Amlodipine Besylate / Benazepril Hydrochloride

Pronunciation

Pronunciation: am-LOE-di-peen BES-i-late/ben-AZ-e-pril HYE-droe-KLOR-ide
Class: Antihypertensive combination

Trade Names

Lotrel
- Capsules, oral amlodipine 2.5 mg/benazepril 10 mg
- Capsules, oral amlodipine 5 mg/benazepril 10 mg
- Capsules, oral amlodipine 5 mg/benazepril 20 mg
- Capsules, oral amlodipine 5 mg/benazepril 40 mg
- Capsules, oral amlodipine 10 mg/benazepril 20 mg
- Capsules, oral amlodipine 10 mg/benazepril 40 mg

Pharmacology

Amlodipine

Inhibits movement of calcium ions across cell membrane in systemic and coronary vascular smooth muscle.

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Benazepril

Competitively inhibits angiotensin I–converting enzyme, resulting in the prevention of angiotensin I conversion to angiotensin II, a potent vasoconstrictor that stimulates aldosterone secretion. This action results in a decrease in sodium and fluid retention, an increase in diuresis, and a decrease in BP.

Indications and Usage

For the treatment of hypertension.

Contraindications

History of angioedema, with or without previous ACE inhibitor treatment; hypersensitivity to amlodipine, benazepril, or any other ACE inhibitor.

Dosage and Administration

Adults

PO Amlodipine 2.5 to 10 mg/benazepril 10 to 40 mg once daily.

Elderly

PO Initially, amlodipine 2.5 mg/day

Renal Function Impairment

Not recommended for use in patients with CrCl less than 30 mL/min.

Hepatic Function Impairment

PO Initially, amlodipine 2.5 mg/day. Titrate dose slowly in patients with severe hepatic impairment.

Storage/Stability

Store at 59° to 86°F. Protect from moisture and light.

Drug Interactions

Aldosterone blockers (eg, eplerenone)

Serious hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Monitor potassium level periodically until effects are established for the aldosterone blocker, and reduce the dose of the aldosterone blocker if necessary.

Aliskiren

May decrease renal excretion of potassium, resulting in hyperkalemia. Closely monitor serum potassium.

Angiotensin II receptor antagonists (eg, valsartan)

Increased risk of renal dysfunction and hyperkalemia. If coadministration cannot be avoided, closely monitor renal function and serum potassium.

Azole antifungal agents (eg, itraconazole)

Azole antifungals may increase the plasma concentrations and pharmacologic effects of amlodipine.

Clozapine

May cause excessive decreases in BP and syncope. Plasma concentrations of clozapine may be increased. Consider a lower starting dosage of clozapine.

Conivaptan

Plasma concentrations of amlodipine may be increased. Clinical monitoring for signs of extended pharmacologic effect of amlodipine is warranted.

COX-2 inhibitors (eg, celecoxib), NSAIDs (eg, indomethacin, ketorolac [nasal])

The antihypertensive effects of benazepril may be reduced. In addition, concomitant use may further deteriorate renal function, especially in patients with renal impairment or volume depletion. The risk of hyperkalemia may also be increased. Monitor BP, renal function, and serum potassium.

Diltiazem

Amlodipine plasma concentrations may be elevated, increasing the pharmacologic effects. Closely monitor BP and adjust the amlodipine dose as needed.

Gold salts

The risk of nitritoid reactions (eg, facial flushing, hypotension, nausea, vomiting) may be increased. Monitor for signs and symptoms of nitritoid reactions.

Iron salts, parenteral (eg, iron dextran)

The risk of adverse reactions to iron salts may be increased. Monitor closely for adverse reactions.

Lithium

Lithium Cl may be decreased, increasing concentrations and the risk of lithium toxicity. Closely monitor serum lithium levels.

Loop diuretics (eg, furosemide)

The effects of loop diuretics may be decreased. Monitor fluid status and for electrolyte abnormalities.

mTOR inhibitors (eg, everolimus, sirolimus)

The risk of angioedema may be increased.

Pergolide

May cause profound hypotension. Start with lower doses of pergolide and monitor BP closely.

Phenothiazines (eg, chlorpromazine)

May produce a synergistic hypotensive effect with postural syncope. Monitor BP (supine and standing).

Potassium preparations (eg, potassium supplements, salt substitutes)

The risk of hyperkalemia, possibly with cardiac arrhythmias or arrest, may be increased with coadministration. Closely monitor serum potassium concentrations.

Potassium-sparing diuretics (eg, amiloride)

The risk of hyperkalemia is increased, especially in high-risk patients (eg, renal impairment). Closely monitor serum potassium and renal function.

