Active ingredients: Captopril
Capoten 25 mg tablets
Capoten 50 mg tablets
Why is Capoten used? What is it for?
Capoten contains the active substance captopril, which belongs to a group of medicines known as ACE inhibitors (angiotensin converting enzyme inhibitors). These medicines are used to treat arterial hypertension (high blood pressure).
Capoten is used for:
- Treat high blood pressure (arterial hypertension) alone or in combination with other blood pressure lowering drugs, especially thiazide diuretics (drugs that help pass urine)
- Treat congestive heart failure (when the heart does not pump enough blood to meet the body's needs). It can be used alone or in combination with diuretics and digitalis (cardiotonic drugs, substances extracted from digitalis flowers)
- Treat heart attack: Short-term to treat clinically stable patients. Long-term to prevent symptomatic heart failure and improve survival.
- Treat kidney disease in patients with type I diabetes (diabetic nephropathy).
Contraindications When Capoten should not be used
DO NOT take Capoten
- If you are allergic (hypersensitive) to captopril or any of the other ingredients of this medicine (listed in section 6).
- If you are allergic to any other ACE inhibitors (medicines from the same group as Capoten, used to lower blood pressure).
- If you have developed angioedema (swelling of the face, tongue or throat) during previous treatment with an ACE inhibitor.
- If you have hereditary (congenital) or idiopathic (no known cause) angioedema.
- If you are more than 3 months pregnant (see section "Pregnancy and breastfeeding")
- If you suffer from a narrowing of the aorta (the largest and most important artery in the human body).
- If you have diabetes or impaired kidney function and you are being treated with a blood pressure lowering medicine containing aliskiren.
Precautions for use What you need to know before taking Capoten
Talk to your doctor or pharmacist before taking Capoten:
- if you have developed angioedema (allergic reaction with symptoms such as swelling of the face, tongue or throat, difficulty in swallowing, difficulty in breathing, intense itching or severe skin rash) not related to previous treatment with an ACE inhibitor
- if you have a cough
- if you have ever had any heart, kidney or liver problems
- if you need hemodialysis (process by which blood purification is obtained by filtration) with particular types of membranes, as there may be reactions to the type of membrane used
- if you have undergone, or are about to undergo, desensitization therapy for allergy to bee or wasp stings
- if you notice any symptoms of infection (such as sore throat or fever) that do not respond quickly to usual treatment due to lack of white blood cells (neutropenia / agranulocytosis)
- if you have low blood pressure (resulting in dizziness or fainting, especially when standing)
- if you are about to undergo general anesthesia for surgery
- if you have been told by a doctor that you have narrowing of the arteries of one or both kidneys
- if you have congestive heart failure, your doctor will monitor your blood nitrogen and creatinine levels against the normal or reference value. It is advisable to cautiously increase physical activity
- if you are on a low-salt diet or are taking potassium supplements or supplements containing potassium salts
- if you have been told by a doctor that you have narrowing of the heart's aortic valve (aortic stenosis)
- if you are taking a blood pressure medicine that reduces potassium levels in the blood, such as thiazide diuretics (see section "Other medicines and Capoten")
- if you are taking a medicine for depression or mental disorders, such as lithium (see section "Other medicines and Capoten")
- if you are taking any of the following medicines used to treat high blood pressure:
- an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans - for example valsartan, telmisartan, irbesartan), particularly if you have diabetes-related kidney problems
- aliskiren.
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (such as potassium) in your blood at regular intervals. See also information under the heading "Do not take Capoten"
- if you have impaired kidney function
- if you are breast-feeding or about to start breast-feeding (see section "Pregnancy and breast-feeding")
This medicine may cause an untrue urine test result for acetone.
You should tell your doctor if you think you are (or could become) pregnant.
Capoten is not recommended in early pregnancy and must not be taken if you are past the third month of pregnancy, as it may cause serious harm to your baby if used at that stage (see "Pregnancy and breast-feeding" section).
Excessive sweating and dehydration, which can cause a sharp drop in blood pressure, must be avoided.
As with other medicines used to lower blood pressure, this medicine may be less effective in black patients.
Children and adolescents
The use of this drug by children and adolescents should always be started under close medical supervision (see section "How to take Capoten").
Interactions Which drugs or foods can modify the effect of Capoten
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Some MEDICINES MAY INTERACT with Capoten. In these cases it may be necessary to change the dosage or stop treatment with some of them. It is important to tell your doctor if you are taking any of the following medications:
- other antihypertensive drugs (e.g. alpha-blockers, beta-blockers, calcium channel blockers)
- potassium-sparing diuretics eg. spironolactone, triamterene or amiloride. These are drugs that reduce the amount of potassium in the urine
- potassium supplements or potassium-containing substitutes
- thiazide or loop diuretics (medicines that promote diuresis by lowering blood pressure)
- drugs for the treatment of acute myocardial infarction (acetylsalicylic acid at cardiological doses, thrombolytics, beta-blockers and / or nitrates)
- vasodilators (e.g. nitroglycerin or other nitrates, used to lower blood pressure)
- drugs to treat mental illness and depression (e.g. lithium, tricyclic antidepressants, antipsychotics)
- allopurinol (drug used to treat gout)
- procainamide (drug used to treat an irregular heartbeat)
- cytostatics (anticancer drugs)
- immunosuppressants (which reduce the activity of the immune system)
- drugs with activity on the sympathetic nervous system (sympathomimetics)
- some medicines to treat pain or inflammation (non-steroidal anti-inflammatory drugs, NSAIDs including indomethacin)
- antidiabetic drugs (drugs that lower blood sugar levels)
- an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also information under "Do not take Capoten" and "Warnings and precautions")
Capoten with food, drink and alcohol
Capoten can be taken regardless of food. Alcohol intensifies the antihypertensive effect of Capoten. Following the simultaneous intake of alcohol and Capoten, a drop in blood pressure is possible when standing upright.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
The use of CAPOTEN is not recommended during the first trimester of pregnancy.
The use of CAPOTEN is contraindicated during the second and third trimester of pregnancy (see section "Do not take Capoten").
