Active ingredients: D acetylsalicylate, L-lysine
CARDYRENE 75 mg powder for oral solution
CARDYRENE 100 mg powder for oral solution
CARDYRENE 160 mg powder for oral solution
CARDYRENE 300 mg powder for oral solution
Why is Cardirene used? What is it for?
Pharmacotherapeutic group
Antithrombotics, antiplatelet agents.
Therapeutic indications
FOR ALL DOSAGES (75 mg - 100 mg - 160 mg - 300 mg)
1. Prevention of major athero-thrombotic events:
- After myocardial infarction
- After stroke or transient ischemic attack (TIA)
- In patients with unstable angina pectoris
- In patients with chronic stable angina pectoris
2. Prevention of re-occlusion of aorto-coronary bypasses and in percutaneous transluminal coronary angioplasty (PTCA)
Prevention of cardiovascular events in patients with overt atheromatous disease, in Kawasaki syndrome, in patients on hemodialysis and in the prevention of thrombosis during extracorporeal circulation
FOR THE DOSAGE OF 100 mg ONLY:
3. Prevention of cardiovascular events in high-risk patients *
* In subjects at high risk of a first major cardiovascular event (10-year risk> 20% based on the risk cards of the Heart Project of the Istituto Superiore di Sanità)
Contraindications When Cardirene should not be used
- Hypersensitivity to acetylsalicylic acid or to any of the excipients, or to other non-steroidal anti-inflammatory drugs (NSAIDs) (cross-reactivity)
- History of asthma induced by administration of acetylsalicylates or substances with similar activity, especially non-steroidal anti-inflammatory drugs, antecedents of hypersensitivity to salicylics (bronchospasm, anaphylactic reactions)
- Third trimester of pregnancy (beyond 24 weeks of gestation) (see Special warnings - pregnancy and breastfeeding)
- Active peptic ulcer, gastroduodenal ulcer in evolution
- Any constitutional or acquired hemorrhagic disease
- Bleeding risk
- Severe hepatic insufficiency
- Severe renal insufficiency (ClCr
- Severe, uncontrolled heart failure
- Co-administration of methotrexate used at doses> 15 mg / week with acetylsalicylic acid at anti-inflammatory doses, or at analgesic or antipyretic doses (see "Interactions")
- Co-administration of oral anticoagulants with acetylsalicylic acid used at anti-inflammatory doses, or at analgesic or antipyretic doses and in patients with a history of gastro-duodenal ulcers (see "Interactions").
- Patients with pre-existing mastocytosis, in whom the use of acetylsalicylic acid can induce severe hypersensitivity reactions (including circulatory shock with flushing, hypotension, tachycardia and vomiting).
The use of this medicine is however contraindicated in children and young people under the age of sixteen.
Precautions for use What you need to know before taking Cardirene
Use with caution: in patients with mild and moderate hepatic insufficiency; in the presence of an intrauterine device.
Concomitant use of antidiabetics, antacids, diuretics, glucocorticoids (see "Interactions").
Interactions Which drugs or foods can modify the effect of Cardirene
Several substances are involved in interactions due to their properties to inhibit platelet aggregation:
Abciximab, acetylsalicylic acid, clopidogrel, epoprostenol, eptifibatide, iloprost and iloprost trometamol, ticlopidine and tirofiban.
The use of different inhibitors of platelet aggregation increases the risk of bleeding, as does their combination with heparin or related molecules, oral anticoagulants or with other thrombolytics, and this possibility must be considered, maintaining regular clinical monitoring.
Contraindicated associations (see "Contraindications"):
- Methotrexate at doses> 15 mg / week at anti-inflammatory doses of acetylsalicylic acid, or at analgesic or antipyretic doses of acetylsalicylic acid: increased toxicity of methotrexate, particularly haematological toxicity (due to the reduction of the renal clearance of methotrexate by the acid acetylsalicylic).
- Oral anticoagulants at anti-inflammatory doses of acetylsalicylic acid, or at analgesic or antipyretic doses of acetylsalicylic acid and in patients with a history of gastro-duodenal ulcer: increased risk of bleeding.
Combinations not recommended:
- oral anticoagulants at analgesic or antipyretic doses of acetylsalicylic acid and in patients with no history of gastro-duodenal ulcer: increased risk of bleeding.
- oral anticoagulants at doses of acetylsalicylic acid used for the inhibition of platelet aggregation and in patients with a history of gastro-duodenal ulcer: increased risk of bleeding. Other non-steroidal anti-inflammatory drugs (NSAIDs), at anti-inflammatory or analgesic or antipyretic doses of acetylsalicylic acid: increased risk of gastrointestinal ulcers and bleeding.
- Low molecular weight heparins (and related molecules) and unfractionated heparins at therapeutic doses in elderly patients (≥ 65 years), regardless of heparin dose, and for anti-inflammatory doses or analgesic or antipyretic doses of acetylsalicylic acid: increase the risk of haemorrhage (inhibition of platelet aggregation and lesion of the gastroduodenal mucosa by acetylsalicylic acid). Another anti-inflammatory drug or another analgesic or antipyretic should be given.
- Clopidogrel (in addition to the approved indications for this combination in patients with acute coronary syndrome): increased risk of haemorrhage. If co-administration cannot be avoided, clinical monitoring is recommended.
- Uricosurics (benzbromarone, probenecid): reduction of the uricosuric effect due to competition for the elimination of uric acid in the renal tubules.
- Ticlopidine: increased risk of bleeding. If co-administration cannot be avoided, clinical monitoring is recommended.
