Benazepril

424.49

424.49

UDM7Q7QWP8

DTXSID5022645

C61645

C09AA07|C - Cardiovascular system

95.9

1.3

Solid

1.3±0.1 g/cm3

148.5 °C

691.2°C at 760 mmHg

371.8±31.5 °C

1.608

1.05e-02 g/L

Store in original container in a cool dark place.

6.40X10-13 mm Hg at 25 °C (est)

D -159° (c = 1.2 in ethanol)

Henry's Law constant = 4.90X10-16 atm-cu m/mol at 25 °C (est)

Crystals from 3-pentanone + methanol (10:1). MW: 490.96. MP: 188-190 °C. Specific optical rotation: -141.0 deg at 25 °C/D (c = 0.9 in ethanol). Soluble in water, ethanol, methanol|Mol wt 396.44. MP: 270-272 °C. Specific optical rotation: -200.5 deg at 25 °C/D (c = 1 in 3 percent aqueous NH4OH) /Benazepril diacid/

22-24/25

Stable under recommended storage conditions. /Benazepril hydrochloride/

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. /Benazepril hydrochloride/

Incompatible materials: Strong oxidizing agents. /Benazepril hydrochloride/

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

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Benazepril hydrochloride/|Skin protection: Handle with gloves. /Benazepril hydrochloride/|Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. /Benazepril hydrochloride/|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). /Benazepril hydrochloride/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Benazepril hydrochloride/|Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /Benazepril hydrochloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. /Benazepril hydrochloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. /Benazepril hydrochloride/|Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Benazepril hydrochloride/|Appropriate engineering controls: General industrial hygiene practice. /Benazepril hydrochloride/|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. /Benazepril hydrochloride/|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.

The most common adverse effects include headache, dizziness, fatigue, somnolence, postural dizziness, nausea, and cough. The most likely symptom of overdosage is severe hypotension.|IDENTIFICATION AND USE: Benazepril is the nonsulfydryl angiotensin converting enzyme (ACE) inhibitor. It is used for treating hypertension and the management of heart failure in human patients and in animals. HUMAN STUDIES: Sensitivity reactions, including anaphylactoid reactions and angioedema (including laryngeal angioedema and tongue edema) are potentially fatal. Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction. Rare ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including benazepril, who develop jaundice or marked elevations of hepatic enzymes should discontinue the drug and receive appropriate monitoring. Human overdoses of benazepril have not been reported, but the most common manifestation of human benazepril overdosage is likely to be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Hypotension can be associated with electrolyte disturbances and renal failure. 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. ANIMAL STUDIES: Single oral doses of 3 g/kg benazepril were associated with significant lethality in mice. Rats, however, tolerated single oral doses of up to 6 g/kg. Reduced activity was seen at 1 g/kg in mice and at 5 g/kg in rats. In doses of 50-500 mg/kg/day benazepril had no adverse effect on the reproductive performance of male and female rats. No evidence of carcinogenicity was found when benazepril was administered to rats and mice for up to two years at doses of up to 150 mg/kg/day. No mutagenic activity was detected in the Ames test in bacteria (with or without metabolic activation), in an in vitro test for forward mutations in cultured mammalian cells, or in a nucleus anomaly test.

Benazepril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations (

Because ACE inhibitors may promote kinin-mediated prostaglandin synthesis and/or release, concomitant administration of drugs that inhibit prostaglandin synthesis (e.g., aspirin, ibuprofen) may reduce the blood pressure response to ACE inhibitors, including enalapril. Limited data indicate that concomitant administration of ACE inhibitors with nonsteroidal anti-inflammatory agents (NSAIAs) occasionally may result in acute reduction of renal function; however, the possibility cannot be ruled out that one drug alone may cause such an effect. ... Aspirin and other NSAIAs also can attenuate the hemodynamic actions of ACE inhibitors in patients with congestive heart failure. Because ACE inhibitors share and enhance the effects of the compensatory hemodynamic mechanisms of heart failure, with aspirin and other NSAIAs interacting with the compensatory mechanisms rather than with a given ACE inhibitor per se, these desirable mechanisms are particularly susceptible to the interaction and a subsequent potential loss of clinical benefits. As a result, the more severe the heart failure and the more prominent the compensatory mechanisms, the more appreciable the interaction between NSAIAs and ACE inhibitors. Even if optimal dosage of an ACE inhibitor is used in the treatment of congestive heart failure, the potential cardiovascular and survival benefit may not be seen if the patient is receiving an NSAIA concomitantly. In several multicenter studies, concomitant admin of a NSAIA (i.e., a single 350-mg dose of aspirin) in patients with congestive heart failure inhibited favorable hemodynamic effects associated with ACE inhibitors, attenuating the favorable effects of these drugs on survival and cardiovascular morbidity. /ACE inhibitors/|Patients receiving coadministration of ACE inhibitor and mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema. Monitor for signs of angioedema. /ACE inhibitors/|Dual Blockade of the Renin-Angiotensin System (RAS) with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Lotensin and other agents that affect the RAS. Do not coadminister aliskiren with Lotensin in patients with diabetes. Avoid use of aliskiren with Lotensin in patients with renal impairment (GFR < 60 mL/min).|Hypoglycemia has been reported rarely in diabetic patients receiving angiotensin-converting enzyme (ACE) inhibitors, including benazepril, concomitantly with insulin or oral antidiabetic agents. Patients receiving these drugs concomitantly should be informed of the possibility of hypoglycemia and monitored appropriately.|For more Interactions (Complete) data for Benazepril (10 total), please visit the HSDB record page.