You should tell your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Capoten before becoming pregnant or as soon as you know you are pregnant and will advise you to take another medicine. Capoten is not recommended in early pregnancy, and must not be taken if you are more than three months pregnant, as it can cause serious harm to your baby if taken after the third month of pregnancy (see section "Do not use Capoten").
Do not make decisions about stopping or continuing therapy without consulting your doctor.
Feeding time
Tell your doctor if you are breastfeeding or about to start breastfeeding.
Breastfeeding of newborn babies (first weeks after birth) and especially premature babies is not recommended while you are taking Capoten.
In the case of older infants, if the treatment is deemed necessary for the mother, the doctor should advise her of the benefits and risks of taking Capoten while breastfeeding, in comparison with other treatments.
Driving and using machines
You should be aware that some possible side effects may affect your ability to drive or use machines. In particular at the beginning of the treatment, when the dosage is changed or in case of simultaneous alcohol intake.
Capoten contains lactose
If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicinal product.
Dose, Method and Time of Administration How to use Capoten: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist. The tablet can be taken before, during or after meals. Dosage must be determined individually.
ADULTS
High blood pressure (hypertension) in patients not being treated with "other anti-hypertensive therapy
The recommended starting dose is 50 mg / day in one or two administrations.
After 2-4 weeks, the dose can be increased to 100 mg / day, again in one or two administrations.
Your doctor may prescribe Capoten alone or in combination with other antihypertensive medicines, mostly thiazide diuretics (medicines that promote diuresis by lowering blood pressure).
High blood pressure (hypertension) in patients already being treated with diuretics
Your doctor will start therapy with a lower dose.
After 2 weeks, the dose can be increased following the scheme above.
Pressure control is generally achieved with daily doses of 50-100 mg of Capoten.
Heart failure
You may be prescribed a lower starting dose of 6.25 mg or 12.5 mg to be taken two or three times a day. The dose may be gradually increased according to your response to treatment.
The maximum daily dose is 150 mg.
Your doctor will monitor you closely at the start of treatment.
Therapy must be started in the hospital.
Heart attack
- Short-term treatment:
This treatment will be started in the hospital as soon as possible after the onset of symptoms. On the third day you will be given a dose of 6.25 mg which is repeatable at 12 hour intervals.
The dose of Capoten will be gradually increased: 12.5 mg three times a day, over the next 2 days and then 25 mg three times a day until discharge.
- Long-term treatment:
Thereafter the dose should be increased up to 150 mg per day given in divided doses.
The dose may be decreased if the blood pressure is too low and treatment can be continued at lower doses.
Kidney disease in association with diabetes
The recommended daily dose of Capoten is 75-100 mg in divided doses.
SENIOR CITIZENS
If you are over 65 your doctor may prescribe a lower dose.
PATIENTS WITH COMPROMISED KIDNEY FUNCTIONALITY
If your kidney function is impaired, your doctor will take this into account when prescribing the dose to be given to you. The elimination of Capoten may be decreased in subjects with impaired renal function, therefore lower than recommended doses or less frequent administrations should be prescribed.
Duration of treatment
According to medical prescription.
Use in children and adolescents
In the event that it is necessary to administer Capoten to children or adolescents, the treatment should be under careful medical supervision. If used in children or infants, the usual starting daily dose is 0.3 mg / kg body weight, divided into 2 or 3 doses.
With children requiring special precautions, the starting dose should be 0.15 mg / kg body weight. The dose will be defined according to the age and weight of the child. It will be adjusted according to the response of the child. child to treatment.
If you forget to take Capoten
Do not take a double dose to make up for a forgotten tablet. Simply wait for the next dose and continue treatment as usual.
If you stop taking Capoten
Do not interrupt or stop taking Capoten without first consulting your doctor. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Capoten
If you have taken too many tablets contact your doctor or go to a hospital straight away.
Symptoms of overdose can consist of:
- low blood pressure
- a noticeable drop in blood pressure which can compromise the level of consciousness
- state of semi-consciousness
- slow heartbeat
- altered concentrations of chemicals in the blood (electrolytic decompensation)
- kidney failure
Therapeutic measures
Captopril can be removed from the circulation by hemodialysis (a method of blood filtration).
Side Effects What are the side effects of Capoten
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The assessment of undesirable effects is based on the following frequency data:
Common (may affect up to 1 in 10 patients):
- Sleep disturbances and difficulty falling asleep (insomnia)
- Changes in taste
- Dizziness
- Cough
- Shortness of breath
- Nausea
- He retched
- Stomach discomfort
- Abdominal pain
- Diarrhea
- Constipation
- Dry mouth
- Poor digestion (dyspepsia)
- Stomach and intestinal ulcerations (peptic ulcer)
- Itchy skin with or without rash, rash, hair loss
Uncommon (may affect up to 1 in 100 patients):
- Loss of appetite
- Headache
- Tingling, pricking or numbness in the limbs or other parts of the body
- Rapid heartbeat and / or fast, irregular heartbeat
- Changes in the rhythm of the heart (arrhythmia)
- Chest pain and / or chest pain secondary to lack of blood and consequently to the lack of oxygen supply to the heart muscle
- Sensation of the heartbeat in the chest (palpitations)
- Low blood pressure, even after the sudden transition from sitting or lying to standing (orthostatic hypotension)
- Problems with blood circulation causing cold sore fingers (Raynaud's syndrome), redness and / or paleness of the skin
- Swelling of the skin especially of the face, lips, tongue or throat (angioedema)
- Chest pain
- Tiredness and / or malaise and / or a feeling of weakness (asthenia)
Rare (may affect up to 1 in 1000 patients):
- Drowsiness
- Irritation of the mucous membrane of the oral cavity and / or ulcerations in the oral cavity
- Swelling of the intestinal mucosa (intestinal angioedema)
- Changes in kidney function, kidney failure, urinating more intensely than normal (polyuria), urinating less than normal (oliguria), urinating more frequently than normal (pollakiuria)
Very Rare (may affect up to 1 in 10,000 patients):
- Changes in blood elements, such as:
- reduction in the number of white blood cells with probable onset of unexplained fever, flu-like symptoms such as sore throat (neutropenia / agranulocytosis);
- decrease in the number of all types of blood cells (pancytopenia) especially in patients with kidney damage;
- reduction in the number of red blood cells; this could cause a sense of weakness, fatigue, general malaise and sometimes poor concentration (anemia);
- reduction in the number of platelets in the blood with an increased tendency to bruise or bleed from the nose (thrombocytopenia);
- increase in a type of white blood cell (eosinophilia)
- presence of protein in the urine (proteinuria)
- Swollen lymph nodes (lymphadenopathy)
- Disease in which one's immune system gives rise to direct responses against components of one's body (autoimmune diseases)
- Drop in blood sugar concentrations (hypoglycemia)
- Increased concentration of potassium in the blood (hyperkalaemia)
- Decreased sodium concentration in the blood (hyponatremia)
- Confusion and / or depression
- Insufficient blood circulation in the brain (e.g. stroke) or fainting
- Blurred vision
- Sudden cessation of the heart's pumping function (cardiac arrest) and / or severe drop in blood pressure following the heart's inability to pump effectively (cardiogenic shock)
- Chest tightening resulting in difficulty breathing (bronchospasm)
- runny nose (rhinitis)
- Certain lung inflammations (such as: allergic alveolitis and / or eosinophilic pneumonia)
- Inflammation of the tongue (glossitis)
- Inflammation of the pancreas (pancreatitis)
- Poor liver function, a condition in which bile cannot flow from the liver to the intestine, including yellowing of the skin (jaundice), inflammation of the liver and even death of part of the liver, increased liver enzymes (eg transaminases) and bilirubin (a reddish yellow pigment contained in bile) and alkaline phosphatase
- Urticaria
- Sensitivity of the skin to sunlight (photosensitivity), severe allergic reactions (with redness, blistering and peeling of the skin, including: Stevens-Johnson syndrome, erythema multiforme, redness of the skin, often with peeling (erythroderma), skin with blisters and sores (pemphigoid), exfoliative dermatitis
- Muscle (myalgia) and / or joint pain (arthralgia)
- Loss of a large amount of protein in the urine (nephrotic syndrome)
- Inability to get or maintain an erection (impotence) and / or breast growth in men
- Fever
- Changes in the results of the following diagnostic tests:
- increased protein in the urine
- increase in a type of white blood cell
- increased potassium concentrations in the blood
- reduction of sodium concentrations in the blood
- increased concentrations of urea, creatinine and / or bilirubin in the blood
- reduction in hemoglobin, which is a component of red blood cells, and reduction in the number of blood cells (measured by means of a blood test called hematocrit)
- High ESR (erythrocyte sedimentation rate), i.e. high laboratory value for the measurement of inflammation)
- positive laboratory values for measuring certain immune reactions (antinuclear antibodies)
In children and adolescents being treated with Capoten, excessive reductions in blood pressure could cause less intense urination than normal (oliguria) and convulsions.The frequency of these effects cannot be estimated from the available data.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Do not store above 25 ° C. Store Capoten in the original container in order to protect from moisture.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Deadline "> Other information
What Capoten contains
The active ingredient is captopril.
25 mg tablets
Each tablet contains 25 mg of captopril
50 mg tablets
Each tablet contains 50 mg of captopril
The other ingredients are: microcrystalline cellulose, lactose, starch, stearic acid.
What Capoten looks like and contents of the pack
Capoten 25 mg tablets
White, square, biconvex tablets with break bar
Pack of 50 tablets.
Capoten 50 mg tablets
White, oblong, biconvex tablets with double break bar.
Pack of 24 tablets.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
CAPOTEN TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
CAPOTEN 25 mg tablets
each tablet contains: active ingredient: captopril 25 mg. Excipients with known effect: lactose
CAPOTEN 50 mg tablets
each tablet contains: active ingredient: captopril 50 mg. Excipients with known effect: lactose
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
CAPOTEN 25 mg tablets: oral, square, biconvex, white tablets with double break bar.
CAPOTEN 50 mg tablets: oral, oblong, biconvex, white tablets with break bar.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Hypertension: CAPOTEN is indicated for the treatment of hypertension. It can be used alone or in combination with other hypotensives, especially thiazide diuretics (see sections 4.3, 4.4, 4.5 and 5.1).
Congestive heart failure: CAPOTEN is indicated in patients with heart failure and is to be used in combination with diuretics and digitalis.
Myocardial infarction: CAPOTEN is indicated post-infarction in patients with left ventricular dysfunction, even in the absence of signs and symptoms of heart failure. Long-term therapy with CAPOTEN can improve survival, delay the onset and progression of heart failure and reduce the risk of reinfarction and the need for coronary revascularization.
Diabetic nephropathy: CAPOTEN is indicated in the treatment of patients with diabetic nephropathy. In these subjects CAPOTEN is able to prevent the progression of renal damage, improving prognosis and survival.
04.2 Posology and method of administration -
CAPOTEN can be taken before, during or after meals. Dosage must be determined individually.
Adults
Hypertension: in patients not being treated with other therapy antihypertensive, start with 50 mg daily of CAPOTEN in one or two administrations. After two to four weeks, if a more marked antihypertensive effect is desired, the dose of CAPOTEN can be increased to 100 mg daily, again in one or two administrations. Subsequently, in patients in whom satisfactory blood pressure control has not been achieved, it is advisable to add a modest dose of thiazide diuretic, eg. 25 mg / day of hydrochlorothiazide (see sections 4.3, 4.4, 4.5 and 5.1).
In hypertensive patients already on diuretic therapy, it is recommended to add CAPOTEN at lower doses (see sections 4.3, 4.4, 4.5 and 5.1). This dosage measure is also recommended for highly sodium and / or volume depleted patients. If after two weeks of this therapy a further antihypertensive effect is desired, increase the dosage of CAPOTEN following the previously described scheme. In the therapy of mild-moderate essential arterial hypertension with CAPOTEN, the control of blood pressure values is generally obtained with daily doses ranging from 50 to 100 mg. In particular cases, or according to the doctor's judgment, it is possible to use higher doses, however not exceeding the 450 mg per day.