- Glucocorticoids (except hydrocortisone replacement therapy) for anti-inflammatory doses of acetylsalicylic acid: increased risk of bleeding.
- Pemetrexed in patients with mild or moderate renal insufficiency (creatinine clearance between 45 ml / min and 80 ml / min): Increased risk of pemetrexed toxicity (due to reduced renal clearance of pemetrexed by acetylsalicylic acid) at doses anti-inflammatory drugs of acetylsalicylic acid.
- Pentoxifylline: increased risk of bleeding
Associations requiring precautions for use:
- Diuretics, angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor antagonists at anti-inflammatory doses of acetylsalicylic acid or analgesic and antipyretic doses of acetylsalicylic acid: acute renal failure may occur in dehydrated patients a due to the reduced glomerular filtration rate secondary to the decrease in the synthesis of renal prostaglandins. In addition, the reduction of the antihypertensive effect may occur. Make sure the patient is hydrated and that kidney function is checked at the start of treatment.
- Methotrexate at doses ≤ 15 mg / week at anti-inflammatory doses, or at analgesic or antipyretic doses of acetylsalicylic acid: increased toxicity of methotrexate, in particular haematological toxicity (due to the reduction of the renal clearance of methotrexate by acetylsalicylic acid Blood cell counts should be checked weekly during the first few weeks of concomitant administration.Careful monitoring is required in patients with (even mild) renal insufficiency, as well as in elderly patients.
- Methotrexate at doses> 15 mg at doses of acetylsalicylic acid used for inhibition of platelet aggregation: increased toxicity of methotrexate, particularly haematological toxicity (due to the reduction of renal clearance of methotrexate by acetylsalicylic acid). Blood cell counts should be checked weekly during the first few weeks of co-administration.Careful monitoring is required in patients with (even mild) renal insufficiency, as well as in elderly patients.
- Clopidogrel (in the approved indications for this combination in patients with acute coronary syndrome): increased risk of haemorrhage. Clinical monitoring is recommended.
- Topical gastrointestinal, antacids and charcoal: increased renal excretion of acetylsalicylic acid due to alkalinization of the urine. It is recommended that gastrointestinal topicals and antacids be administered at least 2 hours away from acetylsalicylic acid.
- Pemetrexed in patients with normal renal function: increased risk of pemetrexed toxicity (due to reduced renal clearance of pemetrexed by acetylsalicylic acid) at anti-inflammatory doses of acetylsalicylic acid. Renal function should be monitored.
- Low molecular weight heparins (and related molecules) and unfractionated heparins, at preventive doses in patients under 65 years of age: the co-administration of drugs that act at different levels of haemostasis increases the risk of bleeding. Therefore, in patients less than 65 years of age, the co-administration of heparins at preventive doses (or related molecules), and acetylsalicylic acid, regardless of the dose, should be evaluated, maintaining clinical and laboratory monitoring. , when necessary.
- Low molecular weight heparins (and related molecules) and unfractionated heparins at therapeutic doses or in elderly patients (≥ 65 years), regardless of the dose of heparin, and for doses of acetylsalicylic acid used for the inhibition of platelet aggregation: increase the risk of haemorrhage (inhibition of platelet aggregation and lesion of the gastroduodenal mucosa by acetylsalicylic acid).
- Thrombolytics: increased risk of bleeding
- Oral anticoagulants at doses of acetylsalicylic acid used for the inhibition of platelet aggregation: increased risk of haemorrhage.
- Other non-steroidal anti-inflammatory drugs (NSAIDs) with doses of acetylsalicylic acid used for the inhibition of platelet aggregation: increased risk of gastrointestinal ulcers and bleeding.
- Glucocorticoids (except hydrocortisone for replacement therapy) for analgesic and antipyretic doses of acetylsalicylic acid: increased risk of bleeding; decreased salicilemia during corticoid treatments and risk of salicylic overdose after discontinuation.
- Acetazolamide: Caution is advised in case of concomitant administration of salicylates and acetazolamide as there is an increased risk of metabolic acidosis.
- Selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline): increased risk of bleeding.
- Antidiabetics (in particular sulfonylureas) and insulin: potentiation of the hypoglycemic effect.
- Metamizole: metamizole when taken concomitantly with acetylsalicylic acid can reduce its effect on platelet aggregation. Therefore, this combination should be used with caution in patients taking low doses of acetylsalicylic acid for cardioprotection.
The treatment effect may be modified if acetylsalicylic acid is taken concomitantly with other medicines such as: anti-rejection drugs (eg cyclosporine, tacrolimus).
Before using acetylsalicylic acid, tell your doctor if you are taking any other medicines (including self-medication).
Warnings It is important to know that:
- In case of co-administration with other medicines, in order to avoid any risk of overdose, make sure that acetylsalicylic acid is absent from the composition of the other medicines.
- Reye's syndrome is a very rare and life-threatening disease and has been observed in children and adolescents with signs of viral infection (particularly chicken pox and flu-like episodes) who have taken acetylsalicylic acid. Consequently, acetylsalicylic acid should be administered to children and adolescents in this situation following the doctor's advice, only when other interventions have failed. In case of persistent vomiting, disturbed consciousness and abnormal behavior, treatment with acetylsalicylic acid should be discontinued .
- In children under 1 month of age, the administration of acetylsalicylic acid is justified only in specific situations and on medical prescription.
- In case of long-term administration of analgesics in high doses, the onset of headache should not be treated with higher doses.
- Regular use of analgesics, particularly the combination of analgesics, can lead to persistent kidney damage, with the risk of kidney failure.
- In patients with G6PD deficiency, acetylsalicylic acid should be administered under close medical supervision due to the risk of haemolysis (see "Undesirable effects").
