Benazepril Hydrochloride And Hydrochlorothiazide

FDA Drug Information • Also known as: Benazepril Hydrochloride And Hydrochlorothiazide, Lotensin Hct

Brand Names: Benazepril Hydrochloride And Hydrochlorothiazide, Lotensin Hct
Drug Class: Thiazide Diuretic [EPC]
Route: ORAL
Dosage Form: TABLET
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: FETAL TOXICITY When pregnancy is detected, discontinue Benazepril HCl and Hydrochlorothiazide as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (see WARNINGS: Fetal Toxicity) .

Description

DESCRIPTION Benazepril hydrochloride USP is a white to off-white crystalline powder, soluble (>100 mg/mL) in water, in ethanol, and in methanol. Benazepril hydrochloride’s chemical name is 3-[[1-(ethoxycarbonyl)-3- phenyl-(1S)-propyl]amino]-2,3,4,5-tetrahydro-2-oxo-1 H -1-(3S)-benzazepine- 1-acetic acid monohydrochloride; its structural formula is Its empirical formula is C 24 H 28 N 2 O 5 ·HCl, and its molecular weight is 460.96. Benazeprilat, the active metabolite of benazepril, is a nonsulfhydryl angiotensin converting enzyme inhibitor. Benazepril is converted to benazeprilat by hepatic cleavage of the ester group. Hydrochlorothiazide USP is a white, or practically white, practically odorless, crystalline powder. It is slightly soluble in water; freely soluble in sodium hydroxide solution, in n -butylamine, and in dimethylformamide; sparingly soluble in methanol; and insoluble in ether, in chloroform, and in dilute mineral acids. Hydrochlorothiazide’s chemical name is 6-chloro-3,4-dihydro-2 H -1,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide; its structural formula is: Its empirical formula is C 7 H 8 ClN 3 O 4 S 2 , and its molecular weight is 297.73. Hydrochlorothiazide is a thiazide diuretic. Benazepril HCl and Hydrochlorothiazide is a combination of benazepril and hydrochlorothiazide USP. The tablets are formulated for oral administration with a combination of 10 or 20 mg of benazepril and 12.5 or 25 mg of hydrochlorothiazide USP. The inactive ingredients of the tablets are cellulose compounds, crospovidone, hydrogenated castor oil, iron oxides (10/12.5 mg, 20/12.5 mg, and 20/25 mg tablets), lactose, polyethylene glycol, talc, and titanium dioxide. chemical-structure-1 chemical-structure-2

What Is Benazepril Hydrochloride And Hydrochlorothiazide Used For?

INDICATIONS AND USAGE Benazepril HCl and Hydrochlorothiazide is indicated for the treatment of hypertension. This fixed combination drug is not indicated for the initial therapy of hypertension (see DOSAGE AND ADMINISTRATION ) .

Dosage and Administration

DOSAGE AND ADMINISTRATION Dose once daily. The dosage may then be increased after 2 to 3 weeks as needed to help achieve blood pressure goals. The maximum recommended dose is 20/25 mg. Switch Therapy: A patient whose blood pressure is not adequately controlled with benazepril alone or with hydrochlorothiazide alone may be switched to combination therapy with Benazepril HCl and Hydrochlorothiazide. The usual recommended starting dose is 10/12.5 mg once daily to control blood pressure. Replacement Therapy: The combination may be substituted for the titrated individual components.

Side Effects (Adverse Reactions)

