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Benazepril Hydrochloride / Hydrochlorothiazide

Pronunciation: ben-AZ-e-pril HYE-droe-KLOR-ide/HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination

Trade Names

Benazepril Hydrochloride/Hydrochlorothiazide
- Tablets, oral benazepril 5 mg/hydrochlorothiazide 6.25 mg

Lotensin HCT
- Tablets, oral benazepril 10 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral benazepril 20 mg/hydrochlorothiazide 12.5 mg
- Tablets, oral benazepril 20 mg/hydrochlorothiazide 25 mg

Pharmacology

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.

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Hydrochlorothiazide

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

For the treatment of hypertension.

Contraindications

Anuric patients; history of angioedema; hypersensitivity to benazepril or any other ACE inhibitor, hydrochlorothiazide, or other sulfonamide derivative.

Dosage and Administration

Adults

PO Benazepril 10 mg/hydrochlorothiazide 12.5 mg or benazepril 20 mg/hydrochlorothiazide 12.5 mg initially in patients not adequately controlled on benazepril monotherapy. Patients whose BP is controlled on hydrochlorothiazide 25 mg daily but who experience significant potassium loss may achieve similar BP control without electrolyte disturbances if they are switched to benazepril 5 mg/hydrochlorothiazide 6.25 mg. Further increases of either or both components depends on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 wk have elapsed.

General Advice

  • May be taken with or without food.
  • This fixed-dose combination is not indicated for the initial therapy of hypertension.
  • The combination may be substituted for the titrated individual components.
  • Correct volume and/or salt depletion before initiating therapy.

Storage/Stability

Do not store above 86°F. Protect from moisture and light.

Drug Interactions

No drug interaction studies have been conducted between benazepril/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the benazepril/hydrochlorothiazide combination.

Aldosterone blockers (eg, eplerenone)

Serious hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Monitor potassium level periodically until aldosterone blocker effects are established. Dosage reduction of the aldosterone blocker may be needed.

Aliskiren

Renal excretion of potassium may be decreased, resulting in hyperkalemia, particularly in diabetic patients and in patients with moderate or severe renal impairment. Coadministration is contraindicated in diabetic patients. Avoid coadministration in patients with CrCl less than 60 mL/min. If coadministration is undertaken, closely monitor serum potassium concentrations and renal function.

Angiotensin II receptor antagonists (eg, valsartan)

Increased risk of renal dysfunction and hyperkalemia. Closely monitor renal function and serum potassium.

Antihypertensives (eg, propranolol)

Additive or potentiation of hypotensive effects may occur.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Cholestyramine, colestipol resins

Hydrochlorothiazide absorption may be impaired. Single doses of either cholestyramine or colestipol resins bind hydrochlorothiazide, reducing GI absorption by up to 85% and 43%, respectively. Separate the administration times by at least 4 h. Adjust diuretic dose as needed.

Clozapine

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

Cyclooxygenase 2 inhibitors (eg, celecoxib), NSAIDs (eg, ibuprofen, indomethacin, ketorolac [nasal])

The diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide and the antihypertensive effects of benazepril may be reduced. In addition, concomitant use may further deteriorate renal function, especially in volume-depleted patients, patients with renal impairment, or elderly patients. The risk of hyperkalemia may also be increased. Monitor BP, renal function, and serum potassium. If an interaction is suspected, it may be necessary to discontinue the NSAID.

Cyclosporine

Acute renal failure has been reported with coadministration. Discontinue benazepril/hydrochlorothiazide if an interaction is suspected. Dose reduction or discontinuation of cyclosporine may be necessary.

Diazoxide

The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood glucose, and serum uric acid. If coadministration cannot be avoided, a decreased dosage of one or both agents may be required.

Digoxin

Hydrochlorothiazide-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Closely monitor plasma concentrations of potassium and magnesium, and monitor patients for signs of digoxin toxicity.

Dofetilide

Plasma concentrations may be increased. Prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Gold salts (eg, sodium aurothiomalate)

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

Insulin

Insulin requirements may increase or decrease, or remain unchanged. Monitor blood glucose and adjust the insulin dose as needed.

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 lithium concentrations and the risk of lithium toxicity. Closely monitor serum lithium levels. Adjust dose of lithium as needed.

Loop diuretics (eg, furosemide)

The effects of loop diuretics may be decreased. Loop diuretics and hydrochlorothiazide have synergistic effects that may result in profound diuresis and electrolyte abnormalities. Monitor fluid status and electrolyte abnormalities.

Mammalian target of rapamycin inhibitors (eg, everolimus, sirolimus)

The risk of angioedema is increased. If an interaction is suspected, stop one or both drugs.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Possible increased responsiveness to the muscle relaxant because of diuretic-induced hypokalemia. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.

Pergolide

May cause profound hypotension. Start with lower doses of pergolide and monitor BP closely. If BP falls, dosage reduction may be needed.

Phenothiazines (eg, chlorpromazine)

May produce a synergistic hypotensive effect with postural syncope. Monitor BP (supine and standing) and adjust dosage of antihypertensive as needed.