Treatment monitoring should be strengthened in the following cases:
- in patients with a history of gastric or duodenal ulcer, or gastrointestinal bleeding, or gastritis
- in patients with renal insufficiency
- in patients with hepatic insufficiency
- in patients with asthma: the occurrence of an asthma attack, in some patients, may be linked to an allergy to non-steroidal anti-inflammatory drugs or to acetylsalicylic acid; in this case, this drug is contraindicated (see Contraindications section)
- in patients with metrorrhagia or menorrhagia (risk of increasing the volume and duration of menstrual periods)
- Gastrointestinal bleeding or ulcers / perforations can occur at any time during treatment, without necessarily the presence of recent signs or a history in the patient. The relative risk is increased in elderly subjects, in subjects with low body weight, and in patients treated with anticoagulants or platelet aggregation inhibitors (see section "Interactions"). In case of gastrointestinal bleeding, treatment should be stopped immediately.
- In consideration of the inhibitory effect of acetylsalicylic acid on platelet aggregation, which occurs even at very low doses and which persists for several days, the patient must be warned of the risk of bleeding in the event of surgery, even of a minor nature ( e.g. tooth extraction).
- At analgesic or antipyretic doses, acetylsalicylic acid inhibits the excretion of uric acid; at the doses used in rheumatology (anti-inflammatory doses), acetylsalicylic acid has a uricosuric effect.
- At high doses used in rheumatology (anti-inflammatory doses), patients should be monitored for possible overdose symptoms. In case of ringing in the ears, hearing difficulties or dizziness, the treatment modalities should be re-evaluated. In children, it is recommended to monitor for salicilism, especially at the start of treatment.
- The use of this medicine is not recommended during breastfeeding (see "Pregnancy and breastfeeding").
Not recommended: in gout.
This medicine should not be used in children and young people under the age of 16 (see "Contraindications").
People over 70 years of age, especially in the presence of concomitant therapies, should use this medicine only after consulting a doctor.
For dosages of acetylsalicylic acid ≥ 500 mg / day:
There is evidence that the drug, by inhibiting cyclo-oxygenase / prostaglandin synthesis, may cause a reduction in female fertility through an effect on ovulation. This effect is reversible on discontinuation of the drug.
Female subjects must be informed of this and in particular women who have fertility problems or who are undergoing fertility investigations.
Pregnancy and breastfeeding:
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
- In the animal: a teratogenic effect was observed.
- In men: on the basis of multiple epidemiological studies (in particular a prospective study in a large number of women) no teratogenic effect of ASA was observed following occasional administration during the first trimester of pregnancy. Data are less numerous for chronic treatments.
The use during pregnancy for long periods and the administration in the last three months of pregnancy must be done only on medical prescription because acetylsalicylic acid can cause haemorrhagic phenomena in the fetus and mother, delivery delays and, in the unborn child, early closure of the duct of Botallo. During the last three months and in particular in the last weeks of pregnancy, it would be advisable to avoid the use of acetylsalicylic acid.
Low doses below 100 mg / day
Clinical studies indicate that acetylsalicylic acid at doses below 100 mg / day appears to be safe only in limited obstetric cases, which require specialist monitoring.
Doses between 100-500 mg / day
There are insufficient clinical data relating to the use of acetylsalicylic acid at doses between 100 mg / day up to 500 mg / day. Therefore, the recommendations below for doses of 500 mg / day and above also apply to this range of dosage (see paragraph below).
Doses of 500 mg / day and more
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations was increased from less than 1% to approximately 1.5%. The risk has been estimated to increase with dose and duration of therapy.
In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the first 24 weeks of pregnancy, acetylsalicylic acid should not be administered except in strictly necessary cases.
If acetylsalicylic acid is used by a woman attempting to conceive or during the first 24 weeks of pregnancy, the dose and duration of treatment should be kept as low as possible.
Beyond 24 weeks of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligo-hydroamnios.
At the end of pregnancy, the mother and the newborn may present:
- prolongation of bleeding time due to inhibition of platelet aggregation, which can occur even after administration of very low doses of acetylsalicylic acid
- inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently, acetylsalicylic acid is contraindicated during the third trimester of pregnancy (after 24 weeks of gestation) (see "Contraindications").
Feeding time
Acetylsalicylic acid passes into breast milk: the intake of ASA is not recommended during breastfeeding due to the possible risk of acidosis and haemorrhagic syndrome in the infant.
Important information about some of the ingredients of Cardirene powder for oral solution
Cardirene contains lactose: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Effects on ability to drive or use machines
No effects of Cardirene on the ability to drive or use machines have been observed.
Dosage and method of use How to use Cardirene: Dosage
IN THE ADULT
1 sachet per day to be dissolved in a glass of water. Treatment should begin with Cardirene 160 mg or Cardirene 300 mg, according to medical prescription, immediately after the first symptoms appear and continue for at least 5 weeks.
It is possible to continue therapy with Cardirene 75 mg or with Cardirene 100 mg.
After myocardial infarction as well as in unstable angina, treatment will be started as soon as possible both in case of first episode and in case of relapse.
The "Prevention of cardiovascular events in high-risk patients *" should be done with the 100 mg dose.
* In subjects at high risk of a first major cardiovascular event (10-year risk> 20% based on the risk cards of the Heart Project of the Istituto Superiore di Sanità).
To be used only on doctor's prescription.
Overdose What to do if you have taken too much Cardirene
In case of accidental ingestion / intake of an excessive dose of Cardirene, notify your doctor immediately or go to the nearest hospital.
