HUAYUAN XIEANZHI Valsartan And Amlodipine Tablets For Hypertension 80mg:5mg*30

[Drug Name]
Generic Name: Valsartan and Amlodipine Tablets (I)
Trade Name: Xie'anzhi Valsartan and Amlodipine Tablets (I) 30 Tablets
Pinyin Full Code: XieAnZhi ZuoShaTanAnLvDiPingPian(I) 30 Tablets

[Main Ingredients]
This product is a compound preparation containing 80 mg of valsartan and 5 mg of amlodipine per tablet.

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

[Indications/Main Functions]
Treatment of essential hypertension. This product is used for patients whose blood pressure cannot be adequately controlled with monotherapy.

[Precautions]
1. Hypotension: In placebo-controlled trials, 0.4% of patients with uncomplicated hypertension treated with valsartan and amlodipine tablets experienced excessive hypotension. Patients with an activated renin-angiotensin system (e.g., those with volume and/or salt depletion taking high-dose diuretics) may experience symptomatic hypotension when receiving angiotensin II receptor antagonists. Correction of volume depletion is recommended prior to initiating valsartan and amlodipine tablets (I), or close clinical monitoring at the start of treatment. Caution should be exercised when initiating treatment in patients with heart failure or a recent myocardial infarction, as well as those undergoing surgery or dialysis. Valsartan administration to patients with heart failure or post-myocardial infarction often results in a decrease in blood pressure, but if dosing instructions are adhered to, discontinuation of treatment due to persistent symptomatic hypotension is generally unnecessary. In controlled clinical trials of patients with heart failure, the incidence of hypotension in patients receiving valsartan was 5.5% compared to 1.8% in the placebo group. In the Valsartan in Acute Myocardial Infarction Trial (VALIANT), the rate of permanent discontinuation of treatment due to hypotension in post-myocardial infarction patients was 1.4% in the valsartan group and 0.8% in the captopril group. 2. Increased Risk of Myocardial Infarction or Angina: Rarely, patients (particularly those with severe obstructive coronary artery disease) may experience an increase in the frequency, duration, or severity of angina or acute myocardial infarction when initiating calcium channel blocker therapy or increasing the dose. The mechanism of this effect is unknown. 3. Hepatic Impairment. 4. Amlodipine Studies: Amlodipine is extensively metabolized by the liver. In patients with hepatic impairment, the plasma elimination half-life (t½) is 56 hours. Therefore, amlodipine should be used with caution in patients with severe hepatic impairment. 5. Valsartan Studies: Valsartan is primarily eliminated via bile. In patients with mild to moderate chronic liver disease, including those with biliary obstructive disease, valsartan exposure (measured by AUC) averages twice that of healthy volunteers (matched for age, sex, and weight). This product should be used with caution in patients with liver disease or biliary obstructive disease.

[Drug Interactions]
Valsartan and Amlodipine Tablets (I) are contraindicated in patients with hypersensitivity to the active ingredient or any of the excipients in this product. This drug is contraindicated in pregnant and lactating women (see [Use in Pregnant and Lactating Women]). There are currently no data on its use in patients with severe renal impairment (creatinine clearance <10 ml/min). This drug should be contraindicated in patients with hereditary angioedema and those who develop angioedema early in treatment with ACE inhibitors or angiotensin II receptor antagonists.

[Pediatric Use]
See package insert for details.

[Elderly Use]
In controlled clinical studies, 323 (22.5%) hypertensive patients treated with this drug were ≥65 years of age, and 79 (5.5%) were ≥75 years of age. No overall differences in the efficacy and safety of this drug were observed in this patient population, but greater sensitivity to the drug cannot be ruled out in some elderly patients. Amlodipine: In studies of amlodipine besylate tablets, there were insufficient numbers of subjects aged 65 years and older to determine whether they respond differently to the drug than younger subjects. Other clinical experience has not revealed differences in responses between elderly and younger patients. In general, elderly patients require careful dose selection, generally starting with the lowest dose. Elderly patients have a higher incidence of decreased liver, kidney, and cardiac function and often have other medical conditions or are currently receiving other medications. Amlodipine clearance is decreased in elderly patients, resulting in an approximately 40-60% increase in the AUC. Therefore, a lower starting dose of 2.5 mg/day is typically used when treating elderly patients with amlodipine. Valsartan: In controlled clinical studies of valsartan, 1214 (36.2%) hypertensive patients treated with valsartan were 65 years of age or older, and 265 (7.9%) were 75 years of age or older. No overall differences in the efficacy or safety of valsartan were observed in this patient population, but greater sensitivity to the drug cannot be ruled out in some elderly individuals.