Potassium preparations (eg, potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium)

Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Closely monitor serum potassium concentrations. Adjust treatment as needed.

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased. Use with caution.

Salicylates (eg, aspirin)

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

Sulfonylureas (eg, glyburide)

The risk of hypoglycemia may be increased with benazepril. Hydrochlorothiazide may increase fasting blood glucose and decrease the hypoglycemic action of sulfonylureas. Closely monitor blood glucose and adjust therapy as needed.

Tizanidine

May cause severe hypotension. Monitor BP.

Tretinoin

The risk of phototoxicity may be increased. Avoid coadministration.

Trimethoprim

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

Laboratory Test Interactions

Hydrochlorothiazide may decrease serum protein-bound iodine levels without signs of thyroid disturbance. Therapy should be interrupted for a few days before carrying out tests of parathyroid function.

Adverse Reactions

Cardiovascular

Postural dizziness (4%); hypotension (1%); flushing, palpitations (up to 1%).

CNS

Dizziness (6%); fatigue (5%); headache (3%); vertigo (2%); somnolence (1%); asthenia, insomnia, nervousness, paresthesia (up to 1%).

Dermatologic

Rash, sweating (up to 1%).

EENT

Rhinitis, sinusitis (more than 1%); tinnitus (up to 1%).

GI

Nausea (1%); anorexia, constipation, diarrhea, dry mouth, dyspepsia, taste perversion, vomiting (up to 1%).

Genitourinary

Urinary frequency (more than 1%); impotence (1%); decreased libido (up to 1%).

Lab Tests

Increased ALT, AST, BUN, glucose, serum creatinine, and uric acid.

Metabolic

Hyperkalemia (1%); hypochloremic alkalosis, hypokalemia, hyponatremia.

Musculoskeletal

Hypertonia (2%); back pain (more than 1%); arthralgia, myalgia (up to 1%).

Respiratory

Cough (2%); upper respiratory tract infection (more than 1%).

Miscellaneous

Flu syndrome (more than 1%); gout, pain (including chest and abdominal pain) (up to 1%).

Precautions

Warnings

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


Monitor

Correct volume and/or salt depletion before initiating therapy. Evaluate renal function and measure serum electrolytes before starting therapy and periodically thereafter. Monitor BP and pulse on a regular basis. Monitor blood glucose in diabetic patients when drug is started or dose is changed. Monitor WBC in patients with collagen-vascular disease.


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.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse effects that have occurred in adults.

Lactation

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; it may be useful to monitor renal function.

Hypersensitivity

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors. Hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma.

Renal Function

Use with caution in severe renal disease. Thiazides may precipitate azotemia in these patients, and the effects of repeated dosing may be cumulative. In patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported.

Hepatic Function

Use with caution because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

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.

Diabetes

Thiazides tend to reduce glucose tolerance; overt diabetes may be precipitated in susceptible patients.

Electrolyte imbalance

Hyperkalemia, hypokalemia, hyponatremia, hypochloremic alkalosis, hypercalcemia, hypophosphatemia, and hypomagnesemia may occur.

Hematologic effects

Neutropenia/agranulocytosis has occurred with other ACE inhibitors, particularly in patients with renal impairment or collagen-vascular 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.

Hyperuricemia

Increased uric acid levels or frank gout may occur.

Hypotension

Symptomatic hypotension may occur, especially in salt- or volume-depleted patients, as a result of dialysis, prolonged diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Correct volume and salt depletion before initiating therapy.

Lipid effects

Thiazides tend to raise serum levels of cholesterol and triglycerides.

Ocular effects

Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms occur within hours to weeks of drug initiation.

Postsympathectomy

The antihypertensive effects of hydrochlorothiazide may be enhanced in the postsympathectomy patient.

Renal effects

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF), treatment with ACE inhibitors has been associated with oliguria or progressive azotemia, and, rarely, acute renal failure and/or death. In addition, increased BUN and serum creatinine may occur.

Systemic lupus erythematosus

Thiazides may exacerbate or activate systemic lupus erythematosus.

Overdosage

Symptoms

Dehydration, electrolyte disturbances (hypochloremia, hypokalemia, hyponatremia), hypotension.

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 breathing), and to stop taking benazepril/hydrochlorothiazide until after consulting with their health care provider.
  • Inform female patients of childbearing age about the consequences of exposure to benazepril/hydrochlorothiazide. Discuss other treatment options with women who are 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, benazepril/hydrochlorothiazide 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 use potassium supplements or salt substitutes containing potassium without consulting the prescribing health care provider.
  • Advise patients to promptly report any indication of infection (eg, sore throat, fever), which could be a sign of neutropenia.
  • Instruct diabetic patients to monitor blood glucose more frequently when drug is started or dose is changed, and to inform health care provider of significant changes in readings.
  • Caution patients to avoid unnecessary exposure to UV light (eg, sunlight, tanning booths), and to use sunscreen and wear protective clothing when exposed to UV light to avoid a photosensitivity reaction.

Copyright © 2009 Wolters Kluwer Health.

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