Losartan Potassium Capsules

1. Mechanism of action Angiotensin II is the main active substance of the renin-angiotensin system. It is a potent vasoconstrictor and plays a major role in the pathophysiological process of hypertension. Angiotensin II binds to AT1 receptors in various tissues (such as vascular smooth muscle, adrenal glands, kidneys and heart), producing a variety of important biological effects including vasoconstriction and aldosterone release. At the same time, it can also stimulate smooth muscle cell proliferation. It has been confirmed that another angiotensin II receptor subtype is AT2, but its role in the functional homeostasis of the cardiovascular system is still unclear. Losartan is a synthetic, potent, orally active drug. Binding tests and pharmacological biological assays have shown that it can selectively bind to AT1 receptors. In vivo studies have shown that losartan and its pharmacologically active carboxylic acid metabolite (E-3174) can block the corresponding physiological effects of angiotensin II synthesized from any source or any route. Compared with other peptide angiotensin II antagonists, losartan has no agonist effect. Losartan selectively acts on AT1 receptors, does not affect the functions of other hormone receptors or important ion channels in the cardiovascular system, and does not inhibit angiotensin converting enzyme (kininase II) that degrades bradykinin. Therefore, effects that are not directly related to blocking AT1 receptors, such as bradykinin-mediated effects or edema (losartan 1.7% placebo 1.9%), are not related to losartan. 2. Toxicity study The LD50 of losartan potassium in male mice orally administered was 2248 mg/Kg (6744 mg/m2) (1124 times the recommended maximum daily dose for adults). The significant minimum lethal dose of this product in mice and rats orally administered was 1000 mg/Kg (3000 mg/m2) and 2000 mg/Kg (11800 mg/m2), respectively, which are 500 times and 1000 times the recommended maximum daily dose for adults (calculated based on a body weight of 50 kg). The potential toxicity of losartan potassium was evaluated by a series of toxicity tests with multiple oral administrations for three months in monkeys and one year in rats and dogs, and no toxicity was found to prevent the use of the drug at therapeutic dose levels. When rats and mice were given the maximum tolerated dose of this product, the observation time was up to 105 weeks and 92 weeks, respectively, and no carcinogenic effect of losartan potassium was found. In vitro alkaline elution tests and chromosome aberration tests showed that the use of losartan potassium at a maximum plasma concentration equivalent to 1700 times the recommended therapeutic dose for humans had no direct mutagenic effect. Male and female rats were given losartan potassium 150 and 300 mg/kg orally every day, respectively, and no effect on reproductive capacity was found. Losartan potassium can cause adverse reactions to rat embryos and newborns, including weight loss, death and/or nephrotoxicity. In addition, the concentrations of losartan potassium and its active metabolites in the milk of rats taking the drug were high.

The main ingredient of this product is losartan potassium. Chemical name: 2-butyl-4-chloro-1-[[2'-(1H-tetrazolyl-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol monopotassium salt. Chemical structure: Molecular formula: C22H22ClKN6O Molecular weight: 461.01

The content of this product is white or off-white granules or powder.

This product is suitable for the treatment of hypertension.

This product can be used together with other antihypertensive drugs. This product can be taken with or without food. For most patients, the usual starting and maintenance dose is 50 mg once a day. The maximum antihypertensive effect can be achieved after 3 to 6 weeks of treatment. In some patients, increasing the dose to 100 mg once a day can produce further antihypertensive effects. For patients with insufficient vascular volume (such as patients treated with high-dose diuretics), a starting dose of 25 mg once a day can be considered (see Precautions). For elderly patients or patients with renal impairment, including patients undergoing hemodialysis, there is no need to adjust the starting dose. For patients with a history of liver damage, a lower dose should be considered (see Precautions).

