Approved on.
Date of revision.
Instructions for Captopril Tablets
Please read the instructions carefully and use under the guidance of your physician
Warning: Fetal toxicity
Drugs that act directly on the renin-angiotensin system may cause damage or death to the developing fetus. Therefore, this product should be discontinued as soon as pregnancy is detected.
[Drug Name
Generic Name: Captopril Tablets
English Name: Captopril Tablets
Hanyu Pinyin: katuopuli Pian
[Ingredients
The main ingredient of this product is Captopril.
Chemical name: 1-[(2S)-2-methyl-3-mercapto-1-propanoyl]-L-proline
Chemical structure formula.
Molecular formula: C9H15NO3S
Molecular weight: 217.29
[Properties
This product is a white or off-white tablet.
[Indications
1. hypertension; 2. heart failure.
[Specifications]
25mg
[Dosage].
Depends on the condition or individual differences. This product should be taken under the direction or supervision of a physician and the dose administered should be individualized and adjusted for efficacy.
Hypertension
Recent antihypertensive medication, the degree of elevated blood pressure, salt restriction, and other clinical conditions need to be considered before treatment is initiated.
The initial dose is 12.5 mg once orally, 2-3 times daily. If satisfactory blood pressure reduction is not obtained after 1 or 2 weeks, the dose may be increased to 50 mg once 2-3 times daily. Patients benefit from concomitant sodium restriction when this product is given alone.
Doses used to treat hypertension usually do not exceed 50 mg 3 times daily. If blood pressure is not satisfactorily controlled after 1 to 2 weeks of treatment at this dose (no combination diuretic), a moderate dose of a thiazide diuretic (e.g., hydrochlorothiazide, 25 mg daily) should be added. The diuretic dose can be considered to be increased every 1 or 2 weeks until target blood pressure is achieved, depending on blood pressure control.
If this product is started in a patient already receiving diuretics, treatment should be initiated under close medical monitoring.
In patients with severe hypertension (e.g., acute progressive hypertension or malignant hypertension), when temporary discontinuation of current antihypertensive therapy is not practical or when immediate lowering of blood pressure to normal levels is needed, then Continue diuretics, but discontinue other antihypertensive medications being treated, and immediately start treatment with this product 25 mg twice or three times daily under close medical monitoring.
If clinically indicated by the patient, the daily dose of this product may be increased under ambulatory medical monitoring every 24 hours or less until satisfactory blood pressure control is achieved or up to the maximum dose of this product. Stronger diuretics, such as furosemide, may also be required when administered according to this regimen.
Heart Failure
This product must be initiated under close medical monitoring.
Patients who may be hyponatremic and/or hypovolemic with normal or low blood pressure who have previously received adequate diuretic therapy prior to initiation of therapy are appropriately treated with an initial dose of 6.25 mg 3 times daily to minimize the extent and duration of the hypotensive response, followed by close monitoring and gradual increase to the usual dose.
The initial dose in most patients is 12.5 mg once 2-3 times daily, with maintenance dosing adjusted according to the patient’s response, clinical status, and tolerability, and gradually increased to 50 mg 2-3 times daily. Dose increments should be made at least 2 weeks apart to assess the patient’s response. Up to 150 mg daily in 2-3 doses.
[Adverse Reactions
Clinical Trials
Adverse events reported in clinical trials of captopril are as follows (number of patients approximately 7000).
Skin: rash, usually with pruritus, sometimes with fever, arthralgia and eosinophilia, incidence 4-7%, depending on the patient’s renal status and drug dose, usually occurring within 4 weeks of treatment initiation, often as a maculopapular rash, rarely as urticaria, usually mild and disappearing after dose reduction, discontinuation or administration of antihistamines. Pruritus without rash occurs in about 2% of patients. 7%-10% of patients with rash are associated with eosinophilia or positive antinuclear antibodies (ANA). Reversible drug-associated aspergillosis-like lesions and photosensitivity have also been reported. Facial flushing or pallor occurs in ≥0.5% of patients.
Cardiovascular: Hypotension has occurred in approximately 1% of patients. tachycardia, chest pain, and palpitations. Angina pectoris, myocardial infarction, Raynaud’s syndrome, and congestive heart failure each occurred in ≤0.3% of patients.
Gastrointestinal: approximately 2-4% of patients (depending on renal status and dose) develop taste disturbance or taste retardation.
