LONGHAI HAIANRUI Irbesartan And Hydrochlorothiazide Tablets For Hypertension 28 Tablets

[Drug Name]
Generic Name: Irbesartan and Hydrochlorothiazide Tablets
Trade Name: HaiAnRui Irbesartan and Hydrochlorothiazide Tablets, 28 Tablets
Pinyin Code: HaiAnRui EBeiShaTanQingLvSaiQinPian 28 Tablets

[Main Ingredients]
This product is a combination preparation. Each tablet contains 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide. Molecular Formula: Irbesartan: C₂₅H₂₈N₆O; Hydrochlorothiazide: C₇H₂Cl₇₃O₄S₂. Molecular Weight: Irbesartan: 428.5; Hydrochlorothiazide: 297.2

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

[Indications/Main Functions]
For the treatment of essential hypertension. This fixed-dose combination is indicated for the treatment of patients whose blood pressure is inadequately controlled with irbesartan or hydrochlorothiazide alone.

[Precautions]
General Precautions: In patients whose vascular tone and renal function depend primarily on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure or renal disease, including renal artery stenosis), treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists may result in acute hypotension, azotemia, oliguria, or rarely, acute renal failure and/or death. As with any antihypertensive drug, excessive blood pressure reduction in patients with ischemic cardiomyopathy or ischemic cardiovascular disease may lead to myocardial infarction or stroke. Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergies or asthma; generally, those with a history of allergies or asthma are more susceptible (see Contraindications). Fetal/Neonatal Morbidity and Mortality: Although there is no experience with this drug in pregnant women, in utero exposure to ACE inhibitors during the second and third trimesters has been reported to result in harm and death to the developing fetus. Therefore, like any drug that directly acts on the renin-angiotensin-aldosterone system, this combination should not be used during pregnancy. If pregnancy is discovered during treatment, treatment with this combination must be discontinued as soon as possible. Hydrochlorothiazide crosses the placenta and is present in umbilical cord blood. Use of hydrochlorothiazide during pregnancy increases the risk of fetal or neonatal jaundice and thrombocytopenia and may be associated with other adverse reactions that occur in adults. Hypotension-Volume Depletion: This combination is rarely associated with symptomatic hypotension in hypertensive patients without other risk factors for hypotension. Symptomatic hypotension may occur in patients with volume and sodium depletion due to use of potent diuretics, severe dietary salt restriction, diarrhea, and vomiting. These conditions should be corrected before treatment with this combination. Thiazides may potentiate the effects of other antihypertensive drugs. Renal Artery Stenosis-Renovascular Hypertension: Increased serum creatinine and/or blood urea nitrogen levels have been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney when using drugs that affect the renin-angiotensin-aldosterone system. Although there is no experience with this product in patients with unilateral or bilateral renal artery stenosis, similar effects of angiotensin II receptor antagonists should be considered. Renal Impairment and Kidney Transplantation: This product should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) (see [Contraindications]). No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance ≥30 ml/min but <60 ml/min). However, this combination should be used with caution. Azotemia associated with thiazide diuretics may occur in patients with renal impairment. When this product is used in patients with renal impairment, serum potassium, creatinine, and uric acid should be monitored regularly. Changes in renal function may occur in sensitive patients after treatment with inhibitors of the renin-angiotensin-aldosterone system. In patients whose renal function depends primarily on the activity of the renin-angiotensin-aldosterone system (e.g., those with severe congestive heart failure or renal impairment), the use of angiotensin-converting enzyme (ACE) inhibitors can result in oliguria and/or progressive azotemia, and rarely, acute renal failure and/or death. There is no experience with the use of this drug in patients who have recently undergone renal transplantation. Hepatic Impairment: Because minor alterations in fluid and electrolyte balance may precipitate hepatic coma in patients with hepatic impairment, caution should be exercised when using thiazide diuretics in such patients. There is no experience with the use of this combination in patients with hepatic impairment. Aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy: As with other vasodilators, caution should be exercised