Active ingredients: Acetylsalicylic acid
ASCRIPTIN tablets
Indications Why is Ascriptin used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antithrombotics, antiplatelet agents
THERAPEUTIC INDICATIONS
Adults:
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
3 Analgesic, antipyretic and anti-inflammatory in rheumatism, rheumatoid arthritis, head and toothache, neuralgia, muscle, joint and menstrual pain, flu and cold symptoms.
Children and adolescents under the age of 16
The medicine is only indicated for: rheumatoid arthritis, rheumatic disease, Kawasaki disease and as an antiplatelet agent.
Contraindications When Ascriptin should not be used
Hypersensitivity to the active substances or to any of the excipients.
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).
Gastro-duodenal ulcer disease, hypersensitivity to salicylates, haemorrhagic diathesis.
Patients with severe hepatic insufficiency.
Patients with severe renal insufficiency (ClCr <30 ml / min)
Severe uncontrolled heart failure.
Concomitant treatment with methotrexate at doses of 15 mg / week or more (see Interactions),
History of asthma induced by administration of salicylates or substances with similar activity, particularly non-steroidal anti-inflammatory drugs,
The use of this medicine is contraindicated in children and young people under the age of 16 except as indicated in the Therapeutic indications section.
Dose> 100 mg / day during the third trimester of pregnancy.
This medicine should not be used in the course of viral diseases, such as chicken pox or flu, due to the risk of Reye's syndrome.
Precautions for use What you need to know before taking Ascriptin
Use with caution in cases of asthma and gout and in patients with mild and moderate hepatic insufficiency.
Interactions Which drugs or foods may change the effect of Ascriptin
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The effect of the treatment may be modified if Ascriptin is taken concomitantly with other medicines such as:
anticoagulants (eg warfarin);
anti-rejection drugs (eg cyclosporine, tacrolimus);
antihypertensives (eg diuretics and ACE inhibitors);
painkillers and anti-inflammatories (e.g. steroids, NSAIDs);
gout medications (probenecid);
anti-cancer and rheumatoid arthritis drugs (methotrexate
Contraindicated associations:
Methotrexate at doses greater than or equal to 15 mg / week:
Increased haematological toxicity of methotrexate (anti-inflammatories generally decrease the renal clearance of methotrexate and salicylates displace methotrexate from its plasma protein binding) (see Contraindications).
Associations requiring precautions for use:
Methotrexate at doses below 15 mg / week:
Increased haematological toxicity of methotrexate (anti-inflammatories generally decrease the renal clearance of methotrexate and salicylates displace methotrexate from its binding to plasma proteins).
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.
Ibuprofen: Experimental data indicate that ibuprofen may inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when drugs are administered concomitantly. However, the limited data and uncertainties relating to their application to the clinical situation do not allow definitive conclusions to be drawn for continued use of ibuprofen; there appears to be no clinically relevant effect from occasional use of ibuprofen (see Special warnings).
Anticoagulants, thrombolytics / other antiplatelet agents: increased risk of bleeding.
Other non-steroidal anti-inflammatory drugs containing salicylates in high doses: increased risk of gastrointestinal ulcers and bleeding due to the synergistic effect.
Selective inhibitors of serotonin re-uptake: increased risk of bleeding in general and of the upper gastrointestinal tract in particular due to a possible synergistic effect.
Systemic alkalizing agents (eg bicarbonates): administration accelerates the excretion of salicylates reducing their therapeutic efficacy.
Ciclosporin: increased cyclosporine-induced nephrotoxicity. Particular attention is recommended, particularly in elderly patients.
Digoxin: increase in the plasma concentration of digoxin due to a decrease in renal excretion.
Antidiabetics, eg. insulin, sulfonylureas: increased hypoglycemic effect for high doses of acetylsalicylic acid, through the hypoglycemic action of acetylsalicylic acid and displacement of sulfonylureas from protein binding sites.
Diuretics in combination with high-dose acetylsalicylic acid: reduction of glomerular filtration through the reduction of prostaglandin synthesis.
Systemic glucocorticoids, with the exception of hydrocortisone used as replacement therapy in Addison's disease: reduction of levels of salicylates in the blood during treatment with corticosteroids and risk of overdose of salicylates after its discontinuation, due to the increased elimination of salicylates due to corticosteroids .