For acetylsalicylic acid the toxic doses are between 200 mg / kg and 300 mg / kg orally.
The risk of overdose is important in the elderly and particularly in young children (therapeutic overdose or, more frequently, accidental intoxication). Overdose with salicylates, particularly in young children, can lead to severe hypoglycemia and potentially fatal intoxication.
In children, an overdose can be fatal as early as 100 mg / kg in a single intake.
With acute and chronic overdose of acetylsalicylic acid, life-threatening non-cardiogenic pulmonary edema may occur.
Taking into account the recommended posology, overdose is unlikely.
Symptoms
- Moderate intoxication: ringing in the ears, feeling of reduced hearing acuity, headache, dizziness, nausea, are indications of overdose and can be controlled by reducing the dosage.
- Severe intoxication: fever, hyperventilation, respiratory alkalosis, ketosis, metabolic acidosis, coma, cardiovascular collapse, respiratory failure, severe hypoglycemia.
Emergency management
For emergency treatment, immediate transfer to a specialized hospital setting is necessary; rapid evacuation of the ingested product by gastric lavage and administration of activated charcoal; control of acid-base balance; alkalinization of urine with monitoring of urine pH, hemodialysis in case of severe poisoning; symptomatic treatment.
If you have any further questions on the use of Cardirene, ask your doctor or pharmacist
Side Effects What are the side effects of Cardirene
Like all medicines, Cardirene can cause side effects, although not everybody gets them. Frequencies cannot be reliably estimated from the available data.
Therefore the frequencies are listed as "not known".
- Disorders of the blood and lymphatic system
Hemorrhagic syndromes (epistaxis, gum bleeding, purpura, etc.) with prolongation of bleeding time. The risk of bleeding may persist for 4-8 days after discontinuation of acetylsalicylic acid. It may cause an increased risk of bleeding in the event of surgery. Intracranial and gastrointestinal bleeding may also occur. Intracranial bleeding could be fatal, especially when the medicine is given to the elderly.
Thrombocytopenia.
Haemolytic anemia in patients with glucose 6 phosphate dehydrogenase (G6PD) deficiency
Pancytopenia, bilinear cytopenia, aplastic anemia, bone marrow failure, agranulocytosis, neutropenia, leukopenia.
- Disorders of the immune system
Hypersensitivity reactions, anaphylactic reactions, asthma, angioedema
- Nervous system disorders
Headache, dizziness, feeling of hearing loss, tinnitus, which are usually indicative of an overdose.
Intracranial hemorrhage
- Gastrointestinal disorders
Abdominal pain, occult or overt gastrointestinal bleeding (haematemesis, melaena, etc.) resulting in iron deficiency anemia. The risk of bleeding is dose dependent. Gastric ulcers and perforations
- Upper gastrointestinal disorders:
esophagitis, erosive duodenitis, erosive gastritis, esophageal ulcers, perforations.
- Lower gastrointestinal disorders:
ulcers of the small (jejunum and ileus) and large intestine (colon and rectum), colitis and intestinal perforations.
These reactions may or may not be associated with haemorrhage and may occur with any dose of acetylsalicylic acid and in patients with or without predictive symptoms and with or without a history of serious gastrointestinal events.
Acute pancreatitis in the context of a hypersensitivity reaction to acetylsalicylic acid.
- Hepatobiliary disorders
Increased liver enzymes, liver damage, especially hepatocellular, chronic hepatitis.
- Skin and subcutaneous tissue disorders
Hives, skin reactions, fixed eruptions.
- Renal and urinary disorders Renal failure.
General disorders and administration site conditions Reye's syndrome (see warnings) Sensitization episodes (edema, urticaria, asthma, anaphylactic crisis).
- Pregnancy, puerperium and perinatal conditions
ASA can prolong labor and delay delivery.
- Respiratory, thoracic and mediastinal disorders
Chronic use may result in non-cardiogenic pulmonary edema which may also occur in the context of a hypersensitivity reaction to acetylsalicylic acid.
- Vascular disorders:
Not known: vasculitis including Schönlein-Henoch purpura.
- Cardiac disorders:
Not known: Kounis syndrome in the context of a hypersensitivity reaction to acetylsalicylic acid.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, including any possible side effects not listed in this leaflet, contact your doctor or pharmacist. Undesirable effects can also be reported directly via the national reporting system at “www.agenziadelfarmaco.gov.it/it/responsabili.” By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Expiration and retention
- Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
- storage
Store in the original container below 25 ° C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children
Composition
Each sachet contains:
Cardirene 75 mg
Active ingredient: D acetylsalicylate, L-lysine 135.00 mg (corresponding to 75 mg of acetylsalicylic acid)
Cardirene 100 mg
Active ingredient: D acetylsalicylate, L-lysine 180.00 mg (corresponding to 100 mg of acetylsalicylic acid)
Cardirene 160 mg
Active ingredient: D acetylsalicylate, L-lysine 288 mg (corresponding to 160 mg of acetylsalicylic acid)
Cardirene 300 mg
Active ingredient: D acetylsalicylate, 540 mg L-lysine (corresponding to 300 mg of acetylsalicylic acid)
Excipients: glycine, mandarin aroma (essential oil of mandarin, citrus juice and lactose), glycyrrhized ammonium.
Pharmaceutical form and content
Powder for oral solution. Box of 30 sachets.
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
CARDYRENE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each sachet contains:
CARDYRENE 75 mg
Active principle : D acetylsalicylate, 135 mg L-lysine (corresponding to 75 mg of acetylsalicylic acid).
CARDYRENE 100 mg
Active principle : D acetylsalicylate, L-lysine 180 mg (corresponding to 100 mg of acetylsalicylic acid).
