Active ingredients: Paracetamol, Propiphenazone, Caffeine
Saridon tablets
Indications Why is Saridon used? What is it for?
Saridon belongs to the therapeutic category of analgesics-antipyretics (medicines used to reduce pain and fever).
Saridon is used for the symptomatic treatment of acute painful states (i.e. short-lived, such as headache, toothache, neuralgia, menstrual pain) and febrile states.
Do not administer for more than 3 consecutive days without consulting your doctor.
Contraindications When Saridon should not be used
Don't take Saridon
- if you are allergic to paracetamol, propiphenazone or caffeine or any of the other ingredients of this medicine (listed in section 6).
- if you are allergic to other chemically closely related substances;
- if you have a history of gastrointestinal bleeding (stomach and intestines) or perforation related to previous active treatments or a history of recurrent peptic (internal mucosa of the stomach, duodenum or "esophagus) haemorrhage / ulcer (two or more distinct episodes of proven ulceration or bleeding);
- if you suffer from haemopathies (blood disorders) such as granulocytopenia (low number of granulocytes, a particular type of white blood cell, in the blood) and intermittent porphyrias (deficiency of an enzyme known as PGB deaminase);
- if you suffer from glucose-6-phosphate dehydrogenase deficiency (a disease commonly called favism);
- if you have severe haemolytic anemia (anemia caused by the destruction of red blood cells);
- if you suffer from severe hepatocellular (insufficient function of liver cells), renal or cardiac insufficiency (the inability of the heart to pump the adequate amount of blood necessary for the body's needs);
- if you are pregnant or breastfeeding (see "Pregnancy and breastfeeding");
Saridon should not be given to children under the age of 12 due to the presence of caffeine.
Precautions for use What you need to know before taking Saridon
Talk to your doctor or pharmacist before taking Saridon:
- if you have or have suffered from stomach or duodenal ulcers; in this case the use of Saridon should be closely monitored by a physician. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be If you have suffered from gastrointestinal toxicity you should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
- if you suffer from renal (reduced kidney function) or hepatic (reduced liver function), Gilbert's syndrome (benign liver disease manifested by excessive and uncontrolled rise in bilirubin) or haematopoietic dysfunction (in the formation of cellular components of the blood);
- if you take any other medicines that contain the same active substance (paracetamol), as if paracetamol is taken in high doses, serious adverse reactions can occur (see also "Other medicines and Saridon");
- if you suffer from asthma, chronic rhinitis or chronic urticaria, as there have been isolated reports of asthma attacks and anaphylactic shock associated with the use of medicines containing propiphenazone and paracetamol;
- if you have heart problems or a history of stroke (cerebrovascular accident) or think you may be at risk for these conditions (for example if you have high blood pressure, high cholesterol level, diabetes or if you smoke) due to the use of some NSAIDs (especially at high doses and for long-term treatments) may be associated with a modest increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke);
- if you have a history of hypertension (high blood pressure) and / or heart failure (the inability of the heart to pump the adequate amount of blood necessary for the body's needs), as in association with treatment with NSAIDs (Anti-inflammatory Drugs Non-Steroidal) have been reported to have fluid retention, hypertension and edema (swelling caused by excessive accumulation of fluid in cells or tissues).
- if you suffer from hyperthyroidism: in this case the use of Saridon should be carefully monitored by a doctor.
Children and adolescents
Saridon should not be taken by children under the age of 12.
Interactions What medications or foods may change the effect of Saridon
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, even those obtained without a prescription. The use of Saridon should be avoided in conjunction with NSAIDs, including selective COX-2 inhibitors.
Take special care if you take:
- Corticosteroids (contain cortisol, a hormone produced by the adrenal glands), as concomitant use increases the risk of gastrointestinal ulceration or bleeding;
- Oral anticoagulants (medicines that prevent blood clots), such as warfarin: NSAIDs (including paracetamol) can increase the effects of anticoagulants, therefore, you should not take paracetamol for long periods without medical supervision, because paracetamol can increase the effects of anticoagulants; in the case of therapy with oral anticoagulants, it is recommended to reduce the doses;
- Antiplatelet agents (medicines that prevent blood clot formation) and selective serotonin reuptake inhibitors (SSRIs, antidepressants), as it increases the risk of gastrointestinal bleeding;
- Diuretics (medicines that increase urine production), ACE inhibitors and angiotensin II antagonists (medicines used to treat high blood pressure), as NSAIDs may reduce the effect of diuretics and other antihypertensive medicines. In case of same-day administration, take special care, especially if you have impaired kidney function (particularly if you are elderly or dehydrated). After initiation of concomitant therapy, you will need to hydrate adequately and your doctor will consider monitoring your renal function.
- Hypoglycaemics (medicines used in the treatment of diabetes), such as acetohexamide, chlorpropamide, tolbutamide;
- Probenecid (medicine used to treat gout and hyperuricaemia [high concentration of uric acid in the blood]): in case of concomitant treatment, your doctor will have to consider a reduction in the dose of paracetamol.
- Medicines that increase the rate of gastric emptying (eg metoclopramide, domperidone), as they lead to an increase in the absorption rate of paracetamol;
- Cholestyramine (medicine used to reduce cholesterol levels in the blood) as it reduces the absorption of paracetamol;
- Chloramphenicol (antibiotic), since paracetamol can increase its half-life (the time it takes to reduce the amount of a medicine in plasma or blood by half) and thus potentially increase its toxicity;
- AZT (zidovudine - antiretroviral, against the attack of some viruses); the simultaneous use of paracetamol and AZT increases the tendency to a reduction in the count of leukocytes or white blood cells (neutropenia). Therefore, the product must not be taken in combination with AZT (zidovudine) except on medical prescription;
- Anti-inflammatory drugs (NSAIDs) and pain relievers (opioids), as co-administration with Saridon results in a reciprocal enhancement of the analgesic effect. The use of Saridon is not recommended if you are being treated with anti-inflammatories.
