Product Overview
[Drug Name]
Generic Name: Valsartan and Hydrochlorothiazide Tablets
Trade Name: Yixintan
English Name: Valsartan and Hydrochlorothiazide Tablets
Chinese Pinyin: Xieshatan Qinglvsaiqing Pian
[Ingredients]
This product is a combination preparation. Each tablet contains 80 mg of valsartan and 12.5 mg of hydrochlorothiazide.
[Appearance]
This product is a film-coated tablet. After removing the coating, it appears white or off-white.
[Indications]
It is used to treat mild to moderate essential hypertension in patients whose blood pressure cannot be adequately controlled with a single drug. This product is not suitable for the initial treatment of hypertension.
[Dosage and Administration]
The recommended dose of valsartan monotherapy is 80 mg once daily. If the antihypertensive effect is unsatisfactory, the daily dose can be increased to 160 mg. The effective dose of hydrochlorothiazide is 12.5 to 50 mg once daily. To reduce dose-independent adverse reactions, combination therapy is generally considered only when monotherapy is inadequate. Adverse reactions to valsartan are generally rare and unrelated to dose. The primary adverse reaction of hydrochlorothiazide is hypokalemia, which is dose-related. The primary dose-independent adverse reaction is pancreatitis. When valsartan and hydrochlorothiazide are used together, the dose of each drug may need to be adjusted. Once the dose adjustment is satisfactory, this product can be substituted for the combination drug at the same dose. Dose Adjustment: Each tablet of this product contains 80 mg of valsartan and 12.5 mg of hydrochlorothiazide. If blood pressure is not adequately controlled with valsartan monotherapy or hydrochlorothiazide 25 mg once daily, or if hypokalemia occurs, this product (containing 80 mg of valsartan/12.5 mg of hydrochlorothiazide) can be used as an alternative, once daily. Maximum antihypertensive effect is achieved within 2-4 weeks of treatment. This product can be taken regardless of mealtime. No dose adjustment is required for patients with mild to moderate renal failure (creatinine clearance ≥ 30 ml/min) or mild to moderate hepatic failure.
[Adverse Reactions]
In two controlled clinical trials involving a total of 1,570 patients, 730 of whom received valsartan in combination with hydrochlorothiazide, the following adverse events were reported: Central Nervous System: Common (>5%): Headache (10.8%; placebo: 17.2%), dizziness. Uncommon (5-0.1%): Fatigue, depression. Upper Respiratory Tract: Uncommon (5-0.1%): Cough, Rhinitis, Sinusitis, Pharyngitis, Upper Respiratory Tract Infection, Epistaxis. Gastrointestinal Tract: Uncommon (5-0.1%): Nausea, Diarrhea, Indigestion, Abdominal Pain. Lower Urinary Tract: Uncommon (5-0.1%): Frequent urination, Urinary Tract Infection. Musculoskeletal System: Uncommon (5-0.1%): Arm or Leg Pain, Arthritis, Myalgia, Sprains and Strains, Muscle Spasms. Other: Uncommon (5-0.1%): Asthenia, Chest Pain, Weakness, Viral Infection, Visual Disturbance, Conjunctivitis. Since the product's launch, rare reports have occurred, including angioedema, rash, pruritus, and other hypersensitivity reactions such as serum sickness and vasculitis. Laboratory tests revealed a decrease in serum potassium greater than 20% in 5.8% of patients treated with the same product, compared to 3.3% of patients receiving placebo. The following adverse events are associated with valsartan alone and not with this product. In rare cases, pinsartan can cause decreases in hemoglobin and hematocrit. In controlled clinical trials, significant decreases (>20%) in hemoglobin and hematocrit occurred in 0.8% and 0.4% of patients treated with pinsartan, respectively, compared to 0.1% in the placebo group. In controlled clinical trials, the incidence of neutropenia in the valsartan and ACE inhibitor groups was 1.9% and 1.6%, respectively. Significant increases in serum creatinine, potassium, and total bilirubin were observed in 0.8%, 4.4%, and 6% of patients treated with valsartan, respectively, compared to 1.6%, 6.4%, and 12.9% of patients treated with ACE inhibitors, respectively. Elevated liver function tests may occur occasionally. No specific laboratory monitoring is required for patients with essential hypertension receiving valsartan. Other adverse events reported in valsartan clinical trials include: Uncommon (5-0.1%): arthralgia, gastroenteritis, and neuralgia. There has been only one case of angioedema reported. A causal relationship with valsartan treatment has not been demonstrated. Hydrochlorothiazide: The following adverse reactions have been reported in patients receiving monotherapy with thiazide diuretics (including hydrochlorothiazide), most of whom were taking doses higher than those used in this product: Electrolyte and metabolic disturbances (see Precautions). Common (>5%): Hypokalemia. Uncommon (5-0.1%): Hyponatremia, hypomagnesemia, and hyperuricemia. Rare (<0.1%): Hypercalcemia, increased blood glucose, glycosuria, and worsening diabetes mellitus. Very rare: Hypochloremic alkalosis. Skin: Uncommon (5-0.1%): Urticaria and other types of rash. Rare (<0.1%): Photosensitivity. Very rare: Necrotizing vasculitis, acute toxic epidermolysis, lupus erythematosus-like reaction, cutaneous lupus erythematosus flare. Gastrointestinal: Uncommon (5-0.1%): Loss of appetite, mild nausea, and vomiting. Rare (<0.1%): Abdominal symptoms, constipation, diarrhea, gastrointestinal symptoms. Very rare: Pancreatitis. Hepatic: Uncommon (<0.1%): Intrahepatic cholestasis or jaundice. Cardiovascular: Uncommon (5-0.1%): Orthostatic hypotension, which may be aggravated by alcohol, anesthetics, or sedatives. Rare (<0.1%): Cardiac arrhythmias. Central nervous system: Uncommon (<0.1%): Headache, dizziness, or photo-headache, sleep disturbances, depression, paresthesias. Sensory organ and visual disturbances, especially during the first few weeks of treatment. Hematologic: Uncommon (<0.1%): Thrombocytopenia, occasionally accompanied by purpura. Very rare: Leukopenia, granulocytopenia, bone marrow suppression, hemolytic anemia. Other rare events (5-0.1%): Impotence. Very rare: Hypersensitivity reactions, including respiratory symptoms of pneumonitis and pulmonary edema.
