Lotensin tablet

Lotensin tablet®
Black Box Warning
Adult Indications and Dosage
Pediatric Indications and Dosage
Contraindications
Warnings
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration and Monitoring
IV Compatibility
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient information
Precautions with Alcohol
Look-Alike Drug Names
Drug Shortage Status
Price

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2], Ahmed Zaghw, M.D. [3]

For information about Benazepril, click here.

Disclaimer

WikiDoc Drug Project is a constellation of drug information for healthcare providers and patients vigorously vetted on the basis of FDA package insert, MedlinePlus, Practice Guidelines, Scientific Statements, and scholarly medical literature. The information provided is not a medical advice or treatment. WikiDoc does not promote any medication or off-label use of drugs. Please read our full disclaimer here.

Black Box Warning

WARNING: FETAL TOXICITY See full prescribing information for complete 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.

Overview

Lotensin tablet is an angiotensin converting enzyme inhibitor drug that is FDA approved for the treatment of hypertension. There is a Black Box Warning for this drug as shown here. Common adverse reactions include cough, dizziness, fatigue, and headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypertension

• Dosing Information

Initial dose (not receiving a diuretic): Lotensin tablet 10 mg PO qd

Initial dose (concurrent diuretic use): the diuretic should be discontinued 2 to 3 days prior to beginning therapy with Lotensin tablet, if blood pressure is not controlled with Lotensin tablet alone, diuretic therapy should be resumed. If the diuretic cannot be discontinued, an initial dose of 5 mg Lotensin tablet should be used.

Maintenance dose: Lotensin tablet 20—40 mg PO qd or Lotensin tablet 10—20 mg PO bid (MAX 80 mg/day)

Lotensin is indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.

The recommended initial dose for patients not receiving a diuretic is 10 mg once a day. The usual maintenance dosage range is 20-40 mg per day administered as a single dose or in two equally divided doses. A dose of 80 mg gives an increased response, but experience with this dose is limited. The divided regimen was more effective in controlling trough (pre-dosing) blood pressure than the same dose given as a once-daily regimen. Dosage adjustment should be based on measurement of peak (2-6 hours after dosing) and trough responses. If a once-daily regimen does not give adequate trough response, an increase in dosage or divided administration should be considered. If blood pressure is not controlled with Lotensin alone, a diuretic can be added.

Total daily doses above 80 mg have not been evaluated.

Concomitant administration of Lotensin with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases of serum potassium.

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of Lotensin. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with Lotensin (see Warnings). Then, if blood pressure is not controlled with Lotensin alone, diuretic therapy should be resumed.

If the diuretic cannot be discontinued, an initial dose of 5 mg Lotensin should be used to avoid excessive hypotension.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Heart Failure, Stage B

• Developed by: American College of Cardiology (ACC) and American Heart Association (AHA)

• Class of Recommendation: Class I

• Level of Evidence: Level A

• Dosing Information

In all patients with a recent or remote history of MI or ACS and reduced EF, ACE inhibitors should be used to prevent symptomatic HF and reduce mortality.

Non–Guideline-Supported Use

Diabetic Nephropathy

• Dosing Information

Benazepril 10 mg PO qd

Kidney Disease, Non-Diabetic

• Dosing Information

Benazepril 10 mg PO qd

Condition 3

• Dosing Information

(Dosage)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Hypertension

• Dosing Information

Initial dose: Lotensin tablet 0.2 mg/kg PO qd (for pediatric patients above the age of 6 years)

Lotensin is indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.

In children, doses of Lotensin between 0.1 and 0.6 mg/kg once daily have been studied, and doses greater than 0.1 mg/kg were shown to reduce blood pressure (see Pharmacodynamics). Based on this, the recommended starting dose of Lotensin is 0.2 mg/kg once per day as monotherapy. Doses above 0.6 mg/kg (or in excess of 40 mg daily) have not been studied in pediatric patients.

For pediatric patients who cannot swallow tablets, or for whom the calculated dosage (mg/kg) does not correspond to the available tablet strengths for Lotensin, follow the suspension preparation instructions to administer benazepril HCl as a suspension.

Treatment with Lotensin is not advised for children below the age of 6 years (see Pediatric Use) and in pediatric patients with glomerular filtration rate <30 mL, as there are insufficient data available to support a dosing recommendation in these groups.