In cases where a rapid reduction in blood pressure is required, it is possible to increase, under medical supervision, the daily dosage of CAPOTEN every 24 hours until satisfactory control of blood pressure is achieved or until the maximum dose of CAPOTEN has been reached. .
Congestive heart failure: the starting dose of CAPOTEN is generally 25 mg 2 or 3 times a day. In order to minimize the incidence and duration of occasional hypotensive effects (possible in patients with already hypothetical congestive heart failure) - see section 4.4 - it is advisable in such cases to initiate therapy with initial doses of 6.25 or 12.5 mg two or three times a day. Generally, the effective dosage is within 150 mg / day. Further increases in daily dosages are to be implemented, if possible, only after two weeks in order to observe whether a satisfactory response is obtained. however, the maximum daily dose of 450 mg should be exceeded.CAPOTEN is used in combination with a diuretic and digitalis at normal doses.Therapy should be initiated in the hospital (see section 4.4).
Myocardial infarction: CAPOTEN therapy is started on day 3, with a repeatable dose of 6.25 mg, at 12 hour intervals. The daily dose of CAPOTEN will be gradually increased: 12.5 mg three times a day, over the next two days; and then 25 mg three times a day, until the patient is discharged. Subsequently, the dosage should be increased, if well tolerated, up to 150 mg / day, in divided doses and continued chronically. In case of symptomatic hypotension, a reduction of the daily dosage may be necessary and the treatment can be continued with lower doses. CAPOTEN can be used in combination with drugs normally used in the therapy of heart attack patients (thrombolytics, ASA, beta-blockers, etc.).
Diabetic nephropathy: the recommended dosage of CAPOTEN in patients with diabetic nephropathy is 75-100 mg / day in divided doses. If further reductions in blood pressure are required, other drugs such as diuretics, beta-blockers, centrally acting antihypertensives and vasodilators may be combined with CAPOTEN (see sections 4.3,
4.4, 4.5 and 5.1). The elimination of CAPOTEN may be decreased in subjects with decreased renal function. Therefore, such patients may respond to treatment with lower doses of the drug or with less frequent dosing. In patients with severely reduced renal function, the initial dose of CAPOTEN should be be reduced with successive small dose increases carried out at intervals of one to two weeks. Furthermore, in these patients, in the case of combination with diuretics, it is necessary to administer loop diuretics and not thiazides.
Elderly patients: in such patients it is advisable to start therapy with low doses.
Children: in these patients, suffering from secondary severe hypertension, the initial dose of CAPOTEN is 0.3 mg / kg, administered under close medical supervision. Treatment in infants and children potentially prone to hypotension, such as those on diuretic therapy, can start with 0.15 mg / kg. The dose of CAPOTEN is administered twice a day, or depending on the individual patient's response.
Patients with renal dysfunction: in the presence of renal dysfunction, CAPOTEN retention occurs. In these patients it is therefore necessary to adjust the dosage. After the desired therapeutic effect is achieved, the following dosage ranges are recommended to avoid drug accumulation:
04.3 Contraindications -
Hypersensitivity to Captopril, to any of the excipients or to any other ACE inhibitor.
History of angioedema associated with previous ACE inhibitor therapy.
Hereditary / idiopathic angioneurotic edema.
Second and third trimester of pregnancy (see sections 4.4 and 4.6).
Aortic stenosis.
The concomitant use of CAPOTEN with aliskiren-containing medicines is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate GFR
04.4 Special warnings and appropriate precautions for use -
AngioedemaAngioneurotic edema of the face, extremities, lips, tongue, glottis and / or larynx has been reported in patients treated with angiotensin converting enzyme inhibitors, including captopril. This can occur at any time during treatment. In such cases, captopril should be promptly discontinued and appropriate monitoring instituted to ensure complete remission of symptoms before the patient is discharged. Swelling limited to the face and lips generally resolves without treatment although antihistamines may be considered helpful in relieving symptoms.
Angioneurotic edema associated with laryngeal edema can be fatal. If there is involvement of the tongue, glottis or larynx, which can lead to airway obstruction, appropriate therapy, which may include an epinephrine 1 solution, should be promptly administered. : 1000 subcutaneous (from 0.3 ml to 0.5 ml) and / or measures to ensure the patency of the airways.
A higher incidence of angioedema has been reported in black patients treated with ACE inhibitors than in non-black patients.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may have an increased risk of angioedema during treatment with an ACE inhibitor (see section 4.3). Intestinal angioedema has been reported rarely in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting) in some cases not preceded by facial angioedema and with normal levels of C-1 esterase. Angioedema was diagnosed with abdominal CT scan, or ultrasound, or at the time of surgery and symptoms resolved after discontinuation of the ACE inhibitor. Intestinal angioedema should be considered in the differential diagnosis of patients treated with ACE inhibitors presenting with abdominal pain (see section 4.8).
Cough: cough has been reported with the use of ACE inhibitors. Typically the cough is nonproductive, persistent and resolves upon discontinuation of therapy.
Hepatic insufficiency: ACE inhibitors have rarely been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is unclear. Patients treated with ACE inhibitors who develop jaundice or marked elevation of liver enzymes should discontinue ACE inhibitor therapy and receive appropriate medical treatment.
Anaphylactoid reactions during exposure to high-flux membranes by lipoprotein dialysis / apheresis: have been reported in patients on hemodialysis with high-flux dialysis membranes or undergoing low-density lipoprotein apheresis with dextran-sulfate absorption. The use of a different type of dialysis membrane or a different class of drugs should be considered in these patients.
Anaphylactoid reactions during desensitizationLife-threatening sustained anaphylactoid reactions have been reported during concomitant administration of another ACE inhibitor in patients receiving desensitizing treatment to hymenoptera venom (eg, insects such as bees, wasps, etc.). In these patients, these reactions were avoided when the ACE inhibitor was temporarily withdrawn but reappeared upon accidental patient re-exposure.
Therefore, caution should be exercised in patients treated with ACE inhibitors undergoing such desensitization procedures.
