMPTOMS/ Rare ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice or hepatitis; may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including lisinopril, who develop jaundice or marked elevations in hepatic enzymes should discontinue the drug and receive appropriate monitoring.

/SIGNS AND SYMPTOMS/ The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution.

For more Human Toxicity Excerpts (Complete) data for LISINOPRIL (22 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Lisinopril

vLess-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Acute Exposure/ The aim of study was to evaluate the effect of commonly used lisinopril, rosuvastatin and their combined action on site-specific nephrotoxicity in rats using clusterin and microalbumin nephrotoxic biomarkers and other related parameters using oral gavage. Rosuvastatin at 2 different doses showed increase in urinary microalbumin levels whereas lisinopril and its combination with rosuvastatin at 2 different doses did not show urinary microalbumin excretion indicating beneficial effects of lisinopril in terms of reducing microalbumin. Urinary clusterin levels significantly increased in high-dose treated animals of lisinopril and rosuvastatin. The use of lisinopril plus rosuvastatin at low dose also led to worsened renal function by raising urinary clusterin levels (217 +/- 4.6 ng/mL) when compared with the control (143 +/- 3.3 ng/mL). Renal histopathology showed multifocal regeneration of tubules indicating proximal tubule damaged. These results indicate that lisinopril (50 mg/kg), rosuvastatin (100 mg/kg), lisinopril+rosuvastatin (20+40 mg/kg) and lisinopril+rosuvastatin (50+100 mg/kg) showed toxicity only on proximal tubules.

/LABORATORY ANIMALS: Acute Exposure/ There have been reports of rash and angioedema in the treatment of hypertension with angiotensin converting enzyme (ACE) inhibitors. To evaluate the inflammatory reaction, we continuously infused lisinopril for three days into the peritoneal cavity of ovalbumin-sensitized guinea-pigs and tested intradermal inflammation with ovalbumin. Inflammatory responses were measured in two perpendicular directions serially, and the areas of rash were used as an index of inflammatory reaction induced by lisinopril. Inflammatory responses were dose-dependently enhanced by treatment with lisinopril. Plasma concentration of lisinopril required to produce 50% of the maximum potentiation of the inflammatory reaction in guinea-pig skin was 40 times plasma unbound concentration after the clinical treatment of lisinopril in patients.

/LABORATORY ANIMALS: Acute Exposure/ Angiotensin-converting enzyme (ACE) inhibitors are of benefit in life-threatening ventricular arrhythmias in patients with congestive heart failure and ventricular tachycardia caused by the onset of myocardial ischemia as well as by reperfusion of an ischemic area. The aim of the present study was to investigate whether direct electrophysiological effects are responsible for these observations. Therefore, we investigated the electrophysiological effects of lisinopril on the whole cardiac conduction and pacemaker system in isolated guinea pig hearts perfused by the method of Langendorff at concentrations of 0.01, 0.1, 1, and 10 uM. Lisinopril did not affect heart rate, atrioventricular, His bundle, or intraventricular conduction at any of the concentrations tested. Likewise the frequency-dependent QT duration was unchanged. At a concentration of 10 uM, lisinopril prolonged effective refractory period evaluated by premature beats (46 +/- 15%, n=8, p<0.01) as well as the rate-dependent effective refractory period (31 +/- 12, n=8, p<0.01) of the atrioventricular conduction. These effects can be explained by lisinopril's action as a minor calcium antagonist at a toxic concentration of 10 uM. The present results show that electrophysiological parameters are not substantially altered by lisinopril. Therefore, several other mechanisms such as the unloading of the left ventricle and/or the suppression of noradrenalin release and the electrolyte (potassium and magnesium) repletion and/or regression of left ventricular hypertrophy as long-term effects may play a major role in the antiarrhythmic efficacy of ACE inhibitors.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The interaction of salt with hypertension-induced left ventricular hypertrophy and its reversal by inhibition of angiotensin converting enzyme were studied in salt sensitive and salt resistant Dahl rats. Eight-week-old rats were fed either a low or high salt diet for three weeks. The colonies were then further divided and either treated with lisinopril or given no treatment for 11 weeks. Untreated salt sensitive rats had higher blood pressures than salt resistant animals. Left ventricular weight and wall thickness in both untreated salt sensitive groups was higher than in the resistant groups. Therapy lowered blood pressures in all groups but those of the high salt group remained higher than the low salt group. Reduction of left ventricular weight and wall thickness took place in either strain only when salt intake was low. Right ventricular and atrial weights were largely unaffected either by salt intake or drug therapy. Plasma renin activity increased and aldosterone levels decreased with lisinopril therapy in all groups except the salt sensitive, high salt group where both remained unchanged at low levels. Lisinopril was effective in reducing blood pressure and left ventricular hypertrophy, but both effects were severely impaired by high salt intake. The major determinant of left ventricular hypertrophy appeared to be afterload, as shown by a good correlation between left ventricular mass and systolic blood pressure, but there was some indication of a possible independent hypertrophic action of salt.