Acetazolamide: Caution is advised in case of concomitant administration of salicylates and acetazolamide as there is an increased risk of metabolic acidosis.
Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) and Angiotensin II receptor antagonists (Sartans) in combination with high dose acetylsalicylic acid: reduced glomerular filtration through inhibition of vasodilating prostaglandins. Also, reduction of the anti-hypertensive effect.
Other antihypertensive agents (beta blockers): decrease of the antihypertensive action due to the inhibiting effect of vasodilating prostaglandins.
Valproic acid: increased toxicity of valproic acid due to displacement from protein binding sites.
Tetracyclines: Mg and Al salts reduce enteric absorption of tetracyclines.
Uricosurics such as probenecid: decreased uricosuric effect (competition with the tubular elimination of uric acid).
Vancomycin: increased risk of vancomycin ototoxicity.
Alcohol: increased damage to the gastrointestinal mucosa and prolonged bleeding time due to the additive effects of acetylsalicylic acid and alcohol.
Warnings It is important to know that:
As with any other salicylate, Ascriptin should be taken on a full stomach.
Mg and Al salts reduce enteric absorption of tetracyclines: it is recommended to avoid their intake during oral tetracycline therapies.
Aluminum hydroxide can cause constipation and an overdose of magnesium salts can cause bowel hypomotility; high doses of this medicine may cause or aggravate intestinal obstruction and pathological ileus in patients at higher risk, such as those with renal impairment, in children less than 2 years of age or the elderly.
Aluminum hydroxide is not well absorbed from the gastrointestinal tract and systemic effects are therefore rare in patients with normal renal function. However, excessive doses or long-term use, or even normal doses in patients with low phosphorus diets or in children under 2 years of age can lead to phosphate elimination (due to an aluminum-phosphate bond) accompanied by an increase in bone resorption and hypercalciuria with risk of osteomalacia. It is advisable to consult your doctor in case of long-term use or in patients at risk of hypophosphataemia.
In patients with G6PD deficiency, acetylsalicylic acid should be administered under close medical supervision due to the risk of haemolysis (see Side Effects).
Preoperative use can hinder intraoperative haemostasis
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.
Ascriptin should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
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.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
The use in pregnancy for long periods and the administration in the last three months of pregnancy must be done only on medical prescription since acetylsalicylic acid can cause haemorrhagic phenomena in the fetus and mother, delay in childbirth and, in the unborn child, early closure of the duct of Botallo. During the last three months and particularly in the last weeks of pregnancy, it would be advisable to avoid the use of acetylsalicylic acid.
- Low doses (up to 100 mg / day)
Clinical studies indicate that doses up to 100 mg / day can be considered safe for use only in obstetrics, which requires specialist monitoring.
- Doses of 100-500 mg / day
There are insufficient clinical data regarding the use of doses above 100 mg / day up to 500 mg / day. Therefore, the recommendations below for doses of 500 mg / day and above also apply to this dose range.
- 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 miscarriage 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 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 loss of pre- and post-implantation 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 and second trimester 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 and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester 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;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently, acetylsalicylic acid at doses> 100 mg / day is contraindicated during the third trimester of pregnancy.
Pregnancy
As it is excreted in breast milk, the use of the medicine is not recommended during breastfeeding due to the risk of producing side effects in the baby.
Effects on ability to drive or use machines
Ascriptin does not affect the ability to drive or use machines.
Important information about some of the ingredients of Ascriptin tablets
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Ascriptin: Dosage
Adults
As an antiplatelet agent:
1 tablet or ½ tablet per day in a single administration.
As an analgesic, antipyretic, antirheumatic:
1-2 tablets 2-4 times a day in the opinion of the doctor.
Children and adolescents under the age of 16
Doses appropriately reduced according to age.
The intake of the tablets containing acetylsalicylic acid should preferably take place on a full stomach, particularly when it is necessary to administer the product in high doses or for long periods of time.
In the treatment of elderly patients the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Overdose What to do if you have taken too much Ascriptin
Salicylate toxicity can be the consequence of chronic overdose, or acute, potentially life-threatening overdose, which also includes accidental ingestion in children.
Overdose with salicylates, particularly in young children, can lead to severe hypoglycemia and potentially fatal intoxication.
Chronic salicylate poisoning can be insidious since the signs and symptoms are nonspecific. Symptoms include dizziness, vertigo, tinnitus, deafness, sweating, nausea and vomiting, headache, confusion, blurred vision, vasodilation and hyperventilation. neurological disorders such as confusion, delirium, seizures and coma).