Proteinuria: Proteinuria may occur particularly in patients with existing impaired renal function or following relatively high doses of ACE inhibitors. Total urinary proteins greater than 1 g / day were observed in 0.7% of patients treated with captopril. Most patients had a history of nephropathy or had received relatively high doses of captopril (over 150 mg / day), or both. Nephrotic syndrome developed in one fifth of patients with proteinuria. In most cases, proteinuria decreased or disappeared within six months, even when captopril treatment was not stopped. Some parameters of renal function, such as BUN and creatinine, are rarely altered in patients with proteinuria.
Patients with previous nephropathy should undergo a urine protein test (dip-stick on the first morning urine) before treatment and periodically thereafter.
Neutropenia / Agranulocytosis: neutropenia / agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors including captopril.
In patients with normal renal function and no other risk factors, neutropenia occurs rarely. Captopril should be used with extreme caution in patients with collagen vascular disease, on immunosuppressive therapy, on allopurinol or procainamide, or with a combination of these risk factors, especially in the presence of pre-existing renal function impairment. Some of these patients develop severe infections which in a few cases do not respond to intensive antibiotic therapy. If captopril is used in these patients, a white blood cell count should be performed prior to initiating therapy with captopril, every two weeks during the first three months of therapy and periodically thereafter.
During treatment all patients should be instructed to report any signs of infection (e.g. sore throat, fever), in which case the leukocyte formula should be determined.
Captopril and other drugs (see section 4.5) should be discontinued if neutropenia (neutrophil count
Hypotension: Hypotension is rarely observed in patients with uncomplicated hypertension. Symptomatic hypotension is more likely to occur in hypertensive patients who are volume and / or sodium depleted following strong diuretic therapy, dietary salt restriction, diarrhea, vomiting or hemodialysis. Sodium volume and / or depletion should be corrected before starting the administration of an ACE inhibitor and the lowest starting dose of the drug should be considered. An exaggerated hypotensive effect may also occur, but with less frequency and less intensity, after the second or third dose. This pronounced response is attributed to the fact that angiotensin II plays an important role in maintaining blood pressure under sodium-volume depleted conditions. The possibility of hypotensive effects can be minimized by discontinuing the diuretic or by increasing sodium intake approximately one week before starting treatment with CAPOTEN. Alternatively, the patient should be kept under medical observation for at least three hours after the initial dose. As with other antihypertensive agents, excessive lowering of blood pressure in patients with ischemic cardiovascular or cerebrovascular disease may increase the risk of myocardial infarction or stroke.If hypotension occurs, the patient should be placed in the supine position, giving him a drip of physiological solution if necessary.
This transient hypotensive response is not a contraindication to the administration of further doses which can be given without difficulty once blood pressure has risen after volume expansion. Patients with severe congestive heart failure at normal or low blood pressure may also present marked drops in blood pressure, which in rare cases were accompanied by arrhythmias or conduction disturbances, after one or other of the initial doses of CAPOTEN. In these cases, in consideration of the potential lowering of blood pressure and severity of congestive heart failure, therapy should be initiated in the hospital. Patients should be followed closely for the first two weeks of treatment and whenever the initial dose of CAPOTEN and / or diuretic is increased.
Surgery / anesthesiaHypotension may occur in patients undergoing major surgery or during treatment with anesthetic agents that lower blood pressure. If hypotension occurs this can be corrected by volume expansion.
Renovascular hypertensionThere is an increased risk of hypotension and renal failure when patients with bilateral renal artery stenosis or artery stenosis of a single functioning kidney are treated with ACE inhibitors. Loss of renal function can occur only with minor changes in serum creatinine. In these patients, therapy should be initiated under close medical supervision with low doses of CAPOTEN, careful dosage adjustments and monitoring of renal function.
Heart failure: Following long-term treatment with captopril, approximately 20% of patients develop stable increases in serum BUN and creatinine that are 20% greater than normal or reference value.
Less than 5% of patients, usually those with severe pre-existing kidney disease, required treatment discontinuation due to progressive creatinine elevation.
Hyperkalemia: Increases in serum potassium have been observed in some patients treated with ACE inhibitors, including captopril.
Patients at risk for developing hyperkalaemia include those with renal insufficiency, diabetes mellitus, or those treated concomitantly with potassium-sparing diuretics, potassium supplements or potassium salt substitutes, or those patients taking other drugs associated with increases in serum potassium (e.g. heparin). If concomitant use of the above drugs is deemed necessary, regular monitoring of serum potassium is recommended.
Hypersensitivity reactions: skin rashes and associated symptoms (itching, fever and occasionally eosinophilia) are a possible occurrence (see section 4.8). The rash is usually mild and disappears within days after a dose reduction and / or administration of an antihistamine for a few days. In some cases, the rash remission occurs spontaneously, without dose modification. Angioedema of the face, oral mucosa, and extremities has occurred in some patients, reversible on discontinuation of the drug.
Information to patients: Patients should be advised to report any signs suggestive of neutropenia (such as sore throat and fever) to their physician immediately. After treatment with CAPOTEN, some patients with congestive heart failure have been able to increase in their physical activity is extraordinary, however it is prudent that such patients are advised to slowly and cautiously increase their physical activity.
Aortic and mitral valve stenosis / obstructive hypertrophic cardiomyopathy / cardiogenic shock: ACE inhibitors should be used with caution in patients with valvular and left ventricular outflow tract obstruction and should be avoided in case of cardiogenic shock and haemodynamically significant obstruction.
Diabetic patients: Blood glucose levels during the first month of treatment with an ACE inhibitor should be carefully monitored in diabetic patients previously treated with oral antidiabetic agents or insulin.
Risk of hypokalaemia: the combination of an ACE inhibitor with a thiazide diuretic does not rule out the presence of hypokalaemia. Therefore, regular monitoring of kalaemia should be performed.
Combination with lithium: CAPOTEN is not recommended in combination with lithium due to the potentiation of lithium toxicity (see section 4.5).
Dual blockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1). If dual block therapy is considered absolutely necessary, this should only be done under the supervision of a specialist and with close and frequent monitoring of kidney function, electrolytes and blood pressure. ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.
Ethnic differences: As with other angiotensin converting enzyme inhibitors, CAPOTEN is apparently less effective in lowering blood pressure in black patients, possibly due to a higher prevalence of low renin levels in the black hypertensive population.
