DIAO Benazepril Hydrochloride Tablets For Hypertension 10mg*20

[Drug Name]
Generic Name: Benazepril Hydrochloride Tablets
Trade Name: DiAo Benazepril Hydrochloride Tablets 10mg*20 Tablets
Pinyin Full Code: DiAo YanSuanBeiNaPuLiPian 10mg*20 Tablets

[Main Ingredients]
The main ingredient of this product is benazepril hydrochloride, whose chemical name is: (1'S,3S)-3-{[1'-(ethoxycarbonyl)-3'-phenylpropyl]-amino}-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid monohydrochloride. Molecular Formula: C24H28N2O5·HCl. Molecular Weight: 460.96

[Properties]
This product is a film-coated tablet that appears white or off-white after removal of the film coating.

[Indications/Main Functions]
1. This product is indicated for the treatment of hypertension and can be used alone or in combination with thiazide diuretics. When using benazepril hydrochloride, the fact that another ACE inhibitor (i.e., captopril) can cause granulocytopenia must be considered, particularly in patients with renal impairment or collagen vascular disease. There is insufficient evidence to demonstrate that benazepril hydrochloride does not carry a similar risk. 2. Congestive Heart Failure. As an adjunctive therapy for patients with congestive heart failure (NYHA class I-IV) who have an inadequate response to digitalis and/or diuretics.

[Specifications]
10mg*20 tablets

[Dosage and Administration]
1. Hypertension: When starting treatment without diuretics, the recommended daily dose is 10mg (1 tablet) once daily. If efficacy is insufficient, the dose can be increased to 20mg (2 tablets) daily. For some patients taking once-daily dosing, the antihypertensive effect may diminish at the end of the dosing interval. In such patients, the total daily dose should be divided into two doses, or a diuretic should be added. The maximum recommended daily dose for the treatment of hypertension is 40mg (4 tablets), taken once or twice. If benazepril hydrochloride alone fails to control blood pressure, a diuretic may be added. Combination use of benazepril hydrochloride with potassium supplements, potassium substitutes, or potassium-sparing diuretics may cause elevated serum potassium. Dosage adjustment for patients with renal impairment: Patients with a creatinine clearance ≥30 ml/min can take the usual dose. For patients with a creatinine clearance <30 ml/min/1.73 m² (serum creatinine >3 mg/dL), the recommended initial dose is 5 mg (half a tablet) once daily. The dose can be increased to 10 mg (one tablet) daily if necessary. If further blood pressure reduction is required, a diuretic or another antihypertensive medication may be added (see Precautions: Hemodialysis Patients). 2. Congestive Heart Failure: This product is indicated as adjunctive therapy for patients with congestive heart failure. The recommended initial dose is 2.5 mg (one-quarter tablet) once daily. Due to the risk of a sharp drop in blood pressure after the first dose, patients require close monitoring when taking this product for the first time (see Precautions). If heart failure symptoms are not effectively relieved after 2-4 weeks, the dose can be increased to 5 mg (half a tablet) once daily, provided the patient does not experience symptomatic hypotension or other unacceptable side effects. Depending on the patient's clinical response, the dose can be increased to 10 mg (one tablet) once daily or even 20 mg (two tablets) once daily at appropriate intervals. This product is effective with a single daily dose, but some patients respond better if the daily dose is divided into two doses. Controlled clinical studies have shown that patients with severe heart failure (NYHA class IV) require a lower dose than those with mild or moderate heart failure (NYHA class I-ш). When the creatinine clearance in patients with heart failure is less than 30 ml/min, the daily dose can be increased to a maximum of 10 mg (one tablet), but a lower initial dose (e.g., 2.5 mg (one-quarter tablet)) may be sufficient.