The main characteristic of acute intoxication is a severe alteration of the acid-base balance, which can vary with age and the severity of the intoxication; the most common presentation in children is metabolic acidosis while respiratory alkalosis is found in adults. Non-cardiogenic pulmonary edema may occur with acute and chronic overdose of acetylsalicylic acid (see Undesirable Effects).
Reported symptoms of acute overdose with aluminum hydroxide and magnesium salts in combination include diarrhea, abdominal pain, vomiting.
High doses of magnesium and aluminum can cause or aggravate intestinal obstruction and pathological ileus in patients at risk (see Special Warnings).
The management of an "intoxication is determined by the" entity, stage and clinical symptoms of the latter and must be implemented according to conventional poisoning management techniques. The main measures to be adopted are the "acceleration of" drug excretion ( gastric lavage, forced alkaline diuresis) and in the restoration of electrolyte and acid-base metabolism. In cases of severe intoxication and if renal function is impaired, hemodialysis is recommended.
In case of accidental ingestion / intake of an excessive dose of Ascriptin, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Ascriptin, ask your doctor or pharmacist.
Side Effects What are the side effects of Ascriptin
Like all medicines, Ascriptin can cause side effects, although not everybody gets them.
The frequency of adverse reactions described below is defined using the following convention: very common (≥ 1/10), common (≥ 1/100,
The following side effects may be encountered during treatment with acetylsalicylic acid:
The undesirable effects of acetylsalicylic acid, in most cases, are a consequence of its pharmacological mechanism of action and mainly affect the gastrointestinal tract. Some kind of side effect occurs in 5% -7% of patients.
Disorders of the blood and lymphatic system
Common: hypoprothrombinemia (at high doses)
Uncommon: anemia
Not known: haematological effects, such as haemorrhagic syndromes (epistaxis, bleeding gums, purpura, etc.) with increased bleeding time have also been reported. This action persists for 4-8 days after stopping treatment with acetylsalicylic acid.
Thrombocytopenia. Haemolytic anemia in patients with glucose 6 phosphate dehydrogenase (G6PD) deficiency (see Special Warnings). Pancytopenia, bilinear cytopenia, aplastic anemia, bone marrow failure, agranulocytosis, neutropenia, leukopenia.
Nervous system disorders
Not known: Sweating, headache and confusion may occur at prolonged high doses. Intracranial haemorrhage which could be fatal, especially when the medicine is given to the elderly.
Ear and labyrinth disorders
Not known: Dizziness, tinnitus and deafness may occur at prolonged high doses. In these cases the treatment must be stopped immediately.
Respiratory, thoracic and mediastinal disorders
Common: rhinitis, paroxysmal bronchospasm, severe dyspnoea
Not known: non-cardiogenic pulmonary edema during chronic use and in the context of hypersensitivity reaction to acetylsalicylic acid.
Gastrointestinal disorders
Common: gastrointestinal haemorrhage (melaena, haematemesis). Abdominal pain, nausea, dyspepsia, vomiting, gastric ulcer, duodenal ulcer.
Not known:
- Upper gastrointestinal disorders: esophagitis, erosive duodenitis, erosive gastritis, esophageal ulcers, perforations.
- Diseases of the lower gastrointestinal tract: 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
Uncommon: hepatotoxicity, particularly in patients with juvenile arthritis
Not known: increased liver enzymes, mainly hepatocellular liver damage, chronic hepatitis
Skin and subcutaneous tissue disorders
Common: urticaria, exanthematous rash, angioedema, fixed eruptions.
Renal and urinary disorders
Not known: renal failure. Prolonged high doses can cause acute renal failure and acute interstitial nephritis.
General disorders and administration site conditions
Uncommon: Reye's syndrome (in patients less than 16 years of age)
Not known: Anaphylactic / anaphylactoid reactions may occur in patients with a history of hypersensitivity to acetylsalicylic acid and / or other non-steroidal anti-inflammatory drugs. This may also occur in patients who have not previously shown hypersensitivity to these drugs.
Pregnancy, puerperium and perinatal conditions
Not known: late delivery.
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.
The following side effects may be encountered during treatment with combinations of magnesium and aluminum hydroxide:
Side effects are not common at recommended doses.
