Hydrochlorothiazide + Benazepril

Indications

Hydrochlorothiazide + Benazepril is used for: Hypertension

Adult Dose

Hypertension Not for initial therapy If BP not controlled with benazepril monotherapy: Initiate with 10 mg/12.5 mg OR 20 mg/12.5 mg PO qDay Increase either or both components based on clinical response Do not increase hydrochlorothiazide component more often than q2-3 wk Hepatic impairment: Dosage adjustment not required

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment CrCl ?30 mL/min: No dosage adjustment CrCl <30 mL/min: Not recommended; loop diuretics preferred

Administration

Oral Administration Food decreases absorption; manufacturer recommends administering 1 hr before meal

Contra Indications

Hypersensitivity to either component or sulfonamides History of hereditary or angioedema associated with or without previous ACE inhibitor treatment Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan Bilateral renal artery stenosis or anuria Do not coadminister with aliskiren in patients with diabetes

Precautions

Excessive hypotension if concomitant diuretics, hypovolemia, hyponatremia Risk of hyperkalemia, especially with renal impairment, DM or those taking concomitant K+-elevating drugs Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with Lotensin HCT should be discontinued and appropriate therapy instituted immediately Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema DM, fluid or electrolyte imbalance, hyperuricemia or gout, SLE, liver disease, renal disease May aggravate digitalis toxicity Sensitivity reactions may occur with or without history of allergy or asthma Biliary cirrhosis or biliary obstruction Myelosuppression Renal impairment may occur Neutropenia/agranulocytosis reported Cough may occur within the first few months Cholestatic jaundice may occur Risk of male sexual dysfunction Avoid concomitant use with lithium Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)

Pregnancy-Lactation

Pregnancy Category: D Lactation: excreted in breast milk, use caution

Interactions

Adverse Effects

Side effects of Hydrochlorothiazide + Benazepril : Benazepril 1-10% Cough (1-10%) Dizziness (4%) Fatigue (2%) Headache (6%) Nausea (1%) Postural dizziness (2%) Serum creatinine increased (2%) Somnolence (2%) <1% Angioedema, ARF if renal artery stenosis, neutropenia, photosensitivity, agranulocytosis, alopecia, anaphylactoid reaction, angina, angioedema, arthralgia, arthritis, asthma, dermatitis, dyspnea, ECG changes, eosinophilia, flushing, gastritis, hemolytic anemia, hyperglycemia, hyperkalemia, hyponatremia, hypotension, impotence, insomnia, leukopenia, neutropenia, palpitations, pancreatitis, postural hypotension, proteinuria, rash, Stevens-Johnson syndrome, syncope, thrombocytopenia, transaminases increased, uric acid increased, vomiting Hydrochlorothiazide Frequency Not Defined Anorexia Epigastric distress Hypotension Orthostatic hypotension Photosensitivity <1% Anaphylaxis, anemia, confusion, dizziness, erythema multiforme skin reactions including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, fatigue, hypomagnesemia, hyponatremia, hypochloremia, headache, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, hypercholesterolemia, muscle weakness or cramps, nausea, purpura, rash, vertigo, vomiting

Mechanism of Action

Benazepril/hydrochlorothiazide is a fixed-combination tablet that combines an angiotensin-converting enzyme (ACE) inhibitor, benazepril, and a thiazide diuretic, hydrochlorothiazide Benazepril prevents the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through inhibition of ACE by competing with physiologic substrate (angiotensin I) for active site of ACE; inhibition of ACE initially results in decreased plasma angiotensin II concentrations & consequently, blood pressure may be reduced in part through decreased vasoconstriction, increased renin activity, & decreased aldosterone secretion Hydrochlorothiazide is a thiazide diuretic that inhibits Na reabsorption in distal renal tubules resulting in increased excretion of Na+ and water, also K+ and H+ ions