Benazepril is 96.7% protein bound while benazeprilat is 95.3% protein bound.

Benazepril is indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.|FDA Label

Benazepril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the therapy of hypertension. Benazepril is associated with a low rate of transient serum aminotransferase elevations and has been linked to rare instances of acute liver injury.

Angiotensin-Converting Enzyme Inhibitors

/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Benazepril is included in the database.|Lotensin is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ... It may be used alone or in combination with thiazide diuretics. /Included in US product label/|ACE inhibitors have been used in the management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and beta-blockers. /Angiotensin-converting enzyme (ACE) inhibitors; NOT included in US product label/|Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists have been shown to slow the rate of progression of renal disease in patients with diabetes mellitus and persistent albuminuria, and use of a drug from either class is recommended in such patients with modestly elevated (30-300 mg/24 hours) or higher (exceeding 300 mg/24 hours) levels of urinary albumin excretion. The usual precautions of ACE inhibitor or angiotensin II receptor antagonist therapy in patients with substantial renal impairment should be observed. /Angiotensin-converting enzyme (ACE) inhibitors; NOT included in US product label/|For more Therapeutic Uses (Complete) data for Benazepril (7 total), please visit the HSDB record page.

/BOXED WARNING/ When pregnancy is detected, discontinue Lotensin as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.|Rare angiotensin-converting enzyme (ACE) inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice; may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including benazepril, who develop jaundice or marked elevations of hepatic enzymes should discontinue the drug and receive appropriate monitoring.|Serum potassium should be monitored periodically in patients receiving Lotensin. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes.|Adverse effects reported in greater than 1% of patients receiving benazepril include headache, dizziness, fatigue, somnolence, postural dizziness, nausea, and cough. Adverse effects reported in greater than 1% of patients receiving benazepril in fixed combination with hydrochlorothiazide include dizziness, fatigue, postural dizziness, headache, cough, hypertonia, vertigo, nausea, impotence, and somnolence. Adverse effects reported in greater than 1% of patients receiving benazepril in fixed combination with amlodipine include cough, headache, dizziness, and edema.|For more Drug Warnings (Complete) data for Benazepril (16 total), please visit the HSDB record page.

Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by esterases to its active Benazeprilat, is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients. Benazepril and Benazeprilat inhibit 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.

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. (See all compounds classified as Angiotensin-Converting Enzyme Inhibitors.)|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. (See all compounds classified as Antihypertensive Agents.)

Bioavailability of oral dosing is 3% to 4% in horses. In humans at least 37% of oral benazepril is absorbed and reaches peak plasma concentration in 0.5 hours to 1 hour. Other studies have shown a peak plasma concentration at a median of 1.5 hours.|Benazepril and benazeprilat are cleared predominantly by renal excretion in healthy subjects with normal renal function. Nonrenal (i.e., biliary) excretion accounts for approximately 11%-12% of benazeprilat excretion in healthy subjects.|The final population pharmacokinetic model in one study estimated the volume of distribution to be 203±69.9L.|The final population pharmacokinetic model of one study estimates the clearance to be 129±30.0L.|/MILK/ Minimal amounts of unchanged benazepril and of benazeprilat are excreted into the breast milk of lactating women treated with benazepril. A newborn child ingesting entirely breast milk would receive less than 0.1% of the mg/kg maternal dose of benazepril and benazeprilat.|Benazepril and benazeprilat are cleared predominantly by renal excretion. About 37% of an orally administered dose was recovered in urine as benazeprilat (20%), benazeprilat glucuronide (8%), benazepril glucuronide (4%) and as trace amounts of benazepril. Nonrenal (i.e., biliary) excretion accounts for approximately 11% - 12% of benazeprilat excretion. The effective half-life of benazeprilat following once daily repeat oral administration of benazepril hydrochloride is 10 to 11 hours. Thus, steady-state concentrations of benazeprilat should be reached after 2 or 3 doses of benazepril hydrochloride given once daily. Accumulation ratio based on AUC of benazeprilat was 1.19 following once daily administration.

Cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite, benazeprilat. Benazepril and benazeprilat are conjugated to glucuronic acid prior to urinary excretion.|Benazepril and benazeprilat are cleared predominantly by renal excretion. About 37% of an orally administered dose was recovered in urine as benazeprilat (20%), benazeprilat glucuronide (8%), benazepril glucuronide (4%) and as trace amounts of benazepril. Nonrenal (i.e., biliary) excretion accounts for approximately 11% - 12% of benazeprilat excretion. The effective half-life of benazeprilat following once daily repeat oral administration of benazepril hydrochloride is 10 to 11 hours. Thus, steady-state concentrations of benazeprilat should be reached after 2 or 3 doses of benazepril hydrochloride given once daily. Accumulation ratio based on AUC of benazeprilat was 1.19 following once daily administration.|After oral dosing in healthy dogs, benazepril is rapidly absorbed and converted into the active metabolite benazeprilat with peak levels of benazeprilat occurring approximately 75 minutes after dosing.|Benazepril is almost completely metabolized to benazeprilat by cleavage of the ester group (primarily in liver). Both benazepril and benazeprilat undergo glucuronidation.

The half life of the prodrug benazepril is 2.7±8.5h. The half life of the active metabolite benazeprilat is 22.3±9.2h The accumulation half life of benazepril is 10 to 11 hours.|The elimination half life of benazeprilat is approximately 3.5 hours in healthy dogs. /Benazeprilat/|The effective half-life of benazeprilat following once daily repeat oral administration of benazepril hydrochloride is 10 to 11 hours. /Benazeprilat/

Benazeprilat, the active metabolite of Benazepril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion.

/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 Benazepril (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ Renal and hemodynamic effects of diet alone and of single oral doses of the nonsulfydryl angiotensin converting enzyme (ACE) inhibitor, benazepril (10 mg), were investigated in eight healthy volunteers under stable conditions of high salt intake (300 mmol NaCl/day) and low salt intake (10 mmol NaCl/day), in a double blind, placebo controlled study. There were no changes in blood pressure between the two dietary extremes either during the run-in period or once sodium balance had been achieved ... Glomerular filtration rates were found to be similar irrespective of the state of salt balance. Both plasma urate concentration and plasma renin activity were significantly elevated in the low salt compared to high salt state. Benazepril caused a greater fall in blood pressure in the sodium depleted state. Significant increases in the mean renal plasma flow, in the order of 15-20%, were seen over 6 hr postbenazepril when compared with placebo response, regardless of the level of salt intake. Glomerular filtration rate over the same period remained unaltered. Benazepril doubled the urinary excretion of sodium over the first 4 hours after dosing whilst on the low salt diet; the equivalent increase during salt loading was approximately 20%. These results suggest that benazepril may exert direct effects on renal tubular function additional to those achieved through ACE blockade.|/SIGNS AND SYMPTOMS/ Sensitivity reactions, including anaphylactoid reactions and angioedema (including laryngeal angioedema and tongue edema) are potentially fatal. Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, benazepril should be discontinued and appropriate therapy (e.g., epinephrine) should be initiated immediately.|/SIGNS AND SYMPTOMS/ Human overdoses of benazepril have not been reported, but the most common manifestation of human benazepril overdosage is likely to be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Hypotension can be associated with electrolyte disturbances and renal failure.|For more Human Toxicity Excerpts (Complete) data for Benazepril (10 total), please visit the HSDB record page.

benazapril

Table: Benazepril Hydrochloride Preparations [Table#6714]|Table: Benazepril Hydrochloride Combination Preparations [Table#6715]

GC-MS determination in plasma and urine.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan