DIAO ANBEI Amlodipine Besylate And Benazepril Hydrochloride Tablets For Hypertension 5mg:10mg*10

[Drug Name]
Generic Name: Amlodipine Besylate and Benazepril Hydrochloride Tablets (II)
Trade Name: Diodipine
English Name: Amlodipine Besylate and Benazepril Hydrochloride Tablets (II)
Chinese Pinyin: Anlüdiping Beinapuli Pian (II)

[Ingredients]
This product is a single-tablet combination preparation consisting of: amlodipine 5mg, benazepril hydrochloride 10mg.

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

[Indications]
This product is used to treat hypertension. It is suitable for patients whose blood pressure cannot be satisfactorily controlled with amlodipine or benazepril alone; or as an alternative to taking amlodipine and benazepril tablets simultaneously. It can be used in cardiology and neurology departments to treat essential hypertension, hypertension with new-onset atrial fibrillation due to left ventricular hypertrophy, hypertension complicated by coronary artery disease, hypertension complicated by left ventricular failure, hypertensive stroke, refractory hypertension, isolated systolic hypertension, hypertension in young and middle-aged patients, and hypertension in the elderly. Nephrology can be used to treat ventricular remodeling in hemodialysis patients, renal hypertension, chronic kidney disease with hypertension, peritoneal dialysis patients with hypertension, early renal damage in hypertension (microalbuminuria), and type 2 diabetic nephropathy with hypertension. Endocrinology can be used to treat type 2 diabetes with hypertension, type 2 diabetic nephropathy with hypertension, and other conditions. Geriatrics can be used to treat elderly patients with essential hypertension, isolated systolic hypertension, and hypertension with coronary artery disease.

[Dosage and Administration]
Amlodipine is an effective treatment for hypertension; the dose is 2.5-10 mg once daily, while the effective dose of benazepril is 10-80 mg.

[Adverse Reactions]
Adverse reactions to the amlodipine/benazepril hydrochloride combination are generally mild and transient, and are not related to age, race, or duration of treatment. 4% of patients taking the combination and 3% of those taking placebo required discontinuation of treatment due to adverse reactions. The most common reasons for discontinuation of treatment in patients taking the combination were cough and edema. Possibly related side effects occurred in 1% of patients taking the combination, including cough (3.3%), headache (2.2%), dizziness (1.3%), and edema (2.1%). Edema and other side effects were dose-dependent with amlodipine and more pronounced in women than in men. Combining amlodipine with benazepril reduced the incidence of edema. Other side effects potentially related to the amlodipine/benazepril hydrochloride combination include: Angioedema: including swelling of the tongue and face (see WARNINGS, Angioedema). General: Asthenia and fatigue. Central nervous system: Insomnia, nervousness, anxiety, drowsiness, tremor, and decreased libido. Skin: Flushing, fever, rash, skin nodules, and dermatitis. Digestive system: Dry mouth, nausea, abdominal pain, constipation, diarrhea, dyspepsia, and esophagitis. Metabolism and nutrition: Hypokalemia. Musculoskeletal: Back pain, myalgia, cramps, and muscle spasms. Respiratory system: Pharyngitis. Genitourinary System: Sexual dysfunction, such as impotence and frequent urination. Adverse reactions observed with benazepril and amlodipine alone are similar to those observed with this combination. Rare cases of Stevens-Johnson syndrome, pancreatitis, hemolytic anemia, pemphigus, and thrombocytopenia have been reported postmarketing with benazepril. Jaundice and elevated liver enzymes (primarily consistent with cholestasis) severe enough to require hospitalization have also been reported with amlodipine. Other adverse reactions of ACE inhibitors and calcium channel blockers include eosinophilic pneumonia (with ACE inhibitors) and gynecomastia (with calcium channel blockers).

[Contraindications]
Hypersensitivity to benazepril, other ACE inhibitors, or amlodipine.
Renal failure (creatinine clearance <30 mL/min).
Pregnancy.

[Precautions]
Renal impairment: This combination should be used with caution in patients with severe renal impairment. In patients with severe congestive heart failure, whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors (including benazepril) may result in oliguria and/or progressive azotemia and (rarely) acute renal failure and/or death. Some hypertensive patients without overt renovascular disease who receive benazepril have experienced mild and transient increases in blood urea nitrogen and serum creatinine, particularly when used with diuretics. A dose reduction of this combination may be necessary. Evaluation of hypertensive patients should always include an assessment of renal function (see Dosage and Administration). Hyperkalemia: Hyperkalemia (serum potassium of at least 0.5 mEq/L, greater than the upper limit of normal) occurs in approximately 1.5% of hypertensive patients treated with this combination. Elevations in serum potassium are generally reversible. Risk factors include renal insufficiency, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes. Patients with Congestive Heart Failure: Although hemodynamic studies and controlled studies in NYHA class II-III patients have shown that amlodipine does not worsen clinical exercise tolerance, left ventricular ejection fraction, or clinical symptoms, studies in NYHA class IV patients have not been conducted. In general, all calcium channel blockers should be used with caution in patients with heart failure. Patients with Hepatic Failure: Benazeprilat levels are largely unchanged in patients with cirrhosis due to liver dysfunction. However, because amlodipine is primarily metabolized by the liver, with a plasma elimination half-life (t½) of 56 hours in patients with hepatic impairment, caution should be exercised in patients with severe hepatic failure treated with this combination. Cough: A persistent, dry cough has been reported with all ACE inhibitors, possibly due to inhibition of endogenous bradykinin degradation, and it always resolves with discontinuation. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. Surgery/Anesthesia: In patients undergoing surgery or anesthetic-induced hypotension, benazeprilat will inhibit angiotensin II formation, potentially leading to compensatory renin release. This resulting hypotension can be corrected with volume expansion.

[Use in Special Populations]
Precautions for Pediatric Patients:
Safety and efficacy have not been established in pediatric patients.
Precautions for Pregnancy and Lactation:
Treatment with ACE inhibitors during pregnancy can cause fetal and neonatal morbidity and mortality. This drug is contraindicated during pregnancy. Dozens of cases have been reported. Once pregnancy is confirmed, this drug should be discontinued immediately, and fetal development should be monitored regularly. When breastfeeding women are treated with benazepril, small amounts of unchanged benazepril and benazeprilat are excreted in breast milk. Therefore, the neonate will receive less than 0.1% of benazepril and benazeprilat through breast milk. It is currently unknown whether amlodipine is excreted in breast milk. Discontinuation of breastfeeding is recommended during treatment with this drug.
Precautions for Elderly Patients:
Benazepril and benazeprilat are primarily excreted through the kidneys, while amlodipine is primarily metabolized in the liver. Elderly patients may have decreased liver and kidney function, so dose adjustments should be made. Elderly patients may require a lower starting dose, and liver and kidney function should be monitored.

[Drug Interactions]
1. Diuretics: Patients receiving diuretic therapy, especially those recently initiated, may occasionally experience excessive hypotension upon initiation of this medication. This can be mitigated by discontinuing the diuretic before initiating the medication or increasing salt intake. 2. Potassium Supplements and Potassium-Sparing Diuretics: Benazepril can mitigate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, etc.) or potassium supplements can increase the risk of hyperkalemia. Caution should be exercised when using these drugs concomitantly, and serum potassium should be monitored frequently. 3. Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant ACE inhibitors and lithium therapy. Caution should be exercised when using these drugs concomitantly, and frequent monitoring of serum lithium levels is recommended. 4. Others: There is no clinical evidence of adverse reactions when benazepril is used concomitantly with oral anticoagulants, beta-adrenergic blockers, calcium channel blockers, cimetidine, diuretics, digoxin, hydralazine, and naproxen. Amlodipine can be used concomitantly with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, nonsteroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic agents.

[Pharmacological Actions]
1. Diuretics: Initiation of this medication may occasionally cause excessive hypotension in patients receiving diuretics, especially those recently initiated. This can be mitigated by discontinuing the diuretic before initiating the medication or increasing salt intake. 2. Potassium Supplements and Potassium-Sparing Diuretics: Benazepril can mitigate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, etc.) or potassium supplements can increase the risk of hyperkalemia. Caution should be exercised when these drugs are used concomitantly, and serum potassium should be monitored frequently. 3. Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving both ACE inhibitors and lithium. Caution should be exercised when these two medications are used concomitantly, and frequent monitoring of serum lithium levels is recommended. 4 Others: Benazepril can be used in combination with oral anticoagulants, beta-adrenergic blockers, calcium channel blockers, cimetidine, diuretics, digoxin, hydralazine and naproxen. There is no clinical evidence of adverse reactions. Amlodipine can be used in combination with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, non-steroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic drugs. Pharmacological action Amlodipine: Amlodipine is a dihydropyridine calcium antagonist. Its interaction with calcium channels is determined by the progressive rate of binding and dissociation between it and the receptor site. It has a greater effect on smooth muscle than on myocardium. It acts directly on vascular smooth muscle, dilates peripheral arteries, reduces peripheral vascular resistance, and lowers blood pressure. Amlodipine does not affect plasma calcium concentration. Within the physiological pH range, amlodipine exists as an ionic compound (pKa = 8.6). Its interaction with calcium channel receptors is characterized by a gradual binding and dissociation from the receptor binding site. Benazepril: Benazepril and its active metabolite, benazeprilat, inhibit angiotensin-converting enzyme (ACE) in humans and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor angiotensin II. Angiotensin II also stimulates the adrenal cortex to secrete aldosterone. ACE inhibition reduces plasma angiotensin II levels, lowers vascular pressure, and decreases aldosterone secretion, which leads to a small increase in serum potassium. Toxicological Studies: Genotoxicity: Amlodipine: The Ames test, in vitro chromosome aberration test, and mouse micronucleus test were all negative. Benazepril: The Ames test, in vitro mammalian cell mutation test, and mouse micronucleus test were all negative. Reproductive toxicity: Oral administration of benazepril:amlodipine (benazepril:amlodipine) to rats at doses up to 15:7.5 mg/kg/day before mating and throughout gestation did not produce significant reproductive toxicity in either sex. Oral administration of a benazepril:amlodipine mixture to rats at doses ranging from 5:2.5 to 50:25 mg/kg/day resulted in dose-related dystocia in all dose groups. Based on body surface area, the 2.5 mg/kg/day amlodipine dose is 3.6 times the maximum recommended human dose; the 5 mg/kg/day benazepril dose is twice the maximum recommended human dose (based on a 50 kg female body weight). Pregnant rats and mice were orally administered a benazepril:amlodipine mixture of 50 mg/kg/day (24 times the maximum recommended human dose based on body surface area, with a body weight of 50 kg) and pregnant rabbits were orally administered a benazepril:amlodipine mixture of up to 1.5 mg/kg/day (0.97 times the maximum recommended human dose based on body surface area, with a body weight of 50 kg). No significant toxicity to the growth and development of the offspring was observed. Amlodipine: Pregnant rats and rabbits were orally administered amlodipine maleate at doses up to 10 mg/kg/day (10 times and 20 times the maximum recommended human dose of 10 mg based on body surface area, with a body weight of 60 kg, respectively). However, oral administration of amlodipine maleate (10 mg/kg/day) for 14 consecutive days before mating, during the mating period, and during pregnancy in rats significantly decreased litter size (50%), significantly increased intrauterine mortality (approximately 5-fold), and prolonged gestation and labor in pregnant rats. Benazepril: Oral administration of benazepril to pregnant rats, mice, and rabbits at maximum doses (based on body surface area) of 60 times the maximum recommended human dose (RMD) for rats, 9 times for mice, and approximately 1 times for rabbits (based on a 50 kg female body weight) did not demonstrate significant effects on growth and development. Carcinogenicity: Amlodipine: Oral administration of amlodipine at 0.5, 1.25, and 2.5 mg/kg/day for two years in mice and rats did not demonstrate carcinogenicity. Based on body surface area, the highest dose in mice was close to the maximum recommended human dose of 10 mg/day, and the highest dose in rats was 2.5 times the maximum recommended human dose. Benazepril: Oral administration of benazepril to mice and rats for two years at a maximum dose of 150 mg/kg/day did not demonstrate carcinogenicity. Based on body surface area, this is 9 times (mice) and 18 times (rats) the maximum recommended human dose, respectively.

Storage: Store in a sealed container away from light.

Specifications: 10 mg: 5 mg x 10 tablets

Packaging: Box

Expiration Date: 24 months

Approval Number: National Medicine Standard H20090309

Manufacturer: Chengdu Diao Pharmaceutical Group Co., Ltd.