LVYIN Enalapril Maleate Dispersible Tablets For Hypertension 5mg*36

[Drug Name]
Generic Name: Enalapril Maleate Dispersible Tablets
Trade Name: LvYin Enalapril Maleate Dispersible Tablets 5mg*36 Tablets
Pinyin Code: LvYin MaLaiSuanYiNaPuLiFenSanPian

[Main Ingredient]
Enalapril Maleate.

[Properties]
This product is white or off-white tablets.

[Indications/Main Functions]
Hypotension.

[Precautions]
Hypotension: Enalapril may cause a significant drop in blood pressure during the initial treatment phase. This is most common in patients experiencing salt and water loss (e.g., those undergoing dialysis, vomiting/diarrhea, or diuretic therapy). Furthermore, most patients with heart failure (with or without renal failure) experience hypotension. Monitoring is essential for these patients during enalapril use. Patients with ischemic heart disease or obstructive cerebrovascular disease must be closely monitored while using enalapril due to the risk of myocardial infarction or shock caused by a significant drop in blood pressure. For these patients, the lowest dose should be started and the dose increased based on monitoring renal function and blood potassium levels. If possible, any diuretics should be temporarily discontinued. Renal Hypertension/Renal Artery Stenosis: Enalapril administration carries a risk of significant hypotension and renal impairment in patients with renal hypertension and pre-existing bilateral or unilateral renal artery stenosis. Even in patients with unilateral renal artery stenosis, renal impairment manifesting as minimal changes in serum creatinine levels can occur. Therefore, these patients should be started with a low dose and hospitalized for dose adjustments. Patients currently taking diuretics should temporarily discontinue diuretics and monitor renal function during the first few weeks of treatment. Renal Failure: Blockade of the renin-angiotensin-aldosterone system can cause changes in renal function in sensitive patients. Therefore, a low dose of enalapril maleate is recommended. Enalapril should be used only after careful consideration of the risks in patients with severe renal failure (creatinine clearance less than 30 ml/min) and those on dialysis. Renal function should also be monitored during use. There have been reports of renal failure with continued ACE inhibitor therapy in patients with severe renal disease and heart failure. When used concomitantly with diuretics, some patients experience asymptomatic changes in blood urea and creatinine levels. If this occurs, reducing the ACE inhibitor dose and/or discontinuing the diuretic is recommended. Dialysis patients: When treated with enalapril maleate and dialysis with polyacrylonitrile or sodium methylallyl sulfide high-flux membranes, anaphylactic reactions (hypersensitivity, even shock) may occur. The first symptoms of anaphylaxis are facial swelling, flushing, hypotension, and dyspnea. These symptoms usually develop within a few minutes of the start of dialysis. Therefore, this combination should be avoided, and alternative dialysis membranes or alternative medications should be used to treat hypertension or heart failure. Hyperkalemia: Enalapril maleate can cause hyperkalemia, especially in patients with renal and/or heart failure. Therefore, potassium-sparing diuretics and potassium supplements should not be taken concomitantly to avoid a significant increase in blood potassium levels. If these medications are necessary, blood potassium levels must be closely monitored. Primary aldosteronism: Patients with primary aldosteronism generally do not respond to antihypertensive medications. Therefore, enalapril is not recommended. Proteinuria: Proteinuria is rare in patients with preexisting renal impairment and those taking high-dose ACE inhibitors. If proteinuria (greater than 1 gram per day) is present, use should be carefully considered before using enalapril. Clinical and laboratory parameters should also be monitored routinely during use. LDL-lipoprotein apheresis/desensitization therapy: Concomitant use of enalapril maleate with LDL-density lipoprotein (LDL) apheresis using dextran sulfate or desensitization to bee or wasp stings carries a risk of life-threatening allergic reactions (e.g., hypotension, dyspnea, vomiting, and allergic skin reactions). If dextran sulfate or bee or wasp sting desensitization therapy is necessary, ACE inhibitors should be temporarily replaced with alternative agents for hypertension or heart failure. Angioedema: Angioedema of the face, extremities, lips, tongue, vocal cords, and/or larynx has been reported rarely with ACE inhibitors (including enalapril). This can occur at any time during treatment. If this occurs, enalapril should be discontinued immediately and the patient monitored. Edema occurring on the face and lips resolves without treatment, although antihistamines can effectively reduce symptoms. Patients with a history of angioedema are more susceptible to angioneurotic edema when taking ACE inhibitors. Black patients are more susceptible. Angioneurotic edema involving the tongue, vocal cords, and larynx can be life-threatening. In such cases, 0.3-0.5 mg of epinephrine must be immediately administered subcutaneously or 0.1 mg of epinephrine should be slowly administered intravenously (following dilution instructions) under electrocardiogram (ECG) and blood pressure monitoring. Hospitalization is necessary. Observation for at least 12-24 hours is required, and discharge is not permitted until symptoms subside. Neutropenia/Agranulocytosis: Neutropenia/Agranulocytosis is rare in patients with hypertension treated with ACE inhibitors. Neutropenia/Agranulocytosis is more common in patients with impaired renal function, particularly those with vascular and tissue disorders (such as lupus erythematosus, scleroderma), or those taking concomitant immunosuppressants. Routine blood counts should be performed in these patients. Neutropenia/agranulocytosis resolves after discontinuation of the drug.

