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Amlodipine and benazepril: Drug information

Amlodipine and benazepril: Drug information
(For additional information see "Amlodipine and benazepril: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Fetal toxicity:

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

Brand Names: US
  • Lotrel
Pharmacologic Category
  • Angiotensin-Converting Enzyme (ACE) Inhibitor;
  • Antianginal Agent;
  • Antihypertensive;
  • Calcium Channel Blocker;
  • Calcium Channel Blocker, Dihydropyridine
Dosing: Adult
Hypertension

Hypertension: Oral: Initial: Amlodipine 2.5 mg/benazepril 10 mg once daily; may titrate dose based on BP response. Patients already taking amlodipine and/or benazepril may be switched to a combination product for individually titrated agents. Maximum: amlodipine 10 mg/benazepril 40 mg once daily.

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: No dosage adjustment necessary.

CrCl ≤30 mL/minute: Use is not recommended.

Dosing: Hepatic Impairment: Adult

There are no specific dosage adjustments provided in the manufacturer's labeling; initiate with lowest dose and titrate slowly. Use with caution; amlodipine elimination prolonged.

Dosing: Older Adult

Refer to adult dosing. Initiate with lowest dose.

Adverse Reactions

See individual agents.

Contraindications

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

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

Warnings/Precautions

Concerns related to adverse effects:

• Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade.

• Angioedema: At any time during treatment (especially following first dose and may appear after months of therapy) angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). Black patients and patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE inhibitor therapy may be at an increased risk. Risk may also be increased with concomitant use of mTOR inhibitor (eg, everolimus) therapy or a neprilysin inhibitor (eg, sacubitril). Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Use is contraindicated in patients with a history of angioedema with or without previous ACE inhibitor treatment.

• Cholestatic jaundice: A rare toxicity associated with ACE inhibitors includes cholestatic jaundice and isolated cases of acute liver failure (some fatal); discontinue if marked elevation of hepatic transaminases or jaundice occurs.

• Cough: An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1 to 4 weeks after discontinuation of the ACE inhibitor. Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation.

• Hyperkalemia: May occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.

• 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 or salt-depleted patients; correct volume and/or salt 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.

• Neutropenia/agranulocytosis: Another ACE Inhibitor, captopril, has been associated with rare cases of agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia. Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Periodically monitor CBC with differential in these patients.

• Peripheral edema: The most common side effect of amlodipine is peripheral edema (dose dependent); occurs within 2 to 3 weeks of starting therapy.

• Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, severe heart failure, post-MI, volume depletion) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider withholding or discontinuation in patients with progressive and/or significant deterioration in renal function.

Disease-related concerns:

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

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

• Hepatic impairment: Use amlodipine with caution in patients with hepatic impairment; may require lower starting dose.

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use amlodipine with caution in patients with hypertrophic cardiomyopathy with left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2020]).

• Renal artery stenosis: Use benazepril with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.

• Renal impairment: Not recommended in patients with severe renal impairment.

Special populations:

• Older adult: Initiate amlodipine at a lower dose in the elderly.

• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

Other warnings/precautions:

• Surgery: 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).

Dosage Forms: US

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

Capsule, Oral:

Lotrel: Amlodipine 5 mg and benazepril hydrochloride 10 mg, Amlodipine 5 mg and benazepril hydrochloride 20 mg, Amlodipine 10 mg and benazepril hydrochloride 20 mg, Amlodipine 10 mg and benazepril hydrochloride 40 mg

Generic: Amlodipine 10 mg and benazepril hydrochloride 20 mg, Amlodipine 10 mg and benazepril hydrochloride 40 mg, Amlodipine 2.5 mg and benazepril hydrochloride 10 mg, Amlodipine 5 mg and benazepril hydrochloride 10 mg, Amlodipine 5 mg and benazepril hydrochloride 20 mg, Amlodipine 5 mg and benazepril hydrochloride 40 mg

Generic Equivalent Available: US

Yes

Pricing: US

Capsules (amLODIPine Besy-Benazepril HCl Oral)

2.5-10 mg (per each): $2.65

5-10 mg (per each): $2.71

5-20 mg (per each): $2.86

5-40 mg (per each): $4.01 - $4.05

10-20 mg (per each): $3.32

10-40 mg (per each): $4.84 - $4.90

Capsules (Lotrel Oral)

5-10 mg (per each): $13.15

5-20 mg (per each): $13.88

10-20 mg (per each): $16.13

10-40 mg (per each): $17.77

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.

Administration: Adult

Administer orally with or without food.

Use: Labeled Indications

Hypertension: Management of hypertension.

Metabolism/Transport Effects

Refer to individual components.