Pregnancy: ACE inhibitor therapy should not be initiated during pregnancy.
The use of ACE inhibitors has been associated with fetal and neonatal injury, and death. Oligohydramnios has also been reported.
For patients planning to become pregnant, alternative antihypertensive treatments with a proven safety profile for use in pregnancy should be used, unless continued therapy with an ACE inhibitor is considered essential. When pregnancy is ascertained, treatment with ACE inhibitors should be stopped immediately and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
Pediatric use: Since renal function is not equivalent to that of adults in infants and young children, lower doses of CAPOTEN should be used, keeping the patient under close medical supervision.
Excessive, prolonged and unpredictable reductions in blood pressure and associated complications, including oliguria and seizures, have been reported.
Important information about some of the excipients:
CAPOTEN contains Lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction -
OTHER ANTI-HYPERTENSIVE AGENTS: captopril has been safely administered as concomitant treatment with other commonly used antihypertensive agents (eg, beta-blockers and long-acting calcium channel blockers). Concomitant with these agents may increase the hypotensive effect of captopril. Treatment with nitroglycerin and other nitrates or other vasodilators should be used with caution.
ALPHA BLOCKING AGENTS: Concomitant use of alpha blocking agents may increase the antihypertensive effect of captopril and increase the risk of orthostatic hypotension.
POTASSIUM SAVING DIURETICS OR POTASSIUM SUPPLEMENTS: ACE inhibitors reduce the potassium loss induced by diuretics. Potassium-sparing diuretics (e.g. spironolactone, triamterene, or amiloride), potassium supplements or substitutes containing potassium salts can lead to significant increases in serum potassium. If concomitant use is indicated due to established hypokalaemia, these should be used with caution and with frequent monitoring of serum potassium (see section 4.4).
Diuretics (thiazides or loop diuretics): Prior treatment with high doses of diuretics may result in volume depletion with risk of hypotension when initiating therapy with captopril (see section 4.4). The hypotensive effect can be reduced by discontinuing the diuretic, by increasing blood volume or salt intake or by initiating therapy with a reduced dose of captopril. However, in specific studies with hydrochlorothiazide or furosemide, no clinically significant drug interactions were found.
DUAL BLOCK OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM: data from clinical studies have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren , is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared with the use of a single agent active on the RAAS system (see sections 4.3, 4.4 and 5.1).
TREATMENTS OF ACUTE MYOCARDIAL INFARCTION: captopril can be used together with acetylsalicylic acid (at cardiological doses), thrombolytics, beta-blockers and / or nitrates in patients with myocardial infarction.
VASODILATING AGENTS: nitroglycerin or other nitrates (used to treat angina) or other vasodilating drugs should, if possible, be discontinued before initiating therapy with CAPOTEN. If these drugs are to be re-administered during therapy with CAPOTEN, these they should be used with caution, and at lower dosages.
TRICYCLIC / ANTIPSYCHOTIC ANTIDEPRESSANTS: ACE inhibitors may potentiate the hypotensive effects of some tricyclic and antipsychotic antidepressants (see section 4.4). Postural hypotension may occur.
ALLOPURINOL, PROCAINAMIDE, CYTOSTATS OR IMMUNOSOPRESSIVE AGENTS: Concomitant administration with ACE inhibitors may lead to an increased risk of leukopenia especially when the latter are used in doses higher than those currently recommended.
AGENTS WITH ACTIVITY ON THE SYMPATHIC NERVOUS SYSTEM: the sympathetic nervous system may be of particular importance in regulating blood pressure in patients receiving captopril alone or in combination with diuretics.
However, agents with sympathetic nervous system activity (e.g. ganglion blocking agents or adrenergic neuron blocking agents) should be used with caution. Drugs that block the beta-adrenergic system add some antihypertensive effects to captopril, but the response is less than additive.
Sympathomimetic: may reduce the antihypertensive effect of ACE inhibitors therefore patients should be carefully monitored. INHIBITORS OF THE ENDOGENOUS SYNTHESIS OF PROSTAGLANDIN: it has been reported that indomethacin may reduce the antihypertensive effects of captopril.
NON-STEROID ANTI-INFLAMMATORY DRUGS: Non-steroidal anti-inflammatory drugs and ACE inhibitors have been shown to exert an additive effect in increasing serum potassium while renal function may be reduced. These effects are, in principle, reversible. Rarely, renal failure may occur. acute, particularly in patients with impaired renal function such as the elderly or dehydrated subjects Chronic administration of NSAIDs may reduce the antihypertensive effect of an ACE inhibitor. Patients should be adequately hydrated and monitoring of renal function should be considered at the initiation of concomitant therapy.
LITHIUM: Reversible increases in serum lithium levels and symptoms of lithium toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Concomitant use of thiazide diuretics may increase the risk of lithium toxicity and further potentiate the risk of lithium toxicity with ACE inhibitors. Therefore, the combination of captopril with lithium is not recommended and, if necessary, a careful control of serum lithium levels.
ANTIDIABETICS: Pharmacological studies have shown that ACE inhibitors, including captopril, may potentiate the blood glucose lowering effect of insulin and oral antidiabetics such as sulphonylurea in diabetic patients. Should this very rare interaction occur, it may be necessary to reduce the dose of the antidiabetic during simultaneous treatment with ACE inhibitors.
CLINICAL CHEMISTRY: captopril can cause a false positive urine test for acetone.
04.6 Pregnancy and breastfeeding -
Pregnancy
The use of CAPOTEN is not recommended during the first trimester of pregnancy (see section 4.4). The use of CAPOTEN is contraindicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4).
Epidemiological evidence on the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded.
For patients planning pregnancy, alternative antihypertensive treatments with a proven safety profile for use in pregnancy should be used unless continued ACE inhibitor therapy is considered essential.
When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately and, if appropriate, alternative therapy should be started.
Exposure to ACE inhibitors during the second and third trimesters is known to induce fetal toxicity (reduced renal function, oligohydramnios, skull ossification retardation, death) and neonatal toxicity (renal failure, hypotension, hyperkalaemia, death) in women. . Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Neonates whose mothers have taken ACE inhibitors should be closely monitored for hypotension (see sections 4.3 and 4.4).
