Irbesartan Hydrochlorothiazide Capsules

This product is a combination of angiotensin-Ⅱ antagonists, namely irbesartan and thiazide diuretic hydrochlorothiazide. The antihypertensive effect of this combination is synergistic and more effective than the antihypertensive effect of any single drug. Irbesartan is a potent, orally effective selective angiotensin-Ⅲ receptor (AT1 subtype) antagonist. Regardless of the source or synthesis pathway of angiotensin-Ⅱ, it can block all the effects of angiotensin-Ⅱ mediated by AT1 receptors. Its selective antagonism of angiotensin-Ⅱ receptors (AT1) leads to increased plasma renin and angiotensin-Ⅱ levels and decreased plasma aldosterone levels. When the recommended dose of irbesartan is given alone to patients without electrolyte disorders, serum potassium will not be significantly affected (see [Precautions] and [Drug Interactions]). Irbesartan does not inhibit angiotensin converting enzyme (ACE or kinase II), under the action of which angiotensin-Ⅱ can be generated, and bradykinin can also be degraded into inactive metabolites. The activity of irbesartan does not require metabolic activation. Hydrochlorothiazide is a thiazide diuretic. The antihypertensive mechanism of thiazide diuretics is not yet fully understood. It can affect the renal tubular reabsorption mechanism of electrolytes and directly increase the excretion of sodium and chloride (roughly equal amounts). Hydrochlorothiazide reduces blood volume, increases plasma renin activity, and increases aldosterone secretion, thereby increasing the excretion of potassium and bicarbonate in urine and reducing serum potassium levels. The combined use of irbesartan can reverse the potassium loss associated with diuretics by blocking the renin-angiotensin-aldosterone system. The diuretic effect of hydrochlorothiazide begins 2 hours after taking the drug, the peak effect occurs at about 4 hours, and can last for about 6-12 hours. The combination of hydrochlorothiazide and irbesartan can produce a dose-related synergistic hypotensive effect within its recommended therapeutic dose range. For patients whose blood pressure is not effectively controlled by irbesartan 300 mg alone, the addition of hydrochlorothiazide 12.5 mg once daily can reduce the placebo-corrected diastolic blood pressure trough value (24 hours after taking the drug) by an additional 6.1 mmHg. The combination of irbesartan 300 mg and hydrochlorothiazide 12.5 mg can further reduce the total systolic/diastolic blood pressure by 13.6/11.5 mmHg after deducting the placebo effect. Patients with mild to moderate essential hypertension taking irbesartan 150 mg and hydrochlorothiazide 12.5 mg daily can reduce the placebo-corrected systolic/diastolic blood pressure trough value (24 hours after taking the drug) by an average of 12.9/6.9 mmHg. The peak effect occurs in 3-6 hours. Using ambulatory blood pressure monitoring to evaluate, once-daily administration of a combination of 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide can produce a 24-hour sustained lowering effect, with a placebo-corrected average systolic/diastolic blood pressure reduction of 15.8/10.0 mmHg in 24 hours. The combination (150/12.5 mg) has a 100% trough/peak effectiveness rate in reducing trough/peak blood pressure as measured by ambulatory blood pressure monitoring. The trough/peak blood pressure reduction effectiveness of the 150/12.5 mg and 300/12.5 mg combination measured by a cuff sphygmomanometer during clinic visits was 68% and 76%, respectively. Once daily administration does not produce an excessive peak blood pressure reduction effect, but the blood pressure reduction effect is safe and effective and lasts for 24 hours. For patients who cannot effectively control their blood pressure with hydrochlorothiazide 25 mg alone, the addition of irbesartan can reduce systolic/diastolic blood pressure by an average of 11.1/7.2 mmHg after deducting the placebo effect. The antihypertensive effect of the combination of irbesartan and hydrochlorothiazide appears after the first dose, is significant within 1-2 weeks, and the maximum effect is 6-8 weeks. In long-term follow-up studies, the antihypertensive effect of irbesartan/hydrochlorothiazide lasts for more than one year. Although the combination has not been specifically studied, no rebound blood pressure increase was observed during treatment with irbesartan or hydrochlorothiazide. There are no studies on the effect of the combination of irbesartan and hydrochlorothiazide on cardiovascular morbidity and mortality. Epidemiological studies have shown that long-term treatment with hydrochlorothiazide reduces the risk of cardiovascular morbidity and mortality. There is no difference in the response of patients of different ages and genders to this combination. When irbesartan is used in combination with low-dose hydrochlorothiazide (such as 12.5 mg per day), its antihypertensive effect in blacks and non-blacks is similar.

