Approval Date:
Revision Date:
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 to the developing fetus or cause death. 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 Katuopuli.
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 with cross indentations on one side.
[Indications
1. hypertension; 2. heart failure.
[Specifications
25 mg
[Dosage].
Depends on the condition or individual differences. This product should be taken under the guidance or supervision of a physician and the dose administered should be individualized and adjusted according to 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 orally once, 2-3 times daily. If satisfactory blood pressure reduction is not achieved after 1 or 2 weeks, the dose may be increased to 50 mg once 2-3 times daily. Patients may 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 (not combined with a diuretic) after 1 to 2 weeks of treatment at this dose, a moderate dose of a thiazide diuretic (eg, 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., acutely advanced 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 required, diuretics should be continued but other ongoing treatment should be discontinued Antihypertensive medication should be discontinued, and treatment with this product 25 mg twice or three times daily should be started immediately under close medical monitoring.
If clinically indicated, 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 until the maximum dose of this product is reached. Stronger diuretics, such as furosemide, may also be required when administered according to this regimen.
Heart Failure
This product must be started 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 advised to use an initial dose of 6.25 mg 3 times daily to minimize the extent and duration of hypotensive response The initial dose of 6.25 mg 3 times daily is appropriate to minimize the extent and duration of the hypotensive response and is monitored closely thereafter and increased gradually to the usual dose.
The initial dose in most patients is 12.5 mg twice to three times daily, with maintenance dosing adjusted according to the patient’s response, clinical status, and tolerability, and tapered to 50 mg twice to three times daily as necessary. Dose increments should be made at least 2 weeks apart to assess patient response. Up to 150 mg/day in 2-3 doses.
[Adverse Reactions
Clinical Trials
The following adverse events were reported in clinical trials of captopril (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 occurs within 4 weeks of treatment initiation, often as a maculopapular rash, rarely as urticaria, usually mild, and resolves with 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, tachycardia, chest pain, and palpitations occur in about 1% of patients. Angina pectoris, myocardial infarction, Raynaud’s syndrome, and congestive heart failure each occurred in ≤0.3% of patients.
Gastrointestinal tract: Taste disturbance occurs in approximately 2%-4% of patients (depending on renal status and dose) or taste retardation.
Hematology: anemia, thrombocytopenia, pancytopenia, neutropenia/granulocyte deficiency.
Immunology: angioedema in about 0.1% of patients: including angioedema of the face, extremities, lips, mucosa, tongue, vocal cords or pharynx, and patients were advised to report immediately to their physician. Angioedema involving the upper airway can cause fatal airway obstruction.
Respiratory tract: coughing occurs in 0.5%-2% of patients.
Renal: renal impairment, renal failure, nephrotic syndrome, polyuria, oliguria, and dysuria were rare (≤ 0.2%), and the relationship with medication use is unclear. Proteinuria.
The following events occurred in approximately 0.5%-2% of patients, but compared with placebo or other treatments used in controlled trials No increased incidence compared to 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; abnormal sensation.
Post-marketing experience
The following is a list of post-marketing clinical adverse events reported for captopril tablets according to body system. In this setting, 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, glossitis, 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, 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 other angiotensin-converting enzyme (ACE) inhibitors, a syndrome with the following has been reported syndrome with the following manifestations: 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 been associated with 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, mild elevation of blood potassium may occur, especially in patients with renal impairment.
Hyponatremia: especially in patients receiving a low sodium diet or in combination with diuretics.
Urea nitrogen (BUN)/serum creatinine: A transient increase in BUN or 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 fall in blood pressure in patients with renal disease or long-term severe hypertension. A rapid fall in prolonged or significantly elevated blood pressure leads to a decrease in glomerular filtration rate and subsequent increase in BUN or serum creatinine levels.
Hematology: positive ANA has been reported.
Liver function tests: elevated serum liver transaminases, alkaline phosphatase and serum bilirubin.
[Contraindication
This product is contraindicated in persons with hypersensitivity to captopril or any of the excipients, or to other ACE inhibitors (eg, in any of the other ACE inhibitor treatment).
This product is contraindicated in mid to late pregnancy. This product should be discontinued as soon as pregnancy is detected.
In patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²) Combination of ACE inhibitors with drugs containing aliskiren is prohibited.
[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 reactions and possible related reactions
Patients receiving ACE inhibitors (including captopril) may experience a variety of adverse reactions, including some serious ones, possibly because ACE inhibitors affect the metabolism of arachidonic acid and peptides (including endogenous bradykinin). adverse reactions.
Head and face angioedema: angioedema has occurred in patients treated with ACE inhibitors, including captopril. The. 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. Therefore, emergency treatment should 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.