[Use During Pregnancy and Lactation]
Women of Childbearing Potential: As a direct-acting drug on the renin-angiotensin-aldosterone system (RAAS), Exforge should be contraindicated in women attempting pregnancy. When prescribing medications that act on the RAAS, healthcare professionals should inform women of childbearing age of the potential risks of taking these medications during pregnancy. During pregnancy: As a medication that directly acts on the RAAS, this medication should not be used during pregnancy ([Contraindications]). Given the mechanism of action of angiotensin II antagonists, fetal harm cannot be ruled out. There have been reports of harm to the developing fetus or fetal death when angiotensin-converting enzyme inhibitors (another class of medications that act on the RAAS) are administered in utero during the second and third trimesters of pregnancy. Furthermore, retrospective data suggest a potential risk of birth defects when angiotensin-converting enzyme inhibitors are used during the first trimester of pregnancy. There have been reports of spontaneous abortion, oligohydramnios, and neonatal renal insufficiency when pregnant women inadvertently take valsartan. Similar to other medications that directly act on the RAAS, this medication should not be used during pregnancy (see [Contraindications]). When prescribing medications that act on the RAAS, healthcare professionals should inform women of the potential risks of this class of medications during pregnancy. If pregnancy is detected during treatment, valsartan amlodipine tablets (I) should be discontinued immediately. There are no adequate clinical data on the use of amlodipine in pregnant women. Animal studies of amlodipine have shown reproductive toxicity at doses 8 times the maximum recommended dose of 10 mg (see [Pharmacology and Toxicology]).

[Specifications]
30 tablets

[Dosage and Administration]
Amlodipine 2.5-10 mg once daily is effective for the treatment of hypertension, while the effective dose of valsartan is 80-320 mg. In clinical trials of once-daily valsartan amlodipine tablets, the antihypertensive effect increased with increasing doses of amlodipine 5-10 mg and valsartan 80-320 mg. Adverse reactions of valsartan are generally dose-independent; adverse reactions of amlodipine are both dose-dependent (primarily peripheral edema) and dose-independent, with the former being more common than the latter. This product can be used as an alternative for patients whose blood pressure is not adequately controlled with monotherapy. Add-on Therapy: Patients whose blood pressure is not adequately controlled with amlodipine or valsartan monotherapy can switch to this product in combination therapy. Patients who experience dose-limiting adverse reactions with amlodipine or valsartan monotherapy can achieve blood pressure control with this product at a lower dose of the single agent combined with the other agent. Alternative Therapy: For ease of dosing, patients receiving amlodipine and valsartan combination therapy can switch to this product at the same dose. For information on discontinuing beta-blockers, see Precautions. Amlodipine and valsartan can be taken with or without food. This product is recommended for use with water. Hepatic and Renal Impairment: No dose adjustment is required for patients with mild to moderate renal impairment. Use with caution in patients with severe renal impairment (see Contraindications). This product should also be used with caution in patients with hepatic impairment or biliary obstructive disease.

[Adverse Reactions]
The safety of this product has been evaluated in five controlled clinical trials involving 5,175 patients, of which 2,613 received the combination of valsartan and amlodipine. The safety of valsartan-amlodipine tablets has been evaluated in over 2,600 patients with hypertension; over 1,440 patients received treatment for more than six months, and over 540 patients received treatment for more than one year. Adverse reactions were generally mild and transient, rarely requiring discontinuation. The overall incidence of adverse reactions was independent of dose and unrelated to gender, age, and race. In placebo-controlled clinical studies, 1.8% of patients treated with valsartan-amlodipine tablets discontinued treatment due to side effects, compared to 2.1% of patients in the placebo group. The most common reasons for discontinuation were peripheral edema (0.4%) and dizziness (0.2%). In placebo-controlled clinical trials, adverse reactions occurring in at least 2% of patients receiving this product and occurring more frequently in the valsartan-amlodipine tablets group (n=1437) than in the placebo group (n=337) included: peripheral edema (5.4% vs. 3.0%), nasopharyngitis (4.3% vs. 1.8%), upper respiratory tract infection (2.9% vs. 2.1%), and dizziness (2.1% vs. 0.9%). Orthostatic events (orthostatic hypotension and postural dizziness) occurred in less than 1% of patients. Other adverse reactions (≥0.2%) occurring in the valsartan-amlodipine tablets group in placebo-controlled clinical trials are listed below. It is not possible to determine whether these adverse reactions are caused by this product.