[Contraindications]
Hypersensitivity to any component of this product or to sulfonamide derivatives. Pregnancy (see [Use in Pregnant and Lactating Women]); severe liver failure, biliary cirrhosis, or cholestasis. Severe renal failure (creatinine clearance 30 ml/min) or anuria. Refractory hypokalemia, hyponatremia, or hypercalcemia, and symptomatic hyperuricemia (history of gout or uric acid stones).
[Precautions]
Serum Electrolyte Changes: Caution is advised when using this product with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that increase serum potassium levels (e.g., heparin). Therefore, serum potassium levels should be monitored regularly. Thiazide diuretics have been associated with hyponatremia and hypochloremic alkalosis. Thiazides can cause hypomagnesemia by increasing renal magnesium excretion. Sodium and/or Volume Depletion: Rarely, symptomatic hypotension may occur when initiating treatment with this drug in patients with severe sodium and/or volume depletion (e.g., high-dose diuretics). Hyponatremia and/or volume depletion should be corrected before initiating treatment with this drug. If hypotension occurs, the patient should be placed in the supine position and normal saline administered as needed. Treatment can be resumed after blood pressure stabilizes. Renal Artery Stenosis: There is no experience with the use of this drug in patients with unilateral or bilateral renal artery stenosis or solitary kidney stenosis. Renal Impairment: No dose adjustment is required for patients with creatinine clearance ≥30 ml/min. Hepatic Impairment: This drug should be used with caution in patients with mild to moderate hepatic impairment that is not cholestatic. However, since the daily dose of valsartan 80 mg does not exceed the recommended limit and the pharmacokinetics of hydrochlorothiazide are not significantly affected by hepatic impairment, no dose adjustment is required in such patients. Systemic Lupus Erythematosus: Thiazide diuretics can trigger or exacerbate systemic lupus erythematosus. Other Metabolic Disorders: Thiazide diuretics can impair glucose tolerance and increase serum cholesterol, triglyceride, and uric acid levels. Effects on Ability to Drive and Operate Machinery: As with other antihypertensive drugs, patients taking this drug should exercise caution when driving and operating machinery. Use with caution in athletes.
[Special Populations]
Precautions for Use in Children: Insufficient data are available regarding the use of this drug in children.
Precautions for Use During Pregnancy and Lactation: Contraindicated in pregnant women.
Precautions for Use in the Elderly: Some elderly individuals (over 65 years) have slightly elevated valsartan concentrations compared with younger volunteers, but these are not clinically significant. Compared with younger individuals, elderly individuals have higher steady-state concentrations of hydrochlorothiazide and significantly decreased systemic elimination. Therefore, elderly patients receiving hydrochlorothiazide therapy require close monitoring.