Intra-intestinal angioedema: In rare cases, intra-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 patients who also received another ACE inhibitor (enalapril) during life-threatening anaphylactic-like reactions occurred during the administration of hymenopteran venom desensitization therapy. 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.
Anaphylactic-like reactions during high-flux dialysis/lipoprotein adsorption dialysis membrane exposure: In patients receiving high-flux dialysis membranes for anaphylactic-like reactions have occurred in patients receiving high-flux dialysis membranes for hemodialysis in combination with ACE inhibition. Anaphylactoid 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 central granulocyte deficiency (<1000/mm3), and about half of these patients developed systemic or oral infections, or granulocyte Deficiency is characterized by other symptoms.
The risk of developing neutropenia depends on the patient’s clinical condition.
Neutropenia is rare (<0.02%) in hypertensive patients with normal renal function (Crs <1.6 mg/dL and no collagen vascular disease).
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 is approximately 0.2%. This is 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-related and usually occurs 3-12 weeks after the initiation of captopril therapy, with the most significant occurring on days 10-30, and neutrophils generally return to normal approximately 2 weeks after stopping captopril. Only patients with clinically complex 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 sorted count should be performed before the start of therapy, every 2 weeks for the first 3 months, and periodically thereafter, followed by tests if 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 drugs usually results in a rapid return to normal white blood cell counts; therefore, after confirming that the patient is neutropenic (neutrophil count<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 treatment initiation.
Total urinary protein of more than 1 g/day was seen in about 0.7% of patients treated with captopril tablets. Of these, about 90% had evidence of prior renal disease or a relatively high dose of captopril therapy (more than 150 mg/day), or both factors were present.
About 1 in 5 patients with proteinuria present with nephrotic syndrome, and in most cases, proteinuria decreases within 6 months with or without continuation of captopril tablets. Renal function indicators (e.g., urea nitrogen and serum creatinine) are rarely affected and the course of therapy is not affected.
If a patient has previous renal disease or if the dose of captopril exceeds 150 mg/day, urinary protein should be estimated before the start of therapy (first morning urine test paper method) and tested regularly; monthly urinary protein tests are recommended. If proteinuria gradually worsens with the use of this product, the use of this product should be suspended or the dosage reduced.
4. Hypotension
Excessive hypotension occurs rarely in patients with hypertension, but may occur in patients with salt/volume depletion (e.g., those on strict dietary sodium restriction or receiving heavy diuretic therapy), in patients with heart failure, or in patients on renal dialysis after taking captopril. Hypotension may occur.
Transient hypotensive reactions are not a contraindication to further dosing and can be continued once the blood pressure has risen.
Patients with heart failure, who usually have normal or low blood pressure, may experience a transient decrease in blood pressure on captopril, with about half of all patients with heart failure having an average decrease in blood pressure of more than 20%. This transient hypotension is most often seen after the first dose of captopril and is usually well tolerated by patients and causes no 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 risk of lower blood pressure with captopril in these patients, they should be monitored closely medically when first treated with captopril.
The hypotensive response can be minimized when captopril tablets are 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 doses of captopril alone or in combination with diuretics are 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 with ACE inhibitor therapy, and the mechanism of this symptom is not known. 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 the combination of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.
8. Renal impairment
Hypertension: Patients with comorbid renal disease, especially those with severe renal artery stenosis, may experience elevations in urea nitrogen and serum creatinine after antihypertensive therapy with captopril, and these elevations are generally 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: In patients receiving long-term treatment with captopril, urea nitrogen and serum creatinine are steadily elevated in about 20% of patients, 20% above 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 captopril is primarily excreted through the kidneys, the rate of captopril excretion decreases in patients with renal impairment and should be administered in smaller doses or less frequently, using smaller increments at a time, in slow increments (once every 1 or 2 weeks ).
In patients with renal impairment, if concomitant diuretics are required, furosemide rather than thiazide is recommended, and the dose should be reduced or the diuretic discontinued if blood urea nitrogen and creatinine are elevated.
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 those with renal impairment, those with diabetes mellitus, those on combination potassium-preserving diuretics, potassium supplements, or potassium-containing salt substitutes, or those taking other medications that cause elevated blood potassium. In particular, blood potassium should be checked when used in combination with a potassium-protective diuretic.
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 anesthesia in patients undergoing major surgery or 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 situations.
Bone marrow suppression.
Inadequate blood supply to the cerebral or coronary arteries may be exacerbated by lower blood pressure and ischemia.
Excessive blood potassium.
Renal impairment resulting in increased potassium, leukocyte and granulocyte reduction, and retention of captopril must be assessed after benefit and risk before use.
Aortic stenosis, when coronary perfusion may be reduced.