Foreign clinical trials have found that this product is well tolerated, with mild and short-lived adverse reactions, and generally no need to terminate treatment. The overall incidence of adverse reactions with losartan is similar to that with placebo. In clinical controlled studies of essential hypertension, the only adverse reaction with an incidence of ≥1%, drug-related, and higher than placebo is dizziness. In addition, less than 1% of patients experience dose-related orthostatic hypotension. Although the incidence of rash in controlled clinical trials is lower than that of placebo, there are individual reports. According to foreign data, in these clinical double-blind controlled studies of essential hypertension, after the use of losartan, regardless of whether it is drug-related, the adverse reactions with an incidence of 1% or more are: In addition to the above adverse events, at least two patients/subjects in clinical studies have experienced potential serious adverse events or other adverse events with an incidence of less than 1% after using losartan. It cannot be determined that these events have a causal relationship with losartan. Systemic: facial edema, fever, orthostatic hypotension, syncope. Cardiovascular system: angina, second degree atrioventricular block, cardiovascular accident, hypotension, myocardial infarction, arrhythmia including atrial fibrillation, palpitations, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation. Digestive system: loss of appetite, constipation, toothache, dry mouth, flatulence, gastritis, vomiting. Blood system: anemia. Metabolism: gout. Musculoskeletal system: arm pain, hip pain, joint swelling, knee pain, skeletal muscle pain, shoulder pain, stiffness, joint pain, arthritis, fibromyalgia, myasthenia. Nervous/psychiatric system: anxiety, anxiety disorder, ataxia, confusion, depression, abnormal dreams, dysesthesia, decreased libido, memory loss, migraine, nervousness, paresthesia, peripheral neuropathy, panic disorder, abnormal sleep, drowsiness, tremor, vertigo. Respiratory system: dyspnea, bronchitis, pharyngeal discomfort, epistaxis, rhinitis, respiratory congestion. Skin: Alopecia, dermatitis, dry skin, eczema, erythema, flushing, photosensitivity, itching, rash, sweating, urticaria. Special senses: Blurred vision, burning and stinging eyes, conjunctivitis, abnormal taste, tinnitus, decreased visual acuity. Genitourinary system: Impotence, nocturia, frequent urination, urinary tract infection. Other adverse reactions reported after the marketing of losartan include: Allergic reactions: Angioedema (including swelling of the larynx and glottis leading to airway obstruction, and/or swelling of the face, lips, pharynx and/or tongue) has been reported in a very small number of patients treated with losartan. Some of these patients had previously developed angioedema due to other drugs, including ACE inhibitors. Vasculitis, including Henoch-Schönlein purpura, has been rarely reported. Gastrointestinal reactions: Hepatitis (rarely reported), abnormal liver function, vomiting. Hematological system: Anemia, thrombocytopenia (rarely reported). Musculoskeletal system: myalgia, arthralgia. Nervous/psychiatric system: migraine, seizures, dysgeusia. Respiratory system: cough. Skin: urticaria, pruritus, erythroderma. Hyperkalemia and hyponatremia have been reported. In a controlled clinical trial in patients with hypertension and left ventricular hypertrophy, losartan was generally well tolerated. The most common drug-related adverse reactions were dizziness, weakness/fatigue, and vertigo. In the LIFE study, among patients without diabetes at baseline, fewer patients in the losartan potassium group developed new diabetes compared with the atenolol group (242 vs. 320, respectively, P < 0.001). Because there was no placebo group in this study, it is unclear whether this result represents a benefit of losartan potassium or an adverse reaction of atenolol. In a controlled clinical trial in patients with type 2 diabetes and proteinuria, losartan was generally well tolerated. The most common drug-related adverse reactions were fatigue/fatigue, dizziness, hypotension, and hyperkalemia (see PRECAUTIONS, HYPOTENOLOL AND ELECTROLYTE/FLUID IMBALANCE). Laboratory Test Results In controlled clinical trials of essential hypertension, few patients treated with losartan experienced clinically important changes in laboratory parameters. Hyperkalemia (serum potassium > 5.5 mEq/L) occurred in 1.5% of patients. In a clinical study in patients with type 2 diabetes and proteinuria, hyperkalemia occurred in 9.9% of patients in the losartan group and 3.4% of patients in the placebo group (see PRECAUTIONS, HYPOTENSION, AND ELECTROLYTE/FLUID IMBALANCE). ALT elevations were rare and returned to normal after discontinuation of the drug. Creatinine, Blood Urea Nitrogen: In patients with essential hypertension, mild increases in blood urea nitrogen or serum creatinine were observed in less than 0.1% of patients treated with losartan alone. Hemoglobin and Hematocrit: Mild decreases in hemoglobin and hematocrit were common in patients treated with losartan alone (mean decreases of approximately 0.11% and 0.09%, respectively). However, these were rarely of clinical importance, and no patient discontinued the drug because of anemia. Liver function tests: Occasionally, there are elevations in liver enzymes and/or serum bilirubin. Among patients with essential hypertension treated with this product alone, one patient (<0.1%) stopped taking the drug due to these laboratory adverse reactions.