ADVERSE REACTIONS Benazepril HCl and Hydrochlorothiazide has been evaluated for safety in over 2500 patients with hypertension; over 500 of these patients were treated for at least 6 months, and over 200 were treated for more than 1 year. The reported side effects were generally mild and transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy due to side effects was required in approximately 7% of U.S. patients treated with Benazepril HCl and Hydrochlorothiazide and in 4% of patients treated with placebo. The most common reasons for discontinuation of therapy with Benazepril HCl and Hydrochlorothiazide in U.S. studies were cough (1.0%; see PRECAUTIONS ), “dizziness” (1.0%), headache (0.6%), and fatigue (0.6%). The side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in more than 1% of patients treated with Benazepril HCl and Hydrochlorothiazide are shown in the table below. Reactions Possibly or Probably Drug Related Patients in U.S. Placebo-Controlled Studies Benazepril HCl and Hydrochlorothiazide N = 665 Placebo N=235 N % N % “Dizziness” 41 6.3 8 3.4 Fatigue 34 5.2 6 2.6 Postural Dizziness 23 3.5 1 0.4 Headache 20 3.1 10 4.3 Cough 14 2.1 3 1.3 Hypertonia 10 1.5 3 1.3 Vertigo 10 1.5 2 0.9 Nausea 9 1.4 2 0.9 Impotence 8 1.2 0 0.0 Somnolence 8 1.2 1 0.4 Other side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in 0.3% to 1.0% of patients treated with Benazepril HCl and Hydrochlorothiazide were the following: Cardiovascular: Palpitations, flushing. Gastrointestinal: Vomiting, diarrhea, dyspepsia, anorexia, and constipation. Neurologic and Psychiatric: Insomnia, nervousness, paresthesia, libido decrease, dry mouth, taste perversion, and tinnitus. Dermatologic: Rash and sweating. Other: Urinary frequency, arthralgia, myalgia, asthenia, and pain (including chest pain and abdominal pain). Other adverse experiences reported in 0.3% or more of Benazepril HCl and Hydrochlorothiazide patients in U.S. controlled clinical trials, and rarer events seen in post-marketing experience, were the following; asterisked entries occurred in more than 1% of patients (in some, a causal relationship to Benazepril HCl and Hydrochlorothiazide is uncertain): Cardiovascular: Syncope, peripheral vascular disorder, and tachycardia. Body as a Whole: Infection, back pain*, flu syndrome*, fever, chills, and neck pain. Dermatologic: Photosensitivity and pruritus. Gastrointestinal: Gastroenteritis, flatulence, and tooth disorder. Neurologic and Psychiatric: Hypesthesia, abnormal vision, abnormal dreams, and retinal disorder. Respiratory: Upper respiratory infection*, epistaxis, bronchitis, rhinitis*, sinusitis*, and voice alteration. Other: Conjunctivitis, arthritis, urinary tract infection, alopecia, and urinary frequency*. Post-Marketing Experience The following adverse reactions have been identified during post-approval use of either benazepril or hydrochlorothiazide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure: Non-melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year. Benazepril Stevens-Johnson syndrome, pancreatitis, hemolytic anemia, pemphigus, and thrombocytopenia, eosinophilic pneumonitis Hydrochlorothiazide Digestive:...

Warnings and Precautions

WARNINGS Anaphylactoid and Possibly Related Reactions Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including benazepril) may be subject to a variety of adverse reactions, some of them serious. Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors. In U.S. clinical trials, symptoms consistent with angioedema were seen in none of the subjects who received placebo and in about 0.5% of the subjects who received benazepril. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with Benazepril HCl and Hydrochlorothiazide should be discontinued and appropriate therapy instituted immediately. When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine injection 1:1000 (0.3 - 0.5 mL) should be promptly administered (see PRECAUTIONS and ADVERSE REACTIONS ). Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to nonblacks. Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema (see PRECAUTIONS ) . Intestinal Angioedema: Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. Anaphylactoid Reactions During Desensitization: Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge. Anaphylactoid Reactions During Membrane Exposure: Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low density lipoprotein apheresis with dextran sulfate absorption. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients with allergy and asthma. Hypotension Benazepril HCl and Hydrochlorothiazide can cause symptomatic...

Drug Interactions

Drug Interactions Neprilysin Inhibitors: Patients taking concomitant neprilysin may be at increased risk for angioedema. Interactions Common for Both Benazepril and Hydrochlorothiazide Potassium Supplements and Potassium Sparing Diuretics: Concomitant use with Benazepril HCl and Hydrochlorothiazide may effect potassium levels. Monitor potassium periodically. mTOR (mammalian target of rapamycin) inhibitors: Patients receiving coadministration of ACE inhibitor and mTOR inhibitor (e.g., tesmsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema (see WARNINGS ) . Lithium: Renal clearance of lithium is reduced by thiazides and increase the risk of lithium toxicity. Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. Monitor lithium levels when used concomitantly with Benazepril HCl and Hydrochlorothiazide. Dual Blockade of the Renin-Angiotensin System (RAS): Dual Blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypertension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Benazepril HCl and Hydrochlorothiazide and other agents that affect the RAS. Do not coadminister aliskiren with Benazepril HCl and Hydrochlorothiazide in patients with diabetes. Avoid use of aliskiren with Benazepril HCl and Hydrochlorothiazide in patients with renal impairment (GFR < 60 mL/min). NSAIDs and Cox-2 selective agents: In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX- 2 inhibitors, with ACE inhibitors, including benazepril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving benazepril and NSAID therapy. The antihypertensive effect of benazepril and hydrochlorothiazide may be attenuated by NSAIDs. Benazepril Benazepril has been used concomitantly with beta-adrenergic-blocking agents, calcium-blocking agents, cimetidine, diuretics, digoxin, hydralazine, and naproxen without evidence of clinically important adverse interactions. Other ACE inhibitors have had less than additive effects with beta adrenergic blockers, presumably because drugs of both classes lower blood pressure by inhibiting parts of the renin-angiotensin system. Interaction studies with warfarin and acenocoumarol have failed to identify any clinically important effects of benazepril on the serum concentrations or clinical effects of these anticoagulants. Gold:...