Each tablet of this product contains 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide. Irbesartan: Molecular formula: C25H28N6O Molecular weight: 428.5 Hydrochlorothiazide: Molecular formula: C7H8ClN3O4S2 Molecular weight: 297.2

This product is a capsule, and the contents are white granules.

For the treatment of essential hypertension. This fixed-dose combination is used to treat patients whose blood pressure cannot be effectively controlled by irbesartan or hydrochlorothiazide alone.

This product is used once a day on an empty stomach or with meals to treat patients whose blood pressure cannot be effectively controlled by 150 mg of irbesartan or hydrochlorothiazide alone. It is recommended that patients adjust the single component (i.e., irbesartan or hydrochlorothiazide) and replace it with the compound. It is not recommended to use a once-daily dose greater than 300 mg of irbesartan/25 mg of hydrochlorothiazide. If necessary, this product can be used in combination with other antihypertensive drugs (see [Drug Interactions]).

Common adverse reactions include headache, dizziness, palpitations, and occasional cough, which are generally mild and transient, and most patients can tolerate the medication. Urticaria and angioedema are rare. Literature reports that the incidence of adverse reactions of this product is greater than 1% including indigestion, heartburn, diarrhea, skeletal muscle pain, fatigue, and upper respiratory tract infection, but there is no significant difference compared with the blank control group.

1. It is contraindicated for those who are allergic to this product. 2. It is contraindicated for pregnant and lactating women.

Precautions for children: The safety and effectiveness of this product in patients under 18 years of age have not been studied. Precautions for pregnancy and lactation: Pregnancy: See [Contraindications] and [Precautions] sections. Thiazide diuretics can cross the placental barrier and appear in the umbilical cord blood, causing decreased placental perfusion, fetal electrolyte disorders and other effects that may occur in adults. There are reports of neonatal thrombocytopenia, fetal or neonatal jaundice caused by maternal use of thiazide drugs. Because this compound contains hydrochlorothiazide, it is not recommended for use in the first three months of pregnancy. Appropriate alternative treatment should be switched when planning pregnancy. In the fourth to ninth months of pregnancy, substances that directly act on the renin-angiotensin system can cause fetal and neonatal renal failure, fetal head dysplasia and fetal death. Therefore, this compound is contraindicated for pregnant women from the fourth to ninth months of pregnancy. If pregnancy is diagnosed, stop using this product as soon as possible. If it has been neglected for a long time, the head and kidney function should be examined by ultrasound. Lactation: Due to potential adverse reactions to infants, this product is contraindicated during lactation (see [Contraindications]). It is not known whether irbesartan is secreted into human breast milk. Irbesartan is secreted into the milk of mice. Thiazides can appear in human breast milk and may inhibit lactation. Elderly precautions: Elderly patients do not need to adjust the dosage.

