Benazepril HCl - General Information
Benazepril HCl, brand name Lotensin®, 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.
Pharmacology of Benazepril HCl
Benazepril HCl, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by estarases to its active Benazepril HClat, 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 HCl and Benazepril HClat 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.
Benazepril HCl for patients
Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE inhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.
Angioedema, including laryngeal edema, can occur at any time with treatment with ACE inhibitors. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, eyes, lips, or tongue, or difficulty in breathing) and to take no more drug until they have consulted with the prescribing physician.
Patients should be cautioned that lightheadedness can occur, especially during the first days of therapy, and it should be reported to the prescribing physician. Patients should be told that if syncope occurs, Lotensin should be discontinued until the prescribing physician has been consulted.
All patients should be cautioned that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.
Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.
Patients should be told to promptly report any indication of infection (e.g., sore throat, fever), which could be a sign of neutropenia.
Benazepril HCl Interactions
Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Lotensin. The possibility of hypotensive effects with Lotensin can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with Lotensin. If this is not possible, the starting dose should be reduced.
Potassium Supplements and Potassium-Sparing Diuretics
Lotensin can attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, they should be given with caution, and the patient’s serum potassium should be monitored frequently.
Interaction studies with warfarin and acenocoumarol failed to identify any clinically important effects on the serum concentrations or clinical effects of these anticoagulants.
Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. These drugs should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased.
No clinically important pharmacokinetic interactions occurred when Lotensin was administered concomitantly with hydrochlorothiazide, chlorthalidone, furosemide, digoxin, propranolol, atenolol, naproxen, or cimetidine.
Lotensin has been used concomitantly with beta-adrenergic-blocking agents, calcium-channel-blocking agents, diuretics, digoxin, and hydralazine, without evidence of clinically important adverse interactions. Benazepril, like other ACE inhibitors, has had less than additive effects with beta-adrenergic blockers, presumably because both drugs lower blood pressure by inhibiting parts of the renin-angiotensin system.
Benazepril HCl Contraindications
Lotensin is contraindicated in patients who are hypersensitive to this product or to any other ACE inhibitor.
Additional information about Benazepril HCl
Benazepril HCl Indication: For the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.
Mechanism Of Action: Benazepril HClat, the active metabolite of Benazepril HCl, 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. Benazepril HClat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.
Drug Interactions: Amiloride Increased risk of hyperkaliemia
Potassium Increased risk of hyperkaliemia
Lithium The ACE inhibitor increases serum levels of lithium
Spironolactone Increased risk of hyperkaliemia
Triamterene Increased risk of hyperkaliemia
Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
Drospirenone Increased risk of hyperkaliemia
Food Interactions: Take without regard to meals.
Food slows absorption without decreasing the quantity absorbed.
Generic Name: Benazepril
Synonyms: Not Available
Drug Category: Antihypertensive Agents; Angiotensin-converting Enzyme Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Benazepril: Benazepril HCl; Benazepril Hydrochloride; Benazeprilum [Latin]; Briem; Cibacen; Cibacene; Lotensin;
Absorption: Peak in plasma within 0.5-1.0 hours. The extent of absorption is at least 37% as determined by urinary recovery and is not significantly influenced by the presence of food in the GI tract.
Toxicity (Overdose): Symptoms of overdose include swelling of face, mouth, hands, or feet, trouble in swallowing or breathing (sudden), hoarseness, fever and chills.
Protein Binding: 96.7%
Biotransformation: Cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite, benazeprilat.
Half Life: 10-11 hours
Dosage Forms of Benazepril HCl: Tablet Oral
Chemical IUPAC Name: 2-[(3S)-3-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid
Chemical Formula: C24H28N2O5
Benazepril on Wikipedia: http://en.wikipedia.org/wiki/Benazepril
Organisms Affected: Humans and other mammals