Drug information of Benazepril

Benazepril


Benazepril is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.

Mechanism of effect

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.

Pharmacodynamic

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.

Pharmacokinetics

Bioavailability: 37%

Onset: 1-2 hr (peak effect with 2-20 mg dose)

Duration: 24 hr (with 5-20 mg dose)

Peak plasma time: 0.5-1 hr (parent drug)

Protein bound: 95-97%

Vd: 8.7 L

Metabolite: Benazeprilat (active)

Half-life: 10-11 hr

Dialyzable: Minimal

Excretion: Urine (primarily); bile (11-12%)

Drug indications

Hypertension

Dosage

Adult

Hypertension

Patients taking a diuretic: 5 mg/day PO initially, to avoid excessive hypotension

Patients not taking a diuretic: 10 mg/day PO

May increase to maintenance dose of 20-40 mg/day PO qDay or divided q12hr

Pediatric

Hypertension

<6 years: Safety and efficacy not established

≥6 years: 0.1-0.6 mg/kg PO qDay initially, not to exceed 5 mg/day; THEN 

Adjust dose based on BP response; not to exceed 0.6 mg/kg/day or 40 mg/day

Drug contraindications

Hypersensitivity

History of hereditary or idiopathic angioedema Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan Concomitant administration with aliskiren in patients with diabetes mellitus or with renal impairment

Side effects

Headache , nausea , vertigo , difficulty urinating , tiredness

ARF if renal artery stenosis

Alerts

Excessive hypotension with or without syncope may occur if hypovolemia/hyponatremia present or if coadministered with diuretics

Dual blockade of the renin-angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure), compared with monotherapy

Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy; avoid combined use of RAS inhibitors; closely monitor blood pressure, renal function and electrolytes in patients on benazepril and other agents that affect the RAS

Not for coadministration with aliskiren in patients with diabetes; avoid use of aliskiren with benazepril in patients with renal impairment (GFR <60 ml/min/1.73 m²)

ACE inhibition causes increased bradykinin levels, which putatively mediates angioedema (higher incidence in black patients)

Cough may occur due to increased bradykinin levels

Cholestatic jaundice reported with use

Avoid use in bilateral renal artery stenosis

Angioedema may occur; coadministration with mTOR inhibitors (eg, temsirolimus) may increase risk for angioedema; discontinue therapy and treat appropriately if angioedema occurs

Renal impairment may occur

Rare cases of agranylocytosis reported ACE inhibitor therapy

May cause hypotension during surgery; additive hypotensive effects may occur with anesthetic agents that produce hypotension (correct by volume expansion)

Deterioration of renal function may occur; may consider discontinuation of therapy in patients with progressive and/or significant deterioration in renal function

Monitor for jaundice or signs of liver failure

Black Box Warnings

Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury and/or death

Points of recommendation

  • Tell all of your health care providers that you take benazepril. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how benazepril affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
  • Have your blood pressure checked often. Talk with your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • If you are on a low-salt or salt-free diet, talk with your doctor.
  • If you are taking a salt substitute that has potassium in it, a potassium-sparing diuretic, or a potassium product, talk with your doctor.
  • Low white blood cell counts have happened with captopril, a drug like this one. This may lead to more chance of getting an infection. Most of the time, this has happened in people with kidney problems, mainly if they have certain other health problems. Call your doctor right away if you have signs of infection like fever, chills, or sore throat. Talk with your doctor.
  • If you are taking benazepril and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • Talk with your doctor before you drink alcohol.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • Tell your doctor if you have too much sweat, fluid loss, throwing up, or loose stools. This may lead to low blood pressure.
  • If you are taking lithium, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with benazepril.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Take with or without food.
  • Take benazepril at the same time of day.
  • Keep taking benazepril as you have been told by your doctor or other health care provider, even if you feel well.
  • To gain the most benefit, do not miss doses.
  • Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
  • A liquid (suspension) can be made if you cannot swallow pills. Talk with your doctor or pharmacist.
  • If a liquid (suspension) is made, shake well before use.
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Pregnancy level

D

category D


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