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Benazepril: Drug information

Benazepril: Drug information
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For additional information see "Benazepril: Patient drug information" and "Benazepril: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Fetal toxicity:

When pregnancy is detected, discontinue benazepril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to a developing fetus.

Brand Names: US
  • Lotensin
Pharmacologic Category
  • Angiotensin-Converting Enzyme (ACE) Inhibitor;
  • Antihypertensive
Dosing: Adult
Hypertension, chronic

Hypertension, chronic:

Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (Ref).

Oral: Initial: 10 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose (eg, increase the daily dose by doubling), as needed, up to 40 mg daily in 1 or 2 divided doses; if additional blood pressure control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute/1.73m2: No dosage adjustment necessary.

CrCl <30 mL/minute/1.73m2:

Initial: 5 mg once daily; maximum dose: 40 mg/day

Hemodialysis: 25% to 50% of usual dose; supplemental dose is not necessary (Ref)

Peritoneal dialysis: 25% to 50% of usual dose; supplemental dose is not necessary (Ref)

Dosing: Liver Impairment: Adult

The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.

Note: In general, use of angiotensin-converting enzyme inhibitors in patients with cirrhosis and ascites should be avoided as use can further diminish renal blood flow and precipitate hepatorenal syndrome (Ref).

Liver impairment prior to treatment initiation:

Initial or dose adjustment in patients with preexisting liver cirrhosis:

Child-Turcotte-Pugh class A to C: No dosage adjustment necessary; avoid use in patients with ascites (Ref).

Dosing: Older Adult

Consider lower initial doses (Ref).

Dosing: Pediatric

(For additional information see "Benazepril: Pediatric drug information")

Hypertension

Hypertension: Note: Dosage must be titrated according to patient’s response; use lowest effective dose

Children ≥6 years and Adolescents: Oral: Initial: 0.2 mg/kg/dose once daily as monotherapy; maximum initial dose: 10 mg/day; maintenance: 0.1-0.6 mg/kg/dose once daily; maximum daily dose: 40 mg/day

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children and Adolescents: CrCl <30 mL/minute/1.73 m2: Use is not recommended (insufficient data exists; dose not established)

Adverse Reactions (Significant): Considerations
Acute kidney injury

Use may be associated with increased blood urea nitrogen (azotemia) and increased serum creatinine, resulting in oliguria and acute kidney injury (AKI). Increases in serum creatinine are expected and usually stabilize within 20% to 30% of baseline; higher increases may indicate high efferent tone (such as with hypovolemia, congestive heart failure, or renal artery stenosis) (Ref).

Mechanism: Related to pharmacologic action; inhibits efferent arteriolar vasoconstriction, lowering glomerular filtration pressure, which can lead to a reduction in the glomerular filtration rate (GFR). Kidney hypoperfusion from systemic hypotension may also occur (Ref).

Onset: Intermediate; increases in serum creatinine generally occur within 2 weeks of initiation and stabilize within 2 to 4 weeks (Ref). However, more immediate increases may occur in patients with other risk factors for AKI (Ref).

Risk factors:

• Patients with low renal blood flow whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II (Ref):

- Low effective circulating volume (sodium or volume depletion)

- Congestive heart failure

- Hypotension or shock

- Renal artery stenosis

• High dose at initiation (Ref)

• Older patients (Ref)

• Preexisting kidney impairment (Ref)

• Concurrent diuretic and/or nonsteroidal anti-inflammatory drug use (Ref)

Angioedema

Angioedema may occur rarely; edema may manifest in the head and neck (potentially compromising the airway) or the intestine (presenting as abdominal pain). Use is contraindicated in patients with idiopathic or hereditary angioedema or previous angioedema associated with any angiotensin-converting enzyme inhibitors or neprilysin inhibitors (Ref).

Mechanism: Related to pharmacologic action (ie, increased bradykinin and substance P, vascular permeability, vasodilation) (Ref).

Onset: Varied; may occur at any time during treatment. Most cases occur within the first week of therapy but may also occur years after therapy (Ref).