Autoimmune diseases such as severe systemic lupus erythematosus, when there is an increased chance of leukopenia or granulocytopenia.
Sudden and severe hypotension may occur with the first dose of captopril in people with strict dietary sodium restriction or on dialysis. hypotension.
13. Do not use if the inner package is opened or damaged.
[For pregnant and lactating women
Medication for Pregnant Women
Captopril 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
Captopril 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 nursing infants taking captopril, the importance of captopril to the mother should be taken into account when making the decision to stop breastfeeding or discontinue the drug.
[Pediatric Use].
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 removing captopril from the circulation in newborns or children by hemodialysis. 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 captopril tablets in pediatric patients have not been established. There is limited experience reported in the literature with the use of captopril in children; weight-based doses are usually comparable to or lower than those in adults.
Infants, especially neonates, may be more sensitive to the adverse hemodynamic effects of captopril. Captopril tablets have been reported to cause excessive, sustained, and unpredictable reductions in blood pressure with oliguria and convulsions 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 antihypertensive effects and the dose of this product should be reduced.
[Drug Interactions
Diuretics: Patients receiving diuretic therapy, especially those who have recently started diuretic therapy, and those receiving a strict Patients on a 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 captopril.
Concomitant use with diuretics enhances the antihypertensive effect, but severe hypotension should be avoided, so discontinuation or reduction of the dose is recommended for former 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: Antihypertensive drugs that cause renin release can amplify the effects of captopril. For example, diuretics (such as thiazides) may activate the renin-angiotensin-aldosterone system.
Drugs that affect sympathetic activity: In patients treated with captopril alone or in combination with diuretics, the sympathetic nervous system is particularly important for blood pressure support. 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 production, elevated blood potassium may occur. Potassium-conserving diuretics such as spironolactone, aminoglutethimide, amiloride, or potassium supplements should only be used for definite hypokalemia and should be used 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: NSAIDs, a nonsteroidal anti-inflammatory drug, may attenuate the hypotensive effect of ACE inhibitors ( including captopril) from their antihypertensive effects. Indomethacin may reduce the antihypertensive effect of captopril, 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 possible development of acute renal failure). These effects are usually reversible. For patients receiving captopril and NSAID therapy, renal function should be monitored regularly.
Lithium: Elevated serum lithium levels and symptoms of lithium toxicity have been reported in patients on combined lithium and ACE inhibitors. Caution should be exercised when combining these agents, 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. ) in patients with diabetes.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
Data from clinical trials show that dual blockade of the renin-angiotensin-aldosterone system (RAAS) by a combination of an ACE inhibitor, an angiotensin II receptor blocker, or aliskiren is associated with adverse effects when compared with the use of only one drug acting on the RAAS. The incidence of adverse events, such as hypotension, hyperkalemia, and decreased renal function (including acute renal failure), is elevated when RAAS is dual blocked with an angiotensin II receptor blocker, or aliskiren, compared with the use of only one agent that acts 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 Interactions
Captopril can 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.
Captopril 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 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 reducing peripheral vascular resistance and decreasing water-sodium retention by inhibiting aldosterone secretion. It also dilates the peripheral vasculature by interfering with the degradation of bradykinin; it also decreases 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 values were seen in mice, rats, and monkeys given captopril orally at doses ranging from 50 to 150 times the maximum recommended human dose (MRHD). Anemia, leukopenia, thrombocytopenia, and bone marrow suppression were seen in dogs given orally at doses 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.
The incidence of gastric erosions/ulcers was elevated 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. 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 effects were observed in mice and rats given captopril 50-1350 mg/kg daily for 2 years, respectively, with the high dose being 150 times the maximum recommended human dose (50 kg, 450 mg). 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%. It takes effect 15 minutes after oral administration, reaches peak blood concentration in about 1 hour, and lasts for 6-12 hours. Food in the gastrointestinal tract can reduce the absorption of captopril 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 mainly captopril disulfide dimers 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, with a maximum therapeutic effect over approximately several weeks.
Captopril does not cross the blood-brain barrier. Captopril is secreted through breast milk and can cross the placenta.
[Storage] Protect from light and keep sealed.
[Package] In plastic bottles, 100 tablets/bottle.
[Expiration date] 24 months
[Executive Standard
[Approval number] 国药准字H14021648
[Manufacturer
Company Name: Shanxi Zhendong Ante Biopharmaceutical Co.
Production Address: No. 908, Ji Cheng Road, Jinzhong City, Shanxi Province (Jinzhong Economic and Technological Development Zone Private Technology Park)
Postal Code: 030600
Tel: 0354-2467987
Fax number: 0354-2461887
Website: www.sxante.com.cn
Contact the manufacturer if you have any questions