Off-Label Use and Dosage (Pediatric)

There is limited information about Off-Label Use and Dosage of Lotensin tablet in pediatric patients.

Contraindications

• Hypersensitivity to benazapril or to any other ACE inhibitor

• History of angioedema with or without previous ACE inhibitor treatment

Warnings

Anaphylactoid and Possibly Related Reactions

Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including Lotensin) may be subject to a variety of adverse reactions, some of them serious.

Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors. In U.S. clinical trials, symptoms consistent with angioedema were seen in none of the subjects who received placebo and in about 0.5% of the subjects who received Lotensin. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with Lotensin should be discontinued and appropriate therapy instituted immediately. Where there is involvement of the tongue, glottis, or larynx, likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine injection 1:1000 (0.3 mL to 0.5 mL) should be promptly administered (see ADVERSE REACTIONS).

Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to nonblacks.

Intestinal Angioedema: Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Anaphylactoid Reactions During Desensitization: Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

Anaphylactoid Reactions During Membrane Exposure: Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption (a procedure dependent upon devices not approved in the United States).

Hypotension

Lotensin can cause symptomatic hypotension. Like other ACE inhibitors, benazepril has been only rarely associated with hypotension in uncomplicated hypertensive patients. Symptomatic hypotension is most likely to occur in patients who have been volume-and/or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume-and/or salt-depletion should be corrected before initiating therapy with Lotensin.

In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or azotemia and, rarely, with acute renal failure and death. In such patients, Lotensin therapy should be started under close medical supervision; they should be followed closely for the first 2 weeks of treatment and whenever the dose of benazepril or diuretic is increased.

If hypotension occurs, the patient should be placed in a supine position, and, if necessary, treated with intravenous infusion of physiological saline. Lotensin treatment usually can be continued following restoration of blood pressure and volume.

Fetal toxicity

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 Lotensin as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Lotensin, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Lotensin for hypotension, oliguria, and hyperkalemia [see Precautions, Pediatric Use].

No teratogenic effects of Lotensin were seen in studies of pregnant rats, mice, and rabbits. On a mg/m2 basis, the doses used in these studies were 60 times (in rats), 9 times (in mice), and more than 0.8 times (in rabbits) the maximum recommended human dose (assuming a 50-kg woman). On a mg/kg basis these multiples are 300 times (in rats), 90 times (in mice), and more than 3 times (in rabbits) the maximum recommended human dose.

Hepatic Failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Adverse Reactions

Clinical Trials Experience

Condition 1

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Condition 1

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Postmarketing Experience

(Description)

Drug Interactions

• Drug 1
• Drug 2
• Drug 3
• Drug 4
• Drug 5

Drug 1

(Description)

Drug 2

(Description)

Drug 3

(Description)

Drug 4

(Description)

Drug 5

(Description)

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): D

Fetal toxicity

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 Lotensin as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Lotensin, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Lotensin for hypotension, oliguria, and hyperkalemia [see Precautions, Pediatric Use].

No teratogenic effects of Lotensin were seen in studies of pregnant rats, mice, and rabbits. On a mg/m2 basis, the doses used in these studies were 60 times (in rats), 9 times (in mice), and more than 0.8 times (in rabbits) the maximum recommended human dose (assuming a 50-kg woman). On a mg/kg basis these multiples are 300 times (in rats), 90 times (in mice), and more than 3 times (in rabbits) the maximum recommended human dose.

Labor and Delivery

FDA Package Insert for Lotensin tablet contains no information regarding Labor and Delivery.

Nursing Mothers

FDA Package Insert for Lotensin tablet contains no information regarding Nursing Mothers.

Pediatric Use

Neonates with a history of in utero exposure to Lotensin

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Benazepril, which crosses the placenta, can theoretically be removed from the neonatal circulation by these means; there are occasional reports of benefit from these maneuvers with another ACE inhibitor, but experience is limited.

The antihypertensive effects of Lotensin have been evaluated in a double-blind study in pediatric patients 7 to 16 years of age (see Pharmacodynamics). The pharmacokinetics of Lotensin have been evaluated in pediatric patients 6 to 16 years of age (see Pharmacokinetics) . Lotensin was generally well tolerated and adverse effects were similar to those described in adults. (See Adverse Reactions). The long-term effects of benazepril on growth and development have not been studied. Infants below the age of 1 year should not be given Lotensin because of the risk of effects on kidney development.