Hematology: anemia, thrombocytopenia, pancytopenia , neutropenia/granulocyte deficiency.
Immunology: angioedema occurs in approximately 0.1% of patients. This includes angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords or pharynx, and patients are advised to report immediately to their physician. Angioedema involving the upper airway can cause fatal airway obstruction.
Respiratory tract: cough occurs in 0.5% to 2% of patients .
Renal: renal impairment, renal failure, nephropathy syndrome, polyuria, oliguria, and dysuria are rare (≤0.2%) and the relationship with medication use is unclear. Proteinuria.
About 0.5%-2% of patients had events that However, no increased incidence was seen compared with placebo or other treatments used in controlled trials: gastric irritation; abdominal pain; nausea; vomiting; diarrhea; loss of appetite; constipation; mouth ulcers; peptic ulcers; dizziness, headache, malaise; fatigue; insomnia; dry mouth; dyspnea; hair loss; and abnormal sensation.
Post-marketing experience
The following is a list of postmarketing clinical adverse events reported for this product by body system. In this setting, the incidence or causality cannot be accurately determined.
General: malaise; gynecomastia.
Cardiovascular: cardiac arrest; cerebrovascular accident or insufficiency ; rapid and irregular heart rate; postural hypotension; syncope, caused by hypotension, especially in the presence of sodium deficiency or hypovolemia.
Skin: herpetic aspergillosis, erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis.
Gastrointestinal: pancreatitis, tongue inflammation, dyspepsia.
Hematology: anemia, including aplastic anemia and hemolytic anemia; leukopenia with granulocytes, with fever and chills.
Hepatobiliary: jaundice, hepatitis, including rare cases of hepatic necrosis cases, cholestasis.
Metabolic: symptomatic hyponatremia.
Musculoskeletal: myalgia, muscle weakness.
Neurologic/psychiatric: ataxia, confusion, depression, nervousness, drowsiness.
Respiratory: bronchospasm, eosinophilic pneumonia, rhinitis.
Special sensations: blurred vision.
Genitourinary tract: impotence.
As with the use of other angiotensin-converting enzyme (ACE) As with other angiotensin-converting enzyme (ACE) inhibitors, a syndrome with the following manifestations has been reported: fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash or other dermatologic manifestations, eosinophilia, and elevated sedimentation (ESR).
Fetal/neonatal morbidity and mortality.
The use of ACE inhibitors during pregnancy has caused fetal and neonatal damage, including hypotension, neonatal craniosynostosis, anuria, reversible or irreversible renal failure and death. Hypohydramnios have also been reported, presumably as a result of decreased fetal renal function; hypohydramnios in this setting have been associated with fetal limb contractures, craniofacial anomalies, and pulmonary insufficiency. Preterm delivery, intrauterine growth retardation, and ductus arteriosus have also been reported. Preterm delivery, ductus arteriosus and other structural cardiac anomalies, and neurological malformations have been reported in the recent literature when drug exposure was limited to early pregnancy.
Laboratory Tests
Serum electrolytes: hyperkalemia, which may occur with a mildly elevated, especially in patients with renal impairment.
Hyponatremia: especially in patients receiving a low sodium diet or in combination with patients on diuretics.
Urea nitrogen (BUN)/serum creatinine: BUN or A transient increase in serum creatinine concentration, especially in patients with volume or salt depletion, or in patients with renal vascular hypertension. It is often transient and tends to occur after a rapid drop in blood pressure in patients with renal disease or prolonged severe hypertension. A rapid fall in prolonged or significantly elevated blood pressure leads to a decrease in glomerular filtration rate and subsequently to an increase in BUN or serum creatinine levels.
Hematology: positive ANA has been reported.
Liver function tests: serum liver transaminases, alkaline phosphatase and serum bilirubin are elevated.
[Contraindication
Allergy to captopril or any of the excipients This product is contraindicated in patients with hypersensitivity to captopril or any of the excipients, or to other ACE inhibitors (eg, patients who have experienced angioedema during treatment with any of the other ACE inhibitors).
This product is contraindicated in mid to late pregnancy. This product should be discontinued as soon as pregnancy is detected.
In diabetes or renal impairment (GFR <60 mL /min/1.73 m²), ACE inhibitors are contraindicated in combination with drugs containing aliskiren.
[Caution].
Food in the stomach may reduce the absorption of this product by 30-40%, so it is advisable to take the drug 1 hour before a meal.