Other antihypertensive drugs: When this product is used in combination with other antihypertensive drugs, its antihypertensive effect may be enhanced. Irbesartan and hydrochlorothiazide (irbesartan and hydrochlorothiazide doses up to 300mg/25mg) can be safely used in combination with other antihypertensive drugs such as calcium channel blockers and beta-blockers. The use of irbesartan with or without thiazide diuretics may lead to hypovolemia if high doses of diuretics have been used beforehand. Taking it at this time may cause hypotension unless the volume depletion is corrected first (see [Precautions]). Lithium: There are reports that when lithium and angiotensin-converting enzyme inhibitors are used in combination, serum lithium can be reversibly increased and toxic effects can occur. In addition, thiazide diuretics can reduce the renal clearance of lithium, so there is an increased risk of lithium poisoning when used in combination with this product. Lithium should be used with caution when used in combination with this product, and careful monitoring of serum lithium concentrations is recommended. Drugs that affect serum potassium: The potassium-excreting effect of hydrochlorothiazide can be weakened by the potassium-sparing effect of irbesartan. However, the effect of hydrochlorothiazide on serum potassium may be potentiated by other drugs that are associated with potassium loss and cause hypokalemia (e.g., other potassium-wasting diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium salt, salicylic acid derivatives). Conversely, based on clinical experience with other drugs that can attenuate the renin-angiotensin system, the co-administration of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that increase serum potassium levels may lead to an increase in serum potassium. Drugs Affected by Serum Potassium Disturbances: When this combination is co-administered with other drugs that are affected by serum potassium disturbances (e.g., digitalis glycosides, antiarrhythmic drugs), regular monitoring of serum potassium is recommended. Additional Information on Interactions with Irbesartan: In healthy male subjects, the pharmacokinetics of digoxin were not altered when co-administered with 150 mg of irbesartan. The pharmacokinetics of irbesartan were not affected when co-administered with hydrochlorothiazide. Irbesartan is primarily metabolized by CYP2C9 and to a lesser extent by glucuronidase. Inhibition of the glucuronyltransferase pathway does not result in clinically significant interactions. In vitro interactions were observed between irbesartan and warfarin, tolbutamide (CYP2C9 substrates) and nifedipine (CYP2C9 inhibitor). However, in healthy male subjects, no significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was co-administered with warfarin, and the pharmacokinetics of irbesartan were not affected when co-administered with nifedipine. There are no studies on the effects of CYP2C9 inducers such as rifampicin on the pharmacokinetics of irbesartan. Based on in vitro data, no interactions occur with drugs whose metabolism depends on cytochrome P450 isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6, GYP2E1 or CYP3A4. Other information about hydrochlorothiazide interactions: The following drugs may interact with thiazide diuretics when used together: Alcohol, barbiturates, or nicotine: may aggravate postural hypotension; Antidiabetic drugs (oral agents and insulin): the dose of antidiabetic drugs may need to be adjusted when used together (see [Precautions]); Cholestyramine and Colestipol resin: when used together with anionic resins, they affect the absorption of hydrochlorothiazide; Corticosteroids, ACTH: electrolyte loss may increase, especially hypokalemia; Digitalis glycosides: thiazide-induced hypokalemia and hypomagnesemia are conducive to digitalis-induced The occurrence of arrhythmias (see [Precautions]); Nonsteroidal anti-inflammatory drugs: The combined use of nonsteroidal anti-inflammatory drugs can reduce the diuretic, natriuretic and hypotensive effects of thiazide diuretics in some patients; Vasoactive amines (such as norepinephrine): The effect of vasoactive amines may be reduced, but not enough to stop using; Non-depolarizing skeletal muscle relaxants (such as tubocurarine): The effect of non-depolarizing skeletal muscle relaxants may be enhanced by hydrochlorothiazide; Anti-gout drugs: Since hydrochlorothiazide can increase serum uric acid levels, its drug dose may need to be adjusted when used in combination; The dosage of probenecid and sulfaquinoxaline may need to be increased. The combined use of thiazide diuretics may increase the allergic reaction to allopurinol; Calcium salts: Thiazide diuretics can reduce calcium secretion and may increase serum calcium levels. If calcium supplements or calcium-retaining drugs (such as vitamin D treatment) must be used, serum calcium levels should be monitored and the corresponding calcium dose should be adjusted; Other drug interactions: Thiazide diuretics may increase the hyperglycemic effect of beta-blockers and diazosin. Anticholinergic drugs (such as atropine, Beperiden) may increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and gastric emptying rate. Thiazide diuretics may increase the risk of adverse reactions caused by amantadine. Thiazide diuretics may reduce the renal excretion of cytotoxic drugs (such as cyclophosphamide, methotrexate) and enhance their bone marrow suppression effects. There is no information on incompatibility.

Keep in airtight and light-proof place.

Each tablet contains 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide.

Tentative 18 months

Yuanhe Pharmaceutical Group Industry Co., Ltd.

• Founded in:

  2000-07-25

• Address:

  Jinerdao, Jinchuan District, Hohhot Economic and Technological Development Zone, Inner Mongolia Autonomous Region

• Tax NO.:

  91150100701468845D

• Registered Funds:

  62 million yuan

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