DAIICHI SANKYO SIWEIKA Olmesartan Medoxomil and Amlodipine Besylate Tablets For Hypertension 20mg:5mg*7

[Drug Name]
Generic Name: Olmesartan Medoxomil (Amlodipine) Tablets
Trade Name: SiWeiKa Olmesartan Medoxomil (Amlodipine) Tablets (20mg, 5mg x 7 tablets)
Pinyin Code: SiWeiKa HAoMeiShaTanZuoAnLvDiPingPian (20mg, 5mg x 7 tablets)

[Main Ingredients]
This product is a combination preparation. The active ingredients are olmesartan medoxomil 20mg and amlodipine besylate 5mg (calculated as amlodipine). (1) Olmesartan medoxomil Chemical name: 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[p-(o-B-1H-tetrazolyl-5-phenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonic acid Molecular formula: C29H30N6O6 Molecular weight: 558.59 (2) Amlodipine benzenesulfonate Chemical name: (+)-2-[(2-aminoethoxy)methyl]-4-(2-fluorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate-5-methyl ester, 3-ethyl ester benzenesulfonate Molecular formula: C20H25CIN2O5·C6H6O3S Molecular weight: 567.05

[Properties]
This product is a film-coated tablet that appears white after removing the coating.

[Indications/Main functions]
It is used to treat essential hypertension. This fixed-dose combination is indicated for adult patients whose blood pressure is inadequately controlled with olmesartan medoxomil or amlodipine alone. A reduction in blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily stroke and myocardial infarction. These benefits have been seen in controlled clinical trials of antihypertensive drugs from multiple pharmacological classes, including this drug. There is no controlled clinical evidence that this drug reduces cardiovascular risk. Hypertension control is part of a comprehensive cardiovascular risk management approach that may include lipid control, diabetes management, antithrombotic therapy, smoking cessation, physical exercise, and sodium restriction. Numerous antihypertensive drugs from multiple pharmacological classes and with different mechanisms of action have demonstrated benefits in reducing cardiovascular morbidity and mortality in randomized, controlled clinical trials, suggesting that these benefits are primarily attributable to the blood pressure-lowering effect rather than other pharmacological properties of the drugs. The most prominent and consistent cardiovascular benefit is a reduction in the risk of stroke, but reductions in the incidence of myocardial infarction and cardiovascular mortality are also common. Increases in either systolic or diastolic blood pressure increase cardiovascular risk. At higher baseline blood pressure levels, the absolute increased risk per mmHg increase in blood pressure is higher. In patients with severe hypertension, even a small reduction in blood pressure can provide significant clinical benefit. The relative magnitude of the risk reduction achieved by lowering blood pressure is similar across populations with varying absolute cardiovascular risk.

