Date of approval.
Date of revision.
Benazepril hydrochloride tablets instructions
Please read the instructions carefully and use under the guidance of a physician
Warning
This product should be discontinued as soon as pregnancy is detected. During the second and third trimester (fourth-ninth month) of pregnancy, drugs of the renin-angiotensin system can cause fetal damage or even death. For more information, see [Medication for Pregnant and Lactating Women].
Drug Name]
Generic name: Benazepril Hydrochloride Tablets
English name: Benazepril Hydrochloride Tablets
Hanyu Pinyin: Yansuan Beinapuli Pian
Ingredients
Active ingredient: Benazepril Hydrochloride
Chemical name: 3-[(1-Ethoxycarbonyl)-3-phenyl-(1S)-propyl]ammonia}-2,3,4,5-tetrahydro-2-oxo-1-hydro-1-(3S)-benzazepine-1-acetic acid monohydrochloride
Chemical structure formula.
Molecular formula: C24H28N2O5-HCl
Molecular weight: 460.96
Properties
This product is a film-coated tablet, which appears white or off-white after removing the film coating.
Indications
For the treatment of hypertension.
Congestive heart failure. As an adjunctive therapy for patients with congestive heart failure (NYHA class II-IV) who do not respond well to digitalis and/or diuretics.
Specification
5mg, 10mg
Dosage and Administration
Hypertension.
The recommended daily dose is 10 mg once daily at the start of treatment in patients without diuretics, and may be increased to 20 mg once daily if efficacy is poor. doses must be adjusted according to blood pressure response and should usually be adjusted every 1 to 2 weeks.
In some patients, the antihypertensive effect may diminish towards the end of the dosing interval, in which case 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 in one or two divided doses.
If the decrease in blood pressure is not satisfactory with this product alone, another antihypertensive agent, such as a thiazide diuretic, calcium antagonist or beta-blocker, may be added (starting with a small dose). In patients who have been previously treated with diuretics, especially those with excessive sodium loss and/or fluid loss, careful consideration should be given to the timing of dosing or tapering of the drug when starting this product. This includes reducing the dose or suspending the diuretic for a period of time (e.g., 2 to 3 days) prior to the start of Benadryl hydrochloride therapy or reducing the starting dose of Benadryl hydrochloride to 5 mg to avoid hypotension (see [Precautions]). Fluid and/or sodium loss should be corrected prior to initiating treatment with this product.
Patients with creatinine clearance greater than or equal to 30 mL/min should take the usual dose. For patients with a clearance of less than 30 mL/min, the initial daily dose is 5 mg, and if necessary, the dose may be increased to 10 mg/day. If further lowering of blood pressure is required, diuretics or another antihypertensive drug may be added.
Congestive Heart Failure.
This product is indicated as an adjunctive therapy for patients with congestive heart failure. The recommended initial dose is 2.5 mg (5 mg, half a tablet) once a day. Because of the risk of a dramatic drop in blood pressure after the first dose, patients should be closely monitored when taking this product for the first time (see [Precautions]). The dose may be adjusted to 5 mg once a day after 2 to 4 weeks if symptoms of heart failure do not resolve effectively, provided the patient does not develop symptomatic hypotension and other unacceptable side effects. Depending on the patient’s clinical response, the dose may be adjusted to 10 mg once a day or even 20 mg once a day at appropriate intervals. This product is effective once a day. In some patients, however, the response may be better if the one-day 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 to moderate heart failure (NYHA class II-III).
In patients who are on prior diuretic therapy, especially those with excessive sodium loss and/or fluid loss, special caution is recommended when adding this product and it should be specifically monitored when administered. Depending on the clinical situation, it may be necessary to consider a dose reduction or temporary discontinuation of diuretic therapy drugs prior to initial treatment with this product. Correction of blood volume and/or sodium loss prior to initiation of therapy with this product.
When creatinine clearance is less than 30 mL/min in patients with heart failure, the daily dose may be increased up to 10 mg, but a lower initial dose [e.g., 2.5 mg (5 mg, half tablet)] may be preferable.
