Product Overview
[Drug Name]
Generic Name: Perindopril tert-Butylamine Tablets
Trade Name: Yashida
English Name: Perindopril tert-Butylamine Tablets
Chinese Pinyin: Perindopril Tablets
[Ingredients]
Perindopril tert-Butylamine salt
[Appearance]
This product is a green, round tablet scored on both sides.
[Indications]
For hypertension and congestive heart failure.
[Dosage and Administration]
Perindopril tablets must be taken before meals because food alters the bioavailability of its active metabolite, perindoprilat. Perindopril is taken once daily.
Essential Hypertension
1. In the absence of sodium depletion or renal failure (i.e., under normal circumstances):
The effective dose is 4 mg/day, taken once in the morning. Depending on the efficacy, the dose can be gradually increased over three to four weeks to a maximum of 8 mg/day. If necessary, a potassium-wasting diuretic can be used concomitantly to further lower blood pressure. 2. Hypertensive Patients Already Treated with Diuretics
2.1 Discontinue diuretics three days prior to starting treatment. Diuretics can be resumed later if necessary.
2.2 Alternatively, initiate treatment with 2 mg and adjust the dose based on the antihypertensive effect.
2.3 Monitor serum creatinine and potassium levels before and during the first 15 days of treatment.
3. Elderly (See: Precautions)
Initiate treatment with a low dose (2 mg/day, taken in the morning) and, if necessary, increase to 4 mg/day after one month. If previous tests indicate renal dysfunction not due to age, the dose may be adjusted based on the patient's renal function. Creatinine clearance accurately reflects renal function in the elderly. It is calculated using Cockroft's formula based on serum creatinine and adjusted for age, weight, and sex:
*Clcr = (140 - age) × weight / 0.814 × serum creatinine (age expressed in years, weight in kilograms, and serum creatinine in mmol/l. This formula applies to adult males; women should multiply by 0.85 for correction.)
Renovascular Hypertension
1. The recommended starting dose is 2 mg/day, with subsequent dose adjustments based on the patient's blood pressure response.
2. Serum creatinine and potassium should be monitored to detect the presence of functional renal insufficiency. (See: Precautions.)
3. In patients with renal insufficiency, the perindopril dose should be adjusted according to the degree of renal insufficiency:
4. If creatinine clearance is ≥60 ml/min, no dose adjustment is required. 5. If creatinine clearance is <60 ml/min, refer to the following table:
Recommended dose for creatinine clearance (ml/min): 30 < creatinine clearance <602 mg/day; 15 < creatinine clearance <302 mg/every other day.
6. Typical medical management for these patients includes regular monitoring of serum potassium and creatinine, such as every two months during stable treatment. In this case, a loop diuretic is recommended.
Hypertensive patients undergoing hemodialysis (Clcr <15 ml/min):
Perindopril is dialyzable. Dialysate clearance is 70 ml/min. Administer 2 mg of perindopril on the day of dialysis.
Congestive heart failure
1. Initiate treatment with a low dose, especially in the following cases:
Low or normal initial blood pressure
Renal failure
Hyponatremia, whether or not drug-induced (diuretic)
2. ACE inhibitors can be used in combination with diuretics, and digitalis glycosides can be added if necessary.
3. It is recommended to start treatment with 2 mg daily in the morning while monitoring blood pressure. Increase to the standard therapeutic dose (2-4 mg per day, taken once) if necessary.
4. The selected daily therapeutic dose should achieve an upright systolic blood pressure of no less than 90 mmHg.
High-risk heart failure patients (severe heart failure, patients receiving high-dose diuretics)
1. Symptomatic hypotension may occur after medication. For such patients, the starting dose should be halved (i.e., 1 mg/day).
2. Serum potassium and creatinine should be monitored with each dose increase and every 3-6 months, depending on cardiac function classification, to assess the safety of treatment.
