Amlodipine Besylate/Benazepril Hydrochloride

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Therapeutic Class
ACE Inhibitor/Calcium Channel Blocker Combination
Clinical Teaching
Patient should avoid activities requiring coordination until drug effects are realized, as drug may cause dizziness.
This drug may cause edema, headache, or angioedema (deep swelling around eyes and lips and sometimes hands and feet).
Instruct patient to report signs/symptoms of peripheral edema, hypotension, or hepatic dysfunction.
Advise patient against sudden discontinuation of drug, as this may cause rebound hypertension.
Patient should avoid use of potassium-containing supplements or salt substitutes unless approved by healthcare professional.
Dosing - Adult
Hypertension, Second-line therapy: initial, amlodipine 2.5 mg/benazepril 10 mg ORALLY once daily; may titrate dose up to amlodipine 10 mg/benazepril 40 mg ORALLY once daily, based on clinical response
Dosing - Dose Adjustment
renal impairment: NOT recommended in patients with severe renal impairment (creatinine clearance less than 30 mL/min/1.73m(2) or serum creatinine greater than or equal to 3 mg/dL)
hepatic impairment: initial dose, amlodipine 2.5 mg/benazepril 10 mg
geriatric: initial dose, amlodipine 2.5 mg/benazepril 10 mg
Dosing - FDA Labeled
Hypertension, Second-line therapy: Adult: yes
Hypertension, Second-line therapy: Pediatric: no
Dosing - Pediatric
safety and efficacy not established in pediatric patients
Contraindications
hypersensitivity to amlodipine or benazepril or to any component of the product
hypersensitivity to ACE inhibitors
Warnings - Precautions

  • angioedema of the head and neck; fatal laryngeal stridor, edema, and angioedema of the face, tongue, or glottis reported.
  • concomitant peripheral vasodilators; acute hypotension reported.
  • congestive heart failure, with or without renal insufficiency; acute hypotension may occur, associated with oliguria, azotemia, and rarely acute renal failure, and death
  • hemodialysis with high flux membranes; anaphylactoid reactions reported
  • hepatic failure/dysfunction; cholestatic jaundice, fulminant hepatic necrosis, and death reported
  • insect venom allergy; may exacerbate the allergic response
  • hymenoptera desensitization; anaphylactoid reactions reported
  • intestinal angioedema
  • obstructive coronary artery disease; exacerbation of angina or myocardial infarction during initial therapy or with dose increases
  • pregnancy; risk of fetal and neonatal morbidity and death
  • renal artery stenosis, unilateral or bilateral; increases in BUN and serum creatinine reported
  • renal disease, severe
  • renal impairment with concomitant collagen-vascular disease; increased risk of agranulocytosis and neutropenia
  • surgery/anesthesia; increased risk of hypotension
  • volume and/or salt depleted patients; hypotension more likely

Adverse Effects - Common
Cardiovascular: Edema
Neurologic: Dizziness, Headache
Respiratory: Cough (3.3%)
Adverse Effects - Serious
Gastrointestinal: Intestinal angioedema
Other: Angioedema, Face, lips, throat; more frequent in Black patients (rare)
Mechanism of Action
Systemic: Amlodipine is a dihydropyridine calcium channel blocking agent. Like the other dihydropyridine agents, amlodipine selectively inhibits calcium influx across cell membranes in cardiac and vascular smooth muscle, with a greater effect on vascular smooth muscle. Amlodipine is a peripheral arteriolar vasodilator; thus it reduces afterload.
Benazepril is a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor and a prodrug for benazeprilat, the active metabolite. Both benazepril and benazeprilat inhibit ACE. ACE catalyzes the conversion of angiotensin I to the vasoconstrictor angiotensin II. Angiotensin II normally stimulates secretion of aldosterone and inhibits the release of renin through a negative feedback mechanism. When ACE activity is inhibited, angiotensin II formation is decreased and the interruption of the negative feedback mechanism results in increased plasma renin concentrations. The reduction of angiotensin II formation also decreases aldosterone secretion and vasoconstriction. The decrease in aldosterone secretion causes a small increase in serum potassium concentrations. Suppression of the renin-angiotensin-aldosterone system is thought to be the primary mechanism through which ACE inhibitors lower blood pressure.
ACE is also known as kininase, an enzyme that degrades bradykinin. Benazepril may increase concentrations of bradykinin, a potent vasodepressor peptide, but its role in the therapeutic effects of this drug combination has not been determined.
Amlodipine exhibits negative inotropic effects in vivo , but appears to have no significant effect on the sinoatrial (SA) or atrioventricular (AV) node in humans.

Clinical Effects - Treatment
ACE INHIBITORS: Decontamination: Consider activated charcoal after a potentially toxic ingestion and if the patient is able to maintain airway or if airway is protected.
ACE INHIBITORS: Hypotensive episode: IV 0.9% NaCl 10-20 ml/kg, dopamine, norepinephrine. Naloxone effective in animal models and several case reports. Angiotensin Amide - IV infusion 8.5 to 18 mcg/min effective in several case reports.
ACE INHIBITORS: Monitoring of patient: Monitor BP, continuous cardiac monitoring, electrolytes, renal function, ECG and urinalysis in symptomatic patients.
CALCIUM ANTAGONISTS: Decontamination: Activated charcoal, gastric lavage; consider late gastric lavage and/or whole bowel irrigation with sustained release.
CALCIUM ANTAGONISTS: Hypotensive episode: IV 0.9% NaCl 10-20 ml/kg. CaCl adult dose 1 g IV over 5 min repeat every 10-20 min up to 4 or 5 (total) doses if needed. Insulin/dextrose: Insulin bolus of 1 unit/kg along with 25 to 50 mL D50W. Begin an insulin infusion of 0.1 to 1 unit/kg/hour and administer sufficient intravenous dextrose to maintain a blood glucose between 100 to 200 mg/dL. Vasopressors such as dopamine, epinephrine, isoproterenol, norepinephrine may be used but are often less effective than insulin/dextrose. Phosphodiesterase inhibitors (inamrinone, milrinone) may also be useful.
CALCIUM ANTAGONISTS: Bradycardia: Administer CaCl, glucagon and pacemaker as necessary. Atropine is usually not effective in this setting.
CALCIUM ANTAGONISTS: Seizure: IV benzodiazepines, barbiturates.
CALCIUM ANTAGONISTS: Acute lung injury: Maintain adequate ventilation and oxygenation; monitor ABGs; PEEP as needed.
CALCIUM ANTAGONISTS: Monitoring of patient: Obtain serial ECGs, continuous cardiac monitoring, BP, electrolytes, renal function, urine output and ABGs.

Toxicology - Clinical Effects
ACE INHIBITORS: OVERDOSE: Hypotension most common overdose effect; acute renal failure is rare. Onset of hypotension is generally within 6 hours of ingestion. ADVERSE EFFECTS: Hypotension, bradycardia, bronchospasm, cough, renal insufficiency, nephrotic syndrome, hyperkalemia, and neutropenia can develop.
CALCIUM ANTAGONISTS: MILD/MODERATE: hypotension, bradycardia, nausea & vomiting common. SEVERE: dysrhythmias, AV conduction delays, metabolic acidosis, hypokalemia, hyperglycemia, syncope, CNS depression, pulmonary edema, acidosis, acute renal failure, rhabdomyolysis, bowel ischemia. ONSET: Usually within 5 hrs, delayed with sustained release.

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