CARDYRENE 160 mg
Active principle : D acetylsalicylate, L-lysine 288 mg (corresponding to 160 mg of acetylsalicylic acid).
CARDYRENE 300 mg
Active principle : D acetylsalicylate, 540 mg L-lysine (corresponding to 300 mg of acetylsalicylic acid).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Powder for oral solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
For all strengths (75 mg - 100 mg - 160 mg - 300 mg)
- Prevention of major athero-thrombotic events:
- After myocardial infarction
- After stroke or transient ischemic attacks (TIA)
- In patients with unstable angina pectoris
- In patients with chronic stable angina pectoris
- Prevention of re-occlusion of aorto-coronary bypasses and in "percutaneous transluminal coronary angioplasty (PTCA)
Prevention of cardiovascular events in patients with overt atheromatous disease, in Kawasaki syndrome, in patients on hemodialysis and in the prevention of thrombosis during extracorporeal circulation
For the dosage of 100 mg only :
- Prevention of cardiovascular events in high risk patients *
* In subjects at high risk of a first major cardiovascular event (10-year risk> 20% based on the risk cards of the Heart Project of the Istituto Superiore di Sanità).
04.2 Posology and method of administration
In the adult
1 sachet per day to be dissolved in a glass of water.
Treatment should start with Cardirene 160 mg or Cardirene 300 mg, as prescribed, immediately after the first symptoms appear and continue for at least 5 weeks.
Therapy with Cardirene 75 mg or Cardirene 100 mg can be continued.
After myocardial infarction as well as in unstable angina, treatment will be started as soon as possible both in case of first episode and in case of relapse.
The "Prevention of cardiovascular events in high-risk patients *". it must be carried out with the dosage of 100 mg.
* In subjects at high risk of a first major cardiovascular event (10-year risk> 20% based on the risk cards of the Heart Project of the Istituto Superiore di Sanità).
To be used only on doctor's prescription.
04.3 Contraindications
• Hypersensitivity to acetylsalicylic acid or to any of the excipients, or to other non-steroidal anti-inflammatory drugs (NSAIDs) (cross-reactivity),
• History of asthma induced by administration of acetylsalicylates or substances with similar activity, especially non-steroidal anti-inflammatory drugs, antecedents of hypersensitivity to salicylics (bronchospasm, anaphylactic reactions),
• Third trimester of pregnancy (beyond 24 weeks of gestation) (see section 4.6)
• Active peptic ulcer, gastroduodenal ulcer in evolution
• Any constitutional or acquired bleeding disease
• Bleeding risk
• Severe hepatic insufficiency
• Severe renal insufficiency
• Severe, uncontrolled heart failure
• Co-administration of methotrexate used at doses> 15 mg / week with acetylsalicylic acid at anti-inflammatory doses, or at analgesic or antipyretic doses (see section 4.5)
• Co-administration of oral anticoagulants with acetylsalicylic acid used at anti-inflammatory, analgesic or antipyretic doses and in patients with a history of gastro-duodenal ulcers (see section 4.5).
• Patients with pre-existing mastocytosis, in whom the use of acetylsalicylic acid can induce severe hypersensitivity reactions (including circulatory shock with flushing, hypotension, tachycardia and vomiting).
The use of this medicine is however contraindicated in children and young people under the age of sixteen.
04.4 Special warnings and appropriate precautions for use
• In case of co-administration with other medicines, in order to avoid any risk of overdose, make sure that acetylsalicylic acid is absent from the composition of the other medicines.
• Reye's syndrome is a very rare and life-threatening disease and has been observed in children and adolescents with signs of viral infection (particularly chicken pox and flu-like episodes) who have taken acetylsalicylic acid. Consequently, acetylsalicylic acid should be administered to children and adolescents in this situation following the doctor's advice, only when other interventions have failed. In case of persistent vomiting, disturbed consciousness and abnormal behavior, treatment with acetylsalicylic acid should be discontinued .
• In children under 1 month of age, the administration of acetylsalicylic acid is justified only in specific situations and on medical prescription.
• In case of long-term administration of analgesics in high doses, the onset of headache should not be treated with higher doses.
• Regular use of analgesics, particularly the combination of analgesics, can lead to persistent kidney damage, with the risk of kidney failure.
• In some severe forms of G6PD deficiency, high doses of acetylsalicylic acid can cause hemolysis. In case of G6PD deficiency, acetylsalicylic acid should be administered under medical supervision.
• Treatment monitoring should be strengthened in the following cases:
- in patients with a history of gastric or duodenal ulcer, or gastrointestinal bleeding, or gastritis
- in patients with renal insufficiency
- in patients with hepatic insufficiency
- in patients with asthma: the occurrence of an asthma attack, in some patients, may be linked to an allergy to non-steroidal anti-inflammatory drugs or to acetylsalicylic acid, in this case, this drug is contraindicated (see section 4.3 )
- in patients with metrorrhagia or menorrhagia (risk of increasing the volume and duration of menstrual periods)
• Gastrointestinal bleeding or ulcers / perforations can occur at any time during treatment, without necessarily the presence of recent signs or a history of the patient. The relative risk is increased in elderly subjects, in subjects with low body weight, and in patients treated with anticoagulants or platelet aggregation inhibitors (see section 4.5). In case of gastrointestinal bleeding, treatment should be stopped immediately.
• In consideration of the inhibitory effect of acetylsalicylic acid on platelet aggregation, which occurs even at very low doses and which persists for several days, the patient must be warned of the risk of bleeding in the event of surgery, even of a minor nature. (e.g. tooth extraction).