[Adverse Reactions]
1. Adverse Reactions in Hypertensive Patients: The safety of benazepril was evaluated in 6,000 hypertensive patients, including over 700 who were treated with benazepril for at least one year. The overall incidence of adverse reactions was similar between the benazepril and placebo groups, and adverse reactions were mild and transient. Adverse reactions were not related to age, duration of treatment, or total dose. The most common reasons for discontinuation were headache (0.6%) and cough (0.5%). In placebo-controlled trials conducted in the United States, adverse reactions with an incidence >1% and possibly related to the study drug included headache, dizziness, fatigue, somnolence, postural dizziness, nausea, and cough. Other adverse reactions reported in controlled clinical trials (less than 1%) and extremely rare post-marketing adverse reactions (some of which are not clearly related to the drug) are as follows: Cardiovascular: symptomatic hypotension 0.3%, postural hypotension 0.4%, syncope 0.1%. Four patients receiving benazepril alone discontinued treatment due to the aforementioned adverse reactions, while nine patients receiving benazepril plus hydrochlorothiazide discontinued treatment. Other adverse reactions reported included angina, palpitations, and limb edema. Fetal/neonatal morbidity and mortality: See Precautions, Pregnant Women. Angioedema: Angioedema has been reported with the use of ACE inhibitors. In clinical studies, only 0.5% of hypertensive patients taking benazepril experienced lip or facial edema; no other manifestations of angioedema were observed. Angioedema with laryngeal edema and shock can be fatal. If edema of the face, limbs, lips, tongue, glottis, or larynx occurs, discontinue benazepril and initiate appropriate treatment immediately (see WARNINGS). Gastrointestinal: Constipation, gastritis, vomiting, pancreatitis, and melena. Psychiatric: Anxiety, decreased libido, insomnia, nervousness, and paresthesias. Skin: Stevens-Johnson syndrome, pemphigus, allergic reactions (dermatitis, pruritus, rash), photosensitivity, flushing. Blood: Thrombocytopenia, hemolytic anemia. Other: Asthma, bronchitis, dyspnea, sinusitis, infection, arthritis, urinary tract infection, impotence, alopecia, arthralgia, myalgia, asthenia, and hyperhidrosis. Other possible serious adverse reactions: Eosinophilic pneumonia has been reported with other ACE inhibitors. Clinical laboratory findings: Creatinine, BUN: Approximately 2% of hypertensive patients without overt renal disease experienced a persistent increase in serum creatinine exceeding 150% of baseline values during benazepril treatment. Most patients recovered with continued treatment, and less than 0.1% of patients experienced concurrent (usually transient) increases in both BUN and creatinine. These increases did not require discontinuation of treatment. These increases are more likely to occur in patients with renal insufficiency or those receiving pre-existing diuretics. Based on experience with other ACE inhibitors, they are more likely to occur in patients with renal artery stenosis. Potassium: Because benazepril reduces aldosterone secretion, elevated potassium may occur. Potassium supplements, potassium substitutes, and potassium-sparing diuretics should be used with caution, and serum potassium should be monitored carefully. Hemoglobin: Decreased hemoglobin is uncommon. According to literature data, only one case of decreased hemoglobin occurred in 2014 patients receiving benazepril monotherapy. Other (causal relationship unclear): Elevated uric acid, blood glucose, serum bilirubin, and liver enzymes have been reported. Hyponatramia, electrocardiographic changes, leukopenia, eosinophilia, and proteinuria have also been reported. In US trials, discontinuation of treatment due to abnormal laboratory test results was less than 0.5%. 2. In patients with heart failure: In controlled clinical trials, 180 patients with heart failure were treated with benazepril hydrochloride at 2 to 20 mg daily. The incidence of common adverse reactions was comparable to that of patients taking placebo, with the only event being dizziness, which was more common in the benazepril hydrochloride group than in the placebo group. The following symptoms occurred more frequently in the benazepril hydrochloride group than in the placebo group: muscle cramps, abdominal pain, fatigue, malaise, and postural dizziness. The incidence of upper respiratory symptoms was higher in the placebo group than in the benazepril hydrochloride group. Laboratory tests revealed no clinically significant changes.

[Contraindications]
Patients with a hypersensitivity to benazepril hydrochloride or any ACE inhibitor. Patients with a history of angioedema. Patients with solitary kidney, transplanted kidney, or bilateral renal artery stenosis and impaired renal function.