[Contraindications]
Valsartan-amlodipine tablets (I) are contraindicated in patients with hypersensitivity to the active ingredient or any of the excipients of this product. Pregnant and lactating women should not use this product (see [Use in Pregnant and Lactating Women]). There are currently no data on its use in patients with severe renal impairment (creatinine clearance <10 ml/min). This drug should be contraindicated in patients with hereditary angioedema and those who develop angioedema early in treatment with ACE inhibitors or angiotensin II receptor antagonists.

[Overdose]
No reports of overdose with this drug have been reported. The primary symptom of valsartan overdose may be hypotension accompanied by dizziness. Amlodipine overdose may cause excessive peripheral vasodilation and potentially reflex tachycardia. Significant and prolonged systemic hypotension and fatal shock have been reported. If the drug has not been taken for a long time, vomiting or gastric lavage may be considered. Activated charcoal administered immediately or two hours after amlodipine administration significantly reduces amlodipine absorption in healthy volunteers. Clinically significant hypotension due to overdose with this drug requires active cardiovascular support, including close monitoring of cardiac and respiratory function, limb elevation, and monitoring of circulating fluid and urine output. Vasoconstrictors may be used to restore vascular tone and blood pressure, if not contraindicated. Intravenous calcium gluconate is also beneficial for reversing the effects of calcium channel blockers. Amlodipine overdose may cause excessive peripheral vasodilation and possible reflex tachycardia. Significant and potentially prolonged systemic hypotension, including fatal outcomes including shock, has been reported. Clinically significant hypotension caused by amlodipine overdose requires active cardiovascular support, including frequent monitoring of cardiac and respiratory function, limb elevation, and attention to circulating blood volume and urination.

[Pharmacology and Toxicology]
This product contains two antihypertensive active ingredients, valsartan and amlodipine, which have complementary mechanisms of action in controlling blood pressure. Amlodipine is a calcium channel blocker, and valsartan is an angiotensin II antagonist. The combined antihypertensive effect of the two ingredients is superior to either ingredient alone.

[Pharmacokinetics]
Linearity: Both valsartan and amlodipine exhibit linear pharmacokinetics. Amlodipine Absorption: Following a single oral therapeutic dose of amlodipine, peak plasma concentrations are reached within 6-12 hours. Absolute bioavailability is 64-80%. Food does not affect the bioavailability of amlodipine. Distribution: The volume of distribution is approximately 21 L/kg. In vitro studies of amlodipine indicate that approximately 97.5% of the circulating drug is bound to plasma proteins in hypertensive patients. Biotransformation: Amlodipine is extensively metabolized (approximately 90%) in the liver to inactive substances. Excretion: Amlodipine is eliminated from plasma in a biphasic manner, with a terminal elimination half-life of approximately 30-50 hours. Steady-state plasma concentrations are reached after 7-8 days of continuous administration. 10% of unchanged amlodipine and 60% of its metabolites are excreted in the urine. Valsartan Absorption: Following a single oral dose of valsartan, absorption is rapid, but the amount absorbed varies widely. The mean absolute bioavailability of valsartan is 23% (range 23 ± 7). Valsartan's pharmacokinetics are linear across the dose range studied. Valsartan shows little accumulation following once-daily oral administration. Plasma concentrations are similar in men and women. Food decreases the area under the concentration-time curve (AUC) of valsartan by 48% and Cmax by 59%. However, starting 8 hours after dosing, plasma concentrations are similar in the fed and fasted states. These reductions in AUC and Cmax do not result in a clinically significant decrease in therapeutic effect, allowing valsartan to be taken with or without food. Distribution: Valsartan is highly bound to serum proteins (94-97%), primarily to serum albumin. Steady-state is reached within one week. The steady-state volume of distribution is approximately 17 liters. Plasma clearance is relatively low (approximately 2 L/hour) compared to hepatic blood flow (approximately 30 L/hour). Elimination: Valsartan exhibits multiexponential decay kinetics (initial alpha half-life <1 hour; terminal beta half-life approximately 9 hours). Absorbed valsartan is excreted primarily unchanged, with approximately 70% excreted in the feces and 30% excreted in the urine. Following oral administration of valsartan/amlodipine tablets, peak plasma concentrations of valsartan and amlodipine are reached within 3 and 6-8 hours, respectively. The rate and extent of absorption of this product are comparable to the bioavailability of valsartan and amlodipine tablets when taken alone.