when using this drug in patients with aortic and mitral stenosis and hypertrophic obstructive cardiomyopathy. Primary Aldosteronism: Patients with primary aldosteronism generally do not respond to antihypertensive drugs that inhibit the renin-angiotensin system; therefore, this drug is not recommended in these patients. Metabolic and Endocrine Effects: Thiazide diuretic therapy may impair glucose tolerance. Patients with diabetes may require adjustments in insulin and oral hypoglycemic medication doses. Symptomatic latent diabetes may develop during thiazide diuretic therapy. Increased cholesterol and triglyceride levels have been associated with thiazide diuretic therapy. However, at the 12.5 mg dose contained in the combined formulation, this effect is minimal or absent. Hyperuricemia and even gout may occur in some patients receiving thiazide diuretics. Electrolyte Imbalances: As with any patient receiving diuretic therapy, serum electrolytes should be measured regularly. Thiazide diuretics, including hydrochlorothiazide, can cause fluid or electrolyte imbalances (hypokalemia, hyponatremia, and hypochloremic alkalosis). Signs of fluid or electrolyte imbalances include dry mouth, thirst, weakness, lethargy, drowsiness, irritability, muscle cramps and pain, muscle fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting. Thiazide diuretics may induce hypokalemia, but coadministration with irbesartan can reduce diuretic-induced hypokalemia. Hypokalemia is most likely to occur in patients with cirrhosis, those with significant diuretic effects, those taking inadequate oral electrolytes, and those taking concomitant corticosteroids or ACTH. Conversely, irbesartan in this product may induce hyperkalemia, particularly in patients with renal impairment and/or heart failure and diabetes mellitus. Appropriate monitoring of serum potassium concentrations is recommended in these patients. Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes should be used with caution when coadministered with this product (see Drug Interactions). There is no evidence that irbesartan will reduce or prevent diuretic-induced hyponatremia. Decreases in blood chloride are generally mild and do not require treatment. Thiazide diuretics may reduce renal calcium excretion, causing intermittent, mild elevations in patients without known abnormalities of calcium metabolism. Significant hypercalcemia suggests underlying hyperparathyroidism. Thiazide diuretics should be discontinued while parathyroid function testing is being performed. Thiazide diuretics have been shown to increase magnesium excretion and may cause hypomagnesemia. Acute Myopia and Secondary Acute Angle-Closure Glaucoma: Sulfonamide or sulfonamide derivatives (drugs with the potential for idiosyncratic reactions) can cause transient myopia and acute angle-closure glaucoma. There have been multiple case reports of acute angle-closure glaucoma associated with hydrochlorothiazide. Symptoms include acute onset of vision loss or eye pain, typically occurring within hours to weeks of drug ingestion. Untreated acute angle-closure glaucoma may result in permanent vision loss. The primary treatment is to discontinue the medication as soon as possible. If intraocular pressure remains uncontrolled, prompt medical or surgical treatment may be necessary. Risk factors for acute angle-closure glaucoma may include a history of allergy to sulfonamide or penicillin. There have been reports of systemic lupus erythematosus being exacerbated or activated by thiazide diuretics. The antihypertensive effect of thiazide diuretics may be increased in patients undergoing sympathectomy. Effects on Driving and Operating Machinery: The effects of this drug on driving and operating machinery have not been studied. However, based on its pharmacodynamic properties, this drug is unlikely to affect these abilities. When driving or operating machinery, the potential for dizziness and fatigue associated with antihypertensive therapy should be considered. Antidoping Tests: The hydrochlorothiazide in this drug may result in a positive antidoping test result. Use with caution in athletes. Dual Blockade of the Renin-Angiotensin-Aldosterone System (RAAS): Concomitant use of irbesartan hydrochlorothiazide with dual blockade of the renin-angiotensin-aldosterone system (RAAS) using angiotensin-converting enzyme inhibitors (ACEIs) or aliskiren is not recommended due to an increased risk of hypotension, hyperkalemia, and changes in renal function. The combination of irbesartan hydrochlorothiazide and aliskiren is contraindicated in patients with diabetes or renal impairment (GFR <60 ml/min/1.73 m²). The combination of irbesartan hydrochlorothiazide and angiotensin-converting enzyme inhibitors (ACEIs) is contraindicated in patients with diabetic nephropathy.

