NOVARTIS LUOTINGXIN Benazepril Hydrochloride Tablets For Hypertension 5mg*14

[Drug Name]
Generic Name: Benazepril Hydrochloride Tablets
Trade Name: Lotensin
English Name: Benazepril Hydrochloride Tablets
Chinese Pinyin: Yansuan Beinapuli pian

[Ingredients]
Active ingredient: Benazepril Hydrochloride

[Properties]
This product is a film-coated tablet. It appears white after the film coating is removed.

[Indications]
1. Hypertension at all stages. 2. Congestive heart failure. 3. As an adjunctive treatment for patients with congestive heart failure (NYHA class II-IV) who are inadequately responsive to digitalis and/or diuretics.

[Dosage and Administration]
1. Hypertension: For patients not taking diuretics, the recommended initial daily dose is 10 mg once daily. If response is inadequate, the dose may be increased to 20 mg daily. The dose should be adjusted based on blood pressure response, typically every 1 to 2 weeks. For some patients, the antihypertensive effect may diminish at the end of the dosing interval. For such patients, the total daily dose should be divided into two doses, or a diuretic should be added. The maximum recommended daily dose of this product for the treatment of hypertension is 40 mg, taken once or divided into two doses. If the blood pressure reduction achieved with this product alone is unsatisfactory, another antihypertensive drug, such as a thiazide diuretic, calcium antagonist, or beta-blocker, can be added (starting with a low dose). If diuretics have been used previously, diuretic therapy should be discontinued for 2 to 3 days before starting Lotensin treatment, but can be continued thereafter if necessary. If diuretic discontinuation is not possible, the initial Lotensin dose should be reduced (5 mg instead of 10 mg) to avoid hypotension (see [Precautions]). Patients with creatinine clearance ≥30 ml/min can take the usual dose. For patients with creatinine clearance <30 ml/min, the initial daily dose is 5 mg, which can be increased to 10 mg/day if necessary. If further blood pressure reduction is still required, a diuretic or another antihypertensive drug can be added. 2. Congestive Heart Failure: This product is indicated for adjunctive treatment of patients with congestive heart failure. The recommended initial dose is 2.5 mg (5 mg, half a tablet) once daily. Due to the risk of a sharp drop in blood pressure after the first dose, patients should be closely monitored when taking this product for the first time (see [Precautions]). If heart failure symptoms are not effectively relieved, the dose can be increased to 5 mg once daily after 2-4 weeks, 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 once daily or even 20 mg once daily at appropriate intervals. This product is effective with a single daily dose. However, some patients may 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 lower doses than patients with mild or moderate heart failure (NYHA class II-III).
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, but a lower initial dose (e.g., 2.5 mg (5 mg, half a tablet)) may be more ideal. 3. Progressive Chronic Renal Insufficiency (CRI): For patients with progressive CRI with or without hypertension, the recommended long-term dose is 10 mg once daily. If additional treatment is required to further lower blood pressure, it can be used in combination with other antihypertensive drugs.

[Adverse Reactions]
1. Angioedema: Lip or facial edema has occurred with this drug. If this symptom occurs, discontinue the drug immediately and monitor the patient until the edema resolves. Edema of the glottis, tongue, or larynx may cause airway obstruction; discontinue the drug and initiate appropriate treatment immediately, such as subcutaneous injection of a 1:1000 epinephrine solution (0.3 ml to 0.5 ml).
2. Hypotension: Patients with severe sodium deficiency and volume depletion may experience hypotension when taking this drug (such as those receiving large amounts of diuretics or dialysis). Diuretics should be discontinued or other measures should be taken to replenish body fluids several days before starting this drug. Patients at risk of severe hypotension (such as those with heart failure) should be closely monitored after the first dose until their blood pressure stabilizes. If hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline.
3. Granulocytopenia: Patients with autoimmune diseases and renal insufficiency are more likely to experience leukopenia or granulocytopenia. For patients with renal insufficiency or leukopenia, check the white blood cell count and differential every two weeks for the first three months and regularly thereafter.
4. Renal Insufficiency: A small number of patients may experience transient increases in blood urea nitrogen (BUN) and creatinine after taking this drug, which resolve with discontinuation of this drug and/or diuretics. For patients with renal insufficiency, renal function should be closely monitored during the first few weeks of treatment and then regularly thereafter. If the creatinine clearance is less than 30 ml/min or if BUN or creatinine levels are elevated while taking this drug, the dose should be reduced and/or diuretics should be discontinued.
5. Other: Elevated serum potassium may occasionally occur, particularly in patients with renal insufficiency. (See inner package insert for details)