1. Allergic-like and possibly related reactions
It is possible that because ACE inhibitors affect the metabolism of arachidonic acid and peptides (including endogenous bradykinin), patients receiving ACE inhibitors (including captopril) may A variety of adverse reactions may occur, including some serious adverse reactions.
Head and facial angioedema: Patients who have received ACE inhibitors, including captopril angioedema in patients treated with ACE inhibitors (including captopril). Sites where edema occurs include the extremities, face, lips, mucous membranes, tongue, vocal cords, and throat. If angioedema involves the tongue, vocal cords and throat, fatal airway obstruction may occur. Emergency treatment should therefore be given immediately. Treatment includes, but is not limited to, discontinuation of the product and rapid subcutaneous injection of 1:1000 epinephrine 0.3-0.5 ml. edema involving the face, oral mucosa, lips, and extremities usually resolves with discontinuation of captopril; only a few cases require medical therapy.
Intestinal angioedema: In rare cases, patients receiving ACE intestinal angioedema occurs in patients treated with ACE inhibitors. These patients present with abdominal pain (with or without nausea or vomiting); in some cases, there is no previous history of facial angioedema, normal C-1 esterase levels, diagnosis based on abdominal CT scan or ultrasound, or surgical diagnosis, and symptoms disappear after discontinuation of ACE inhibitors. Patients treated with ACE inhibitors present with abdominal pain, and the differential diagnosis should include intestinal angioedema.
Anaphylactic-like reactions during desensitization: 2 cases receiving concomitant treatment with another Life-threatening anaphylactic-like reactions occurred in patients who were given desensitization therapy for Hymenoptera venom with another ACE inhibitor (enalapril). These reactions disappeared after suspension of the ACE inhibitor, but reappeared upon inadvertent re-initiation. Therefore, caution should be maintained in performing these desensitizations in patients treated with ACE inhibitors.
High Flux Dialysis/Lipoprotein Adsorption Dialysis Membrane Exposure During Hypersensitivity-like reactions: Hypersensitivity-like reactions have occurred in patients receiving high-flux dialysis membranes for hemodialysis in combination with ACE inhibition. Anaphylactic-like reactions have also been reported in dialysis patients using dextran sulfate adsorbed LDL. In these patients, the use of other types of dialysis membranes or the use of other types of drugs should be considered.
2. Neutropenia/granulocyte deficiency
The use of captopril has caused myelodysplasia, which leads to centrophil deficiency (<1000/mm3), and about half of these patients developed systemic or oral infections, or other symptomatic features of granulocyte deficiency.
The risk of developing neutropenia depends on the patient’s clinical status.
Neutropenia is rare in hypertensive patients with normal renal function (Crs <1.6 mg/dL and no collagen vascular disease) (< 0.02%).
In patients with some degree of renal impairment (serum creatinine of at least 1.6 mg/dL) and without collagen vascular disease, clinical trials have shown that the risk of neutropenia risk was about 0.2%. 15 times higher than the corresponding incidence in patients with simple hypertension. The relatively high daily dose of captopril in these patients should be considered especially in view of their diminished renal function. In patients with renal failure, neutropenia has occurred with the combination of allopurinol and captopril, so increased vigilance is warranted.
In patients with renal impairment associated with collagen vascular disease (eg, SLE, scleroderma), clinical trials have shown a 3.7% incidence of neutropenia.
Neutropenia is dose dependent and usually occurs 3-12 weeks after the start of captopril therapy, with the most pronounced on days 10-30. Generally, neutrophils return to normal after approximately 2 weeks of captopril discontinuation. Only patients with clinically complicated disease develop severe infections. Death occurs in about 13% of neutropenia cases, but almost all deaths occur in patients with severe disease, with collagen vascular disease, renal failure, heart failure, or on immunosuppressive therapy, or in patients with a combination of these complicating factors.
Renal function should be evaluated concurrently with any evaluation of patients with hypertension or heart failure.
If a patient with renal impairment is taking captopril, a white blood cell count and sorting count should be performed before treatment is started, every 2 weeks for the first 3 months, and periodically thereafter. Follow up with a check when there are signs of infection.
If a patient has collagen disease (such as severe SLE) or is taking other medications known to have an effect on white blood cells or immune response, especially if renal function is impaired , when there is an increased chance of leukopenia or granulocytopenia, captopril must be used only after assessing the benefits and risks, and caution should be exercised after starting the drug.