[Drug Interactions]
During the 4th to 9th month of pregnancy (see [Use in Pregnant and Lactating Women]). During lactation (see [Use in Pregnant and Lactating Women]). Patients with known hypersensitivity to the active ingredient or any of the excipients in this product, or to other sulfonamide derivatives (hydrochlorothiazide is a sulfonamide derivative). In general, patients with a history of allergies or bronchial asthma are more likely to experience an allergic reaction. This product is contraindicated in patients with anuria. The following contraindications are associated with hydrochlorothiazide: - Severe renal impairment (creatinine clearance <30 mL/min); - Refractory hypokalemia, hypercalcemia; - Severe hepatic impairment, biliary cirrhosis, and cholestasis. The combination of irbesartan hydrochlorothiazide and aliskiren is contraindicated in patients with diabetes or moderate to severe renal impairment (glomerular filtration rate <60 mL/min/1.73 m²). The combination of irbesartan hydrochlorothiazide and angiotensin-converting enzyme inhibitors (ACEIs) is contraindicated in patients with diabetic nephropathy.

[Specifications]
28 tablets

[Dosage and Administration]
Oral administration, on an empty stomach or with meals. The usual starting and maintenance dose is one tablet once daily, which can be increased to two tablets once daily depending on the condition. This product is used to treat patients whose blood pressure is not effectively controlled with irbesartan or hydrochlorothiazide alone. It is recommended that patients adjust the dose of the individual components (i.e., irbesartan or hydrochlorothiazide) in combination therapy before using a fixed-dose combination. Once the doses of the individual components are fixed in the combination, this combination can be substituted. The following situations allow for direct conversion from single-component therapy to combination therapy: This product 150mg/12.5mg combination can be used for patients whose blood pressure is not effectively controlled with irbesartan 150mg or hydrochlorothiazide alone. Once-daily doses greater than irbesartan 300mg/hydrochlorothiazide 25mg are not recommended. If necessary, this product can be used in combination with other antihypertensive medications (see [Drug Interactions]).

