Product Overview
[Drug Name]
Generic Name: Irbesartan and Hydrochlorothiazide Tablets
Trade Name: HaiAnRui Irbesartan and Hydrochlorothiazide Tablets (14 tablets)
Pinyin Code: HaiAnRui EBeiShaTanQingLvSaiQinPian 14Pian
[Main Ingredients]
This product is a combination preparation. Each tablet contains 150mg of irbesartan and 12.5mg of hydrochlorothiazide. Molecular Formula: Irbesartan: C25H28N6O; Hydrochlorothiazide: C7H8CIN3O4S2. 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.
[Specifications]
14 tablets
[Dosage and Administration]
Oral administration, on an empty stomach or with food. 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 inadequately 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 initiating 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 inadequately controlled with irbesartan 150mg or hydrochlorothiazide alone. Once daily doses greater than irbesartan 300mg/hydrochlorothiazide 25mg are not recommended. This product can be used in combination with other antihypertensive medications if necessary (see [Drug Interactions]).
[Adverse Reactions]
The incidence of adverse reactions listed below uses the following definitions: very common (31/10); common (31/100); uncommon (31/1000, <1/100); rare (31/10000, <1/1000); and very rare (<1/10000). 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: Neurologic Abnormalities Common: Dizziness Occasional: Orthostatic dizziness Cardiac Abnormalities Occasional: Hypertension, edema, syncope, tachycardia Vascular Abnormalities Occasional: Flushing Gastrointestinal Abnormalities Common: Nausea/vomiting Occasional: Diarrhea, dry mouth Skeletal Muscle, Connective Tissue, and Bone Abnormalities Occasional: Distal limb edema, muscle/skeletal pain Skin and Subcutaneous Tissue Abnormalities Occasional: Rash Kidney and Urinary Tract Abnormalities Common: Urinary abnormalities Reproductive System and Breast Abnormalities Occasional: Altered libido, sexual dysfunction Systemic Abnormalities and Administration Site Conditions Common: Fatigue Occasional: Asthenia Examination: Patients in the irbesartan/hydrochlorothiazide group experienced few clinically significant changes in laboratory parameters. Common: Increased blood urea nitrogen (BUN), creatinine, and creatine kinase; Uncommon: 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-1 receptor antagonists, a small number of cases of hypersensitivity reactions such as rash, urticaria, and angioedema have occurred since the marketing of irbesartan alone. Metabolic and nutritional disorders; Hyperkalemia; Neurological disorders; Headache, vertigo; Ear and labyrinthine disorders; Tinnitus; Respiratory, chest, and diaphragmatic disorders; Cough; Gastrointestinal disorders; Dysgeusia, dyspepsia; Hepatobiliary disorders; Hepatitis, elevated liver enzymes, jaundice; Skeletal muscle, connective tissue, and bone disorders; Arthralgia, myalgia; Kidney 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: Uncommon: Electrocardiogram (ECG) Abnormalities; Gastrointestinal Abnormalities: Uncommon: Abdominal Pain; Skin and Subcutaneous Tissue Abnormalities: Uncommon: Itching; Systemic Abnormalities and Administration Site Conditions: Uncommon: Chest Pain, Extreme Asthenia. Postmarketing experience with the individual components is as follows: Irbesartan: Similar to other angiotensin-1 receptor antagonists, very rare hypersensitivity reactions (angioedema, urticaria, and anaphylactic shock) have been reported since the marketing of irbesartan monotherapy. During postmarketing surveillance, the following very rare adverse reactions have been reported: 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 (regardless of drug-related use) include: Blood and lymphatic system: aplastic anemia, bone marrow suppression, hemolytic anemia, leukopenia, neutropenia/granulocytopenia, thrombocytopenia Psychiatric disorders: depression, sleep disturbances Neurological disorders: dizziness, paresthesia, restlessness, lightheadedness Eye 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: pancreatic Adenitis, 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 and administration site disorders: fever Tests: electrolyte imbalances (including hypokalemia and hyponatremia), glycosuria, hyperglycemia, elevated serum uric acid, elevated cholesterol and triglycerides
[Contraindications]
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 sulfonamides (hydrochlorothiazide is a sulfonamide). 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 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.
[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 receptor blockers 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 medications. Renal Artery Stenosis - Renal Vascular 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 insufficiency (creatinine clearance <30 ml/min) (see Contraindications). No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance 330 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 susceptible patients following 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 lead to 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: In patients with hepatic impairment, even minor changes in fluid and electrolyte balance may precipitate hepatic coma; therefore, 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 for 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. Elevated 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 Abnormalities: As with any patient receiving diuretic therapy, serum electrolytes should be measured regularly. Thiazide diuretics, including hydrochlorothiazide, can cause fluid or electrolyte abnormalities (hypokalemia, hyponatremia, and hypochloremic alkalosis). Signs of fluid or electrolyte abnormalities 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 with inadequate oral electrolyte intake, and those taking corticosteroids or ACTH. Conversely, irbesartan in this product may induce hyperkalemia, particularly in patients with impaired renal function and/or heart failure and diabetes. 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 (see Drug Interactions). There is no evidence that irbesartan will reduce or prevent diuretic-induced hyponatremia. Decreases in serum chloride are usually 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. Marked hypercalcemia suggests underlying hyperparathyroidism. Thiazide diuretics should be discontinued while parathyroid function is being evaluated. Thiazide diuretics have been shown to increase magnesium excretion and may cause hypomagnesemia. Acute myopia and secondary acute angle-closure glaucoma: Sulfonamide or sulfonamide-like agents (drugs with the potential for idiosyncratic reactions) can cause transient myopia and acute angle-closure glaucoma. Several case reports of acute angle-closure glaucoma associated with hydrochlorothiazide have been reported. Symptoms include acute onset of vision loss or eye pain, typically occurring within hours to weeks of taking the drug. 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 sulfonamides or penicillin. There have been reports of thiazide diuretics exacerbating or reactivating systemic lupus erythematosus. The antihypertensive effect of thiazide diuretics may be increased in patients undergoing sympathectomy. Effects on driving and operating machinery: This product has not been studied for its effects on driving and operating machinery. However, based on its pharmacodynamic properties, it is unlikely that this product will 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 product 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 angiotensin-converting enzyme inhibitors (ACEIs) or aliskiren for dual blockade of the renin-angiotensin-aldosterone system is not recommended due to the increased risk of hypotension, hyperkalemia, and changes in renal function. The combination of irbesartan hydrochlorothiazide with aliskiren is contraindicated in patients with diabetes or renal impairment (GFR <60 ml/min/1.73 m²). The combination of irbesartan hydrochlorothiazide with angiotensin-converting enzyme inhibitors (ACEIs) is contraindicated in patients with diabetic nephropathy.