Risk factors:

• Black patients (estimated 4- to 5-fold higher risk); the mechanism for this is not completely understood but may be related to genetic variants (Ref)

• Females (Ref)

• Smoking history (Ref)

• Previous history of angioedema (Ref)

• Age >65 years (Ref)

• Seasonal allergies (Ref)

• Concurrent use of mechanistic target of rapamycin (mTOR) inhibitors (eg, everolimus) (Ref)

• Concurrent use of neprilysin inhibitor (contraindicated)

Cough

A dry, hacking, nonproductive cough that is typically associated with tickling or scratching in the throat may occur with angiotensin converting enzyme inhibitors (ACEI) in adult and pediatric patients (Ref). Recurrence is likely with rechallenge (Ref). Resolution of cough typically occurs 1 to 4 weeks after ACEI discontinuation but may persist for up to 3 months (Ref).

Mechanism: Various proposed mechanisms. May be related to pharmacologic action (ie, increased bradykinin and substance P, resulting in accumulation in the lungs and bronchoconstriction) (Ref).

Onset: Varied; within hours to 4 weeks after initiation but can be delayed for up to 6 months (Ref).

Risk factors:

• Females (Ref)

• Possibly certain genetic variants (some of which may be independent of the bradykinin pathway) (Ref)

Hyperkalemia

Hyperkalemia (elevated serum potassium) may occur with angiotensin converting enzyme inhibitors (ACEI), including benazepril.

Mechanism: Related to pharmacologic action; inhibits formation of circulating angiotensin II, which leads to efferent arteriole vasodilation and subsequent lowering of glomerular filtration rate, which lowers potassium elimination. Additionally, interferes with the generation and release of aldosterone from the adrenal cortex, leading to an impairment of potassium excretion from the kidney (Ref).

Risk factors:

• Disease states associated with hyperkalemia (congestive heart failure, diabetes mellitus, chronic kidney disease) (Ref)

• Concurrent use of medications which cause hyperkalemia (ACEI, angiotensin receptor blockers, spironolactone, nonsteroidal anti-inflammatory drugs, beta blockers, heparin, tacrolimus, cyclosporine) (Ref)

• Acute kidney injury (elevated BUN and/or serum creatinine) (Ref)

• High dietary intake of potassium or concurrent use of potassium supplements (including potassium-containing salt substitutes) (Ref)

• Baseline elevated potassium level (≥5 mmol/L) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%: Nervous system: Dizziness (4%), drowsiness (2%), headache (6%), orthostatic dizziness (2%)

Frequency not defined:

Cardiovascular: Flushing, hypotension

Dermatologic: Alopecia, diaphoresis, pemphigus, skin photosensitivity, Stevens-Johnson syndrome

Endocrine & metabolic: Decreased libido

Gastrointestinal: Constipation, gastritis, melena, nausea, vomiting

Genitourinary: Impotence, urinary frequency, urinary tract infection

Hematologic & oncologic: Hemolytic anemia, thrombocytopenia

Infection: Infection

Nervous system: Anxiety, fatigue, hypertonia, insomnia, nervousness, paresthesia

Neuromuscular & skeletal: Arthralgia, arthritis, asthenia, myalgia

Respiratory: Asthma, bronchitis, cough, dyspnea, sinusitis

Postmarketing:

Cardiovascular: ECG changes

Dermatologic: Psoriasis (Song 2021)

Endocrine & metabolic: Hyponatremia, increased serum glucose, increased uric acid

Gastrointestinal: Pancreatitis (Muchnick 1999)

Genitourinary: Proteinuria

Hematologic & oncologic: Agranulocytosis (Hashmi 2016), eosinophilia

Hepatic: Cholestatic hepatitis (Palta 2009), increased liver enzymes, increased serum bilirubin

Hypersensitivity: Angioedema (Cuculi 2008)

Contraindications

Hypersensitivity to benazepril, other ACE inhibitors, or any component of the formulation; history of angioedema (with or without prior ACE inhibitor therapy); concomitant use with aliskiren in patients with diabetes mellitus; coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2); pregnancy; breastfeeding; rare hereditary problems of galactose intolerance (eg, galactosemia, congenital Lactase deficiency or glucose-galactose malabsorption).

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors.

• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation.

Disease-related concerns:

• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.

• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor blood pressure and renal function carefully to avoid rapid development of renal failure (AASLD [Runyon 2013]).

• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.

• Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity.

• Diabetes: Use with caution in patients with diabetes receiving insulin or oral antidiabetic agents; may be at increased risk for episodes of hypoglycemia.

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2024]).

• Renal impairment: Use with caution in preexisting renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment.

Special populations:

• Race/Ethnicity: Some studies suggest that when used as monotherapy for hypertension, the BP-lowering effects of renin-angiotensin system (RAS) inhibitors (eg, ACE inhibitors) may be somewhat less pronounced in Black patients (ACC/AHA [Whelton 2018]). The mechanism is not known but may be related to social determinants of health rather than race, as pharmacogenetic differences have not been found to adequately predict BP response (Brewster 2013; Gardner 2022). These observed BP differences were not apparent when RAS inhibitors were used as part of combination therapy (eg, combined with a calcium channel blocker or thiazide diuretic) (Jamerson 2008). Drug selection should be individualized and based on multiple patient-specific factors and not purely race/ethnicity (Holt 2022).

• Surgical patients: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Based on current research and clinical guidelines in patients undergoing non-cardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Lotensin: 10 mg, 20 mg, 40 mg

Generic: 5 mg, 10 mg, 20 mg, 40 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Benazepril HCl Oral)

5 mg (per each): $0.08 - $1.05

10 mg (per each): $0.10 - $1.05

20 mg (per each): $0.14 - $1.05

40 mg (per each): $0.19 - $1.05

Tablets (Lotensin Oral)

10 mg (per each): $2.30

20 mg (per each): $2.30

40 mg (per each): $2.30

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Generic: 5 mg, 10 mg, 20 mg

Administration: Pediatric

Oral: May be administered without regard to food.

Use: Labeled Indications

Hypertension, chronic: Management of hypertension.

Medication Safety Issues
Sound-alike/look-alike issues:

Benazepril may be confused with Benadryl

Lotensin may be confused with Lioresal, lorcaserin, lovastatin

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Aliskiren: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider Therapy Modification

Allopurinol: Angiotensin-Converting Enzyme Inhibitors may increase hypersensitivity effects of Allopurinol. Risk C: Monitor

Alteplase: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor

Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification

Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Angiotensin II Receptor Blockers: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider Therapy Modification

Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may increase therapeutic effects of Angiotensin II. Risk C: Monitor

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor

Aprotinin: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may increase myelosuppressive effects of AzaTHIOprine. Risk C: Monitor

Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor

Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid

Dapoxetine: May increase orthostatic hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor

Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Dipeptidyl Peptidase-IV Inhibitors: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor

Drospirenone-Containing Products: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor

Everolimus: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor

Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Ferric Gluconate. Risk C: Monitor

Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor

Finerenone: Angiotensin-Converting Enzyme Inhibitors may increase hyperkalemic effects of Finerenone. Risk C: Monitor

Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor

Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor

Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk X: Avoid

Heparin: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Heparins (Low Molecular Weight): May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Icatibant: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor

Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Risk C: Monitor

Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid

Lanthanum: May decrease serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme (ACE) inhibitors at least two hours before or after lanthanum. Risk D: Consider Therapy Modification

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor

Lithium: Angiotensin-Converting Enzyme Inhibitors may increase serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider Therapy Modification

Loop Diuretics: May increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor

Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nicorandil: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents (Topical): May decrease therapeutic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor

Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification

Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor

Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor

Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Polyethylene Glycol-Electrolyte Solution: Angiotensin-Converting Enzyme Inhibitors may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor

Potassium Salts: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Potassium-Sparing Diuretics: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor

Pregabalin: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor

Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Racecadotril: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor

Ranolazine: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Sacubitril: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid

Salicylates: May decrease therapeutic effects of Angiotensin-Converting Enzyme Inhibitors. Salicylates may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Sirolimus Products: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased. Risk C: Monitor

Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may increase nephrotoxic effects of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor

Sparsentan: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk X: Avoid

Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may increase hyperkalemic effects of Tacrolimus (Systemic). Risk C: Monitor

Temsirolimus: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor

Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor

Thiazide and Thiazide-Like Diuretics: May increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Tolvaptan: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Trimethoprim: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Management: Consider avoiding coadministration if possible. If combined, monitor serum potassium closely, particularly for patients with other risk factors (eg, renal impairment, older age, and other medications that increase potassium. Risk X: Avoid

Urapidil: And Angiotensin-Converting Enzyme Inhibitors may interact via an unclear mechanism. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider Therapy Modification

Urokinase: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor

Reproductive Considerations

Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. Angiotensin-converting enzyme (ACE) inhibitors are fetotoxic. Transition patients prior to conception to an agent preferred for use during pregnancy unless treatment with an ACE inhibitor is absolutely necessary (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).

Pregnancy Considerations

Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Exposure to an angiotensin-converting enzyme (ACE) inhibitor during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 2019; ESC [Regitz-Zagrosek 2018]). Following exposure during the second or third trimesters, drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. ACE inhibitor use during pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Monitor infants exposed to an ACE inhibitor in utero for hyperkalemia, hypotension, and oliguria. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function.

Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).

Discontinue ACE inhibitors as soon as possible once pregnancy is detected. Agents other than ACE inhibitors are recommended for the treatment of chronic hypertension during pregnancy (ACOG 2019; ESC [Cífková 2020]; SOGC [Magee 2022]). Consider the use of ACE inhibitors only for pregnant patients with hypertension refractory to other medications (ACOG 2019). Closely monitor pregnant patients on ACE inhibitors with serial ultrasounds.

Breastfeeding Considerations

Benazepril, and the active metabolite benazeprilat, are present in breast milk.

Data related to the presence of benazepril and benazeprilat in breast milk are available following maternal administration of oral benazepril 20 mg/day for 3 days to 9 normotensive breastfeeding women (postpartum age not noted). The average peak breast milk concentrations were benazepril 2.0 ± 1.1 pmol/g and benazeprilat 4.6 ± 1.9 pmol/g. Using the average milk concentrations, authors of the study calculated relative infant dose (RID) to be <0.1% of the weight adjusted maternal dose. In addition, poor oral absorption of benazeprilat would limit potential exposure to a breastfeeding infant (Kaiser 1989). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

When postpartum treatment with an angiotensin-converting enzyme (ACE) inhibitor is needed, available guidelines consider benazepril to be acceptable for use in lactating patients (ESC [Cífková 2020]). Avoid breastfeeding if high maternal doses of an ACE inhibitor are needed (ACOG 2019).

Monitoring Parameters

Blood pressure; BUN, serum creatinine, electrolytes (eg, potassium [especially in patients on concomitant potassium-sparing diuretics, potassium supplements and/or potassium containing salts]); if patient has collagen vascular disease and/or kidney impairment, periodically monitor CBC with differential. If angioedema is suspected, assess risk of airway obstruction (eg, involvement of tongue, glottis, larynx, and/or history of airway surgery).

Mechanism of Action

Competitive inhibition of angiotensin I being converted to angiotensin II, a potent vasoconstrictor, through the angiotensin I-converting enzyme (ACE) activity, with resultant lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion

Pharmacokinetics (Adult Data Unless Noted)

Reduction in plasma angiotensin-converting enzyme (ACE) activity:

Onset of action: Peak effect: 1 to 2 hours after 2 to 20 mg dose (Nussberger 1987; Nussberger 1989)

Duration: >90% inhibition for 24 hours after 5 to 20 mg dose (Balfour 1991)

Reduction in blood pressure:

Peak effect: Single dose: 2 to 4 hours; Continuous therapy: 2 weeks (Fogari 1990)