Progressive chronic renal insufficiency (CRI)
For patients with progressive chronic renal insufficiency with/without hypertension, the recommended long-term dose is 10 mg once daily, which may be combined with other antihypertensive drugs if additional therapy is needed to further lower blood pressure.
Adverse Reactions
This product is well tolerated. The following are the adverse reactions associated with Benazepril and other ACE inhibitors.
Adverse reactions to the drug in children are similar to those in adults. No information is available on long-term dosing in children and its effects on growth, pubertal development, and general development.
Adverse reactions reported from multiple sources (Table 1) were ranked by frequency of occurrence, first and most frequently, using the following stipulations: very common (≥ 1/10); common (≥ 1/100, < 1/10); rare (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000 ) and very rare (< 1/ 10,000), including individual case reports. Within each frequency group, adverse reactions are listed in descending order.
Table 1
Hematologic and lymphatic disorders Very rare: hemolytic anemia , thrombocytopenia (see [Precautions]) Immune system disorders Rare: angioedema, lip and facial edema (see [Precautions]) Psychiatric disorders Rare: insomnia, nervousness and sensory abnormalities Neurologic disorders Common: headache, dizziness Rare: drowsiness Very rare: taste disturbances Ear and vestibular disorders Very rare: tinnitus Heart disorders Common: palpitations, upright intolerance symptoms Rare: symptomatic hypotension, chest pain, angina, arrhythmias Very rare: myocardial infarction Vascular disorders Common: flushing Respiratory, thoracic and mediastinal disorders Common: cough, upper respiratory tract infection symptoms Gastrointestinal disorders Common: gastrointestinal disorders Rare: diarrhea, constipation, nausea, vomiting, abdominal pain Very rare: pancreatitis Hepatobiliary immune disorders Rare: hepatitis (mainly Cholestatic hepatitis), cholestatic jaundice (see [Precautions]) Skin and subcutaneous tissue disorders Common: rash, pruritus, photosensitivity reactions Rare: aspergillosis Very rare: Stevens-Johnson syndrome Musculoskeletal and connective tissue disorders Rare: arthralgia, arthritis, myalgia Renal and urinary disorders Common: dysuria Rare: elevated blood urea nitrogen levels, elevated serum Very rare: impaired renal function (see [Precautions]) Systemic discomfort and site of administration reactions Common: fatigue
Post-marketing adverse drug reactions reported with Benazepril
Based on post-marketing experience, the following adverse drug reactions have been identified (Table 2). Because these reactions were voluntarily reported by groups with uncertain sample sizes, it was not always possible to reliably estimate their frequency.
Table 2
Hematologic and lymphatic system disorders Granulocyte deficiency, neutropenia Immune system disorders Small bowel angioedema, allergic-like reactions Metabolic and nutritional disorders Hyperkalemia Ocular disorders Visual impairment
Laboratory Tests
Similar to other ACE inhibitors, treatment with this product alone may result in a mild increase in blood urea nitrogen and serum creatinine in some patients (less than 0.1%) with essential hypertension, which may recover upon discontinuation of the drug. The likelihood of elevation of these indicators increases when combined with diuretics or in patients with renal artery stenosis (see [Precautions]).
Contraindications
Known hypersensitivity to Benadryl, related compounds, or any of the excipients of this product.
History of angiotensin-converting enzyme inhibitor-induced or non-angiotensin-converting enzyme inhibitor-induced angioedema.
Pregnant women (see [Pregnancy and Lactation]).
Combine ACE inhibitors (including this product) or angiotensin receptor antagonists (ARBs) with aliskiren in patients with type II diabetes mellitus (see [Drug Interactions]).
Combine ACE inhibitors (including this product) with enkephalinase inhibitors (e.g., sacubitril). This product should not be taken 36 hours prior to starting sacubitril valsartan sodium tablets (a drug containing enkephalinase inhibitors) and 36 hours after stopping sacubitril valsartan sodium tablets treatment (see [Precautions] and [Drug Interactions]).
[Precautions].