Feeding time
Limited pharmacokinetic data demonstrate very low concentrations in breast milk. Although these concentrations appear to be clinically irrelevant, the use of Lactating Capoten is not recommended for preterm infants and in the first few weeks after delivery, due to the hypothetical risk of cardiovascular and renal effects and because there is not enough clinical experience.
In older infants, if treatment is deemed necessary for the mother, Capoten can be taken while breastfeeding, but in this case the infant should be followed for possible adverse effects.
04.7 Effects on ability to drive and use machines -
As with other antihypertensive agents, the ability to drive and use machines may be reduced, for example at the start of treatment or when the dose is changed, and even when the medicine is used in combination with alcohol, these effects depend on the susceptibility of the drug. individual.
04.8 Undesirable effects -
Frequency is described using the following convention: common (≥1 / 100 to
Disorders of the blood and lymphatic system:
very rare: neutropenia / agranulocytosis (see section 4.4), pancytopenia particularly in patients with renal dysfunction (see section 4.4), anemia (including aplastic and haemolytic anemia), thrombocytopenia, lymphadenopathy, eosinophilia, autoimmune diseases (including disease-like manifestations) from serum) and / or positive ANA titration.
Metabolism and nutrition disorders:
rare: anorexia
very rare: hyperkalaemia, hypoglycaemia (see section 4.4).
Psychiatric disorders:
common: sleep disturbances
very rare: confusion, depression.
Nervous system disorders:
common: impaired taste, dizziness rare: somnolence, headache and paraesthesia
very rare: cerebrovascular accidents including stroke and syncope.
Eye disorders:
very rare: blurred vision
Cardiac pathologies:
uncommon: tachycardia or tachyarrhythmia, angina pectoris, palpitations very rare: cardiac arrest, cardiogenic shock
Vascular disorders:
uncommon: hypotension (see section 4.4), Raynaud's syndrome, flushing, pallor
Respiratory, thoracic and mediastinal disorders:
common: dryness, irritating cough (no secretion) (see section 4.4) and dyspnoea
very rare: bronchospasm, rhinitis, allergic alveolitis / eosinophilic pneumonia
Gastrointestinal disorders:
common: nausea, vomiting, gastric irritation, abdominal pain, diarrhea, constipation, dry mouth
rare: aphthous stomatitis / ulcerations, intestinal angioedema (see section 4.4)
very rare: glossitis, peptic ulcer, pancreatitis
Hepatobiliary disorders:
very rare: hepatic impairment and cholestasis (including jaundice), hepatitis including necrosis, elevated liver enzymes and bilirubin
Skin and subcutaneous tissue disorders:
common: pruritus with or without rash, rash and alopecia.
uncommon: angioedema (see section 4.4)
very rare: urticaria, Stevens Johnson syndrome, erythema multiforme, photosensitization, erythroderma, penphigoid reactions and exfoliative dermatitis.
Musculoskeletal and connective tissue disorders:
very rare: myalgia, arthralgia
Renal and urinary disorders:
rare: disturbance of renal function including renal failure, polyuria, oliguria, increased frequency to urinate
very rare: nephrotic syndrome
Reproductive system and breast disorders:
very rare: impotence, gynecomastia.
General disorders and administration site conditions:
uncommon: chest pain, fatigue, malaise very rare: fever
Diagnostic tests:
very rare: proteinuria, eosinophilia, increased serum potassium, decreased serum sodium, increased BUN, serum creatinine and serum bilirubin, decreased hemoglobin, hematocrit, leukocytes, thrombocytes, positive ANA titration, elevated ESR.
Morbidity and fetal / neonatal mortality:
the use of ACE inhibitors during pregnancy has been associated with fetal and neonatal harm including hypotension, neonatal cranial hypoplasia, anuria, reversible or irreversible renal failure and death. Oligohydramnios has also been reported, possibly due to decreased renal function of the fetus oligohydramnios in this state has been associated with fetal limb contracture, craniofacial deformation and development of pulmonary hypoplasia. Prematurity, intrauterine growth retardation and patency of the ductus arteriosus have also been reported. Recently, following limited exposure to the drug. in the first trimester of pregnancy, prematurity, patent ductus arteriosus and other structural cardiac malformations, and neurological malformations have been reported (see sections 4.4 and 4.6).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
Symptoms of overdose are: severe hypotension, shock, stupor, bradycardia, electrolyte disturbances and renal failure.
Measures to prevent absorption (eg gastric lavage, administration of adsorbents and sodium sulfate within 30 minutes after intake) and accelerate elimination should be applied if ingestion is recent. If hypotension occurs, the patient should be placed in an anti-shock position and a "salts and liquids supplementation should be rapidly achieved."
Treatment with angiotensin-II should be considered. Bradycardia or extensive vagal reactions should be treated with atropine. The use of a pacemaker may be considered.
Captopril can be removed from the circulation by hemodialysis.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: ACE inhibitors, unassociated
ATC code: C09AA01
Mechanism of action: CAPOTEN (captopril) inhibits the Angiotensin I to Angiotensin II (ACE) converting enzyme in the renin-angiotensin-aldosterone system (RAA); it also blocks kininase II (identical to ACE) responsible for the degradation of kinins (bradykinin), substances with direct or prostaglandin-mediated vasodilator action However, there is no real correlation between renin levels and drug response.
Effects: reduction of peripheral resistance, reduction of circulating volume due to reduction of aldosterone.
Result: decrease in blood pressure, in supine and standing position. The beginning of the decrease in blood pressure occurs after about 15 ". The "maximum effect occurs after about 90". The blood pressure lowering effects of captopril and thiazide diuretics add up. Duration of effect: dose-dependent.
Clinical and haemodynamic effects in hypertensive: no increase in the cardiac index; no increase in heart rate. In the kidney: increased blood flow. Experimental and clinical studies have shown the ability of Captopril to induce a regression of ventricular hypertrophy, maintaining normal systolic function and inducing an improvement in ventricular filling capacity in the first diastolic phase.