[Specifications]
20mg: 7 5mg tablets

[Dosage and Administration]
Dosage: Tablets should be swallowed with ample water (e.g., a glass of water). Do not chew the tablets and take them at the same time each day. The recommended adult dose is one tablet once daily. This product can be used for patients whose blood pressure is inadequately controlled with olmesartan medoxomil 20mg or amlodipine 5mg alone. Before switching to a fixed-dose combination tablet, it is recommended to gradually adjust the dose of the individual components. Depending on the clinical situation, switching directly from monotherapy to a fixed-dose combination tablet may also be considered. After one to two weeks of treatment, the dose can be increased to the maximum dose as needed. The maximum recommended dose is no more than two tablets per day (i.e., olmesartan medoxomil 40mg/amlodipine 10mg). For convenience, patients taking olmesartan medoxomil and amlodipine tablets can switch to this product containing the same dosage. This product can be taken with or without food. Elderly (265 years): The recommended dose generally does not require adjustment in the elderly; however, increasing the dose should be done with caution. Amlodipine clearance is decreased in elderly patients. Patients aged 75 years or older should start with amlodipine 2.5 mg as monotherapy or as an add-on. If the olmesartan medoxomil dose needs to be titrated to a maximum daily dose of 40 mg, blood pressure should be closely monitored. Patients with Renal Impairment: For patients with mild to moderate renal impairment (creatinine clearance 20-60 mL/min), the maximum recommended dose of olmesartan medoxomil is 20 mg once daily, as experience with higher doses in this patient population is limited. This product is not recommended for patients with severe renal impairment (creatinine clearance <20 mL/min). Serum potassium and creatinine levels should be monitored during treatment in patients with moderate renal impairment. Patients with Hepatic Impairment: This drug should be used with caution in patients with mild to moderate hepatic impairment. For patients with moderate hepatic impairment, the recommended starting dose of olmesartan medoxomil is 10 mg once daily, with a maximum dose of 20 mg once daily. Patients with hepatic impairment who are already receiving diuretics and/or other antihypertensive medications should be closely monitored for changes in blood pressure and renal function. There is no experience with olmesartan medoxomil in patients with severe hepatic impairment. Like all calcium channel blockers, amlodipine has a prolonged half-life in patients with hepatic impairment, and a recommended dose has not been established. Therefore, Sevikar should be used with caution in these patients. The pharmacokinetics of amlodipine have not been studied in patients with severe hepatic impairment. Patients with hepatic impairment should initiate treatment with the lowest dose of amlodipine and titrate the dose gradually. This drug is contraindicated in patients with severe hepatic impairment. The safety and efficacy of this drug in children and adolescents under 18 years of age have not been established. No data are currently available.

[Adverse Reactions]
See package insert for details.

[Contraindications]
This product is contraindicated in patients with a biological allergy to its ingredients or dihydropyridines. This product should not be used in combination with aliskiren in patients with diabetes or renal impairment (GFR < 60 mL/min). Pregnancy (see [Use in Pregnant and Lactating Women]). Severe hepatic insufficiency and biliary obstruction (see [Precautions]). Because it contains amlodipine, this product is also contraindicated in patients with the following conditions: - Severe hypotension; - Shock (including cardiogenic shock); - Left ventricular outflow tract obstruction (e.g., high-grade aortic stenosis); - Hemodynamically unstable heart failure following acute myocardial infarction.