Disorders of the immune system
Not known: hypersensitivity reactions, such as itching, urticaria, angioedema and anaphylactic reactions.
Gastrointestinal disorders:
Uncommon: diarrhea or constipation (see Special warnings).
Pathologies of metabolism and nutrition
Not known:
hypermagnesemia,
hyperalluminemia,
hypophosphataemia, during prolonged use or in high doses or even at normal doses of the medicinal product in patients with low phosphorus diets or in children under 2 years of age, which can cause increased bone resorption, hypercalciuria, osteomalacia (see Warnings special).
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. Side effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety of this medicine.
Expiry 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.
Store below 30 ° C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
COMPOSITION
One breakable tablet contains:
Active principles: Acetylsalicylic acid 300 mg, Magnesium hydroxide 80 mg, Aluminum oxide hydrate 91.50 mg (corresponding to 70 mg of Aluminum hydroxide).
Excipients: Cornstarch; Talc; Lactose; Magnesium stearate.
PHARMACEUTICAL FORM AND CONTENT
"Tablets" 20 divisible 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
ASCRIPTIN TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One breakable tablet contains:
- Active principles:
Acetylsalicylic acid 300 mg;
magnesium hydroxide 80 mg;
aluminum oxide hydrate 91.50 mg
(corresponding to 70 mg of aluminum hydroxide).
Excipients with known effects: lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Adults
1. 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
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
3. Analgesic, antipyretic and anti-inflammatory in rheumatism, rheumatoid arthritis, head and toothache, neuralgia, muscle, joint and menstrual pain, flu and cold symptoms.
Children and adolescents under the age of 16
The medicine is only indicated for: rheumatoid arthritis, rheumatic disease, Kawasaki disease and as an antiplatelet agent.
04.2 Posology and method of administration
Adults
As an antiplatelet agent:
1 tablet or ½ tablet per day in a single administration.
As an analgesic, antipyretic, antirheumatic:
1-2 tablets 2-4 times a day, in the opinion of the doctor.
Children and adolescents under the age of 16
Doses appropriately reduced according to age.
The intake of the tablets containing acetylsalicylic acid should preferably take place on a full stomach, particularly when it is necessary to administer the product in high doses or for long periods of time. In the treatment of elderly patients, the dosage must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
04.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
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).
Gastro-duodenal ulcer disease, hypersensitivity to salicylates, haemorrhagic diathesis.
Patients with severe hepatic insufficiency.
Patients with severe renal insufficiency (ClCr
Severe uncontrolled heart failure,
Concomitant treatment with methotrexate at doses of 15 mg / week or more (see section 4.5),
History of asthma induced by administration of salicylates or substances with similar activity, particularly non-steroidal anti-inflammatory drugs,
The use of this medicinal product is contraindicated in children and young people under the age of 16 except as indicated in section 4.1.
Dose> 100 mg / day during the third trimester of pregnancy.
This medicine should not be used in the course of viral diseases, such as chicken pox or flu, due to the risk of Reye's syndrome.
04.4 Special warnings and appropriate precautions for use
As with any other salicylate, Ascriptin should be taken on a full stomach.
Mg and Al salts reduce enteric absorption of tetracyclines: it is recommended to avoid their intake during oral tetracycline therapies.
Aluminum hydroxide can cause constipation and an overdose of magnesium salts can cause bowel hypomotility; high doses of this medicine may cause or aggravate intestinal obstruction and pathological ileus in patients at higher risk, such as those with renal impairment, in children less than 2 years of age or the elderly.
Aluminum hydroxide is not well absorbed from the gastrointestinal tract and systemic effects are therefore rare in patients with normal renal function. However, excessive doses or long-term use, or even normal doses in patients with low phosphorus diets or in children under 2 years of age can lead to phosphate elimination (due to an aluminum-phosphate bond) accompanied by an increase in bone resorption and hypercalciuria with risk of osteomalacia. It is advisable to consult your doctor in case of long-term use or in patients at risk of hypophosphataemia.
Use with caution in cases of asthma, gout and in patients with mild and moderate hepatic insufficiency.
In patients with G6PD deficiency, acetylsalicylic acid should be administered under close medical supervision due to the risk of haemolysis (see section 4.8).
Preoperative use can hinder intraoperative haemostasis.
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.