Congestive heart failure: decreases systemic vascular resistance; increases cardiac output (due to increased output); pulmonary capillary pressure decreases; it does not increase heart rate. Overall, there is a reduction in both pre-load and after-load. CAPOTEN improved long-term survival in subjects with acute myocardial infarction who had ventricular dysfunction (ejection fraction ≤ 40%) even in the absence of signs or symptoms of heart failure. The prognosis of these patients was improved and there was a reduction in the onset and progression of heart failure and also in the need for hospitalization for this pathology. In addition, a lower incidence of re-infarction was observed in patients treated with CAPOTEN. These effects were additive to those of the basic post-infarct therapy (thrombolytics, aspirin, beta-blockers, etc.), and independent of age, sex, site of the infarction and extent of ventricular dysfunction. The mechanism of action of CAPOTEN that can justify the aforementioned effects consists in the reduction of the progressive left ventricular dilatation (remodeling) and the deterioration of the ventricular function, together with an anti-ischemic activity and the inhibition of the neurohumoral activation frequently present in these patients. .
Metabolic effects: CAPOTEN does not modify the glucose and lipid metabolism, nor does it alter the levels of uric acid. Controlled clinical studies conducted in subjects with insulin-dependent diabetes and proteinuria have shown a 51% reduction in the deterioration of renal function and a similar decrease in events clinical (need for dialysis therapy, renal transplantation, death) compared to the control group. The effect of treatment in reducing the progression of renal damage is independent of the reduction in blood pressure. In addition, in other studies conducted on diabetic subjects with microalbuminuria CAPOTEN reduced the extent of proteinuria and slowed the decline in renal function over the course of 2 years of treatment. Tachyphylaxis does not develop (observation after 30 months of uninterrupted therapy).
Two large randomized controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA Nephron-D (The Veterans Affairs Nephropathy in Diabetes)) have examined the use of the combination of an ACE inhibitor with an antagonist of the angiotensin II receptor.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus associated with evidence of organ damage. VA NEPHRON-D was a study conducted in patients with type 2 diabetes mellitus and diabetic nephropathy. These studies did not demonstrate any significant beneficial effect on renal and / or cardiovascular outcomes and mortality, while an increased risk of hyperkalaemia, acute renal injury and / or hypotension was observed compared to monotherapy.
These results are also relevant for other ACE inhibitors and angiotensin II receptor antagonists, given their similar pharmacodynamic properties.
ACE inhibitors and angiotensin II receptor antagonists should therefore not be used simultaneously in patients with diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascualr and Renal Disease Endpoints) was a study aimed at verifying the advantage of adding aliskiren to standard therapy of an ACE inhibitor or an angiotensin II receptor antagonist in patients with diabetes mellitus. type 2 and chronic kidney disease, cardiovascular disease, or both. The study was terminated early due to an increased risk of adverse events. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group than in the placebo group, and adverse events and serious adverse events of interest (hyperkalaemia, hypotension and renal dysfunction) were reported more frequently in the aliskiren group than in the placebo group.
05.2 "Pharmacokinetic properties -
It is rapidly absorbed. Maximum concentrations are reached approximately one hour after administration. On an empty stomach, the average minimum absorption is approximately 75%. This absorption is reduced by up to 35-
40% in the presence of food in the gastrointestinal tract. Approximately 25-30% of absorbed CAPOTEN binds to plasma proteins. The hematic half-life of radioactivity after a radioactive dose is probably less than 3 hours (unchanged Capropril). 75% of CAPOTEN is eliminated in the urine (50% unchanged and the remainder in conjugated form). Most of a dose is eliminated within 12 hours. Lactation: In a study of twelve women taking captopril 100 mg orally 3 times a day the mean peak milk value was 4.7 mcg / L and occurred 3.8 hours after dosing. Based on these data, the maximum daily dose that a nursing infant would receive is less than 0.002% of the maternal daily dose.
05.3 Preclinical safety data -
Acute toxicity: Oral LD50 6000 mg / kg; intravenous 1000 mg / kg; intraperitoneal 400 mg / kg in mice.
Subacute toxicity: Dogs: (treated 4 months) 100 mg / kg / day and 200 mg / kg / day orally: no signs of toxicity. Rats: (treated 3 months) 50 mg / kg / day, 150 mg / kg / day and 450 mg / kg / day orally - No evidence of haematochemical toxicity - Slight weight reduction, dose dependent.
Chronic toxicity: Dogs (treated 1 year) 50 mg / kg / day, 100 mg / kg / day. No toxicity effect. Rats (treated 2 years) 50 mg / kg / day, 150 mg / kg / day and 450 mg / kg / day orally - Slight dose-dependent weight reduction. Slight reduction in erythrocytes, slight leukocytosis, slight increase in azotemia in the group treated with higher doses. Monkeys (treated 1 year): no side effects at 50 mg / kg / day.
Teratology: Rats: no effect on fertility, no embryotoxic, foetotoxic or teratogenic action, no harmful effects on rats or offspring up to doses of 400 mg / kg during gestation. Rabbits: No embryotoxic evidence, however 21, 31, 94 and 94% of fetuses treated with 15, 50, 150 and 450 mg / kg respectively died several days after stopping treatment.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Microcrystalline cellulose, starch, lactose, stearic acid;
06.2 Incompatibility "-
None known.
06.3 Period of validity "-
3 years.
06.4 Special precautions for storage -
Store at a temperature not exceeding 25 ° C. Store in original container to protect from moisture.
06.5 Nature of the immediate packaging and contents of the package -
CAPOTEN 25 mg tablets: box containing 50 tablets of 25 mg in blister packs.
CAPOTEN 50 mg tablets: box containing 24 tablets of 50 mg in blister packs.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
BRISTOL-MYERS SQUIBB S.r.l. Via Virgilio Maroso, 50 - Rome
08.0 MARKETING AUTHORIZATION NUMBER -
CAPOTEN 25 mg tablets - 50 tablets: A.I.C. No. 024446015.
CAPOTEN 50 mg tablets - 24 tablets: A.I.C. No. 024446027.
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
May 2010.