Allergic-like reactions and related reactions
Because ACE inhibitors can affect the metabolic response to eicosanoids and peptides (including endogenous bradykinin), patients taking ACE inhibitors (including benazepril hydrochloride) may experience adverse reactions, some of which may be severe.
Angioedema
Edema of the face, lips, tongue, voice box, and larynx has been reported with ACE inhibitors (including Benadryl hydrochloride). If this symptom occurs, discontinue the product immediately and monitor the patient carefully until the swelling disappears. If edema of the face and lips only occurs, the condition often resolves without treatment or with antihistamines. Angioedema of the larynx can be fatal. If the tongue, vocal cords, or larynx are involved, appropriate treatment should be given immediately, such as subcutaneous 1:1000 epinephrine injection (0.3 mL to 0.5 mL) and/or measures to ensure that the patient’s airway is open.
During treatment with ACE inhibitors, patients of black African origin are more likely to experience the adverse effect of edema than patients of other ethnic groups.
Patients may be at increased risk of angioedema when combining ACE inhibitors with mTOR (mammalian target protein of rapamycin) inhibitors (e.g., tesilomorph, sirolimus, everolimus) or enkephalinase inhibitors (e.g., sacubitril) (see [Drug Interactions]).
Allergy-like reactions in desensitization therapy
Fatal allergic-like reactions occurred in two patients taking ACE inhibitors while receiving desensitization therapy against a hymenopteran insect toxin (wasp oxytetracycline). In other patients in the same situation, timely interruption of ACE inhibitors prevented these reactions, but the reactions recurred after continuation of the drug. This product must be discontinued prior to desensitization therapy.
Allergic-like reactions in dialysis
Allergic-like reactions have been reported in patients on high permeability membrane dialysis while on ACE inhibitors. In addition, anaphylactoid reactions have likewise been reported in patients treated with LDL isolation by dextran sulfate adsorption.
Symptomatic hypotension
As with other ACE inhibitors, symptomatic hypotension has occurred rarely. However, hypotension may occur with ACE inhibitor therapy in patients receiving large amounts of diuretics, controlled dietary sodium intake, dialysis treatment, severe sodium deficiency due to diarrhea or vomiting, or in cases of hypovolemia. Discontinuing diuretics or taking other measures to replenish fluids a few days before starting treatment with this product may reduce the risk of hypotension. If hypotension does occur, the patient should be placed in a recumbent position and, if necessary, sedated with saline. Transient hypotensive reactions are not a contraindication to further treatment and are generally considered acceptable to continue after the blood pressure has rebounded with volume expansion.
In patients with severe congestive heart failure, ACE inhibitor therapy may result in hypotension with the potential for hypuria and/or progressive azotemia, and (less commonly) acute renal failure. In this group of patients, close monitoring should be performed at the time of initiation of the drug. Particular attention should be paid to the patient during the first two weeks of therapy and when increasing the dosage of Benadryl or diuretics.
Granulocyte deficiency/neutropenia
Captopril, another ACE inhibitor, has been found to cause granulocyte deficiency and myelosuppression. It occurs more often in patients with renal insufficiency, especially in patients with collagen vascular disease (e.g., lupus erythematosus or scleroderma). There are insufficient trial data to determine whether benazepril also causes granulocyte deficiency. As with other ACE inhibitors, patients with vascular collagen disease (especially if the disease is associated with impaired renal function) should have their white blood cell counts checked regularly.
Hepatitis and Liver Failure
Cholestatic hepatitis has been reported in a very small number of cases in patients treated with ACE inhibitors, with isolated cases of liver failure (some of which are fatal). The mechanism is not known. ACE inhibitors should be discontinued and patients monitored once jaundice or significant elevations in liver enzymes occur.