For more Non-Human Toxicity Excerpts (Complete) data for LISINOPRIL (12 total), please visit the HSDB record page.

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Prinivil as soon as possible.

Monitor renal function periodically in patients treated with Prinivil. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on Prinivil. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Prinivil.

Symptomatic hypotension may occur, sometimes associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death. Patients at particular risk include those with heart failure with systolic blood pressure less than 100 mm Hg, hyponatremia, high-dose or recent intensive diuretic therapy, recent increase in diuretic dose, dialysis, or severe volume and/or salt depletion of any etiology. In such patients, it may be advisable to discontinue the diuretic (except in patients with heart failure), reduce the diuretic dosage, or cautiously increase salt intake, if possible, prior to initiating lisinopril therapy. Treatment with lisinopril must not be initiated in patients with acute myocardial infarction at risk of further serious hemodynamic deterioration following treatment with a vasodilator (e.g., systolic blood pressure of 100 mm Hg or lower) or in those with cardiogenic shock. Marked hypotension may occur in patients with congestive heart failure-potential for myocardial infarction or stroke in those with acute myocardial infarction1 2 or ischemic cardiovascular or cerebrovascular disease.

Like other vasodilators, lisinopril should be administered with caution in patients with obstruction in the outflow tract of the left ventricle (e.g., aortic stenosis, hypertrophic cardiomyopathy).

Black patients: ACE inhibitors not as effective for decreasing blood pressure. Increased incidence of angioedema. /ACE inhibitors/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Treatment and supportive measures: Monitor blood pressure and heart rate for 6 hours after ingestion. If symptomatic or significant hypotension develops, observe for at least 24 hours. 1. If hypotension occurs, treat it with supine positioning and IV fluids. Vasopressors are rarely necessary. 2. Treat angioedema with usual measures (eg, diphenhydramine, corticosteroids) and discontinue the ACE inhibitors. Switching to an AR blocker may not be appropriate as angioedema has also been reported with these agents. 3. Treat hyperkalemia if it occurs. /Angiotensin blockers and ACE inhibitors/

For more Antidote and Emergency Treatment (Complete) data for LISINOPRIL (6 total), please visit the HSDB record page.

◉ Summary of Use during Lactation；Because of the low levels of lisinopril in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants.；◉ Effects in Breastfed Infants；Five women who were taking lisinopril reported any perceived adverse effects in their infants. Four taking doses of 5, 10 and 20 mg daily reported no adverse effects in their infants. One had taken 5 mg of lisinopril daily and breastfed her 1-year-old since birth, exclusive probably through 6 months and extensively thereafter. The fifth women reported that her infant’s “poop smelled unpleasant and was often green”, but she continued breastfeeding and taking lisinopril. It is not clear if the infant’s condition was related to lisinopril.；◉ Effects on Lactation and Breastmilk；In a pilot study of the treatment of patients with postpartum hypertension, patients were randomized to either 12.5 mg hydrochlorothiazide plus 10 mg of lisinopril (n = 31) or 30 mg of nifedipine (n = 36) daily. The dosages could be increased to 12.5 mg hydrochlorothiazide plus 20 mg of lisinopril and then to 25 mg hydrochlorothiazide with 20 mg lisinopril. Nifedipine dosage was increased in 30 mg increments to a maximum daily dose of 120 mg daily. At discharge, 21 hydrochlorothiazide-lisinopril mothers (70%) were breastfeeding while19 nifedipine mothers (53%) were breastfeeding.