[Precautions]
General 1. Renal Impairment: Inhibition of the renin-angiotensin-aldosterone system may result in changes in renal function in susceptible patients. In patients with severe congestive heart failure, renal function may be dependent on the activity of the renin-angiotensin-aldosterone system. Treatment with angiotensin-converting enzyme inhibitors (including benazepril hydrochloride) in such patients may result in oliguria, progressive azotemia (rarely), acute renal failure, and even death. In studies of hypertensive patients with solitary or bilateral renal artery stenosis, benazepril hydrochloride administration was associated with elevations in blood urea nitrogen (BUN) and serum creatinine. These elevations resolved with discontinuation of benazepril, diuretics, or both. For patients with these and other renal diseases, renal function should be closely monitored during the first few weeks of benazepril therapy and regularly thereafter. In some hypertensive patients without renal vascular disease or renal impairment, elevations in BUN and serum creatinine are mild and transient, particularly when benazepril hydrochloride is combined with diuretics. Patients with preexisting renal impairment are more likely to experience elevations in BUN and serum creatinine and should reduce the benazepril hydrochloride dose or discontinue diuretics. 2. Hemodialysis Patients: Anaphylactoid reactions have been reported in patients receiving certain ACE inhibitors while on hemodialysis with a high-flow semipermeable membrane. For such patients, consideration should be given to switching to a different type of semipermeable membrane or taking a different antihypertensive medication. 3. Hyperkalemia: In clinical trials, approximately 1% of hypertensive patients treated with benazepril hydrochloride developed hyperkalemia (serum potassium at least 0.5 mEq/dL above the upper limit of normal). Risk factors for hyperkalemia include renal insufficiency, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes. These factors should be considered when using benazepril hydrochloride. 4. Cough: ACE inhibitors have been reported to cause a persistent, dry, nonproductive cough that often resolves after discontinuation of therapy. ACE inhibitor use can cause cough and should be considered in the differential diagnosis of cough. 5. Hepatic Impairment: In patients with hepatic impairment due to cirrhosis, benazepril plasma concentrations remain unchanged. 6. Surgery/Anesthesia: Patients receiving ACE inhibitors should inform their anesthesiologist before surgery. In patients undergoing surgery or receiving anesthetics that lower blood pressure, compensatory renin release can promote angiotensin I production. Benazepril's inhibition of angiotensin I production will result in a significant decrease in blood pressure. Hypotension caused by this mechanism can be corrected by volume replacement. Warnings: 1. Allergic Reactions and Possible Related Reactions: Because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and peptides (including endogenous bradykinin), patients taking ACE inhibitors (including benazepril hydrochloride) may experience a variety of adverse reactions, some of which are serious. 2. Angioedema: Angioedema of the face, hands, feet, mouth, lips, tongue, glottis, and larynx has been reported in patients taking ACE inhibitors. In US clinical trials, no placebo-treated subjects experienced angioedema, while approximately 0.5% of patients taking benazepril experienced angioedema. Laryngeal angioedema can be fatal. If laryngeal wheezing or angioedema of the face, tongue, or glottis occurs, discontinue the drug immediately and initiate treatment immediately. Because swelling of the tongue, glottis, or larynx can lead to airway obstruction, appropriate treatment should be initiated immediately, such as immediate subcutaneous injection of 1:1000 epinephrine (0.3-0.5 ml). 3. Allergic Reactions During Desensitization: Two patients undergoing desensitization therapy for hymenopteran insect venoms experienced fatal allergic reactions while taking ACE inhibitors. Discontinuation of ACE inhibitor use in these patients avoided the allergic reactions, but the reactions recurred upon reinitiation. 4. Hypotension: Benazepril hydrochloride can cause symptomatic hypotension. Similar to other ACE inhibitors, hypotension is rare in patients with uncomplicated hypertension taking benazepril hydrochloride. Symptomatic hypotension often occurs in patients with chronic diuretic use that causes decreased blood volume and sodium levels, or in patients with inadequate sodium intake, dialysis, diarrhea, or vomiting. Blood volume and/or salt deficiencies should be corrected before starting benazepril hydrochloride therapy. In patients with congestive heart failure, with or without renal insufficiency, the use of ACE inhibitors can cause hypotension, oliguria, azotemia, and rarely, acute renal failure and death. Such patients should be carefully monitored before starting benazepril. Physicians should provide close monitoring during the first two weeks of treatment and whenever the benazepril or diuretic dosage is increased. If hypotension occurs, the patient should be placed supine, and normal saline should be administered intravenously as needed. Benazepril hydrochloride treatment can usually be continued after blood pressure and blood volume have been restored. 5. Neutropenia/Agranulocytosis: Captopril has been shown to cause agranulocytosis and bone marrow suppression. This is rare in uncomplicated patients but is more common in patients with renal impairment, particularly those with collagen vascular diseases such as systemic lupus erythematosus or scleroderma. Clinically, there is insufficient evidence to demonstrate that benazepril does not cause agranulocytosis with the same frequency. Patients with collagen vascular diseases, particularly those with renal impairment, should closely monitor their white blood cell count. 6. Liver Failure: ACE inhibitors have been reported to be associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis, sometimes resulting in death. The mechanism of this syndrome is unknown. Patients receiving ACE inhibitors who develop jaundice or significant elevations in liver enzymes should have their ACE inhibitors discontinued and receive appropriate treatment and follow-up. 7. Effects on driving and operating machines: Patients taking this product rarely experience central nervous system symptoms. Like other antihypertensive drugs, patients should pay attention to these effects when driving and operating machines.