Treatment with Lotensin is not recommended in pediatric patients less than 6 years of age (see Adverse Reactions), and in children with glomerular filtration rate <30 mL/min as there are insufficient data available to support a dosing recommendation in these groups. (See Pharmacokinetics.)

Geriatric Use

FDA Package Insert for Lotensin tablet contains no information regarding Geriatric Use.

Gender

FDA Package Insert for Lotensin tablet contains no information regarding Gender.

Race

FDA Package Insert for Lotensin tablet contains no information regarding Race.

Renal Impairment

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors, including Lotensin, may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. In a small study of hypertensive patients with renal artery stenosis in a solitary kidney or bilateral renal artery stenosis, treatment with Lotensin was associated with increases in blood urea nitrogen and serum creatinine; these increases were reversible upon discontinuation of Lotensin or diuretic therapy, or both. When such patients are treated with ACE inhibitors, renal function should be monitored during the first few weeks of therapy. Some hypertensive patients with no apparent preexisting renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when Lotensin has been given concomitantly with a diuretic. This is more likely to occur in patients with preexisting renal impairment. Dosage reduction of Lotensin and/or discontinuation of the diuretic may be required. Evaluation of the hypertensive patient should always include assessment of renal function (see DOSAGE AND ADMINISTRATION).

Hepatic Impairment

FDA Package Insert for Lotensin tablet contains no information regarding Hepatic Impairment.

Females of Reproductive Potential and Males

FDA Package Insert for Lotensin tablet contains no information regarding Females of Reproductive Potential and Males.

Immunocompromised Patients

FDA Package Insert for Lotensin tablet contains no information regarding Immunocompromised Patients.

Others

Hyperkalemia: In clinical trials, hyperkalemia (serum potassium at least 0.5 mEq/L greater than the upper limit of normal) occurred in approximately 1% of hypertensive patients receiving Lotensin. In most cases, these were isolated values which resolved despite continued therapy. 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, which should be used cautiously, if at all, with Lotensin (see Drug Interactions).

Cough: Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Surgery/Anesthesia: In patients undergoing surgery or during anesthesia with agents that produce hypotension, benazepril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.

Administration and Monitoring

Administration

Oral

Monitoring

Hypertensive patients with renal artery stenosis in a solitary kidney or bilateral renal artery stenosis

When hypertensive patients with renal artery stenosis in a solitary kidney or bilateral renal artery stenosis patients are treated with ACE inhibitors, renal function should be monitored during the first few weeks of therapy.

Potassium Supplements and Potassium-Sparing Diuretics

Concomitant potassium supplements and potassium-sparing diuretics use with Lotensin may effect potassium levels. Monitor potassium periodically.

Condition 3

(Description regarding monitoring, from Warnings section)

IV Compatibility

FDA Package Insert for Lotensin tablet contains no information regarding IV Compatibility.

Overdosage

Acute Overdose

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, which can be associated with electrolyte disturbances and renal failure.

Laboratory determinations of serum levels of benazepril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of benazepril overdose.

Management

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of benazepril and its metabolites. Benazepril is only slightly dialyzable, but dialysis might be considered in overdosed patients with severely impaired renal function (see WARNINGS).

Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of benazepril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of benazepril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat benazepril overdose by infusion of normal saline solution.

If ingestion is recent, activated charcoal should be considered. Gastric decontamination (e.g., vomiting, gastric lavage) may be considered in individual cases, in the early period after ingestion.

Patients should be closely monitored for blood pressure and clinical symptoms. Supportive management should be employed to ensure adequate hydration and to maintain systemic blood pressure.

In the case of marked hypotension, physiological saline solution should be administered intravenously; depending on the clinical situation the use of vasopressors (e.g., catecholamines i.v.) may be considered.

Chronic Overdose

Signs and Symptoms

FDA Package Insert for Lotensin tablet contains no information regarding Chronic Overdose.

Management

FDA Package Insert for Lotensin tablet contains no information regarding Chronic Overdose.

Pharmacology

Mechanism of Action

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.