Protease inhibitors (eg, indinavir, ritonavir)

The antihypertensive effects of amlodipine may be increased. Use with caution.

Salicylates (eg, aspirin)

Hypotensive and vasodilator effects may be reduced. May need to stop salicylates if BP control or renal function deteriorates. A lower dosage of salicylates may avoid this interaction.

Simvastatin

Plasma concentrations and pharmacologic effects of simvastatin may be increased. Do not exceed a daily dose of simvastatin 20 mg when amlodipine is coadministered.

Sulfonylureas (eg, glyburide)

The risk of hypoglycemia may be increased with benazepril. Closely monitor clinical and laboratory findings.

Tizanidine

May cause severe hypotension. Monitor BP.

Trimethoprim

May cause hyperkalemia, resulting in cardiac arrhythmias or arrest. Elderly patients with renal impairment or patients on high-dose trimethoprim are at increased risk. Closely monitor serum potassium.

Adverse Reactions

CNS

Headache (2%); dizziness (1%); anxiety; asthenia; decreased libido; fatigue; insomnia; nervousness; tremor.

Dermatologic

Dermatitis; rash; skin nodule.

GI

Abdominal pain; constipation; diarrhea; dry mouth; dyspepsia; esophagitis; nausea.

Genitourinary

Polyuria; sexual problems, such as impotence.

Metabolic

Hyperkalemia (2%); hypokalemia.

Musculoskeletal

Back pain; cramps; muscle cramps; musculoskeletal pain.

Respiratory

Cough (3%); pharyngitis.

Miscellaneous

Edema, including dependent edema, angioedema, and facial edema (2%); flushing; hot flashes; neutropenia.

Precautions

Warnings

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


Monitor

Ensure that volume and/or salt depletion have been corrected before initiating therapy. Evaluate renal function and measure serum electrolytes before starting therapy and periodically thereafter. Monitor BP and pulse on a regular basis.


Pregnancy

Category D . 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 pregnancy as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimesters of pregnancy. 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.

Lactation

Amlodipine

Undetermined.

Benazepril

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

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.

Hypersensitivity

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors.

Renal Function

Do not use in patients with severe renal disease (CrCl less than 30 mL/min).

In a small study of hypertensive patients with unilateral or bilateral renal artery stenosis, treatment with benazepril was associated with increases in BUN and serum creatinine.

Hepatic Function

Titrate dose slowly in patients with severe hepatic impairment.

Angioedema

Angioedema of the face, extremities, lips, tongue, glottis, and larynx, as well as intestinal angioedema, has been reported. Angioedema associated with laryngeal edema may be fatal. Black patients have been reported to have a higher incidence of angioedema compared with nonblack patients.

Cough

Persistent, nonproductive cough has been reported with all ACE inhibitors.

Cardiovascular effects

Increased frequency, duration, or severity of angina or acute MI may occur, particularly in those with severe obstructive coronary artery disease.

Hepatic effects

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. In addition, elevations of serum bilirubin and elevations of liver enzymes have been reported.

Hyperkalemia

Has been reported.

Hypotension

Decreases in BP may occur, especially in salt- or volume-depleted patients, as a result of dialysis, prolonged diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Symptomatic hypotension is also possible in patients with severe aortic stenosis.

Renal effects

Benazepril use has been associated with increases in BUN and serum creatinine.

In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with benazepril may be associated with oliguria or progressive azotemia and (rarely) with acute renal failure and/or death.

Surgery/Anesthesia

In patients undergoing surgery or during anesthesia with agents that produce hypertension, benazepril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.

Uric acid

Elevations of uric acid have been reported.

Overdosage

Symptoms

Pulmonary edema, vasodilation, with consequent hypotension and tachycardia.

Patient Information

  • Inform patients that angioedema, including laryngeal edema, can occur at any time with ACE inhibitor treatment. Advise patients to immediately report to their health care provider any signs or symptoms suggesting angioedema (swelling of the face, eyes, lips or tongue, or difficulty in breathing) and to not take more drug until after consulting with their health care provider.
  • Female patients of childbearing age should be told about the consequences of exposure to ACE inhibitors. Discuss other treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their health care provider as soon as possible.
  • Caution patients that light-headedness can occur, especially during the first few days of therapy, and that it should be reported to the prescribing health care provider. Inform patients that if syncope occurs, amlodipine/benazepril should be discontinued until the health care provider has been consulted. Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, with the same consequences of light-headedness and possible syncope.
  • Advise patients not to take potassium supplements or salt substitutes containing potassium without consulting their health care provider.

Copyright © 2009 Wolters Kluwer Health.

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