Product Overview
[Drug Name]
Generic Name: Candesartan Cilexetil Dispersible Tablets
Trade Name: YuanRui Pharmaceutical AoBiXin Candesartan Cilexetil Dispersible Tablets 4mg*14 Tablets
Pinyin Full Code: YuanRuiZhiYao AoBiXin KanDiShaTanZuoFenSanPian 4mg*14Pian
[Main Ingredients]
Candesartan Cilexetil.
[Properties]
This product is a white tablet with a sweet taste.
[Indications/Main Functions]
Essential hypertension.
[Precautions]
1. Use with caution (the following patients should use the drug with caution). (1) Patients with bilateral or single renal artery stenosis (see 2. Important Basic Precautions). (2) Patients with hyperkalemia may have worsening liver function, and it is speculated that the clearance rate of the active metabolite candesartan is low, so it should be taken from a small dose and used with caution (refer to [Pharmacokinetics]). (3) Patients with severe renal dysfunction (due to excessive blood pressure reduction, renal function may worsen, so start with 2 mg once a day and use with caution). (4) Patients with a history of drug allergy. (5) Elderly patients (see [Medication for Elderly Patients]). 2. Important basic precautions. (1) Patients with bilateral or unilateral renal artery stenosis, when taking drugs that affect the renin-angiotensin-aldosterone system, may increase the risk of renal function due to decreased renal blood flow and filtration pressure. Unless it is considered necessary for treatment, this drug should be avoided as much as possible. (2) Because it may aggravate hyperkalemia, patients with hyperkalemia should avoid taking this drug as much as possible unless it is considered necessary for treatment. In addition, patients with renal dysfunction and uncontrolled diabetes should pay close attention to their blood potassium levels because they are prone to developing hyperkalemia. (3) Taking this preparation may sometimes cause a sharp drop in blood pressure. In particular, when taking this preparation for the following patients, it should be started with a low dose. When increasing the dose, the patient's condition should be carefully observed and the dosage should be increased slowly. Patients undergoing hemodialysis. Patients who are strictly undergoing salt restriction therapy. Patients taking diuretic and antihypertensive drugs (especially those who have recently started taking diuretic and antihypertensive drugs). (4) Due to the same antihypertensive effect, dizziness and staggering may occur, so caution should be exercised when performing operations such as high-altitude work and driving a vehicle. (5) It is best to stop taking this drug 24 hours before surgery.
[Drug Interactions]
1. Patients with a history of allergy to the ingredients of this drug. 2. Pregnant women (refer to [Use in Pregnant and Lactating Women]).
[Use in Children]
The safety of this drug for children has not been determined (no experience).
[Use in Elderly Patients]
It is generally believed that excessive blood pressure reduction should not be used in the elderly (it may cause cerebral infarction, etc.). It should be used with caution while the patient is under observation.
[Use During Pregnancy and Lactation]
In rats administered intragastrically with this preparation at doses exceeding 10 ml/kg per day, an increase in neonatal hydronephrosis was observed. Furthermore, there have been reports of oligohydramnios, fetal and neonatal death, neonatal hypotension, renal failure, hyperkalemia, cranial hypoplasia, and limb contractures possibly due to oligohydramnios in hypertensive patients treated with angiotensin II receptor blockers (including candesartan cilexetil) or angiotensin-converting enzyme inhibitors. Therefore, this drug is contraindicated in pregnant women or women of childbearing potential. In rats administered intragastrically with this preparation at doses exceeding 10 mg/kg per day, an increase in neonatal hydronephrosis was observed. Furthermore, neonatal hydronephrosis was increased only in rats administered at 300 mg/kg per day in late pregnancy or during lactation. Therefore, lactating women should avoid this drug, and if necessary, should discontinue breastfeeding.
[Specifications]
4mg*14 tablets (Obixin)
[Dosage and Administration]
Oral administration. Can be dissolved in water orally, sucked, or swallowed. Generally, adults should take candesartan cilexetil once daily; the dose can be increased to 12mg if necessary. Patients with severe renal impairment should start with 2mg. If blood pressure cannot be controlled with candesartan cilexetil alone, a diuretic can be added, or it can be used in combination with other antihypertensive medications.