Use with caution
Impaired renal function
Changes in renal function may occur in some sensitive patients. In patients with congestive heart failure, whose renal function may be dependent on the renin-angiotensin-aldosterone system, treatment with ACE inhibitors may result in hypuria and/or progressive azotemia, as well as acute renal failure (less common). In a small study of hypertension in patients with one or both renal artery stenoses, benazepril hydrochloride was associated with elevated blood urea nitrogen and serum creatinine values. These elevations were restored after interruption of treatment with benazepril hydrochloride or diuretics. Therefore, renal function should be closely monitored during the first few weeks of treatment when ACE inhibitors are administered to the above patients. Some patients with hypertension who do not have significant prior renal vascular disease may experience elevated (usually slight and temporary) blood urea nitrogen and serum creatinine values, particularly with the combination of benazepril hydrochloride and diuretics. These reactions are more likely to occur in patients who have previously suffered from impaired renal function. In such cases, it may be necessary to reduce the dose of Benadryl hydrochloride and/or interrupt the diuretic. Examination of hypertensive patients should always include an assessment of their renal function (see [DOSAGE AND ADMINISTRATION]).
The combination of ACE inhibitors (including this product) or ARBs with aliskiren should be avoided in patients with severely impaired renal function (GFR less than 30 mL/min) (see [Drug Interactions]).
Cough
Persistent cough has been reported following the use of ACE inhibitors and may be due to inhibition of endogenous bradykinin degradation. This symptom is always relieved after interruption of treatment. A differential diagnosis of cough must be considered for cough caused by ACE inhibitors.
Surgery/anesthesia
Patients who are receiving ACE inhibitors should inform the anesthesiologist before surgery. When using anesthetics that lower blood pressure, it should be noted that angiotensin I produced due to compensatory renin release can be blocked by ACE inhibitors during conversion to angiotensin II, and the resulting decrease in blood pressure can be corrected by volume expansion.
Hyperkalemia
Elevated serum potassium is occasionally seen during ACE inhibitor therapy. In clinical trials for the treatment of hypertension, there have been no interruptions in the use of benazepril hydrochloride because of hyperkalemia. Risk factors for hyperkalemia include renal insufficiency, diabetes mellitus, and the combination of drugs used to treat hyperkalemia (see [Drug Interactions]). In a trial involving patients with progressive chronic kidney disease, some patients discontinued their medication because of hyperkalemia. Therefore, it is important to monitor serum potassium in patients with progressive chronic kidney disease who are taking benazepril hydrochloride.
Aortic stenosis, mitral stenosis
As with other vasodilators, special care should be taken when using this drug in patients with aortic stenosis and mitral stenosis.
Dual blockade of the renin-angiotensin system (RAS).
Caution should be exercised when ACE inhibitors (including this product) are used in combination with other drugs that block the RAS, such as ARBs or aliskiren (see [Drug Interactions]).
Effects on driving and operating machinery
As with other antihypertensive drugs, patients taking this product should be aware of these effects when driving and operating machinery.
Pregnant women and nursing mothers
This product is not recommended for women during pregnancy (see [Contraindications]).
Women of childbearing age and pregnant women
The administration of ACE inhibitors to pregnant women will likely result in fetal or neonatal morbidity or death. Dozens of such cases have been reported in the worldwide data literature.
The use of ACE inhibitors in early pregnancy is associated with an increased risk of congenital defects. In addition, the use of ACE inhibitors during mid- and late pregnancy may result in fetal and neonatal impairment, including hypotension, neonatal cranial anomalies, anuria, reversible or irreversible impaired renal function, and even death. The resulting excess amniotic fluid also often leads to limb contractures, facial deformities, and poor lung development in infants. Preterm delivery, intrauterine growth retardation, and ductus arteriosus have also been reported, but it is uncertain whether these symptoms are related to ACE inhibitors.
Once pregnancy is confirmed, ACE inhibitors should be discontinued immediately and fetal growth should be monitored regularly. ACE inhibitors (including benazepril hydrochloride) should also be avoided in women who are planning to become pregnant. Women of childbearing age should be specifically informed of the potential risks associated with the use of ACE inhibitors (including Benazepril hydrochloride). The drug should be administered only after careful consideration and discussion of the associated risks and benefits.
Lactating women
Benadryl and benazeprilat have been found to be secreted into breast milk, but only at a maximum concentration of 0.3% in plasma. The amount of Benadryl that can reach the infant’s body circulation is negligible. Although it is unlikely to have adverse effects on breastfed infants, it is still not recommended to take this product during breastfeeding.