[Adverse Reactions]
The incidence of adverse reactions listed below uses the following definition conventions: Very common (≥1/10); Common (≥1/100); Uncommon (≥1/1000, <1/100); Rare (≥1/10,000, <1/1000); Very rare (<1/10,000). Irbesartan/hydrochlorothiazide combination tablets: In placebo-controlled trials in patients with hypertension, the overall incidence of adverse reactions did not differ between the irbesartan/hydrochlorothiazide group and the placebo group. The incidence of treatment discontinuation due to clinical or laboratory adverse events was lower in the irbesartan/hydrochlorothiazide group than in the placebo group. Adverse events were not related to dose (within the recommended dose range), sex, age, race, or treatment duration. In placebo-controlled trials, 898 hypertensive patients received various doses of irbesartan/hydrochlorothiazide (ranging from 37.5 mg/6.25 mg to 300 mg/25 mg of irbesartan/hydrochlorothiazide). The following adverse reactions were reported: Nervous system disorders Common: dizziness Infrequent: orthostatic dizziness Cardiac disorders Infrequent: hypertension, edema, syncope, tachycardia Vascular disorders Infrequent: flushing Gastrointestinal disorders Common: nausea/vomiting Infrequent: diarrhea, dry mouth Muscle, connective tissue, and bone disorders Infrequent: distal extremity edema, musculoskeletal pain Skin and subcutaneous tissue disorders Infrequent: rash Renal and urinary tract disorders Common: urination abnormalities Reproductive system and breast disorders Infrequent: altered libido, sexual dysfunction General disorders and administration site conditions Common: fatigue Infrequent: asthenia Examinations: Few patients in the irbesartan/hydrochlorothiazide group had clinically significant changes in laboratory parameters. Common: Increased blood urea nitrogen (BUN), creatinine, and creatine kinase. Rare: Decreased serum potassium and sodium levels. In addition, the following adverse reactions have been reported since the marketing of the irbesartan/hydrochlorothiazide combination: Immune system disorders. Rare: As with other angiotensin-II receptor antagonists, hypersensitivity reactions such as rash, urticaria, and angioedema have occurred in a small number of cases since the marketing of irbesartan alone. Metabolic and nutritional disorders: Hyperkalemia. Neurological disorders: Headache, dizziness. Ear and labyrinth disorders: Tinnitus. Respiratory, chest, and diaphragmatic disorders: Cough. Gastrointestinal disorders: Taste disturbances, dyspepsia. Hepatobiliary disorders: Hepatitis, elevated liver enzymes, jaundice. Skeletal muscle, connective tissue, and bone disorders: Arthralgia, myalgia. Renal and urinary tract disorders: Renal impairment, including renal failure in some high-risk patients. Additional information about the individual components: In addition to the adverse reactions listed above for the combination product, previously reported adverse reactions with the use of one of the individual components also require attention as potential adverse reactions. Irbesartan: Cardiac Abnormalities Rarely: Electrocardiogram (ECG) abnormalities Gastrointestinal Abnormalities Rarely: Abdominal pain Skin and Subcutaneous Tissue Abnormalities Rarely: Pruritus General Abnormalities and Administration Site Conditions Rarely: Chest pain, extreme weakness Postmarketing experience with the individual components is listed below: Irbesartan: Similar to other angiotensin-II receptor antagonists, very rare hypersensitivity reactions (angioedema, urticaria, and anaphylactic shock) have been reported since the marketing of irbesartan monotherapy. The following very rare adverse reactions have been reported during postmarketing surveillance: dizziness, asthenia, hyperkalemia, jaundice, myalgia, increased creatine kinase, increased liver function test levels, hepatitis, tinnitus, and impaired renal function, including occasional renal failure in at-risk populations. Hydrochlorothiazide: Adverse events reported with hydrochlorothiazide alone (whether or not related to the drug being taken) include: Hematologic and Lymphatic System: Aplastic anemia, bone marrow suppression, hemolytic anemia, leukopenia, neutropenia/granulocytopenia, thrombocytopenia Psychiatric Disorders: Depression, sleep disturbances Neurologic Disorders: Dizziness, paresthesia, restlessness, lightheadedness Ocular Disorders: Transient blurred vision, xanthoopia, secondary acute angle-closure glaucoma Cardiac Disorders: Arrhythmias Vascular Disorders: Orthostatic Hypotension Respiratory, Thoracic, and Diaphragmatic Disorders: Dyspnea (including pneumonia, pulmonary edema) Gastrointestinal Disorders: Pancreatitis, anorexia, constipation, diarrhea, gastric irritability, decreased appetite, sialadenitis Hepatobiliary Disorders: Jaundice (intrahepatic biliary jaundice) Skin and Subcutaneous Tissue Disorders: Allergic reactions, toxic epidermal necrolysis, cutaneous lupus erythematosus-like reactions, necrotizing vasculitis (phlebitis, cutaneous phlebitis), photosensitivity reactions, rash, urticaria. Skeletal muscle, connective tissue, and bone disorders: Muscle cramps, weakness. Kidney and urinary tract disorders: Interstitial nephritis, renal dysfunction. Systemic disorders and administration site conditions: Fever. Examination: Electrolyte imbalances (including hypokalemia and hyponatremia), glycosuria, hyperglycemia, elevated serum uric acid, elevated cholesterol, and elevated triglycerides.

[Contraindications]
During the fourth to ninth month of pregnancy (see [Use in Pregnant and Lactating Women]). During lactation (see [Use in Pregnant and Lactating Women]). Known hypersensitivity to the active ingredient or any of the excipients in this product, or to other sulfonamide derivatives (hydrochlorothiazide is a sulfonamide derivative). In general, patients with a history of allergies or bronchial asthma are more likely to experience allergic reactions. This product is contraindicated in patients with anuria. The following contraindications are associated with hydrochlorothiazide: - Severe renal impairment (creatinine clearance <30 mL/min); - Refractory hypokalemia and hypercalcemia; - Severe hepatic impairment, biliary cirrhosis, and cholestasis. The combination of irbesartan and hydrochlorothiazide with aliskiren is contraindicated in patients with diabetes or moderate to severe renal impairment (glomerular filtration rate <60 mL/min/1.73 m²). The combination of irbesartan and hydrochlorothiazide with angiotensin-converting enzyme inhibitors (ACEIs) is contraindicated in patients with diabetic nephropathy.