◈ What is lisinopril?；Lisinopril is part of a class of medications called angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors help relax blood vessels and lower blood pressure. Lisinopril has been used to treat high blood pressure, protect the kidneys in people with diabetes, and lower the chance of death during a heart attack. Some brand names for lisinopril are Prinivil®, Qbrelis®, and Zestril®. Lisinopril is also available in combination with a medication called hydrochlorothiazide (Zestoretic®).ACE inhibitors should be avoided during the second and third trimesters of pregnancy. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.；◈ I am taking lisinopril, but I would like to stop taking it before getting pregnant. How long does the drug stay in my body?；The time it takes the body to metabolize (to process) medication is not the same for everyone. In healthy, non-pregnant adults, it takes up to 72 hours, on average, for most of the lisinopril to be gone from the body.；◈ I take lisinopril. Can it make it harder for me to get pregnant?；It is not known if lisinopril can make it harder to get pregnant.；◈ Does taking lisinopril increase the chance of miscarriage?；Miscarriage is common and can occur in any pregnancy for many different reasons. Studies have not been done to see if lisinopril increases the chance for miscarriage.；◈ Does taking lisinopril increase the chance of birth defects?；Birth defects can happen in any pregnancy for different reasons. Out of all babies born each year, about 3 out of 100 (3%) will have a birth defect. It is not known if lisinopril increases the chance for birth defects when taken during the first trimester.；◈ Does taking lisinopril in pregnancy increase the chance of other pregnancy-related problems?；Talk with your healthcare provider right away if you are pregnant and taking any ACE inhibitor, including lisinopril.When used after the first trimester, ACE inhibitors such as lisinopril can cause low levels of amniotic fluid (fluid that surrounds the fetus during pregnancy). Low levels of amniotic fluid can lead to health problems for the developing fetus. Some of these problems include poor lung development, poor growth, poor development of the skull bones, birth defects, and problems with the development of the kidneys. In the most severe cases, fetal death could occur. ACE inhibitors can also cause low blood pressure and kidney failure in the newborn baby. There are some cases of babies who have died from these complications.；◈ Does taking lisinopril in pregnancy affect future behavior or learning for the child?；Studies have not been done to see if lisinopril can increase the chance of behavior or learning issues for the child.；◈ What screenings or tests are available to see if my pregnancy has birth defects or other issues?；Prenatal ultrasounds can be used to screen for some birth defects, such as skull bone and kidney defects. Ultrasound can also be used to track the growth of the pregnancy and the level of amniotic fluid (fluid that surrounds the fetus during pregnancy). Talk with your healthcare provider about any prenatal screenings or testing that are available to you. There are no tests available during pregnancy that can tell how much effect there could be on future behavior or learning.；◈ Breastfeeding while taking lisinopril:；There are no studies looking at the use of lisinopril while breastfeeding. This means it is not known what effect, if any, lisinopril could have on a child that is exposed to lisinopril from breastmilk. Be sure to talk to your healthcare provider about all your breastfeeding questions.；◈ If a man takes lisinopril, could it affect fertility or increase the chance of birth defects?；Studies have not been done to see if lisinopril could affect male fertility (ability to get a woman pregnant) or increase the chance of birth defects above the background risk. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including lisinopril, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

C09AA03

C - Cardiovascular system；C09 - Agents acting on the renin-angiotensin system；C09A - Ace inhibitors, plain；C09AA - Ace inhibitors, plain；C09AA03 - Lisinopril

QC - Cardiovascular system；QC09 - Agents acting on the renin-angiotensin system；QC09A - Ace inhibitors, plain；QC09AA - Ace inhibitors, plain；QC09AA03 - Lisinopril

Lisinopril is an angiotensin converting enzyme inhibitor used to treat hypertension, heart failure, and myocardial infarction. Lisinopril is not a prodrug, and functions by inhibition of angiotensin converting enzyme as well as the renin angiotensin aldosterone system. It has a wide therapeutic index and a long duration of action as patients are generally given 10-80mg daily.