In general, discontinuation of this and other medications usually results in a rapid normalization of the white blood cell count, therefore, it is important to be careful when confirming that the patient is neutropenic (neutrophil count & lt;1000/mm3), the physician should discontinue captopril and follow the patient closely for the duration of the disease.
3. Proteinuria
Often occurs within 8 months of the start of treatment.
Total urinary protein greater than 1 g/day was seen in about 0.7% of patients treated with this product. Of these, approximately 90% had evidence of prior renal disease, or a relatively high dose of this product (more than 150 mg/day), or both of these factors.
About 1 in 5 patients with proteinuria develop nephrotic syndrome, and in most cases, proteinuria decreases within 6 months with or without continuation of the product. Renal function indicators (e.g., urea nitrogen and serum creatinine) are rarely affected and the course of therapy is not affected.
If the patient has previous renal disease or if the dose of captopril exceeds 150 mg/day, urine protein should be estimated before the start of therapy (first morning urine test paper method), and regular Urine protein should be tested, and it is recommended that the urine protein test be performed once a month. If proteinuria gets progressively worse with this product, the product should be suspended or the dosage reduced.
4.
Excessive hypotension occurs rarely in patients with hypertension, but patients with salt/volume depletion (e.g., those on strict dietary sodium restriction or receiving heavy diuretic therapy), patients with heart failure, or hypotension may occur after administration of captopril in patients undergoing renal dialysis.
Transient hypotensive reactions are not a contraindication to further dosing and can be continued once the blood pressure has risen.
Patients with heart failure usually have normal or low blood pressure, and such patients may experience a transient decrease in blood pressure on captopril, with the average decrease in blood pressure exceeding 20% in Patients with heart failure account for about half of all patients with heart failure. This transient hypotension is usually well tolerated after the first dose of the product and does not cause symptoms or only transient, mild dizziness, although a very small number of patients have experienced arrhythmias or conduction block. About 3.6% of patients with heart failure discontinue captopril because of the occurrence of hypotension.
Because of the potential for lower blood pressure with captopril in these patients, they should be monitored closely medically when first receiving captopril.
The hypotensive response is minimized when the product is taken at an initial dose of 6.25 mg or 12.5 mg (twice or three times daily). Medical monitoring should be performed for at least 1 hour after the initial dose. Patients should be followed closely for the first 2 weeks after treatment initiation and as the dose of captopril and/or diuretics is increased.
The occurrence of hypotension is not in itself a reason to discontinue captopril. Patients with heart failure usually experience some reduction in diastolic blood pressure when first treated with captopril, and this reduction in diastolic blood pressure is beneficial to the patient. The decrease is greatest early in treatment, stabilizes within 1-2 weeks, and usually returns to pre-treatment levels within 2 months, unaccompanied by a decrease in efficacy.
5. Fetal/neonatal morbidity and mortality
When administered during pregnancy, ACE inhibitors can jeopardize fetal development and even cause fetal death. If a patient is found to be pregnant, the product should be discontinued as soon as possible.
6. Liver Failure
For hepatic failure, very few cases presenting with cholestatic jaundice and hepatocellular damage and (sometimes) fatalities have been reported when treated with ACE inhibitors, and the mechanism of this symptom is not The mechanism of this symptom is not clear. Patients who develop jaundice or significantly elevated liver enzymes should discontinue treatment with ACE inhibitors and receive appropriate medical follow-up.
7. Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
The combination of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalemia, and decreased renal function (including acute renal failure) . Therefore, dual blockade of RAAS by a combination of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.
8. Renal impairment
Hypertension: Patients with combined renal disease, especially those with severe renal artery stenosis, will experience elevations in urea nitrogen and serum creatinine after antihypertensive therapy with captopril, and these These elevations are usually reversible after discontinuation of the drug. At this time, it may be necessary to reduce the dose of captopril and/or discontinue diuretics and, if necessary, discontinue the product. However, maintaining adequate renal perfusion while returning blood pressure to normal levels is nearly impossible for some patients.
Heart failure: About 20% of patients receiving long-term treatment with captopril have steadily elevated urea nitrogen and serum creatinine that are 20% higher than normal or baseline values. Less than 5% of patients (usually those with pre-existing severe renal disease) require discontinuation of this product because of progressive creatinine elevation. Subsequent improvement is likely to depend on the severity of the patient’s underlying renal disease.