[Pediatric Use].
The safety and efficacy of this product in pediatric patients have not been established.
Geriatric Use]
The recommended drug dosage and precautions for elderly patients 65 years of age or older are the same as for younger adults (see [Pharmacokinetics]).
Drug Interactions]
Dual blockade of the RAS system with ACE inhibitors, ARBs, or aliskiren: Combining ACE inhibitors (including this product) with other drugs that block the RAS increases the incidence of hypotension, hyperkalemia, and changes in renal function compared to monotherapy. Blood pressure, renal function, and electrolytes should be monitored closely in patients using this product in combination with other drugs affecting the RAS (see [Precautions]).
ACE inhibitors (including benazepril) or ARBs in combination with aliskiren should be avoided in patients with severe renal impairment (GFR less than 30 mL/min) (see [Precautions]).
In patients with type II diabetes, the combination of ACE inhibitors (including this product) or ARBs with aliskiren is strictly prohibited.
Diuretics: Patients on diuretics or with fluid deficiencies may occasionally have low blood pressure during the initial treatment with ACE inhibitors. Early discontinuation of diuretics for 2 to 3 days before starting treatment with this product will minimize the likelihood of hypotension in such patients. (See [DOSAGE AND ADMINISTRATION] and [PRECAUTIONS]).
Drug-induced hyperkalemia: Potassium-preserving diuretics (e.g., spironolactone, aminopterin, amiloride), potassium supplements or salt substitutes containing potassium, and other drugs (e.g., cyclosporine, heparin, etc.) may cause significant elevations in serum potassium and therefore are not recommended in combination with these drugs when patients are treated with ACE inhibitors (including benazepril). However, if combination is deemed necessary, blood potassium levels should be closely monitored.
Non-steroidal anti-inflammatory drugs (NSAIDs): The antihypertensive efficacy of ACE inhibitors has been found to be reduced when combined with indomethacin and other NSAIDs. However, in a controlled clinical trial, indomethacin did not affect the antihypertensive efficacy of benazepril hydrochloride, and no pharmacokinetic interactions were found between aspirin and benazepril in healthy volunteers. The combination of NSAIDs and ACE inhibitors (including benazepril) may increase the risk of renal damage and hyperkalemia. Therefore, monitoring of renal function and potassium concentrations is recommended.
Lithium: Increased serum lithium concentrations and signs of lithium toxicity have been reported in patients taking ACE inhibitors and receiving concomitant lithium therapy. Therefore, caution should be exercised with regard to these combined treatments and frequent testing of serum lithium concentrations is recommended. The risk of lithium toxicity may be increased if diuretics are used concomitantly.
Drug-induced angioedema: Patients may be at increased risk of angioedema when combined with ACE inhibitors and dipeptidyl peptidase-IV inhibitor drugs (e.g., vincristine), mTOR inhibitors (e.g., tesilomox, sirolimus, everolimus), or enkephalinase inhibitors (e.g., sacubitril) (see [Precautions]).
Other drugs with antihypertensive effects: This product may potentiate the antihypertensive effects of other antihypertensive drugs. The drug dose must be adjusted accordingly.
Glucose-lowering drugs: There have been rare cases of hypoglycemia in diabetic patients treated with insulin or oral hypoglycemic agents while taking ACE inhibitors (including Benazepril). Therefore, such patients need to be warned of the possibility of hypoglycemic reactions and monitored accordingly.
Erythropoietin: When combined with ACE inhibitors (including Benadryl), patients may have a reduced response to erythropoietin.
Gold: Rare nitrite-like reactions (including flushing, nausea, vomiting, and hypotension) have been reported in patients treated with gold for injection (gold thiodisodium) in conjunction with ACE inhibitors.
Propofol: Pre-treatment with propofol may increase the pharmacodynamic effects of ACE inhibitors and may require dose adjustment.