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. Hypertensive patients treated with Lotensin alone for up to 52 weeks had elevations of serum potassium of up to 0.2 mEq/L. Similar patients treated with Lotensin and hydrochlorothiazide for up to 24 weeks had no consistent changes in their serum potassium (see PRECAUTIONS).

Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. In animal studies, benazepril had no inhibitory effect on the vasopressor response to angiotensin II and did not interfere with the hemodynamic effects of the autonomic neurotransmitters acetylcholine, epinephrine, and norepinephrine. ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Lotensin remains to be elucidated.

While the mechanism through which benazepril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, benazepril has an antihypertensive effect even in patients with low-renin hypertension (see INDICATIONS AND USAGE).

Structure

Benazepril hydrochloride is a white to off-white crystalline powder, soluble (>100 mg/mL) in water, in ethanol, and in methanol. Its chemical name is benazepril 3-[[1-(ethoxy-carbonyl)-3-phenyl-(1S)-propyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-(3S)-benzazepine-1-acetic acid monohydrochloride; its structural formula is

Its empirical formula is C24H28N2O5•HCl, and its molecular weight is 460.96.

Benazeprilat, the active metabolite of benazepril, is a non-sulfhydryl angiotensin-converting enzyme inhibitor. Benazepril is converted to benazeprilat by hepatic cleavage of the ester group.

Lotensin is supplied as tablets containing 5 mg, 10 mg, 20 mg, and 40 mg of benazepril hydrochloride for oral administration. The inactive ingredients are colloidal silicon dioxide, crospovidone, hydrogenated castor oil (5-mg, 10-mg, and 20-mg tablets), hypromellose, iron oxides, lactose, magnesium stearate (40-mg tablets), microcrystalline cellulose, polysorbate 80, propylene glycol (5-mg and 40-mg tablets), starch, talc, and titanium dioxide.

Pharmacodynamics

Single and multiple doses of 10 mg or more of Lotensin cause inhibition of plasma ACE activity by at least 80%-90% for at least 24 hours after dosing. Pressor responses to exogenous angiotensin I were inhibited by 60%-90% (up to 4 hours post-dose) at the 10-mg dose.

Pharmacokinetics

Following oral administration of Lotensin, peak plasma concentrations of benazepril are reached 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.

Cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite, benazeprilat. Peak plasma concentrations of benazeprilat are reached 1-2 hours after drug intake in the fasting state and 2-4 hours after drug intake in the nonfasting state. The serum protein binding of benazepril is about 96.7% and that of benazeprilat about 95.3%, as measured by equilibrium dialysis; on the basis of in vitro studies, the degree of protein binding should be unaffected by age, hepatic dysfunction, or concentration (over the concentration range of 0.24-23.6 µmol/L).

Benazepril is almost completely metabolized to benazeprilat, which has much greater ACE inhibitory activity than benazepril, and to the glucuronide conjugates of benazepril and benazeprilat. Only trace amounts of an administered dose of Lotensin can be recovered in the urine as unchanged benazepril, while about 20% of the dose is excreted as benazeprilat, 4% as benazepril glucuronide, and 8% as benazeprilat glucuronide.

The kinetics of benazepril are approximately dose-proportional within the dosage range of 10-80 mg.

In adults, the effective half-life of accumulation of benazeprilat following multiple dosing of benazepril hydrochloride is 10-11 hours. Thus, steady-state concentrations of benazeprilat should be reached after 2 or 3 doses of benazepril hydrochloride given once daily.

The kinetics did not change, and there was no significant accumulation during chronic administration (28 days) of once-daily doses between 5 mg and 20 mg. Accumulation ratios based on AUC and urinary recovery of benazeprilat were 1.19 and 1.27, respectively.

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. In patients with renal failure, biliary clearance may compensate to an extent for deficient renal clearance.

In patients with renal insufficiency, the disposition of benazepril and benazeprilat in patients with mild-to-moderate renal insufficiency (creatinine clearance >30 mL/min) is similar to that in patients with normal renal function. In patients with creatinine clearance ≤30 mL/min, peak benazeprilat levels and the initial (alpha phase) half-life increase, and time to steady state may be delayed (see DOSAGE AND ADMINISTRATION).