Absorption: Rapid (37%); food does not alter significantly; metabolite (benazeprilat) itself unsuitable for oral administration due to poor absorption

Distribution: Vd: ~8.7 L (Balfour 1991)

Protein binding:

Benazepril: ~97%

Benazeprilat: ~95%

Metabolism: Rapidly and extensively hepatic to its active metabolite, benazeprilat, via enzymatic hydrolysis; extensive first-pass effect

Half-life elimination: Benazeprilat: Effective: 10 to 11 hours; Terminal: Children: 5 hours, Adults: 22 hours

Time to peak:

Parent drug: 0.5 to 1 hour

Active metabolite (benazeprilat): Fasting: 1 to 2 hours; Nonfasting: 2 to 4 hours

Excretion:

Urine (trace amounts as benazepril; 20% as benazeprilat; 12% as other metabolites)

Clearance: Nonrenal clearance (ie, biliary, metabolic) appears to contribute to the elimination of benazeprilat (11% to 12%), particularly patients with severe renal impairment; hepatic clearance is the main elimination route of unchanged benazepril

Dialysis: ~6% of metabolite removed within 4 hours of dialysis following 10 mg of benazepril administered 2 hours prior to procedure; parent compound not found in dialysate

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: In those with CrCl 30 mL/minute or less, peak benazeprilat levels and initial half-life increase and time to steady state may be delayed.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Cibacen;
  • (AR) Argentina: Boncordin;
  • (BE) Belgium: Cibacen;
  • (BG) Bulgaria: Cibacen;
  • (BR) Brazil: Bhena | Cloridrato de benazepril | Lotensin;
  • (CH) Switzerland: Cibacen;
  • (CN) China: Lotensin | Luo ting xin | Zaprace;
  • (DE) Germany: Benazepril | Benazepril 1 A Pharma | Benazepril AL | Benazepril Beta | Benazepril Heumann | Benazepril Hexal | Cibacen | Cibacen cor;
  • (DO) Dominican Republic: Lotensin;
  • (EC) Ecuador: Lotensin;
  • (EE) Estonia: Lotensin;
  • (EG) Egypt: Cibacen | Unitense;
  • (ES) Spain: Cibacen | Labopal;
  • (FR) France: Benazepril Actavis | Benazepril EG | Benazepril Mylan | Briem | Cibacene;
  • (GR) Greece: Cibacen;
  • (HU) Hungary: Lotensin;
  • (ID) Indonesia: Cibacen;
  • (IE) Ireland: Cibacen;
  • (IL) Israel: Benazepril Teva | Cibacen;
  • (IN) India: Benace;
  • (IT) Italy: Benazepril EG | Benazepril Sandoz | Cibacen | Tenkuoren | Tensanil | Zinadril;
  • (JO) Jordan: Cibacen | Zenoril;
  • (JP) Japan: Benazep | Cibacen | Prebase | Tatsujipin;
  • (KR) Korea, Republic of: Cibacen;
  • (KW) Kuwait: Cibacen;
  • (LT) Lithuania: Lotensin;
  • (LU) Luxembourg: Cibacen;
  • (LV) Latvia: Lotensin;
  • (MA) Morocco: Cibacen;
  • (MX) Mexico: Lotensin;
  • (NL) Netherlands: Cibacen;
  • (NZ) New Zealand: Cibacen;
  • (PH) Philippines: Cibacen;
  • (PL) Poland: Benazepril stada | Lisonid | Lotensin;
  • (PR) Puerto Rico: Benazepril HCL | Lotensin;
  • (PT) Portugal: Benazepril Actavis | Benazepril generis;
  • (RO) Romania: Benazepril stada | Cibacen | Lotensin;
  • (RU) Russian Federation: Lotensin;
  • (SA) Saudi Arabia: Cibacen;
  • (TR) Turkey: Cibacen;
  • (TW) Taiwan: Cibacen;
  • (UY) Uruguay: Lotensin;
  • (VN) Viet Nam: Lavezzi;
  • (ZA) South Africa: Cibace
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