[Drug Interactions]
Enalapril is contraindicated in the following cases: 1. Hypersensitivity to enalapril maleate or other ACE inhibitors or any of their components. 2. Known history of angioedema (e.g., angioedema with previous ACE inhibitor therapy, hereditary/congenital angioedema). 3. Renal artery stenosis (bilateral or unilateral in patients with unilateral renal disease). 4. Postrenal transplantation. 5. Hemodynamically relevant aortic or mitral stenosis, or hypertrophic cardiomyopathy. 6. Primary aldosteronism. 7. Primary liver disease or liver failure. 8. Pregnancy. 9. Lactation. 10. During treatment with enalapril, the concomitant use of polyacrylonitrile or sodium methyl allyl sulfide high-flux membranes (e.g., AN69) for hemofiltration or hemofiltration carries the risk of allergic reactions (hypersensitivity, even shock). Therefore, this combination should be avoided. Other medications (non-ACEIs) can be used to treat hypertension or heart failure, or alternative dialysis membranes can be used.

[Pediatric Use]
Enalapril is not recommended for children due to a lack of experience with its use in children. Avoid accidental use by children.

[Elderly Use]
Elderly patients respond better to ACE inhibitors than younger patients. For patients older than 65 years, start with a dose of 2.5 mg and closely monitor blood pressure and representative laboratory parameters.

[Pregnant and Breastfeeding Use]
ACE inhibitors are contraindicated in pregnant and breastfeeding women. If treatment with enalapril maleate is necessary, pregnancy should be terminated, and contraception should be used during treatment. ACE inhibitors can be harmful to the fetus, especially in the last six months. If pregnancy occurs during treatment, alternative medications should be used to reduce the risk to the fetus. There are insufficient safety data for pregnancy. In recent years, there have been reports of fetal harm from ACE inhibitors, such as craniosacral dysplasia, intrauterine growth retardation, oligohydramnios, anuria, and even neonatal death. The likely cause is the antihypertensive effect on the fetus during the last six months of pregnancy. The effect of ACEI on the fetus during the first three months of pregnancy is unknown. ACEIs are secreted in breast milk. There is no experience with their use during breastfeeding. Enalapril should not be used during breastfeeding.

[Specifications]
5mg*36 tablets

[Dosage and Administration]
For patients with severe renal hypertension who are experiencing salt and water loss (e.g., dialysis, vomiting/diarrhea, diuretic therapy), treatment with enalapril may initially cause a significant drop in blood pressure. If possible, correct salt and/or fluid loss before initiating enalapril. Reduce or discontinue diuretics if necessary. These patients should be started with the lowest dose of enalapril, 2.5 mg, in the morning. During initial administration, dose increases, and/or diuretic use, observation should be maintained for at least 8 hours to avoid unforeseen hypotensive reactions. For patients with malignant hypertension, enalapril treatment must be performed in a hospital setting. Unless otherwise directed by a physician, take the following medication: Hypertension: The usual initial dose is 5 mg (one enalapril tablet) taken in the morning. If blood pressure does not return to normal, the dose can be increased to 10 mg (two enalapril tablets). Dosage increases may be initiated after 3 weeks of treatment. The maintenance dose is generally 10 mg/day, with a maximum dose of 40 mg/day. Dosage for moderate renal impairment (creatinine clearance 30-60 ml/min) and elderly patients (over 65 years): The initial dose is 2.5 mg (half an enalapril tablet) taken in the morning. The maintenance dose is generally 5-10 mg/day (one to two enalapril tablets). The maximum dose should not exceed 20 mg/day (four enalapril tablets). Dosage for patients with severe renal impairment (creatinine clearance less than 30 ml/min and dialysis): The initial dose is 2.5 mg (half an enalapril tablet) taken in the morning. Dialysis patients should take the drug after dialysis. The maintenance dose is generally 5 mg/day (one enalapril tablet). The maximum dose should not exceed 10 mg/day (two enalapril tablets). Dosage is taken regardless of meals; the full daily dose is generally taken once in the morning. If needed, it can be divided into two doses, morning and evening. The duration of treatment is determined by the attending physician.