Because this product is primarily excreted through the kidneys, the rate of excretion of this product is decreased in patients with renal impairment and should be administered in smaller doses or at lower dosing frequencies, each time using smaller increments, in slow increments (once every 1 or 2 weeks).
In patients with renal impairment, if concomitant diuretics are required, furosemide is recommended over thiazides, and the dose of this product should be reduced or concomitantly discontinued with diuretics in the presence of increased blood urea nitrogen and creatinine.
9. Hyperkalemia
Elevated blood potassium has been found in some patients treated with ACE inhibitors, including captopril. Patients at risk for hyperkalemia while receiving ACE inhibitors include patients with renal impairment, diabetes mellitus, and patients who are using a combination of potassium-preserving diuretics, potassium supplements, or salt substitutes containing potassium or are taking other medications that can cause elevated blood potassium. In particular, blood potassium should be checked when used in combination with potassium-preserving diuretics.
10.
Cough has been reported in patients on all ACE inhibitors. This cough is characterized by absence of sputum, persistence, and relief after discontinuation of the drug. ACE inhibitor-induced cough should be included in the differential diagnosis of cough.
11. Surgery/anesthesia
Captopril blocks angiotensin II formation caused by compensatory renin release during patients undergoing major surgery or anesthesia with drugs that can produce hypotension. If hypotension occurs and it is believed that the hypotension is due to this mechanism, it can be corrected with volume expansion.
12. Use this product with caution in the following conditions.
Bone marrow suppression.
Inadequate blood supply to the cerebral or coronary arteries may be exacerbated by lower blood pressure and increased ischemia.
Hyperkalemia.
Renal impairment resulting in increased blood potassium, leukocyte and granulocyte reduction and retention of this product must be used only after evaluation of benefit and risk.
Aortic stenosis, when coronary perfusion may be reduced.
Autoimmune diseases such as severe systemic lupus erythematosus. There is an increased chance of leukopenia or granulocytopenia at this time.
People on strict dietary sodium restriction or dialysis, when the first dose of Sudden and severe hypotension may occur with this product.
13. Do not use if the inner package is open or damaged.
[For pregnant and lactating women
Medication for Pregnant Women
This product can pass through the placenta, and its use by pregnant women can affect fetal development and cause fetal and neonatal damage or even death, so it is contraindicated in pregnant women.
For nursing mothers
This product is excreted into breast milk, and the concentration of captopril in breast milk is approximately 1% of the maternal blood concentration. Because of the potential for serious adverse reactions in the nursing infant following administration of captopril, the importance of this product to the mother should be taken into account when making decisions to discontinue breastfeeding or discontinue the drug.
[Pediatric Dosage].
Neonates exposed to captopril in utero: If oliguria or hypotension occurs, attention should be focused on blood pressure support and renal perfusion. As a way to reverse hypotension and/or replace already abnormal renal function, blood exchange therapy or dialysis may be required.
While hemodialysis can remove captopril from the circulation in adults, there are insufficient data on the effectiveness of hemodialysis in removing captopril from the circulation in newborns or children. There are insufficient data. Peritoneal dialysis is not effective in removing captopril; there is no information on the removal of captopril from the systemic circulation by blood exchange therapy.
The efficacy and safety of this product in pediatric patients have not been established. There is limited experience reported in the literature with the use of captopril in children; weight-based dosing is usually comparable to or lower than in adults.
Infants, especially neonates, may be more sensitive to the adverse hemodynamic effects of captopril. Excessive, sustained, and unpredictable reductions in blood pressure with oliguria and convulsions have been reported in infants.
This product should be used only in pediatric patients who have failed other antihypertensive treatments.
[Geriatric use
The elderly are more sensitive to the antihypertensive effect and the dose of this product should be reduced.
[Drug Interactions
Diuretics: patients receiving diuretic therapy Patients, especially those who have recently started diuretic therapy and those receiving a strict salt-restricted diet or on dialysis, occasionally experience a dramatic drop in blood pressure, usually seen within the first hour after the first dose of this product.
Concomitant use with diuretics results in an increased antihypertensive effect, but severe hypotension should be avoided, so discontinuation or reduction of the dose is recommended for those previously using diuretics. This product is started in small doses and the dose is gradually adjusted.
Drugs with vasodilating activity: concomitant use may cause hypotension. Therefore, if possible, stop using nitroglycerin or other nitrates (for angina pectoris) or other drugs with vasodilating activity before starting treatment with this product. If these drugs are combined during treatment with this product, they should be given with caution and started at a lower dose.