[Drug Interactions]
The antihypertensive efficacy of this drug may be enhanced by concomitant use with other antihypertensive drugs. Caution is advised when using this drug with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that increase serum potassium (e.g., heparin), and serum potassium levels should be monitored. There have been reports of reversible increases in serum potassium concentrations and lithium toxicity with the concomitant use of lithium, ACE inhibitors, and/or thiazide diuretics. There is no experience with the concomitant use of valsartan and lithium. Therefore, regular monitoring of serum lithium levels is recommended when lithium and this product are co-administered. No clinically significant interactions have been observed between valsartan alone and any of the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, and glyburide. Because this product contains a thiazide diuretic, the following interactions may occur: Concomitant use with nonsteroidal anti-inflammatory drugs (e.g., salicylic acid derivatives, indomethacin) may reduce the diuretic and antihypertensive activity of the thiazide component of this product. Concomitant hypovolemia may lead to acute renal failure. Concomitant use of potassium-wasting diuretics (e.g., furosemide), corticosteroids, adrenocorticotropic hormone (ACTH), amphotericin B, carbenoxolone, penicillin G, or salicylate derivatives can exacerbate potassium and/or magnesium depletion. Hypokalemia or hypomagnesemia caused by thiazides can increase the risk of arrhythmias in patients taking cardiac glycosides. Thiazide diuretics enhance the effects of curare-like muscle relaxants. Adjustment of insulin or oral antidiabetic medication doses may be necessary. Concomitant use of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol. The risk of adverse reactions caused by amantadine may be increased. Thiazides may also potentiate the hyperglycemic effects of diazoxide. Thiazides may reduce the renal excretion of cytotoxic drugs (e.g., cyclophosphamide, methotrexate), thereby increasing their myelosuppressive effects. The bioavailability of thiazide diuretics may be increased when anticholinergic drugs (e.g., atropine, biperiden) are coadministered, possibly as a result of decreased gastrointestinal motility and slower gastric emptying. There have been isolated reports of hemolytic anemia associated with the combined use of hydrochlorothiazide and methyldopa. Cholestyramine and colestipol reduce the absorption of thiazide diuretics. The combined use of thiazide diuretics with vitamin D or calcium salts can enhance the effect of increasing serum calcium. The combined use of cyclosporine may increase the risk of hyperuricemia and cause gout symptoms.
[Pharmacological Actions]
Pharmacological Actions: Valsartan: Angiotensin I is converted to angiotensin II (AGII) by angiotensin-converting enzyme (ACE). AGII is a key active component of the renin-angiotensin-aldosterone system (RAAS). It binds to specific receptors on the cell membranes of various tissues and exerts a wide range of physiological effects, including direct and indirect involvement in blood pressure regulation. Angiotensin II is a potent vasoconstrictor that exerts a direct pressor effect, promotes sodium reabsorption, and stimulates aldosterone secretion. Valsartan is an orally effective, specific angiotensin II (AT) receptor antagonist. It selectively targets the AT1 receptor subtype, with an affinity 20,000 times stronger for the AT1 receptor than for the AT2 receptor. The AT1 receptor subtype mediates the physiological responses of angiotensin II, while the AT2 receptor subtype is not involved in cardiovascular effects. Valsartan has no partial agonist activity at the AT1 receptor. Valsartan does not inhibit ACE (also known as kininase II), the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin. Valsartan lacks ACE inhibition and does not cause retention of bradykinin and substance P, making it less likely to induce cough. Clinical trials comparing valsartan with ACE inhibitors demonstrated a significantly lower incidence of dry cough in the valsartan group (2.6%) compared with the ACE inhibitor group (7.9%) (P < 0.05). In a clinical trial of patients who developed dry cough after receiving ACE inhibitors, cough was reported in 19.5% of patients in the valsartan, 19.0% of patients in the diuretic, and 68.5% of patients in the ACE inhibitor group (P < 0.05). In clinical trials, the incidence of cough in patients treated with valsartan and hydrochlorothiazide was 2.9%. Valsartan has no effects on other hormone receptors or ion channels known to play important roles in cardiovascular regulation. Valsartan lowers elevated blood pressure without affecting heart rate. In most patients, a single oral dose produces a blood pressure-lowering effect within 2 hours, peaks in 4 to 6 hours, and maintains its effect for more than 24 hours after dosing. In long-term treatment, maximal antihypertensive efficacy is achieved after 2 to 4 weeks and is maintained. Combination therapy with hydrochlorothiazide significantly enhances the antihypertensive effect of valsartan. Abrupt discontinuation of valsartan therapy does not cause rebound hypertension or other side effects. Valsartan does not affect fasting total cholesterol, triglycerides, blood glucose, or uric acid levels in hypertensive patients. The primary site of action of thiazide diuretics, such as hydrochlorothiazide, is the proximal distal convoluted tubule. Studies have shown that high-affinity receptors exist in the renal cortex, serving as the primary binding and site of action for thiazide diuretics, inhibiting sodium chloride transport in the proximal distal convoluted tubule. Thiazides act by inhibiting the co-transport of sodium and chloride ions. Competition for chloride ions at these sites can affect electrolyte reabsorption, directly increasing sodium and chloride excretion and indirectly reducing plasma volume, which in turn increases plasma renin activity, aldosterone secretion, and potassium excretion, leading to lower serum potassium. Because the renin-aldosterone system is angiotensin II-dependent, the concomitant use of angiotensin II receptor antagonists can reduce potassium loss associated with thiazide diuretics.
[Storage] Store tightly sealed in a cool, dry place (not exceeding 20°C).
[Specification] 80mg: 12.5mg x 7 tablets
[Packaging] Box
[Validity Period] 36 months
[Approval Number] National Medicine Standard H20052481
[Manufacturer] Zhejiang Yinggelai Pharmaceutical Co., Ltd.