[Precautions]
1. Fetal Toxicity: This drug may cause fetal harm when used by pregnant women. During the second and third trimesters of pregnancy, the use of drugs that directly act on the renin-angiotensin system can reduce fetal renal function and increase fetal and neonatal morbidity and mortality. The resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformities. Potential neonatal adverse reactions include craniosynostosis, anuria, hypotension, renal failure, and death. Once pregnancy is detected, this drug should be discontinued as soon as possible. (See [Use in Pregnant and Lactating Women]). 2. Hypotension in Patients with Hypovolemia or Hyponatremia: Symptomatic hypotension may occur after the first dose of olmesartan medoxomil. Patients with renin-angiotensin system stimulation, such as those with hypovolemia and/or hyponatremia (e.g., those receiving high-dose diuretics, dietary salt restriction, diarrhea, or vomiting), are particularly susceptible to these reactions. Therefore, treatment with this drug must be initiated under close medical supervision. If hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline. Transient hypotension is not a contraindication for further treatment; treatment with this drug can be continued once blood pressure stabilizes. 3. Vasodilation: Because the vasodilation effect of amlodipine, a component of this drug, is gradual, there have been rare reports of acute hypotension following oral amlodipine administration. However, as with any other peripheral vasodilator, olmesartan medoxomil and amlodipine should be used with caution, especially in patients with severe aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy. 4. Patients with severe coronary artery obstructive disease, particularly those with concomitant severe coronary artery obstructive disease, may experience increased frequency, prolonged duration, and exacerbated severity of angina or acute myocardial infarction when initiating or increasing the dose of calcium channel blockers. The mechanism of action is unclear. 5. Patients with congestive heart failure: Caution should be exercised in the treatment of patients with heart failure. In a long-term, placebo-controlled trial of amlodipine in patients with severe heart failure (NYHA class II and IV), the incidence of pulmonary edema was higher in the amlodipine group than in the placebo group. Calcium channel inhibitors, including amlodipine, should be used with caution in patients with congestive heart failure due to the potential for increased risk of future cardiovascular events or death. 6. Patients with Renal Impairment: There are no data on the use of this medication in patients with renal insufficiency. There is no experience with this medication in patients with recent renal transplantation or end-stage renal impairment (i.e., creatinine clearance <12 mL/min). For patients with mild to moderate renal impairment (creatinine clearance 20-60 mL/min), the maximum recommended dose of olmesartan medoxomil is 20 mg once daily, as experience with higher doses in this patient population is limited. This medication is not recommended for patients with severe renal impairment (creatinine clearance <20 mL/min). Monitoring of serum potassium and creatinine levels during treatment is recommended in patients with renal impairment. Due to its inhibitory effect on the renin-angiotensin-aldosterone system, changes in renal function may be expected in sensitive patients treated with olmesartan medoxomil. The use of ACE inhibitors and angiotensin receptor blockers in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure) may result in oliguria and/or progressive azotemia, acute renal failure, and/or death (rarely). Because this product contains olmesartan medoxomil, similar outcomes are expected in such patients. There have been reports that ACE inhibitors may increase serum creatinine or blood urea nitrogen (BUN) in patients with unilateral or bilateral renal artery stenosis. There is no experience with long-term use of olmesartan medoxomil in such patients, but similar outcomes are expected with olmesartan medoxomil and this product. Renal impairment does not significantly affect the pharmacokinetics of amlodipine. Therefore, patients with renal failure can receive the usual starting dose. 7. Patients with Hepatic Impairment: There are no data on the use of this product in patients with hepatic impairment; however, exposure to amlodipine and olmesartan medoxomil is increased in patients with hepatic impairment. Amlodipine is extensively metabolized primarily by the liver, with a plasma elimination half-life (t½) of 56 hours in patients with severe hepatic impairment. For patients with moderate hepatic impairment, the dose of olmesartan medoxomil should not exceed 20 mg. Therefore, this drug should be used with caution in patients with mild to moderate hepatic impairment and contraindicated in patients with severe hepatic impairment. Amlodipine clearance is decreased in patients with hepatic impairment. Patients with hepatic impairment should start with a 2.5 mg dose as monotherapy or as an adjunct to amlodipine. The lowest dose of this drug is 20 mg of olmesartan medoxomil/5 mg of amlodipine; therefore, this drug should be used with caution in patients with impaired hepatic function. 8. Sprue-like enteropathy: Severe chronic diarrhea accompanied by significant weight loss has been reported in patients taking olmesartan for months to years, possibly due to a localized delayed-type hypersensitivity reaction. Intestinal biopsies often reveal villous atrophy. If a patient develops these symptoms while taking olmesartan, other causes should be excluded. If no other cause is found, consider discontinuing this drug. If diarrhea does not improve within one week of discontinuing medication, further medical evaluation (such as by a gastroenterologist) is indicated. 9. Patients with bilateral renal artery stenosis or unilateral renal artery stenosis are at increased risk of severe hypotension and renal insufficiency when treated with medications that affect the renin-angiotensin-aldosterone system. 10. Hyperkalemia: As with other angiotensin II receptor antagonists and ACE inhibitors, hyperkalemia may occur during treatment, especially in patients with renal impairment and/or heart failure. Close monitoring of serum potassium levels is recommended for patients at risk of hyperkalemia. Particular caution should be exercised when concurrently administering potassium supplements, potassium-sparing diuretics, potassium-containing rehydration salts, or other medications that may increase serum potassium levels (such as heparin). Close monitoring of serum potassium levels is recommended. 11. Effects on Ability to Drive and Use Machinery: This drug has a minimal to moderate effect on the ability to drive and use machinery. Patients receiving antihypertensive medications may experience occasional dizziness, headache, nausea, or fatigue, which may impair reflexes. Caution is recommended, especially during the initial treatment phase. 12. As with all antihypertensive medications, excessively lowering blood pressure in patients with ischemic heart disease or ischemic cerebrovascular disease may lead to myocardial infarction or stroke.