Ascriptin should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
This medicinal product should not be used in children and young people under the age of 16 (see contraindications 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.
Ascriptin 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
The effect of the treatment may be modified if Ascriptin is taken concomitantly with other medicines such as:
- anticoagulants (eg warfarin);
- anti-rejection drugs (eg cyclosporine, tacrolimus);
- antihypertensives (eg diuretics and ACE inhibitors);
- painkillers and anti-inflammatories (eg steroids, NSAIDs);
- drugs for gout (probenecid);
- anti-cancer and rheumatoid arthritis drugs (methotrexate)
Contraindicated associations:
Methotrexate in doses greater than or equal to 15 mg / week:
Increased haematological toxicity of methotrexate (anti-inflammatories generally decrease the renal clearance of methotrexate and salicylates displace methotrexate from its plasma protein binding) (see section 4.3).
Associations requiring precautions for use:
Methotrexate at doses below 15 mg / week:
Increased haematological toxicity of methotrexate (anti-inflammatories generally decrease the renal clearance of methotrexate and salicylates displace methotrexate from its binding to plasma proteins).
Metamizole: metamizole when taken concomitantly with acetylsalicylic acid can reduce the "effect on" platelet aggregation. Therefore, this combination should be used with caution in patients taking low doses of acetylsalicylic acid for cardioprotection.
Ibuprofen: Experimental data indicate that ibuprofen may inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when drugs are administered concomitantly.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 (see sections 4.4 and 5.1).
Anticoagulants, thrombolytics / other antiplatelet agents: increased risk of bleeding.
Other non-steroidal anti-inflammatory drugs containing salicylates in high doses: increased risk of gastrointestinal ulcers and bleeding due to the synergistic effect.
Selective serotonin re-uptake inhibitors: increased risk of bleeding in general and of the upper gastrointestinal tract in particular, due to a possible synergistic effect.
Systemic alkalizers (e.g. bicarbonates): administration accelerates the excretion of salicylates reducing their therapeutic efficacy.
Ciclosporin: increased cyclosporine-induced nephrotoxicity. Particular attention is recommended, particularly in elderly patients.
Digoxin: increase in the plasma concentration of digoxin due to a decrease in renal excretion.
Antidiabetics, eg. insulin, sulfonylureas: increased hypoglycemic effect for high doses of acetylsalicylic acid, through the hypoglycemic action of acetylsalicylic acid and displacement of sulfonylureas from protein binding sites.
Diuretics in combination with high-dose acetylsalicylic acid: reduction of glomerular filtration through the reduction of prostaglandin synthesis.
Systemic glucocorticoids, with the exception of hydrocortisone used as replacement therapy in Addison's disease: reduction of levels of salicylates in the blood during treatment with corticosteroids and risk of overdose of salicylates after its discontinuation, due to the increased elimination of salicylates by corticosteroids.
Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) and Angiotensin II receptor antagonists (Sartans) in combination with high dose acetylsalicylic acid: reduced glomerular filtration through the inhibition of vasodilating prostaglandins. Furthermore, reduction of the anti-hypertensive effect.
Other antihypertensives (beta blockers): decrease in the antihypertensive action due to the inhibiting effect of vasodilating prostaglandins.
Valproic acid: increased toxicity of valproic acid due to displacement from protein binding sites.
Tetracyclines: Mg and Al salts reduce enteric absorption of tetracyclines.
Uricosurics such as probenecid: decreased uricosuric effect (competition with the tubular elimination of uric acid).
Vancomycin: increased risk of vancomycin ototoxicity.
Alcohol: increased damage to the gastrointestinal mucosa and prolonged bleeding time due to the additive effects of acetylsalicylic acid and alcohol.
04.6 Pregnancy and lactation
Pregnancy
The use in pregnancy for long periods and the administration in the last three months of pregnancy must be done only on medical prescription since acetylsalicylic acid can cause haemorrhagic phenomena in the fetus and mother, delay in childbirth and, in the unborn child, early closure of the duct of Botallo. During the last three months and particularly in the last weeks of pregnancy, it would be advisable to avoid the use of acetylsalicylic acid.
- Low doses (up to 100 mg / day)
Clinical studies indicate that doses up to 100 mg / day can be considered safe for use only in obstetrics, which requires specialist monitoring.
- Doses of 100-500 mg / day
There are insufficient clinical data regarding the use of doses above 100 mg / day up to 500 mg / day. Therefore, the recommendations below for doses of 500 mg / day and above also apply to this dose range.
