Included as part of the "PRECAUTIONS" Section
Lotensin can cause fetal harm when administered to a pregnant woman. 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 [see Use In Specific Populations].
Angioedema And Anaphylactoid Reactions
Head and Neck Angioedema
Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx including some fatal reactions, have occured in patients treated with Lotensin. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Lotensin should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor [see CONTRAINDICATIONS]. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients.
Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin)
inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema [see DRUG INTERACTIONS].
Intestinal angioedema has occurred 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. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.
Anaphylactoid Reactions During Desensitization
Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.
Anaphylactoid Reactions During Dialysis
Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Impaired Renal Function
Monitor renal function periodically in patients treated with Lotensin. 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 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 Lotensin. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Lotensin.
Lotensin can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure, or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mm Hg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology.
In such patients, follow closely for the first 2 weeks of treatment and whenever the dose of benazepril or diuretic is increased. Avoid use of Lotensin in patients who are hemodynamically unstable after acute MI.
In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Lotensin may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs, correct by volume expansion.
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 [see DRUG INTERACTIONS].
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.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
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. When compared on the basis of body weights, this dose is 110 times the maximum recommended human dose. When compared on the basis of body surface areas, this dose is 18 and 9 times (rats and mice, respectively) the maximum recommended human dose (calculations assume a patient weight of 60 kg). 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. In doses of 50 to 500 mg/kg/day (6 to 60 times the maximum recommended human dose based on mg/m2 comparison and 37 to 375 times the maximum recommended human dose based on a mg/kg comparison), Lotensin had no adverse effect on the reproductive performance of male and female rats.
Use In Specific Populations
Lotensin can cause fetal harm when administered to a pregnant woman. 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. 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. When pregnancy is detected, discontinue Lotensin as soon as possible.
The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the general U.S. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Disease-associated Maternal and/or Embryo/fetal Risk
Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.
Fetal/Neonatal Adverse Reactions
Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. 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. 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. If oliguria or hypotension occur in neonates with a history of in utero exposure to Lotensin, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function.
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.
The antihypertensive effects of Lotensin have been evaluated in a double-blind study in pediatric patients 7 to 16 years of age [see CLINICAL PHARMACOLOGY]. The pharmacokinetics of Lotensin have been evaluated in pediatric patients 6 to 16 years of age [see CLINICAL PHARMACOLOGY]. Infants below the age of 1 year should not be given Lotensin because of the risk of effects on kidney development.
Safety and effectiveness of Lotensin have not been established in pediatric patients less than 6 years of age or in children with glomerular filtration rate < 30 mL/min/1.73m2 [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
Of the total number of patients who received benazepril in U.S. clinical studies of Lotensin, 18% were 65 or older while 2% were 75 or older. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Benazepril and benazeprilat are substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see DOSAGE AND ADMINISTRATION].
ACE inhibitors, including Lotensin, as monotherapy, have an effect on blood pressure that is less in Black patients than in non-Blacks.
Dose adjustment of Lotensin is required in patients undergoing hemodialysis or whose creatinine clearance is ≤ 30 mL/min. No dose adjustment of Lotensin is required in patients with creatinine clearance > 30 mL/min [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].