Other: The pharmacokinetics of Benazepril will not be affected by the following drugs: dihydroketorol, furosemide, chlorothiazide, digoxin, propranolol, atenolol, nifedipine, amlodipine, metronidazole, aspirin, or cimetidine. Similarly benazepril hydrochloride administration does not significantly affect the pharmacokinetics of these drugs (cimetidine kinetics have not been studied).
[Drug Overdose].
Signs and Symptoms.
Although overdose with this product is very limited, the main symptom expected is significant hypotension, which may be accompanied by electrolyte disturbances and renal failure.
Treatment.
If drug intake is not prolonged, active carbon may be considered. In individual cases, early gastric decontamination (e.g., emetic, gastric lavage, etc.) may be considered after drug administration.
The patient’s blood pressure and clinical signs should be closely monitored. Supportive therapy should be used to ensure that adequate hydration can take place and that systemic blood pressure is maintained.
If significant hypotension occurs, saline should be administered intravenously; depending on the clinical situation, vasopressor drugs (e.g., catecholamines intravenously) may be considered.
Although the active metabolite benazeprilat can only be dialyzed in small amounts, dialysis can still be used as an adjunct to normal elimination in patients with drug overdose and suffering from severe renal impairment.
Pharmacology and Toxicology
Pharmacological effects
Benazepril is a precursor drug, hydrolyzed to produce the active metabolite benazeprilat, which inhibits angiotensin-converting enzyme (ACE), blocks the conversion of angiotensin I to angiotensin II, resulting in a decrease in the plasma concentration of angiotensin II, thereby reducing vascular resistance, and decreases aldosterone secretion, which may result in a mild increase in serum potassium. Diminished negative feedback mechanisms of renin release can lead to elevated plasma renin activity. Benazeprilat inhibits ACE more strongly than benazepril. Results from animal studies showed that benazepril did not inhibit the increase in blood pressure caused by angiotensin II and did not affect the hemodynamic changes induced by the autonomic transmitters acetylcholine, epinephrine, and norepinephrine. Benazepril exerts its hypotensive effect mainly by inhibiting the renin-angiotensin-aldosterone system, and it also has hypotensive effect on low-renin hypertension.
Toxicological studies
Genotoxicity.
Benazepril Ames test (with or without metabolic activation), mammalian cell forward mutation test, and in vivo micronucleus test results were negative.
Reproductive toxicity.
No adverse effects on reproductive function were observed in male and female rats given Benadryl 50-500 mg/kg/day, (converted from body weight, equivalent to 60 to 625 times the maximum recommended human dose of ~0.8 mg/kg).
The application of drugs acting on the renin-angiotensin system in women during pregnancy can cause impaired fetal renal function and increase the risk of fetal and neonatal birth defects and death. Fetal renal impairment results in low amniotic fluid and may be accompanied by pulmonary insufficiency, fetal limb contractures and facial deformities. See [For Pregnant and Lactating Women].
Carcinogenicity.
Benadryl was administered orally to mice and rats at 150 mg/kg/day for 2 years, and no carcinogenicity was observed.
Pharmacokinetics
1. Absorption.
At least 37% of oral benazepril hydrochloride is absorbed. The precursor drug is rapidly converted into the pharmacologically active metabolite Benazeprilat. The plasma concentrations of benazepril and benazeprilat reach their peak at 30, 60, and 90 minutes, respectively, after benazepril hydrochloride is taken on an empty stomach.
The absolute bioavailability of benazeprilat after oral administration of benazepril hydrochloride was 28% of the utilization after intravenous administration of the metabolite. Taking the drug after eating delays the absorption of Benadryl, but does not affect the amount absorbed or the conversion to Benadryl. Therefore, this product can be taken during or between meals.
In the dose range of 5~20mg, the AUC and plasma concentration values of Benazepril and Benazeprilat are approximately proportional to the size of the dose. However, in studies with a broader dose range of 2 to 80 mg, less proportional to the dose was observed, possibly due to saturation of Benadryl with ACE binding.
There was no change in the pharmacokinetics of this product after multiple doses (5-20 mg once a day). There was no accumulation of benazepril. Benazeprilat accumulates in small amounts. Its steady-state AUC was 20% higher than the AUC at the first dosing interval. The effective cumulative half-life of Benadryl is 10~11 hours and reaches steady state after 2~3 days.