1. Those who are allergic to any ingredient of this product are prohibited from using. 2. Pregnant women should use with caution.

Precautions for children: Foreign trials have shown that this product has an antihypertensive effect in hypertensive children aged 1 month to 16 years. Evidence from adequate controlled studies in children and adults and literature reports on its use in children support the use of this product in these age groups. In foreign countries, 50 hypertensive children aged 1 month to 16 years old were given losartan orally once a day at a dose of approximately 0.54-0.77 mg/Kg (average dose) to conduct a pharmacokinetic study of losartan. Losartan forms active metabolites in all age groups. In general, the pharmacokinetics of losartan and its active metabolites are similar between the age groups studied and are consistent with the existing adult pharmacokinetics. In a foreign clinical study involving 177 hypertensive children aged 6-16 years, patients weighing ≥20Kg to <50Kg took 2.5, 25 or 50 mg of losartan per day, and patients weighing ≥50Kg took 5, 50 or 100 mg of losartan per day. Once daily dosing reduces trough blood pressure in a dose-related manner. Dose-related effects of losartan were observed in all subgroups (e.g., age, Tanner stage, sex, race). However, the lowest doses studied, 2.5 mg and 5 mg, equivalent to an average daily dose of 0.7 mg/kg, did not show antihypertensive effects consistent with other doses. In this study, the product was generally well tolerated. For patients who can swallow tablets and weigh ≥20 kg to <50 kg, the recommended dose is 25 mg once daily. The maximum dose can be increased to 50 mg once daily. For patients weighing >50 kg, the starting dose is 50 mg once daily. The maximum dose can be increased to 100 mg once daily. For pediatric patients with insufficient vascular volume, correction should be given before taking this product. The adverse event profile of pediatric patients is similar to that found in adults. This product is not recommended for use in children with a glomerular filtration rate of less than 30 mL/min/1.73 m2 or children with liver impairment. Since there are no data for use in neonates, this product is also not recommended. Precautions during pregnancy and lactation: Pregnant women should use with caution. Precautions for the elderly: In clinical studies, there is no age difference in the effectiveness and safety of this product.

In clinical pharmacokinetic studies, no clinically significant drug interactions with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole, and erythromycin have been confirmed. Rifampicin and fluconazole have been reported to reduce the levels of active metabolites. The clinical consequences of these interactions have not been evaluated. As with other drugs that inhibit angiotensin II and its effects, this product can cause an increase in serum potassium when used with potassium-sparing diuretics (such as spironolactone, triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes. As with other drugs that affect sodium excretion, lithium excretion may be reduced. Therefore, if lithium salts are used in combination with angiotensin II receptor antagonists, lithium salt levels should be carefully monitored. Nonsteroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effects of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists may be weakened by NSAIDs including COX-2 inhibitors. In some patients with renal impairment who are taking NSAIDs, including selective cyclooxygenase-2 inhibitors, concurrent use of angiotensin II receptor antagonists may result in further renal impairment. These effects are usually reversible.

Sealed and stored in a dry place.

50mg

24 months

Chengdu Hengrui Pharmaceutical Co., Ltd.

• Founded in:

  2001-03-07

• Address:

  No. 18, Baicao Road, West Park, Chengdu Hi-tech Zone

• Tax NO.:

  91510100727431952L

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  29.18 million yuan

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