[Adverse Reactions]
Clinical Side Effects: 1. Headache, fatigue, dizziness, mood or sleep disturbances, cramps; 2. Orthostatic or non-orthostatic hypotension (see: Precautions); 3. Rare rash; 4. Stomach pain, anorexia, nausea, abdominal pain, dysgeusia; 5. Dry cough has been reported in association with ACE inhibitor use; this cough is characteristically persistent but resolves after discontinuation of the drug. If this occurs, consider considering the drug as a possible cause. 6. Very rare: Angioedema (Quigan's edema) (see: Warnings); Effects on Laboratory Values: 1. Moderate elevations in blood urea and creatinine, which resolve after discontinuation of treatment. These elevations are more common in patients with renal artery stenosis, hypertension, or renal failure receiving diuretic therapy. 2. In patients with glomerulonephropathy, ACE inhibitors may induce proteinuria. 3. Hyperkalemia, usually transient. 4. Anemia has been reported (see: Precautions) in patients with specific conditions (renal transplantation, hemodialysis) receiving ACE inhibitors.
[Contraindications]
This product is contraindicated in children, pregnant women, and lactating women who are allergic to it. The dose should be carefully adjusted for patients with renovascular hypertension, surgery, anesthesia, or renal insufficiency.
[Precautions]
1. Blood pressure, serum electrolytes (sodium, potassium, carbon dioxide-binding capacity), blood urea nitrogen, and serum creatinine should be checked before use and reviewed regularly.
2. Patients with renal dysfunction or leukocytopenia should have their white blood cell count and differential count checked every two weeks during the first three months and regularly thereafter.
3. Urine protein should be checked monthly.
4. Hemoglobin and renal parameters should be closely monitored for patients taking multiple medications.
[Special Use]
Precautions for Children: This product is contraindicated in children.
Precautions for Pregnancy and Lactation: This product is contraindicated in pregnant women and lactating women.
Precautions for the Elderly: Renal function and serum potassium should be checked before starting treatment (see: Dosage and Administration). The initial dose should be adjusted based on blood pressure changes. Caution should be exercised in patients with water and sodium loss to avoid a sudden drop in blood pressure.
[Drug Interactions]
Contraindications: 1. Potassium-sparing diuretics (amiloride, potassium canrenoate, spironolactone, triamterene, alone or in combination), except for the treatment of heart failure (low-dose ACE inhibitors plus low-dose thiazide diuretics), and potassium salts. Hyperkalemia (can be fatal, especially in patients with renal failure, where the drugs have a synergistic effect on increasing serum potassium) can occur. Except in patients with hypokalemia, do not use potassium supplements or potassium-sparing diuretics with ACE inhibitors. 2. Lithium. ACE inhibitors can increase blood lithium concentrations to toxic levels (reduced renal excretion of lithium). If ACE inhibitors are necessary, closely monitor blood lithium levels and adjust the dose. 3. Estramustine: Increased risk of angioedema. Use with caution: 1. Nonsteroidal anti-inflammatory drugs and acetylsalicylic acid (aspirin) ≥3 g/day. In high-risk patients (elderly and/or dehydrated), combined use of ACE inhibitors and NSAIDs can cause acute renal failure by reducing glomerular filtration and inhibiting vasodilator prostaglandin synthesis, thereby weakening the antihypertensive effect. Therefore, adequate rehydration and renal function monitoring are recommended at the start of treatment. 2. Antidiabetic agents (insulin, sulfonylureas): Regarding captopril and enalapril, ACE inhibitors can enhance the blood sugar-lowering effect in patients receiving insulin and sulfonylurea hypoglycemics. However, symptoms of hypoglycemia are rare (improved glucose tolerance reduces insulin requirements). Increase self-monitoring of blood sugar. 3. Baclofen: Enhances antihypertensive effects. Monitor blood pressure and adjust antihypertensive medication dosages as necessary. 4. Thiazide diuretics: In patients with pre-existing water and sodium depletion, initiating ACE inhibitor therapy carries the risk of sudden hypotension and/or acute renal failure. For patients with hypertension who have previously experienced sodium and water loss from diuretic therapy (especially those who have recently received diuretics, a low-salt diet, or hemodialysis), the following recommendations apply: 1. Discontinue diuretics before initiating ACE inhibitor therapy. If necessary, resume non-potassium-sparing diuretics. Alternatively, start ACE inhibitor therapy at a low dose and gradually increase the dose. 2. For patients with congestive heart failure who are currently taking diuretics, if necessary, start ACE inhibitor therapy at a low dose after reducing the non-potassium-sparing diuretic dose. 2.1 In all cases, monitor renal function (serum creatinine) during the first few weeks of ACE inhibitor therapy. 