2. Distribution.
The binding rate of Benadryl and Benazeprilat to serum proteins (mainly albumin) is approximately 95%. The binding rate is not affected by age. The steady-state distribution of Benadryl is 9 liters.
3. Metabolism.
The precursor drug benazepril is rapidly and completely converted to the pharmacologically active metabolite benazeprilat, with peak plasma concentrations 90 minutes after administration, mainly due to the involvement of hydrolases in the liver in this conversion. The other two metabolites are the acetyl-glucosinolate conjugates of benazepril and benazeprilat.
4. Elimination.
The pharmacokinetics of Benadryl are characterized by rapid elimination from plasma (complete elimination within 4 hours), and Benadryl is eliminated in two phases. The initial half-life is 3 hours and the terminal half-life is approximately 22 hours. The terminal elimination phase (from the 24th hour onwards) suggests a firm binding of Benadryl to ACE.
Benazepril is mainly eliminated metabolically and Benazeprilat is mainly eliminated via the kidney and bile. Patients with normal renal function are eliminated primarily via the kidneys. Metabolic elimination of Benazeprilat is a secondary route. After oral administration of Benadryl hydrochloride, less than 1% of the original form of Benadryl is found in the urine, and 20% is excreted from the urine in the form of Benadryl pull.
5. Pharmacokinetics of special clinical conditions.
Hypertensive patients
Steady-state plasma trough concentrations of benazepril correlate with the daily dose of the drug.
Patients with congestive heart failure
Absorption of benazepril and conversion of benazepril to benazeprilat are not affected. Because of the slowed rate of elimination, steady-state plasma trough concentrations of Benadryl are higher than in healthy or hypertensive patients.
Age, Mild to Moderate Renal Injury, Nephrotic Syndrome, and Liver Injury
The pharmacokinetics of Benazepril and Benazeprilat are rarely affected by age and mild to moderate renal impairment (creatinine clearance 30 mL/min to 80 mL/min) and nephrotic syndrome. In patients with abnormal liver function due to cirrhosis, the pharmacokinetics and bioavailability of Benazeprilat are not affected, and no dose adjustment is necessary in these patients.
Severe kidney injury and end-stage renal disease
The pharmacokinetics of Benazeprilat is affected by severe renal insufficiency (creatinine clearance less than 30 mL/min) and requires dose reduction due to slow elimination and high accumulation. Even in advanced renal disease, Benadryl and Benazeprilat are still eliminated from plasma, when the pharmacokinetic properties are similar to those of severe renal failure. Non-renal (metabolic or biliary) clearance may compensate for the lack of renal clearance.
Hemodialysis
After 2 hours of benazepril hydrochloride administration, routine hemodialysis has no effect on plasma benazepril and benazeprilat concentrations, so no drug supplementation is required after dialysis. Only a small percentage of Benadryl is excreted through dialysis.
The pharmacokinetics of Benazepril hydrochloride are not affected by the following drugs: dihydrocortisone, furosemide, chlorothiazide, digoxin, propranolol, atenolol, nifedipine, amlodipine, metronidazole, aspirin, or cimetidine. Similarly, Benazepril hydrochloride administration does not significantly affect the pharmacokinetics of these drugs (cimetidine kinetics were not studied).
Storage
Store in a sealed, dry place.
Keep out of the reach of children.
Packaging
Double aluminum packaging.
5mg: 7tablets/plate, 28tablets/box
10mg: 7 tablets/plate, 7 tablets/box, 14 tablets/box
【Expiration date】 24 months
【Execution standard
【Approval number】.
5mg：Guo yao zhen zi H20054771
10mg：GuoYaoZhenZi H20043648
Manufacturer
Company Name: Shenzhen Xinlitai Pharmaceutical Co.
Production Address: No. 1, Planning Road 5, Longtian Street, Pingshan District, Shenzhen
Zip code: 518118
Telephone number: (0755) 83867888
Fax number: (0755) 83867338
Website: www.salubris.com