- 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 and second trimester 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 and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester 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;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently, acetylsalicylic acid at doses> 100 mg / day is contraindicated during the third trimester of pregnancy.
Feeding time
As it is excreted in breast milk, the use of the medicine is not recommended during breastfeeding due to the risk of producing side effects in the baby.
04.7 Effects on ability to drive and use machines
Ascriptin does not affect the ability to drive or use machines.
04.8 Undesirable effects
The frequency of adverse reactions described below is defined using the following convention: very common (≥ 1/10), common (≥ 1/100,
The following side effects may be encountered during treatment with acetylsalicylic acid:
The undesirable effects of acetylsalicylic acid, in most cases, are a consequence of its pharmacological mechanism of action and mainly affect the gastrointestinal tract. Some kind of side effect occurs in 5% -7% of patients.
Disorders of the blood and lymphatic system
Common: hypoprothrombinemia (at high doses)
Uncommon: anemia
Not known: haematological effects, such as haemorrhagic syndromes (epistaxis, bleeding gums, purpura, etc.) with increased bleeding time have also been reported. This action persists for 4-8 days after stopping treatment with acetylsalicylic acid.
Thrombocytopenia.
Haemolytic anemia in patients with glucose 6 phosphate dehydrogenase (G6PD) deficiency (see section 4.4).
Pancytopenia, bilinear cytopenia, aplastic anemia, bone marrow failure, agranulocytosis, neutropenia, leukopenia.
Nervous system disorders
Not known: Sweating, headache and confusion may occur at prolonged high doses.
Intracranial haemorrhage which could be fatal, especially when the medicine is given to the elderly.
Ear and labyrinth disorders
Not known: Dizziness, tinnitus and deafness may occur at prolonged high doses. In these cases the treatment must be stopped immediately.
Respiratory, thoracic and mediastinal disorders
Common: rhinitis, paroxysmal bronchospasm, severe dyspnoea
Not known: non-cardiogenic pulmonary edema during chronic use and in the context of hypersensitivity reaction to acetylsalicylic acid.
Gastrointestinal disorders:
Common: gastrointestinal haemorrhage (melaena, haematemesis). Abdominal pain, nausea, dyspepsia, vomiting, gastric ulcer, duodenal ulcer.
Not known:
• 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.
Hepatobiliary disorders
Uncommon: hepatotoxicity, particularly in patients with juvenile arthritis
Not known: increased liver enzymes, mainly hepatocellular liver damage, chronic hepatitis.
Skin and subcutaneous tissue disorders
Common: urticaria, exanthematous rash, angioedema, fixed eruptions.
Renal and urinary disorders
Not known: renal failure.
Prolonged high doses can cause acute renal failure and acute interstitial nephritis.
General disorders and administration site conditions
Uncommon: Reye's syndrome (in patients less than 16 years of age)
Not known: Anaphylactic / anaphylactoid reactions may occur in patients with a history of hypersensitivity to acetylsalicylic acid and / or other non-steroidal anti-inflammatory drugs. This may also occur in patients who have not previously shown hypersensitivity to these drugs.
Pregnancy, puerperium and perinatal conditions
Not known: late delivery.
The following side effects may be encountered during treatment with combinations of magnesium and aluminum hydroxide:
Side effects are not common at recommended doses.
Disorders of the immune system
Not known: hypersensitivity reactions, such as itching, urticaria, angioedema and anaphylactic reactions.
Gastrointestinal disorders:
Uncommon: diarrhea or constipation (see section 4.4).
Pathologies of metabolism and nutrition
Not known:
hypermagnesemia,
hyperalluminemia,
hypophosphataemia, during prolonged use or at high doses or even at normal doses of the medicinal product in patients on low phosphorus diets or in children less than 2 years of age, which can cause increased bone resorption, hypercalciuria, osteomalacia (see section 4.4).
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. "Italian Medicines Agency. Website: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Salicylate toxicity can be the consequence of chronic overdose, or acute, potentially life-threatening overdose, which also includes accidental ingestion in children.
Overdose with salicylates, particularly in young children, can lead to severe hypoglycemia and potentially fatal intoxication.