Angiotensin II constricts coronary blood vessels and is positively inotropic, which under normal circumstances, would increase vascular resistance and oxygen consumption. This action can eventually lead to myocyte hypertrophy and vascular smooth muscle cell proliferation. Lisinopril is an angiotensin converting enzyme inhibitor (ACEI), preventing the conversion of angiotensin I to angiotensin II. This action prevents myocyte hypertrophy and vascular smooth muscle cell proliferation seen in untreated patients. Increased levels of bradykinin also exhibit vasodilating effects for patients taking ACEIs. Lisinopril also inhibits renin's conversion of angiotensin to angiotensin I.

Orally active angiotensin-converting enzyme inhibitor.

Lisinopril inhibits angiotensin converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium.

The action of the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the consequences of myocardial reoxygenation and oxidative damage was assessed in cultured chick embryonic ventricular cardiomyocytes. Lisinopril, 10(-8) M to 10(-6) M, produced a significant (P < 0.05) dose-dependent enhancement of the restoration of contractile frequency occurring during myocardial reoxygenation but did not alter the depression in contractile frequency during hypoxia. Lisinopril significantly (P < 0.05) shifted the dose-response relationship of ammonium persulfate-induced reduction in cardiac contractile frequency. Lisinopril significantly (P < 0.05) reduced the effect of another oxidative agent, tertbutylhydroperoxide which produced a time-dependent reduction in cardiac contractile frequency. Lisinopril did not alter cardiac contractile frequency in the absence of hypoxia or ammonium persulfate or tertbutylhydroperoxide. The viability of cardiomyocytes, assessed by trypan blue exclusion, paralleled the changes in cardiac contractile frequency. Lisinopril significantly (P < 0.05) improved viability of cardiomyocytes exposed to either ammonium persulfate or tertbutylhydroperoxide. Lisinopril did not display any antioxidant properties against the free radical alpha,alpha-diphenyl-beta-picrylhydrazyl. These data suggest that lisinopril accelerates the recovery of cardiomyocytes during reoxygenation and blunts the effects of oxidative agents through mechanisms involving the endogenous renin angiotensin system and/or a direct cellular action.

Lisinopril has an effective half life of accumulation of 12.6h and a terminal half life of 46.7h.

The plasma half-life controlling accumulation during chronic administration is 12-13 hr and the absorbed drug is eliminated via glomerular filtration.

The accumulation half-life averages 12.6 hours despite a terminal serum half-life of approximately 40 hours /in healthy volunteers/.

Upon multiple dosing, lisinopril exhibits an effective half-life of 12 hours.

Lisinopril is not metabolized and is excreted as the unchanged drug.

Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine.

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LISINOPRIL ANHYDROUS

Established Pharmacologic Class [EPC] - Angiotensin Converting Enzyme Inhibitor

Mechanisms of Action [MoA] - Angiotensin-converting Enzyme Inhibitors

Lisinopril anhydrous is an Angiotensin Converting Enzyme Inhibitor. The mechanism of action of lisinopril anhydrous is as an Angiotensin-converting Enzyme Inhibitor.

LISINOPRIL

A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).

Lisinopril is 6-60% orally bioavailable with an average of 25% bioavailability. Lisinopril reaches a Cmax of 58ng/mL with a Tmax of 6-8h. Lisinopril's absorption is not affected by food.

Lisinopril is entirely eliminated exclusively in the urine.

The apparent volume of distribution of lisinopril is 124L.

A 30kg child has a typical clearance of 10L/h, which increases with renal function. The mean renal clearance of lisinopril in healthy adult males is 121mL/min.

Steady state is attained after two daily doses (every 24 hours) in healthy volunteers. The drug is not metabolized but is eliminated via the kidneys.

In dogs, lisinopril's bioavilability ranges from 24-50% with peak levels occurring approximately 4 hours after dosing. Lisinopril is distributed poorly into the CNS. It is unknown if it is distributed into maternal milk, but it does cross the placenta.

MEDICATION (VET)

MEDICATION

Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiotonic Agents

Use (kg; approx.) in Germany (2009): >5000；Use (kg) in USA (2002): 11300；Consumption (g per capita; approx.) in Germany (2009): 0.0611；Consumption (g per capita) in the USA (2002): 0.0401；Excretion rate: 1；Calculated removal (%): 75.1

Table: Lisinopril Preparations [Table#6361]

Table: Lisinopril Combinations Preparations [Table#6362]