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect 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 enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

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

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect 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 diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the 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

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy

AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy

CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Charcoal, Activated: May decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy

CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of AmLODIPine. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of AmLODIPine. Risk C: Monitor therapy

Dabigatran Etexilate: AmLODIPine may diminish the therapeutic effect of Dabigatran Etexilate. Risk C: Monitor therapy

Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination

Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

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

Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy

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

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Finerenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

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

Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect 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 combination

Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Inhalational Anesthetics: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

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

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Lanthanum: May decrease the 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

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the 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

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification

Loop Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Lovastatin: AmLODIPine may increase the serum concentration of Lovastatin. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the adverse/toxic effect of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor therapy

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

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

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect 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 enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Polyethylene Glycol-Electrolyte Solution: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

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

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Ranolazine: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Red Yeast Rice: AmLODIPine may increase the serum concentration of Red Yeast Rice. Risk C: Monitor therapy

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

Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Simvastatin: AmLODIPine may increase the serum concentration of Simvastatin. Management: Dose of simvastatin should not exceed 20 mg daily if coadministering with amlodipine. If coadministering with simvastatin and amlodipine, close laboratory and clinical monitoring for signs and symptoms of rhabdomyolysis is warranted. Risk D: Consider therapy modification

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification

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

Sparsentan: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk X: Avoid combination

Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

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

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Tolvaptan: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

Urapidil: May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider therapy modification

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

Food Interactions

See individual agents.

Pregnancy Considerations

[US Boxed Warning]: When pregnancy is detected, discontinue amlodipine/benazepril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Refer to individual monographs for additional information.

Breastfeeding Considerations

Amlodipine, benazepril, benazeprilat are present in breast milk.

Refer to individual monographs for additional information.

Monitoring Parameters

BUN, electrolytes, serum creatinine, and blood pressure. In patients with renal impairment and/or collagen vascular disease, monitor CBC with differential periodically.

Mechanism of Action

Amlodipine: Directly acts on vascular smooth muscle to produce peripheral arterial vasodilation reducing peripheral vascular resistance and blood pressure.

Benazepril: Competitive inhibition of angiotensin I being converted to angiotensin II, a potent vasoconstrictor, through the 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)

See individual agents.

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

  • (AR) Argentina: Adrebloc | Amlodine duo | Arteriosan plus | Coroval B | Ilduc duo | Pelmec duo | Terloc Duo;
  • (BD) Bangladesh: Amlozep | Benadip | Cacetor | Lodiben;
  • (BR) Brazil: Press plus;
  • (CO) Colombia: Amlibon B;
  • (DO) Dominican Republic: Amloben | Ampliron plus | Coroval B | Vasocal Ek;
  • (EC) Ecuador: Amlibon B;
  • (EG) Egypt: Amlo-ace | Amlozapril | Loadless | Magnetrel | Norvapril;
  • (PE) Peru: Blotril;
  • (PR) Puerto Rico: Amlodipine & benazepril hcl | Amlodipine and benazepril hcl | Amlodipine and benazepril hydrochloride | Amlodipine Benazepril | Amlodipine besylate and Benazepril HCl | Amlodipine besylate and benazepril hydrochl. | Amlodipine besylate and benazepril hydrochlor | Amlodipine/benazepril hcl | Lotrel;
  • (PY) Paraguay: Ampliron plus;
  • (UY) Uruguay: Ambix | Terloc Duo;
  • (VE) Venezuela, Bolivarian Republic of: Amlibon B | Lodipin-plus
  1. Amlodipine Besylate and Benazepril Hydrochloride [prescribing information]. Sellersville, PA: Teva; February 2011.
  2. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(23):2610-2642. [PubMed 22064600]
  3. Jorgensen MG, “Prevalence of Amlodipine-Related Gingival Hyperplasia,” J Periodontol, 1997, 68(7):676-8. [PubMed 9249639]
  4. Lotrel (amlodipine/benazepril) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; April 2021.
  5. Naito T, Kubono N, Deguchi S, et al. Amlodipine passage into breast milk in lactating women with pregnancy-induced hypertension and its estimation of infant risk for breastfeeding. J Hum Lact. 2015;31(2):301-306. doi: 10.1177/0890334414560195. [PubMed 25447596]
  6. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2020;76(25):e159-e240. doi:10.1016/j.jacc.2020.08.045 [PubMed 33229116]
  7. Wynn RL, “An Update on Calcium Channel Blocker-Induced Gingival Hyperplasia,” Gen Dent, 1995, 43(3):218-22. [PubMed 8940577]
  8. Wynn RL, “Calcium Channel Blockers and Gingival Hyperplasia,” Gen Dent, 1991, 39(4):240-3. [PubMed 1916193]
  9. Wynn RL, "Calcium Channel Blockers and Gingival Hyperplasia-An Update," Gen Dent, 2009, 57(2):105-7. [PubMed 19552357]
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