[Adverse Reactions]
1. Serious adverse effects (incidence unknown). 1) Angioedema: Angioedema, which may be a symptom of swelling of the face, lips, tongue, pharynx, or larynx, should be carefully observed. If any abnormality is observed, discontinue the medication and administer appropriate treatment. 2) Syncope and loss of consciousness: Excessive blood pressure reduction may cause syncope and temporary loss of consciousness. In such cases, discontinue the medication and administer appropriate treatment. Patients undergoing hemodialysis, those on strict salt restriction, or those recently taking diuretic-lowering antihypertensive medications may experience a rapid drop in blood pressure. Therefore, these patients should be started with a lower dose of this drug. If the dose needs to be increased, the patient should be closely monitored and the dosage should be increased slowly. 3) Acute renal failure: Acute renal failure may occur, so the patient should be closely monitored. If abnormalities are detected, the drug should be discontinued and appropriate treatment should be implemented. 4) Deterioration of liver function or jaundice: Given the possibility of liver dysfunction or jaundice, such as elevated ASP (GOT), AL (GPT), or GTP, the patient should be closely monitored. If abnormalities are detected, the drug should be discontinued and appropriate treatment should be implemented. 5) Agranulocytosis: Agranulocytosis may occur, so the patient should be closely monitored. If abnormalities are detected, the drug should be discontinued and appropriate treatment should be implemented. 6) Rhabdomyolysis: Symptoms such as myalgia, weakness, increased CK, and myosin in the blood and urine may occur. If these symptoms occur, the drug should be discontinued and appropriate treatment should be implemented. 7) Interstitial pneumonitis: Interstitial pneumonitis, accompanied by fever, cough, dyspnea, and abnormal chest X-rays, may occur. If the above symptoms occur, the medication should be discontinued and appropriate treatment should be implemented, such as treatment with corticosteroids. 2. Other adverse effects: 1) Allergic reactions: rash, eczema, urticaria, itching (0.1<5%). 2) Circulatory system: dizziness, dizziness when standing up, palpitations, fever (0.1<5%); cardiac contractions, atrial fibrillation (<0.1%). 3) Psychoneurological system: headache, heaviness of the head, insomnia, drowsiness, numbness of the tongue (0.1<5%); numbness of the limbs (<0.1%). 4) Digestive system: nausea, vomiting, loss of appetite, stomach discomfort, pain at the moment, diarrhea, stomatitis (0.1<5%); abnormal taste (<0.1%). 5) Liver: increased GOT, PTA, ALP, and LDH (0.1<5%). 6) Blood: Anemia, leukopenia, leukocytosis, eosinophilia, decreased platelet count (0.1 < 5%). 7) Kidney: Increased blood nitrogen (BUN), hepatic anhydride, proteinuria (0.1 < 5%). 8) Other: Fatigue, weakness, epistaxis, frequent urination, edema, cough, increased potassium, total cholesterol, CPK, CPR, uric acid, decreased serum total protein (0.1 < 5%); hyponatremia (< 0.1%). Note: 1) Discontinue use in these cases. 2) Reduce the dose or discontinue the drug and provide appropriate treatment.
[Contraindications]
1. Patients with a history of allergy to any of the ingredients in this product. 2. Pregnant women (see [Use in Pregnant and Lactating Women]).
[Overdose]
The most common symptoms of overdose are: hypotension, dizziness, and tachycardia. Additionally, parasympathetic nervous system stimulation can also lead to bradycardia. Preparing for treatment should prevent hypotension.
[Pharmacology and Toxicology] Candesartan cilexetil is rapidly hydrolyzed in vivo into its active metabolite, candesartan. Candesartan is an angiotensin II AT receptor antagonist. By binding to vascular smooth muscle AT receptors, it antagonizes the contractile effects of angiotensin II, thereby reducing peripheral vascular resistance. Others believe that candesartan exerts its antihypertensive effects by inhibiting adrenal aldehyde secretion. Studies in patients with hypertension have shown that repeated administration of this drug can increase plasma renin activity, angiotensin I, and angiotensin II concentrations. Continuous administration of 2-8 mg once daily can reduce systolic and diastolic blood pressure, left ventricular myocardial mass, and peripheral vascular resistance, while having no effect on cerebral blood flow in patients with hypertension. Oral administration of 100 and 1000 mg/kg of this drug once daily to mice for 104 weeks revealed no carcinogenic effects. The drug has been shown to be non-genotoxic by microbial and mammalian mutation assays, in vivo and extrachromosomal aberration assays, and unscheduled DNA synthesis assays in rats. It is administered to females. Once-daily administration of this drug to male rats at a dose of 300 mg/kg demonstrated no effects on reproductive performance. In acute toxicity studies, single oral administration of 2000 mg/kg of candesartan cilexetil to mice, rats, and children resulted in no lethality. In mice, the lethal dose was higher than 1000 mg/kg but lower than 2000 mg/kg.
[Pharmacokinetics]
After oral administration, this drug is rapidly and completely hydrolyzed to candesartan after absorption from the gastrointestinal tract. It is then metabolized to inactive metabolites in the liver through O-deethylation. The pharmacokinetics of candesartan are linear after single and repeated doses (32 mg oral dose). After repeated dosing, candesartan and its inactive metabolites do not accumulate in the serum. Peak plasma concentrations are reached 3-4 hours after administration, and the absolute bioavailability of candesartan cilexetil is 15%. Foods high in esters do not affect the bioavailability of candesartan cilexetil. Candesartan has a volume of distribution of 0.13 L/kg and is highly bound to plasma proteins (>99%), preventing it from penetrating red blood cells. Protein binding remains unchanged even after plasma concentrations exceed the recommended dose range. Studies in rats have shown that candesartan has difficulty crossing the blood-brain barrier, but it can cross the placenta and be distributed to the fetus. This drug is primarily excreted unchanged in urine and feces (via bile), with an elimination half-life of approximately 9 hours. The total plasma clearance is 0.37 ml/min/kg, and the renal clearance is 0.19 ml/min/kg. Following oral administration of candesartan, approximately 26% is excreted unchanged in the urine. Following a single oral dose of candesartan cilexetil, 33% is excreted in urine and 67% in feces.