[Contraindications]
1. Patients with known hypersensitivity to benazepril, related compounds, or any of the excipients of this product.
2. Patients with a history of angioedema caused by or not caused by angiotensin-converting enzyme inhibitors.
3. Pregnant women (see [Use in Pregnant and Lactating Women]).

[Precautions]
1. Anaphylactic and Related Reactions: Because ACE inhibitors can affect the metabolism of eicosanoids and peptides (including endogenous bradykinin), patients taking ACE inhibitors (including Lotensin) may experience adverse reactions, some of which may be severe.
2. Angioedema: Edema of the face, lips, tongue, glottis, and larynx has been reported with the use of ACE inhibitors (including Lotensin). If such symptoms occur, discontinue this product immediately and monitor the patient carefully until the swelling resolves. If only facial and lip edema occurs, this symptom will resolve without antihistamines or treatment. Angioedema with laryngeal edema and shock can be fatal. Edema of the tongue, glottis, or larynx requires prompt and appropriate treatment.

[Special Use]
Precautions for Pediatric Use:
No data are available on the safety and efficacy of this drug in children.
Precautions for Pregnancy and Lactation:
This drug should not be used by pregnant women (see [Contraindications]). 1. Pregnancy: ACE inhibitors used by pregnant women may cause fetal or neonatal morbidity or death. Dozens of such cases have been reported in the literature worldwide. Use of ACE inhibitors during the second and third trimesters of pregnancy may cause fetal and neonatal harm, including hypotension, neonatal skull deformity, anuria, reversible or irreversible renal impairment, and even death. The resulting polyhydramnios often leads to limb contractures, facial deformities, and pulmonary hypoplasia in infants. Premature birth, intrauterine growth retardation, and patent ductus arteriosus have also been reported, but it is unclear whether these symptoms are related to ACE inhibitor use. Use of ACE inhibitors during the first trimester is associated with an increased risk of birth defects. Once pregnancy is confirmed, ACE inhibitors should be discontinued immediately, and fetal growth and development should be monitored regularly. ACE inhibitors (including Lotensin) should also be avoided in women planning pregnancy. Women of childbearing age should be specifically informed of the potential risks of taking ACE inhibitors (including Lotensin). They should only be administered after careful consideration and discussion of the associated risks and benefits. 2. Breastfeeding Women: Benazepril and benazeprilat have been found to be excreted in breast milk, but the maximum concentration is only 0.3% of that in plasma. Negligible amounts of benazeprilat reach the infant's systemic circulation. Although adverse effects on breastfed infants are unlikely, this drug is not recommended for use during breastfeeding.
Precautions for Elderly Patients:
This drug should be used in the same manner as adults.