• At analgesic or antipyretic doses, acetylsalicylic acid inhibits the excretion of uric acid; at the doses used in rheumatology (anti-inflammatory doses), acetylsalicylic acid has a uricosuric effect.
• At high doses used in rheumatology (anti-inflammatory doses), patients should be monitored for possible overdose symptoms. In case of ringing in the ears, hearing difficulties or dizziness, the treatment modalities should be re-evaluated. In children, it is recommended to monitor for salicilism, especially at the start of treatment.
• The use of this medicinal product is not recommended during lactation (see section 4.6).
Use with caution: in patients with mild and moderate hepatic insufficiency; in the presence of an intrauterine device.
Concomitant use of antidiabetics, antacids, diuretics, glucocorticoids (see section 4.5).
Not recommended: in gout.
This medicinal product should not be used in children and young people under the age of 16 (see section 4.3).
People over 70 years of age, especially in the presence of concomitant therapies, should use this medicine only after consulting a doctor.
Cardirene 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
Several substances are involved in interactions due to their properties to inhibit platelet aggregation:
Abciximab, acetylsalicylic acid, clopidogrel, epoprostenol, eptifibatide, iloprost and iloprost trometamol, ticlopidine and tirofiban.
The use of different inhibitors of platelet aggregation increases the risk of bleeding, as does their combination with heparin or related molecules, oral anticoagulants or with other thrombolytics, and this possibility must be considered, maintaining regular clinical monitoring.
Contraindicated combinations (see section 4.3) :
• Methotrexate at doses> 15 mg / week at anti-inflammatory doses, or at analgesic or antipyretic doses of acetylsalicylic acid: increased toxicity of methotrexate, in particular haematological toxicity (due to the reduction of renal clearance of methotrexate by acetylsalicylic acid) .
• Oral anticoagulants at anti-inflammatory, or analgesic or antipyretic doses of acetylsalicylic acid and in patients with a history of gastro-duodenal ulcer: increased risk of bleeding.
Combinations not recommended :
• oral anticoagulants at analgesic or antipyretic doses of acetylsalicylic acid and in patients with no history of gastro-duodenal ulcer: increased risk of bleeding.
• oral anticoagulants at doses of acetylsalicylic acid used for the inhibition of platelet aggregation and in patients with a history of gastro-duodenal ulcer: increased risk of bleeding. Other non-steroidal anti-inflammatory drugs (NSAIDs), at anti-inflammatory doses, or at analgesic or antipyretic doses of acetylsalicylic acid: increased risk of gastrointestinal ulcers and bleeding.
• low molecular weight heparins (and related molecules) and unfractionated heparins at therapeutic doses in elderly patients (≥ 65 years), regardless of the dose of heparin, and for anti-inflammatory doses or for analgesic or antipyretic doses of acetylsalicylic acid: increased risk of bleeding (inhibition of platelet aggregation and lesion of the gastroduodenal mucosa by acetylsalicylic acid). Another anti-inflammatory drug or another analgesic or antipyretic should be given.
• Clopidogrel (in addition to the approved indications for this combination in patients with acute coronary syndrome): increased risk of haemorrhage. If co-administration cannot be avoided, clinical monitoring is recommended.
• Uricosurics (benzbromarone, probenecid): reduction of the uricosuric effect due to competition for the elimination of uric acid in the renal tubules.
• Ticlopidine: increased risk of bleeding. If co-administration cannot be avoided, clinical monitoring is recommended.
• Glucocorticoids (except hydrocortisone replacement therapy) for anti-inflammatory doses of acetylsalicylic acid: increased risk of bleeding.
• Pemetrexed in patients with mild or moderate renal insufficiency (creatinine clearance between 45 ml / min and 80 ml / min): Increased risk of pemetrexed toxicity (due to the reduced renal clearance of pemetrexed by acetylsalicylic acid) a anti-inflammatory doses of acetylsalicylic acid.
• Pentoxifylline: increased risk of bleeding
Associations requiring precautions for use :
• Diuretics, angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor antagonists at anti-inflammatory doses of acetylsalicylic acid or analgesic and antipyretic doses of acetylsalicylic acid: acute renal failure may occur in dehydrated patients due to the reduced glomerular filtration rate secondary to the decrease in the synthesis of renal prostaglandins. In addition, the reduction of the antihypertensive effect may occur. Make sure the patient is hydrated and that kidney function is checked at the start of treatment.
• Methotrexate at doses ≤ 15 mg / week at anti-inflammatory doses, or at analgesic or antipyretic doses of acetylsalicylic acid: increased toxicity of methotrexate, in particular haematological toxicity (due to the reduction of the renal clearance of methotrexate by the acid Acetylsalicylic) Blood cell counts should be checked weekly during the first few weeks of concomitant administration.Careful monitoring is required in patients with (even mild) renal insufficiency, as well as in elderly patients.
• Methotrexate at doses> 15 mg at doses of acetylsalicylic acid used for inhibition of platelet aggregation: increased toxicity of methotrexate, particularly haematological toxicity (due to the reduction of renal clearance of methotrexate by acetylsalicylic acid). Blood cell counts should be checked weekly during the first few weeks of co-administration.Careful monitoring is required in patients with (even mild) renal impairment, as well as in elderly patients.
• Clopidogrel (in the approved indications for this combination in patients with acute coronary syndrome): increased risk of haemorrhage. Clinical monitoring is recommended.
• Topical gastrointestinal, antacids and charcoal: increased renal excretion of acetylsalicylic acid due to alkalinization of the urine. It is recommended that gastrointestinal topicals and antacids be administered at least 2 hours away from acetylsalicylic acid.