Drugs that cause renin release: Drugs that can cause renin release Antihypertensive drugs can amplify the effects of captopril. For example, diuretics (such as thiazides) may activate the renin-angiotensin-aldosterone system.
Drugs that affect sympathetic activity: When treated with this product alone or in combination with a diuretic The sympathetic nervous system is particularly important for blood pressure support in patients treated with this product alone or in combination with diuretics. Combination with drugs affecting sympathetic activity (ganglionic blockers or adrenergic nerve blockers) and beta-blockers can cause enhanced antihypertensive effects and should be used with caution.
Potassium-raising drugs: Because captopril decreases aldosterone Because captopril decreases aldosterone production, elevated blood potassium may occur. Potassium-preserving diuretics such as spironolactone, aminoglutethimide, amiloride, or potassium supplements should only be used in definite hypokalemia and with caution, as concomitant use may cause a significant increase in blood potassium. Salt substitutes containing potassium should also be used with caution.
Inhibitors of endogenous prostaglandin synthesis: non-steroidal anti-inflammatory drugs NSAIDs may attenuate the hypotensive effects of ACE inhibitors (including captopril). Indomethacin may reduce the antihypertensive effect of this product, especially in the setting of low-renin hypertension. Other NSAIDs (e.g., aspirin) may also have this effect. Combined use of NSAIDs (including selective cyclooxygenase 2 (COX-2) inhibitors) and ACE inhibitors (including captopril) in elderly patients, patients with volume failure (including those treated with diuretics), or patients with renal impairment may result in worsening renal function (including the possibility of acute renal failure). These effects are usually reversible. For patients receiving captopril and NSAID therapy, renal function should be monitored regularly.
Lithium: In patients on combined lithium and ACE inhibitors In patients combining lithium and ACE inhibitors, elevated serum lithium levels and symptoms of lithium toxicity have been reported. Caution should be exercised when combining these drugs, and frequent monitoring of serum lithium levels is recommended. The risk of lithium toxicity may be increased with concomitant use of diuretics.
Glucose-lowering medications: ACE inhibitors (including captopril) May enhance the glucose-lowering effects of insulin and oral hypoglycemic agents (e.g., sulfonylureas) in patients with diabetes.
Renin-angiotensin-aldosterone system (RAAS ) dual blockade
Data from clinical trials show that dual blockade of the renin-angiotensin-aldosterone system (RAAS) by a combination of ACE inhibitors, angiotensin II receptor blockers, or aliskiren When dual blockade of the RAAS is performed, there is an increased incidence of adverse events (e.g., hypotension, hyperkalemia, and decreased renal function (including acute renal failure)) when compared with the use of only one agent acting on the RAAS. Most patients receive no additional benefit from the combination of two RAAS inhibitors over monotherapy. In general, the combination of RAAS inhibitors should be avoided. Blood pressure, renal function, and electrolytes should be monitored closely in patients treated with this and other drugs that affect the RAAS.
The combination of ACE inhibitors and angiotensin II receptor blockers is contraindicated in patients with diabetic nephropathy.
The combination of aliskiren and this product should be avoided in patients with renal impairment (glomerular filtration rate GFR <60 ml/min).
Drug/Lab Test Interactions
This product may cause false positive urinary acetone tests.
The antihypertensive effect is enhanced when combined with other antihypertensive drugs.
[Drug overdose
Overdose can cause hypotension, and correction of hypotension should be considered first when drug overdose occurs. The medication should be discontinued immediately and may be optionally corrected by intravenous saline augmentation while the patient’s blood pressure is being restored.
Cartopril in the circulation of adults can be cleared by hemodialysis, but there are insufficient data to demonstrate that hemodialysis is equally effective in the clearance of cartopril in neonates or children. However, there are insufficient data to demonstrate that hemodialysis is equally effective in the clearance of captopril in neonates or children. Peritoneal dialysis is not effective in clearing circulating captopril, and it is unclear whether replacement blood therapy can clear captopril from the body.
[Pharmacology and Toxicology
Pharmacological effects
Captopril is a competitive angiotensin-converting enzyme inhibitor that prevents the conversion of angiotensin I to angiotensin II, thereby decreasing peripheral vascular It can also dilate the peripheral vasculature by interfering with the degradation of bradykinin; it can also reduce pulmonary capillary wedge pressure and pulmonary vascular resistance, increasing cardiac output and exercise tolerance time.