2.2 Potassium-sparing diuretics can be used alone (amiloride, potassium canrenoate, spironolactone, triamterene) or in combination with New York Heart Association class III or IV patients with an ejection fraction of 35% who are already taking ACE inhibitors and loop diuretics. Failure to adhere to the prescribing guidelines for combined medications can lead to hyperkalemia, which can be fatal. Therefore, hyperkalemia and renal insufficiency should be excluded before medication use, and serum potassium and creatinine should be closely monitored (measure weekly during the first month of treatment and monthly thereafter). Possible Combinations: 2.3 Amifostine: Enhanced antihypertensive effect. 3. Tricyclic antidepressants, neuroleptics: Increased antihypertensive effect and risk of orthostatic hypotension (synergistic effect). 4. Cortisone, tecocticoids (oral) (except corticosteroids used as replacement therapy for Addison's disease): Reduced antihypertensive effect (corticosteroids cause sodium and water retention). 5. Urinary tract alpha-blockers: alfuzosin, prazosin, terazosin, tamsulosin: Enhanced antihypertensive effect and increased risk of orthostatic hypotension.
[Pharmacological Actions]
1. Perindopril is an angiotensin-converting enzyme inhibitor (ACEI). Angiotensin-converting enzyme converts angiotensin I to angiotensin II. Angiotensin II has a significant vasoconstrictor effect and stimulates the adrenal cortex to secrete aldosterone. Perindopril can lead to: 1.1 Decreased aldosterone secretion. 1.2 Increased renin activity due to the lack of aldosterone's side feedback. 1.3 Long-term use reduces total peripheral arterial resistance and preferentially affects muscle and renal blood flow, without sodium and fluid retention or reflex tachycardia. 2. Like all thiazolidinone converting enzyme inhibitors, perindopril inhibits the degradation of bradykinin, a strong peptide vasodilator, into inactive peptides. Perindopril can lower blood pressure in patients with low or normal renin levels. 3. Perindopril acts through its active ingredient, perindoprilat; other metabolites are inactive. Characteristics of antihypertensive effects Treatment of hypertension 1. Perindopril can be used to treat various degrees of hypertension: mild, moderate, or severe. It reduces systolic and diastolic blood pressure in both supine and standing positions. 2. After a single dose, the maximum antihypertensive effect occurs 4-6 hours later and lasts for more than 24 hours. 3. Residual inhibition of angiotensin-converting enzyme (ACE) remains high (nearly 80%) after 24 hours. 4. For patients who respond effectively, blood pressure can return to normal after one month of treatment, and drug resistance does not develop. 5. No rebound blood pressure occurs after cessation of treatment. 6. Perindopril has a vasodilatory effect, restoring the elasticity of large arteries and reducing left ventricular hypertrophy. 7. Combination with thiazide diuretics can produce a synergistic effect when necessary. Combination of ACE inhibitors and thiazide diuretics can reduce the risk of hypokalemia caused by taking diuretics alone. Treatment of heart failure 1. Three studies on chronic heart failure showed that compared with other similar drugs, perindopril lowered blood pressure more gradually, and a sudden drop in blood pressure rarely occurred. 2. Hemodynamic mechanism of action in heart failure 3. Perindopril reduces cardiac load: 3.1 May dilate veins by altering prostaglandin metabolism: reducing preload. 3.2 Reduce total peripheral vascular resistance: reducing afterload. Studies in patients with heart failure have shown: 3.3 Reduced left and right ventricular filling pressures 3.4 Reduced total peripheral vascular resistance 3.5 Increased cardiac output and cardiac index 3.6 Increased regional muscle blood flow and improved exercise endurance
[Storage] Store in a dark, airtight container in a cool, dark place (no higher than 20°C).
[Specification] 8mg x 15 tablets
[Packaging] Box
[Expiry Date] 24 months
[Approval Number] National Medicine Standard H20103382
[Manufacturer] Servier (Tianjin) Pharmaceutical Co., Ltd.