[Adverse Reactions]
Enalapril is well tolerated. The following adverse reactions may occur when using enalapril and ACE inhibitors. Cardiovascular System: A significant drop in blood pressure (hypotension, orthostatic hypotension) may occur during the initial stages of treatment, in patients with salt and/or fluid loss (such as those taking diuretics), heart failure, severe hypertension, renal hypertension, and when the dosage of enalapril and/or diuretics is increased. This can be accompanied by dizziness, pallor, and visual confusion. Loss of consciousness is rare. The following side effects may be caused by excessive blood pressure reduction with ACE inhibitors: tachycardia, palpitations, arrhythmias, chest pain, angina, myocardial infarction, transient ischemic stroke, and brain damage. Kidney: Renal damage may occasionally occur or worsen. In some cases, acute renal failure may result. Proteinuria has rarely been observed, sometimes accompanied by worsening renal function. Respiratory System: Dry cough, sore throat, hoarseness, and bronchitis may occur occasionally. Rarely, dyspnea, sinusitis, rhinitis, bronchospasm/asthma, pulmonary infiltrates, stomatitis, glossitis, and dry mouth may occur. ACE inhibitors have been reported to cause angioedema of the larynx, pharynx, and/or tongue. Digestive System/Liver: Nausea, abdominal pain, and dyspepsia may occur occasionally. Rarely, vomiting, diarrhea, constipation, and loss of appetite may occur. A rare case of a combination of events, initially cholestatic jaundice followed by hepatic necrosis (sometimes fatal), has been reported during ACE inhibitor therapy. However, the relationship between the two is unclear. If jaundice or significant elevations in liver enzymes occur, ACE inhibitor use should be discontinued immediately and the patient placed under medical supervision. ACE inhibitors have been reported to cause abnormal liver function tests, hepatitis, liver failure, pancreatitis, and intestinal obstruction. Skin, Vascular: Allergic reactions such as rash, urticaria, and pruritus, and angioedema affecting the lips, face, and/or extremities may occur occasionally. Severe skin reactions, such as pemphigus, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, or toxic epidermal necrolysis, have been reported. Skin lesions may be accompanied by fever, myalgia/myositis, arthralgia/arthritis, vasculitis, serositis, eosinophilia, leukocytosis, and increased ESR and/or ANA. If a serious skin reaction is suspected, contact the attending physician immediately and, if necessary, discontinue treatment with enalapril maleate tablets. ACE inhibitors have been reported to cause psoriatic skin changes, photosensitivity, flushing, sweating, alopecia, onychomycosis, and exacerbation of Raynaud's syndrome. Neurological: Headache and drowsiness may occur occasionally. Rarely, coma, depression, sleep disturbances, impotence, peripheral sensory abnormalities, imbalance, muscle spasms, nervousness, confusion, tinnitus, blurred vision, and hemiskeletal anemia may occur. Laboratory tests (blood and urine): Occasionally, decreased hemoglobin, hematocrit, white blood cells, and thrombocytopenia may occur. Rarely, anemia, thrombocytopenia, neutropenia, and increased eosinophilia may occur. Agranulocytosis and Fanconi syndrome may occur in patients with renal dysfunction, collagen disorders, and concomitant use of allopurinol, procainamide, or other immunosuppressants. Hemolysis/hemolytic anemia, as well as hemolysis/hemolytic anemia associated with G-6-PDH deficiency, has also been reported. However, a causal relationship with ACE inhibitors has not been established. Patients with renal dysfunction may occasionally experience increased blood and urine concentrations, increased creatinine, and potassium levels, and decreased sodium levels. Patients with diabetes may experience increased potassium levels (hyperkalemia). Increased urinary protein excretion may be detected. Rarely, elevated bilirubin and liver enzyme levels may occur. Important: Laboratory tests, such as those listed above, should be routinely obtained before and during enalapril therapy. Plasma electrolytes, creatinine, and blood counts should be monitored for initial therapy, high-risk patients (renal failure, collagen disorders), and patients taking immunosuppressants, cytostatics, allopurinol, and procainamide. Fever, lymphadenopathy, and/or pharyngitis while taking enalapril should prompt prompt white blood cell count monitoring. Effects on Ability to Drive and Operate Machines/Reactions: The frequency and severity of reactions vary depending on individual circumstances, especially when starting treatment, increasing the dose, changing medications, and when consuming alcohol concurrently. Driving and operating machines should be strictly restricted in these situations.