• Pemetrexed in patients with normal renal function: increased risk of pemetrexed toxicity (due to reduced renal clearance of pemetrexed by acetylsalicylic acid) at anti-inflammatory doses of acetylsalicylic acid. Renal function should be monitored.
• Low molecular weight heparins (and related molecules) and unfractionated heparins, at preventive doses in patients under 65 years of age: the co-administration of drugs that act at different levels of haemostasis increases the risk of bleeding. Therefore, in patients less than 65 years of age, the co-administration of heparins at preventive doses (or related molecules), and acetylsalicylic acid, regardless of the dose, should be evaluated, maintaining clinical and laboratory monitoring. , when necessary.
• Low molecular weight heparins (and related molecules) and unfractionated heparins at therapeutic doses or in elderly patients (≥ 65 years), regardless of the dose of heparin, and for doses of acetylsalicylic acid used for the inhibition of platelet aggregation: increased risk of bleeding (inhibition of platelet aggregation and lesion of the gastroduodenal mucosa by acetylsalicylic acid).
• Thrombolytics: increased risk of bleeding
• Oral anticoagulants at doses of acetylsalicylic acid used for the inhibition of platelet aggregation: increased risk of bleeding.
• Other non-steroidal anti-inflammatory drugs (NSAIDs) with doses of acetylsalicylic acid used for the inhibition of platelet aggregation: increased risk of gastrointestinal ulcers and bleeding.
• Glucocorticoids (except hydrocortisone for replacement therapy) for analgesic and antipyretic doses of acetylsalicylic acid: increased risk of bleeding; decreased salicilemia during corticoid treatments and risk of salicylic overdose after discontinuation.
• Selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline): increased risk of bleeding.
• Antidiabetics (in particular sulfonylureas) and insulin: potentiation of the hypoglycemic effect
• Experimental data indicate that ibuprofen may inhibit the effects of low dose acetylsalicylic acid on platelet aggregation when the drugs are administered concomitantly (see section 5.1).
However, the limited data and the uncertainties relating to their application to the clinical situation do not allow definitive conclusions to be drawn for the continued use of ibuprofen; there appears to be no likely clinically relevant effect from the occasional use of ibuprofen (see section 5.1).
04.6 Pregnancy and lactation
Pregnancy
- In the animal: a teratogenic effect has been observed.
- In men: on the basis of multiple epidemiological studies (in particular a prospective study in a large number of women) no teratogenic effect of ASA has been observed following occasional administration during the first trimester of pregnancy. Data are less numerous for chronic treatments.
The use during pregnancy for long periods and the administration in the last three months of pregnancy must be done only on medical prescription because acetylsalicylic acid can cause haemorrhagic phenomena in the fetus and mother, delivery delays and, in the unborn child, early closure of the duct of Botallo. During the last three months and in particular in the last weeks of pregnancy, it would be advisable to avoid the use of acetylsalicylic acid.
- Low doses below 100 mg / day
Clinical studies indicate that acetylsalicylic acid at doses below 100 mg / day appears to be safe only in limited obstetric cases, which require specialist monitoring.
- Doses between 100-500 mg / day
There are insufficient clinical data regarding the use of acetyl salicylic acid at doses between 100 mg / day up to 500 mg / day. Therefore, the recommendations below for doses of 500 mg / day and above also apply to this range. dosage (see paragraph below).
- Doses of 500 mg / day and more
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations was increased from less than 1% to approximately 1.5%. The risk has been estimated to increase with dose and duration of therapy.
In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the first 24 weeks of pregnancy, acetylsalicylic acid should not be administered except in strictly necessary cases.
If acetylsalicylic acid is used by a woman attempting to conceive or during the first 24 weeks of pregnancy, the dose and duration of treatment should be kept as low as possible.
Beyond 24 weeks of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligo-hydroamnios.
At the end of pregnancy, the mother and the newborn may present:
- prolongation of bleeding time due to inhibition of platelet aggregation, which can occur even after the administration of very low doses of acetylsalicylic acid
- inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently, acetylsalicylic acid is contraindicated during the third trimester of pregnancy (after 24 weeks of gestation) (see section 4.3).
Feeding time
Acetylsalicylic acid passes into breast milk: it is therefore not recommended to take ASA during breastfeeding due to the possible risk of acidosis and haemorrhagic syndrome in the infant (see section 4.4).
04.7 Effects on ability to drive and use machines
No effects of Cardirene on the ability to drive or use machines have been observed.
04.8 Undesirable effects
Frequencies cannot be reliably estimated from the available data. Therefore the frequencies are listed as "not known".
Disorders of the blood and lymphatic system haemorrhagic syndromes (epistaxis, gum bleeding, purpura, etc.) with prolongation of bleeding time. The bleeding risk may persist for 4-8 days after discontinuation of acetylsalicylic acid. It may cause an increased risk of bleeding in the event of surgery. Intracranial and gastrointestinal bleeding may also occur.
Immune system disorders Hypersensitivity reactions, anaphylactic reactions, asthma, angioedema
Nervous system disorders
Headache, dizziness, feeling of hearing loss, tinnitus, which are usually indicative of an overdose.
Intracranial hemorrhage.
Gastrointestinal disorders
Abdominal pain, occult or overt gastrointestinal bleeding (haematemesis, melaena, etc.) resulting in iron deficiency anemia. The risk of bleeding is dose-dependent.
• Upper gastrointestinal disorders:
esophagitis, erosive duodenitis, erosive gastritis, esophageal ulcers, ulcers, perforations.