Chronic salicylate poisoning can be insidious since the signs and symptoms are nonspecific. Symptoms include dizziness, vertigo, tinnitus, deafness, sweating, nausea and vomiting, headache, confusion, blurred vision, vasodilation and hyperventilation. neurological disorders such as confusion, delirium, seizures and coma).
The main characteristic of acute intoxication is a severe alteration of the acid-base balance, which can vary with age and the severity of the intoxication; the most common presentation in children is metabolic acidosis while respiratory alkalosis is found in adults.
Non-cardiogenic pulmonary edema may occur with acute and chronic overdose of acetylsalicylic acid (see section 4.8).
Reported symptoms of acute overdose with aluminum hydroxide and magnesium salts in combination include diarrhea, abdominal pain, vomiting.
High doses of magnesium and aluminum can cause or aggravate intestinal obstruction and pathological ileus in patients at risk (see section 4.4).
The management of an "intoxication is determined by the" entity, stage and clinical symptoms of the latter and must be implemented according to conventional poisoning management techniques. The main measures to be adopted are the "acceleration of" drug excretion ( gastric lavage, forced alkaline diuresis) and in the restoration of electrolyte and acid-base metabolism. In cases of severe intoxication and if renal function is impaired, hemodialysis is recommended.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antithrombotics, antiplatelet agents.
ATC code: B01AC06.
Evaluation of "in vivo" buffering capacity. Oral administration of Ascriptin in Wistar rats in comparison with ASA and with AL (OH) 3 + Mg (OH) 2 highlights the non-influence of the acid component on the buffering action of the alkaline component.
The analgesic, antipyretic and anti-inflammatory properties of Ascriptin, evaluated by classical pharmacological models, have shown to be comparable to those recognized for acetylsalicylic acid at the same doses as those contained in Ascriptin.
Treatment with single sub-toxic doses of Ascriptin (460-676 mg / kg orally in the Wistar rat) causes an "alteration of the acid-base balance" of the blood similar to that caused by equal doses of acetylsalicylic acid. There is also a modest increase in total acidity, however the quantity of free hydrochloric acid is less than that caused by the administration of acetylsalicylic acid, in doses equal to those contained in Ascriptin.
The antiplatelet activity of Ascriptin was highlighted by evaluating the inhibition of thromboxane in healthy volunteers: in all the subjects studied a complete inhibition appeared within 60 minutes of administration and persisted for at least 24 hours.
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 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
The oral administration of Ascriptin showed a rapid absorption of the acetylsalicylic acid contained in it: the peak is reached within 60 "with serum levels between 2.76 and 6.75 mg / ml.
Bioavailability.
"In vitro" it has been shown that magnesium and aluminum hydroxides significantly increase the dissolving power of acetylsalicylic acid.
The absorption was the same for both free acetylsalicylic acid and that contained in Ascriptin; however, the higher dissolution rate leads, for Ascriptin, to a faster and higher serum salicylate peak.
"In vivo" the magnesium and aluminum hydroxides, with no systemic effects, buffer, for a time of about 32 minutes, the pH of the gastric juice around 3-5 values, therefore close to the pK of acetylsalicylic acid and consequently they accelerate and facilitate its absorption, thus protecting the gastroduodenal mucosa from the irritating and damaging effects of acetylsalicylic acid.
05.3 Preclinical safety data
For acute administration. DL50 rat S.D. per os: 2030 mg / kg.
The proven non-influence of the antacid component on the well known low acute toxicity of acetylsalicylic acid rendered further acute toxicity tests useless.
For prolonged administration. Wistar rats 30 days. Daily oral administrations of 338/667 and 1015 mg / kg. Doses up to 667 mg / kg were well tolerated. At a dose of 1015 mg / kg (140 times higher than the comparative therapeutic dose), on the other hand, there is a negative action on weight and accentuated mortality.
Wistar rats growing 150 days. Daily oral administrations of 200 mg / kg (30 times higher than the comparative therapeutic dose) do not affect body growth (weight), blood count, liver function, weight and appearance of major organs.
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
Cornstarch; lactose; talc; magnesium stearate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store below 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Box of 20 divisible tablets in opaque blister.
06.6 Instructions for use and handling
No special instructions for disposal.
07.0 MARKETING AUTHORIZATION HOLDER
Sanofi S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
A.I.C. n. 023075029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
16.04.1975 / 01.06.2010
10.0 DATE OF REVISION OF THE TEXT
October 2014.