Toxicological studies
General toxicity
Repeated dosing toxicity tests were conducted in mice, rats, dogs, and monkeys (mice: 2 years; rats: 2 years; dogs: 47 weeks, 1 year; monkeys: 1 year), and drug-related toxicity included effects on hematopoiesis, nephrotoxicity, gastric erosion/ulcer, and retinal vascular degeneration.
Decreases in hemoglobin and/or erythrocyte pressure volume were seen in mice, rats, and monkeys when captopril was given orally at doses 50 to 150 times the maximum recommended human dose (MRHD). values decreased. Anemia, leukopenia, thrombocytopenia, and bone marrow suppression were seen in dogs given orally at doses ranging from 8 to 30 times the MRHD. The decrease in hemoglobin and erythrocyte pressure values was significant and reversible in mice and rats after only 1 year. In the canine test, significant anemia was seen at all dose levels (8 to 30 times MRHD), with moderate to significant leukopenia occurring at 15 and 30 times MRHD, respectively, and thrombocytopenia at 30 times MRHD. The anemia was reversible after discontinuation of the drug. Bone marrow suppression occurred to varying degrees: in the 1-year study, it was seen in dogs that died or were executed in a near-death state; however, in the 47-week study, myelosuppression was reversed at doses 30 times the MRHD. Proliferation of the paraglomerular apparatus was seen in mice and rats given captopril orally at doses 7 to 200 times the MRHD, in monkeys given at doses 20 to 60 times the MRHD, and in dogs at doses 30 times the MRHD.
Gastric erosion/ulcerations were seen in male rats given orally at doses 20 and 200 times the MRHD, and in dogs and monkeys given orally at 30 and 65 times the MRHD, respectively. The incidence of gastric erosion/ulcer was increased when given orally at 30 times MRHD in dogs and 65 times MRHD in monkeys. Gastric ulcers and intestinal ulcers were seen in rabbits given captopril orally for 5-7 days at approximately 30 times the dose of MRHD. In rats given captopril orally for 2 years, progressive irreversible changes in retinal vascular canal diameters were seen at all dose levels (7x to 200x MRHD) in a dose-related manner. They appeared as early as week 88 of dosing, with a progressive increase in incidence thereafter, and were irreversible after discontinuation of the drug.
Carcinogenicity
No carcinogenic effect was observed in mice and rats given captopril 50-1350 mg/kg daily in distribution for 2 years, and the high dose was 150 times the maximum recommended human dose (50 Kg The high dose was 150 times of the maximum recommended human dose (50Kg, 450mg). The highest doses in mice and rats were 13 and 26 times the maximum recommended human dose, respectively, based on body surface area conversion.
[Pharmacokinetics
Captopril tablets are rapidly absorbed after oral administration, with absorption rates above 75%. Onset of action is 15 minutes after oral administration, with peak blood concentrations reached in approximately 1 hour. It lasts for 6-12 hours. Food in the stomach and intestines can reduce the absorption of this product by 30-40%, so it is advisable to take the drug 1 hour before a meal. Based on 14C-labeling studies, more than 95% of the absorbed drug is excreted via urine within 24 hours, with 40%-50% being prodrug and the remainder being primarily captopril disulfide dimer and captopril-cysteine disulfide. The plasma protein binding of the drug is approximately 25-30%. The apparent clearance half-life of total radioactivity in the blood is approximately less than 3 hours. Studies have not accurately determined the half-life of protopril, but it is likely to be less than 2 hours. Drug retention occurs with renal impairment. The antihypertensive effect is progressive, reaching maximum therapeutic effect in about several weeks.
Captopril does not cross the blood-brain barrier. Captopril is secreted through breast milk and can cross the placenta.
[Storage].
Store under 25℃ in a sealed container under shade.
[Packaging
Packaged in plastic bottles, 100 tablets/bottle.
[Expiration date
24 months
[Executive Standard
[Approval Number
State Pharmacopoeia H13021309
[Manufacturer
Company Name: Shiyang Group Ouyi Pharmaceutical Co.
Manufacturing Address: No. 99, Hainan Road, Shijiazhuang Economic and Technological Development Zone
Postal code:052165
Inquiries: 8009111886 (please call from a landline) 4006128666
Fax number: 0311-67809458