• Lower gastrointestinal disorders:
ulcers of the small (jejunum and ileus) and large intestine (colon and rectum), colitis and intestinal perforations.
These reactions may or may not be associated with haemorrhage and may occur with any dose of acetylsalicylic acid and in patients with or without predictive symptoms and with or without a history of serious gastrointestinal events.
Hepatobiliary disorders
Increased liver enzymes, liver damage, especially hepatocellular.
Skin and subcutaneous tissue disorders
Urticaria, skin reactions
General disorders and administration site conditions
Reye's syndrome (see section 4.4)
Sensitization episodes (edema, urticaria, asthma, anaphylactic crisis).
Pregnancy, puerperium and perinatal conditions:
ASA can prolong labor and delay delivery.
Respiratory, thoracic and mediastinal disorders
Chronic use may result in non-cardiogenic pulmonary edema which may also occur in the context of a hypersensitivity reaction to acetylsalicylic acid.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions that occur after authorization of the medicinal product is important, as it allows continuous monitoring of the benefit / risk ratio of the medicinal product.
04.9 Overdose
For acetylsalicylic acid the toxic doses are between 200 mg / kg and 300 mg / kg per os.
The risk of overdose is important in the elderly and particularly in young children (therapeutic overdose or, more frequently, accidental intoxication), where it can be fatal. Taking into account the recommended posology, overdose is unlikely, even in the elderly.Moreover, intoxication (therapeutic overdose or accidental intoxication) manifests itself with the following symptoms:
Symptoms:
Moderate intoxication: ringing in the ears, feeling of reduced hearing acuity, headache, dizziness, nausea, are indications of overdose and can be controlled by reducing the dosage.
Severe intoxication: fever, hyperventilation, respiratory alkalosis, ketosis, metabolic acidosis, coma, cardiovascular collapse, respiratory failure, severe hypoglycemia.
With acute and chronic overdose of acetylsalicylic acid, life-threatening non-cardiogenic pulmonary edema may occur.
In children, an overdose can be fatal as early as 100 mg / kg in a single intake.
Emergency treatment:
• immediate transfer to a specialized hospital setting
• gastric lavage and administration of activated charcoal
• control of the acid-base balance
• alkalinization of urine with monitoring of urine pH
• hemodialysis in case of severe poisoning
• Symptomatic treatment.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antithrombotics, antiplatelet agents.
ATC code: B01AC06.
Analgesic, antipyretic, antiplatelet agent. At high doses anti-inflammatory. Acetylsalicylic acid (ASA) is an inhibitor of platelet activation: blocking platelet cyclo-oxygenase by acetylation, it inhibits the synthesis of thromboxane A2, a physiological activating substance released from platelets which would have a role in the thrombotic complications of atheromatous lesions.
Repeated doses of 20 to 325 mg result in an "inhibition of" enzymatic activity of 30 - 95%. At doses above 325 mg, inhibitory activity is only slightly increased and the effect on platelet aggregation is nearly identical.
The inhibitory effect is not exhausted during prolonged treatments and furthermore the enzymatic activity gradually resumes with the renewal of the platelets within 24 - 48 hours after the end of the treatment.
At the recommended posology, ASA reduces endothelial prostacyclin synthesis: the clinical significance of this effect is unclear and apparently less relevant in clinical practice than its theoretical potential.
ASA prolongs bleeding times by approximately 50 - 100% on average, but individual variations may be found.
Experimental data indicate that ibuprofen may inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when the drugs are administered concomitantly. In one study, following administration of a single 400 mg dose of ibuprofen, taken within 8 hours before or 30 minutes after the administration of acetylsalicylic acid (81 mg), there was a decrease in the effect of acetylsalicylic acid on thromboxane formation and platelet aggregation. However, the limited data and the uncertainties relating to their application to the clinical situation do not allow definitive conclusions to be drawn for the continued use of ibuprofen; there appears to be no clinically relevant effect from the occasional use of ibuprofen.
05.2 Pharmacokinetic properties
Absorption
After absorption, lysine acetylsalicylate cleaves into ASA and lysine in plasma. ASA is rapidly hydrolyzed into salicylic acid.
Distribution
The maximum plasma concentration is reached after 30 - 40 minutes from the intake according to the state of fasting or not of the subject.
In plasma, salicylates are largely bound to plasma proteins.
Metabolism
Salicylates are transformed in the liver (conjugation and hydroxylation) into inactive metabolites.
The accumulation kinetics which must be taken into account in the case of prolonged treatments at high doses are attributable to the saturable character of glycine conjugation on the acid function of salicylic acid and to the glucuroconjugation on the phenolic function: the elimination half-life of salicylic acid is dose dependent.
Elimination
All metabolites, as well as salicylic acid, are eliminated by the kidney.
There clearance it increases with increasing urinary pH.
05.3 Preclinical safety data
There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Glycine, mandarin aroma (mandarin essential oil, citrus juice and lactose), glycyrrhized ammonium.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years.
06.4 Special precautions for storage
Store in the original container at a temperature below 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
Sachets in coupled aluminum / polyethylene.
Box of 30 sachets.
06.6 Instructions for use and handling
Dissolve the contents of the sachet in a glass of water.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
sanofi-aventis S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
CARDYRENE 75 mg Powder for Oral Solution - AIC 028717041
CARDYRENE 100 mg Powder for Oral Solution - AIC 028717039
CARDYRENE 160 mg Powder for Oral Solution - AIC 028717015
CARDYRENE 300 mg Powder for Oral Solution - AIC 028717027
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
First authorization: 28.01.1996
Renewal: 29.02.2006
10.0 DATE OF REVISION OF THE TEXT
June 2013