[Contraindications]
Enalapril is contraindicated in the following cases: 1. Hypersensitivity to enalapril maleate or other ACE inhibitors or any of their components. 2. Known history of angioedema (e.g., angioedema with previous ACE inhibitor therapy, hereditary/congenital angioedema). 3. Renal artery stenosis (bilateral or unilateral in patients with unilateral renal disease). 4. Post-renal transplantation. 5. Hemodynamically relevant aortic or mitral stenosis, or hypertrophic cardiomyopathy. 6. Primary aldosteronism. 7. Primary liver disease or liver failure. 8. Pregnancy. 9. Lactation. 10. During enalapril treatment, the concomitant use of polyacrylonitrile or sodium methyl allyl sulfide high-flux membranes (such as AN69) for hemofiltration or hemofiltration carries the risk of allergic reactions (hypersensitivity, even shock). Therefore, such concomitant use should be avoided. Other medications (non-ACEI) can be used to treat hypertension or heart failure, or a different dialysis membrane can be used.

[Overdose]
An excessive drop in blood pressure caused by an enalapril maleate overdose can be dangerous. Immediately notify a physician in this situation. Physicians should be aware of the following symptoms of poisoning: Depending on the severity of the overdose, the following may occur: severe hypotension, bradycardia, cardiogenic shock, electrolyte imbalances, and renal failure. Treatment of poisoning: Depending on the symptoms and severity, in addition to conventional treatment for enalapril maleate removal (such as gastric lavage, administration of adsorbents and sodium sulfate within 30 minutes of enalapril maleate administration), close monitoring of vital signs and aggressive treatment are essential. Enalapril maleate can be removed by dialysis. Hypotension should be treated with sodium chloride and volume loading. If unresponsive, intravenous catecholamines should be administered. Angiotensin II therapy may be considered. If persistent bradycardia occurs, pacing therapy should be initiated. Electrolyte and serum creatinine levels must be continuously monitored.

[Pharmacology and Toxicology]
Pharmacological Action: Enalapril maleate is hydrolyzed in the liver to enalaprilat, a renin-angiotensin-converting enzyme inhibitor (ACEI). Renin-angiotensin-converting enzyme (ACE) is a peptidyl dipeptidase that converts angiotensin I (AgI) to the vasoconstrictor angiotensin II (AgII). Inhibition of ACE reduces tissue and plasma AgII formation, decreases aldosterone secretion, and increases plasma potassium concentration. This weakened negative feedback effect of AgII on renin secretion leads to increased plasma renin activity. ACE also degrades bradykinin (a vasodilating peptide), and ACE inhibition increases the activity of the circulating and local kallikrein-kinin system (which also increases the activity of the prostaglandin system). The blood pressure-lowering effects and some side effects of ACE inhibitors are related to this mechanism. In patients with hypertension, enalapril maleate lowers supine and sitting blood pressure without causing compensatory heart rate increases. On hemodynamic testing, enalapril maleate significantly reduces peripheral vascular resistance. Enalapril maleate generally has no significant effect on renal blood flow or glomerular filtration rate. In most patients, the blood pressure-lowering effect of enalapril maleate appears approximately one hour after ingestion, with peak effect occurring four to six hours after ingestion. Maximum blood pressure-lowering effect generally occurs three to four weeks after the prescribed dose. Long-term treatment at the recommended dose maintains the blood pressure-lowering effect. Short-term discontinuation of enalapril maleate does not result in a rebound blood pressure response. Hemodynamic studies in patients with heart failure have shown that enalapril maleate reduces peripheral circulatory resistance, increases venous capacitance, reduces cardiac preload and afterload (lowers cardiac perfusion pressure), increases cardiac output, and improves cardiac stroke index and stress response. Toxicity studies: No mutagenic or carcinogenic effects of enalapril maleate were observed in relevant in vitro and in vivo studies.

[Pharmacokinetics]
Enalapril maleate is a prodrug that is activated in the liver to the active enalaprilat. Drug absorption (approximately 50-70%) is unaffected by concomitant food intake. Peak plasma concentrations are reached 3-4 hours after oral administration, and plasma protein binding is approximately 50%. Enalaprilat is primarily excreted via the kidneys. After repeated dosing, the cumulative half-life (effective half-life) is 11 hours, and the elimination half-life is 35 hours. Enalaprilat clearance is reduced in patients with renal impairment, depending on the degree of renal impairment. Enalaprilat is dialyzable. Hemodialysis can reduce the plasma concentration of enalaprilat by approximately 46%. Enalaprilat can also be removed by peritoneal dialysis.