Benazepril

Benazepril is used for: Hypertension

Oral Hypertension Adult: Initially, 10 mg once daily. Maintenance: 20-40 mg/day as a single or in 2 divided doses. Max: 80 mg/day. Patients on diuretics: Initially, 5 mg once daily. Heart failure Adult: Initially, 2.5 mg once daily adjusted according to response to max 20 mg/day.

Oral Hypertension <6 years: Safety and efficacy not established Child: >6 yr 0.2 mg/kg once daily. Maintenance: 0.6 mg/kg once daily. Max: 40 mg/day.

Renal impairment: CrCl (ml/min) Dosage Recommendation <30 Initially, 5 mg once daily. Max: 40 mg/day.

May be taken with or without food.

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

Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury and/or death 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 Discontinue immediately if pregnancy occurs (see Black Box Warnings) ACE inhibitors are less effective in black patients 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 Monitoring Parameters Periodic monitoring of serum creatinine, and K levels. Monitor renal function periodically. Monitor blood pressure after initiation. Monitor serum potassium periodically. Monitor for jaundice or signs of liver failure.

Pregnancy Benazepril can cause fetal harm when administered to a pregnant woman; use of drugs that act on renin-angiotensin system during 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 first trimester have not distinguished drugs affecting renin-angiotensin system from other antihypertensive agents; when pregnancy is detected, discontinue Benazepril as soon as possible Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly Oligohydramnios in pregnant women who use drugs affecting renin-angiotensin system in second and third trimesters of pregnancy can result in 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 renin-angiotensin system for a particular patient, apprise the mother of potential risk to fetus Perform serial ultrasound examinations to assess intra-amniotic environment; fetal testing may be appropriate, based on week of pregnancy; patients and physicians should be aware, however, that oligohydramnios may not appear until after fetus has sustained irreversible injury; closely observe infants with histories of in utero exposure to drug for hypotension, oliguria, and hyperkalemia; if oliguria or hypotension occur in neonates with a history of in utero exposure to drug 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 Lactation Minimal amounts of unchanged benazepril and of benazeprilat are excreted into the breast milk of lactating women receiving therapy; a newborn child ingesting entirely breast milk would receive less than 0.1% of mg/kg maternal dose of benazepril and benazeprilat

Additive hyperkalaemic effects w/ K-sparing diuretics, K supplements, other drugs that can cause hyperkalaemia. May increase lithium concentration and toxicity. Diuretics: Excessive drop in blood pressure Antidiabetics: Increased risk of hypoglycaemia NSAIDS: Increased risk of renal impairment and loss of antihypertensive efficacy Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia Lithium: Symptoms of lithium toxicity Contraindicated (2) aliskiren sacubitril/valsartan Serious - Use Alternative (39) allopurinol aspirin aspirin rectal azilsartan candesartan celecoxib choline magnesium trisalicylate diclofenac diflunisal eprosartan etodolac fenoprofen flurbiprofen ibuprofen ibuprofen IV indomethacin irbesartan iron dextran complex ketoprofen ketorolac ketorolac intranasal linagliptin lofexidine losartan meclofenamate mefenamic acid meloxicam nabumetone naproxen olmesartan oxaprozin piroxicam pregabalin salsalate sodium phosphates, IV sulindac telmisartan tolmetin valsartan

Side effects of Benazepril : 1-10% Cough (1-10%) Headache (6%) Dizziness (4%) Fatigue (2%) Postural dizziness (2%) Serum creatinine increased (2%) Somnolence (2%) Nausea (1%) ARF if renal artery stenosis (1%)

Angiotensin-converting enzyme (ACE) inhibitors dilate arteries and veins by competitively inhibiting the conversion of angiotensin I to angiotensin II (a potent endogenous vasoconstrictor) and by inhibiting bradykinin metabolism; these actions result in preload and afterload reductions on the heart ACE inhibitors also promote sodium and water excretion by inhibiting angiotensin-II-induced aldosterone secretion; elevation in potassium may also be observed ACE inhibitors also elicit renoprotective effects through vasodilation of renal arterioles ACE inhibitors reduce cardiac and vascular remodeling associated with chronic hypertension, heart failure, and myocardial infarction