When dialysis was started 2 hours after ingestion of 10 mg of benazepril, approximately 6% of benazeprilat was removed in 4 hours of dialysis. The parent compound, benazepril, was not detected in the dialysate.

In patients with hepatic insufficiency (due to cirrhosis), the pharmacokinetics of benazeprilat are essentially unaltered. The pharmacokinetics of benazepril and benazeprilat do not appear to be influenced by age.

In pediatric patients, (N=45) hypertensive, age 6 to 16 years, given multiple daily doses of Lotensin (0.1 to 0.5 mg/kg), the clearance of benazeprilat for children 6 to 12 years old was 0.35 L/hr/kg, more than twice that of healthy adults receiving a single dose of 10 mg (0.13 L/hr/kg). In adolescents, it was 0.17 L/hr/kg, 27% higher than that of healthy adults. The terminal elimination half-life of benazeprilat in pediatric patients was around 5 hours, one-third that observed in adults.

Nonclinical Toxicology

FDA Package Insert for Lotensin tablet contains no information regarding Nonclinical Toxicology.

Clinical Studies

Hypertension

Adult

In single-dose studies, Lotensin lowered blood pressure within 1 hour, with peak reductions achieved 2-4 hours after dosing. The antihypertensive effect of a single dose persisted for 24 hours. In multiple-dose studies, once-daily doses of 20-80 mg decreased seated pressure (systolic/diastolic) 24 hours after dosing by about 6-12/4-7 mmHg. The trough values represent reductions of about 50% of that seen at peak.

Four dose-response studies using once-daily dosing were conducted in 470 mild-to-moderate hypertensive patients not using diuretics. The minimal effective once-daily dose of Lotensin was 10 mg; but further falls in blood pressure, especially at morning trough, were seen with higher doses in the studied dosing range (10-80 mg). In studies comparing the same daily dose of Lotensin given as a single morning dose or as a twice-daily dose, blood pressure reductions at the time of morning trough blood levels were greater with the divided regimen.

The antihypertensive effects of Lotensin were not appreciably different in patients receiving high- or low-sodium diets.

In normal human volunteers, single doses of benazepril caused an increase in renal blood flow but had no effect on glomerular filtration rate. Use of Lotensin in combination with thiazide diuretics gives a blood-pressure-lowering effect greater than that seen with either agent alone. By blocking the renin-angiotensin-aldosterone axis, administration of Lotensin tends to reduce the potassium loss associated with the diuretic.

Pediatric

In a clinical study of 107 pediatric patients, 7 to 16 years of age, with either systolic or diastolic pressure above the 95th percentile, patients were given 0.1 or 0.2 mg/kg then titrated up to 0.3 or 0.6 mg/kg with a maximum dose of 40 mg once daily. After four weeks of treatment, the 85 patients whose blood pressure was reduced on therapy were then randomized to either placebo or benazepril and were followed up for an additional two weeks. At the end of two weeks, blood pressure (both systolic and diastolic) in children withdrawn to placebo rose by 4 to 6 mmHg more than in children on benazepril. No dose-response was observed for the three doses.

How Supplied

Lotensin is available in tablets of 5 mg, 10 mg, 20 mg, and 40 mg, packaged with a desiccant in bottles of 100 tablets.

Each tablet is imprinted with LOTENSIN on one side and the tablet strength (“5,” “10,” “20,” or “40”) on the other.

• National Drug Code (NDC):

put table here

• Storage: Do not store above 30°C (86°F). Protect from moisture. Dispense in tight container (USP).
• Manufactured by: Novartis Pharmaceuticals Corporation, Suffern, New York 10901
• Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936

Images

Drug Images

Package and Label Display Panel

File:Lotensin tablet 5mg Display Panel.png

Patient Information

Patient Information from FDA

Pregnancy: Female patients of childbearing age should be told about the consequences of exposure to Lotensin during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

Angioedema: 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.

Symptomatic Hypotension: 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.

Hyperkalemia: Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.

Neutropenia: Patients should be told to promptly report any indication of infection (e.g., sore throat, fever), which could be a sign of neutropenia.

Patient Information from NLM

For patient information about benazepril from NLM, click here.

Precautions with Alcohol

Alcohol-Lotensin tablet interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Look-Alike Drug Names

There are no look-alike drug names published in the ISMP Medication Safety Alert.

Drug Shortage Status

Price

References