[Drug Interactions]
1. In patients taking diuretics or experiencing fluid depletion, initial treatment with ACE inhibitors may occasionally result in hypotension. Discontinuing diuretics 2-3 days before initiating this drug can reduce the incidence of hypotension. (See [Dosage and Administration] and [Precautions]). 2. Patients taking ACE inhibitors should avoid coadministration with potassium-sparing diuretics (such as spironolactone, triamterene, and amiloride), as well as potassium supplements or potassium-containing electrolyte solutions, as this may lead to a significant increase in serum potassium. If coadministration is necessary, serum potassium levels should be closely monitored.
3. Increased serum lithium concentrations and symptoms of lithium toxicity have been reported in patients taking ACE inhibitors and concurrently receiving lithium therapy. Therefore, caution should be exercised regarding such combined therapy, and regular monitoring of serum lithium concentrations is recommended. The risk of lithium toxicity may be increased if diuretics are used concurrently.
4. The antihypertensive efficacy of ACE inhibitors has been shown to be reduced when used concurrently with indomethacin. However, in a controlled clinical trial, indomethacin did not affect the antihypertensive efficacy of Lotensin.
5. Rare cases of hypoglycemia have occurred in diabetic patients receiving insulin or oral hypoglycemic agents concurrently with ACE inhibitors (including benazepril). Therefore, such patients should be warned of the potential for hypoglycemia and monitored accordingly. 6. Patients receiving injectable gold preparations (sodium aurothiobutyrate) concurrently with ACE inhibitors have experienced rare nitrite-like reactions (including flushing, nausea, vomiting, and hypotension).

[Pharmacological Action]
This product is a prodrug that hydrolyzes into the active substance, benazeprilat, which inhibits angiotensin-converting enzyme (ACE), preventing the conversion of angiotensin I to angiotensin II. This reduces the symptoms associated with angiotensin II, namely vasoconstriction and aldosterone production (the latter leading to renal tubular sodium and water reabsorption and increased cardiac output). Lotensin reduces the reflex sympathetic response to vasodilation that increases heart rate. 1. Hypertension: Like other ACE inhibitors, Lotensin also reduces the degradation of the vasodilator bradykinin by inhibiting kininase. This inhibitory effect contributes to its antihypertensive efficacy. Lotensin generally lowers sitting, supine, and standing blood pressure in patients with all stages of hypertension. In most patients, the antihypertensive effect begins one hour after a single oral dose, with maximum antihypertensive effect achieved between two and four hours. The antihypertensive effect persists for at least 24 hours after administration. With repeated dosing, the maximum antihypertensive effect is achieved after one week per dose and is maintained with long-term treatment. The maintenance of the antihypertensive effect is independent of patient race, age, or baseline plasma renin activity. The antihypertensive effect of Lotensin is not significantly associated with dietary sodium content. Abrupt discontinuation of Lotensin treatment does not result in a sudden increase in blood pressure. In a study of healthy subjects, a single dose of Lotensin resulted in an increase in renal blood flow but had no effect on glomerular filtration rate. The antihypertensive effects of Lotensin and thiazide diuretics are synergistic. Combining Lotensin with other antihypertensive medications, including beta-blockers and calcium channel blockers, generally results in a more potent antihypertensive effect. 2. Congestive Heart Failure (CHF): In patients with CHF previously treated with digitalis and diuretics, Lotensin can increase cardiac output and exercise tolerance, and reduce pulmonary artery wedge pressure, systemic vascular resistance, and blood pressure. Heart rate may also decrease slightly. Lotensin can also help reduce adverse reactions such as fatigue and edema and improve NYHA class in patients with CHF. Clinical trials have shown that once-daily dosing can improve hemodynamics over a 24-hour period. 3. Progressive Chronic Renal Failure: In a three-year, multicenter, double-blind, placebo-controlled clinical trial, 583 patients with renal disease (with and without hypertension) of varying etiologies and serum creatinine levels of 1.4 to 4 mg/dL (creatinine clearance of 30 to 60 mU/min) were randomly assigned to receive either a 10 mg placebo or Lotensin once daily. To control blood pressure, patients in both study groups received additional oral antihypertensive medications as needed. Compared with the placebo group, the risk of a doubling of serum creatinine or the need for hemodialysis was reduced by 53% in the Lotensin group. Lotensin also lowered blood pressure and significantly reduced proteinuria. In patients with polycystic kidney disease, Lotensin did not slow the rate of renal function decline. However, Lotensin can still be used in these patients to control hypertension.

Storage: Store tightly closed below 30°C.

Specifications: 5mg x 14 tablets

Packaging: Box

Expiration Date: 36 months

Approval Number: National Medicine Standard H20000292

Manufacturer: Beijing Novartis Pharmaceuticals Co., Ltd.