Contraindications

CONTRAINDICATIONS Benazepril HCl and Hydrochlorothiazide is contraindicated in patients who are anuric. Benazepril HCl and Hydrochlorothiazide is also contraindicated in patients who are hypersensitive to benazepril, to any other ACE inhibitor, to hydrochlorothiazide, or to other sulfonamide-derived drugs. Hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma. Benazepril HCl and Hydrochlorothiazide is also contraindicated in patients with a history of angioedema with or without previous ACE inhibitor treatment. Benazepril HCl and Hydrochlorothiazide is contraindicated in combination with a neprilysin (e.g., sacubitril). Do not administer Benazepril HCl and Hydrochlorothiazide within 36 hours of switching to or from sacubitril/valsartan a neprilysin inhibitor (see WARNINGS and PRECAUTIONS ) . Do not coadminister aliskiren with angiotensin receptor blockers, ACE inhibitors, including Benazepril HCl and Hydrochlorothiazide in patients with diabetes.

Overdosage

OVERDOSAGE No specific information is available on the treatment of overdosage with Benazepril HCl and Hydrochlorothiazide; treatment should be symptomatic and supportive. Therapy with Benazepril HCl and Hydrochlorothiazide should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance, and hypotension should be treated by established procedures. Single oral doses of 1 g/kg of benazepril caused reduced activity in mice, and doses of 3 g/kg were associated with significant lethality. Reduction of activity in rats was not seen until they had received doses of 5 g/kg, and doses of 6 g/kg were not lethal. In single-dose studies of hydrochlorothiazide, most rats survived doses up to 2.75 g/kg. Data from human overdoses of benazepril are scanty, but the most common manifestation of human benazepril overdosage is likely to be hypotension. In human hydrochlorothiazide overdose, the most common signs and symptoms observed have been those of dehydration and electrolyte depletion (hypokalemia, hypochloremia, hyponatremia). If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. Laboratory determinations of serum levels of benazepril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of benazepril overdose. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of benazepril and its metabolites. Benazeprilat is only slightly dialyzable, but dialysis might be considered in overdosed patients with severely impaired renal function (see WARNINGS ) . Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of benazepril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of benazepril is achieved through vasodilation and effective hypovolemia, it is...

How Supplied

HOW SUPPLIED Benazepril HCl USP and Hydrochlorothiazide USP is available in tablets of three different strengths: Benazepril HCl Hydrochlorothiazide Tablet Color 10 mg 12.5 mg light pink 20 mg 12.5 mg grayish violet 20 mg 25 mg red Tablets of each strength are supplied in bottles that contain a desiccant and 100 tablets. The National Drug Codes for the various packages are: Dose Bottle of 100 Tablet Imprint 10/12.5 NDC 0574-0227-01 452 20/12.5 NDC 0574-0229-01 453 20/25 NDC 0574-0228-01 454 Tablets are oblong and scored, with “LOTENSIN HCT” on one side and appropriate number imprinted on the other side. Storage: Do not store above 86°F (30°C). Protect from moisture and light. Dispense in a tight, light‑resistant container (USP). Distributed By: Padagis TM Allegan, MI 49010 www.padagis.com 37Y00 RC J5 Rev 11-22 Manufactured for: Validus Pharmaceuticals LLC Parsippany, NJ 07054 © 2022 Validus Pharmaceuticals LLC 60160-04 November 2022

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.