- Ethinylestradiol (contraceptive), because paracetamol increases its bioavailability (the amount absorbed);
- Lamotrigine (antiepileptic), as it can reduce the bioavailability (the amount absorbed) of paracetamol;
- Protective agents (misoprostol or proton pump inhibitors): Concomitant use of protective agents should be considered in elderly patients and also in patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events.
- Tropisetron and granisetron (antiemetics, medicines used for nausea and vomiting): these medicines can completely inhibit the analgesic effect of paracetamol.
If you are being treated with rifampicin (antibiotic), cimetidine (medicine against stomach acid) or with antiepileptic medicines (phenytoin, glutethimide, phenobarbital, carbamazepine) use paracetamol with extreme caution and only under strict medical supervision. interfere with the determination of uricaemia (by the phosphotungstic acid method) and with that of blood glucose (by the glucose-oxidase-peroxidase method). If you need to undergo blood tests such as those listed above, please inform your doctor.
Saridon with alcohol
The product may interact with alcohol; moderate alcohol intake in conjunction with paracetamol intake, even at low doses, may increase the risk of liver (liver) damage.
Warnings It is important to know that:
Pregnancy and breastfeeding
Saridon should not be used during pregnancy and breastfeeding. Avoid using the medicine even if you suspect you are pregnant or plan to have a mother.
Driving and using machines
Due to the possible onset of vertigo, dizziness or somnolence, Saridon may impair the ability to drive and use machines.
Dosage and method of use How to use Saridon: Dosage
Always take this medicine exactly as described in this leaflet or as directed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
Take Saridon on a full stomach. Swallow the medicine with a large amount of water.
The recommended doses are:
Adults: 1-2 tablets, up to a maximum of 4 tablets in 24 hours.
Use in elderly patients and in patients with a history of ulcer: Elderly patients should follow the minimum dosages indicated above
Warning: do not exceed the indicated doses without medical advice. Do not administer for more than 3 consecutive days without consulting your doctor.
Consult your doctor if the disorder occurs repeatedly or if you have noticed any recent changes in its characteristics.
Overdose What to do if you have taken too much Saridon
In the event of an overdose, paracetamol can cause serious damage to liver cells which can lead to massive and irreversible destruction of the same. Due to the presence of caffeine, always for high doses, hyperstimulation with excitement, insomnia, muscle tremor, nausea, vomiting, increased urinary volume, increased heart rate, heartbeat (palpitations) and a reduction in the visual field may occur. Kidney damage following tubular necrosis (the destruction of kidney tubular cells) has been described. In general, continued use of paracetamol, especially in combination with other analgesics, can lead to permanent kidney damage and kidney failure (analgesic nephropathy). Taking more than recommended amounts incorrectly can cause seizures. If you accidentally ingest / take too much of Saridon, notify your doctor immediately or go to the nearest hospital.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Saridon
Like all medicines, this medicine can cause side effects, although not everybody gets them.
When gastrointestinal bleeding or ulceration occurs in patients taking Saridon the treatment should be discontinued.
Serious side effects:
If fever or sore throat appears during treatment, discontinue therapy and consult your doctor. G.
Rare skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs). The highest risk appears to be in non-steroidal anti-inflammatory drugs (NSAIDs). early stages of therapy, since the onset of the reaction in most cases occurs within the first month of treatment. Stop taking Saridon at the first appearance of a skin rash, mucosal lesions or any other signs of allergy.
The adverse reactions listed below derive from spontaneous reports and therefore it is not possible to organize them by frequency categories.
Skin (skin) and subcutaneous tissue disorders:
Skin reactions of various types and severities have been reported, including:
- rash,
- itch;
- urticaria;
- allergic edema and angioedema (swollen and itchy skin areas located most frequently in the extremities, external genitalia and face, especially in the eye and lip region);
- generalized acute exanthematous pustulosis (eruption of superficial small pustules);
- fixed erythema (red-purple erythematous patches);
- erythema multiforme (bright red skin lesions caused by inflammation of the blood vessels);
- bullous reactions including Stevens-Johnson syndrome and epidermal necrolysis (very rarely) (two serious skin diseases with possible fatal outcome).
Immune system disorders:
- hypersensitivity reactions (allergic reactions) such as cyanosis (bluish discoloration of the skin and mucous membranes), sweating, nausea, hypotension (low blood pressure), dyspnoea (difficulty in breathing), asthma, edema of the larynx (swelling larynx often accompanied by difficulty in breathing), anaphylactoid reaction, anaphylactic reaction, anaphylactic shock (possible symptoms of an anaphylactic reaction are: a severe and sudden drop in blood pressure, rapid or slow heart rate, unusual tiredness or weakness, anxiety, agitation, dizziness, loss of consciousness, difficulty in breathing [from laryngeal obstruction or bronchospasm] or swallowing).
Disorders of the blood and lymphatic system (blood disorders):
- changes in blood cell counts (shown in blood tests), such as thrombocytopenia (reduced number of platelets in the blood), thrombocytopenic purpura (coagulation disease), leukopenia (reduced number of white blood cells), anemia (reduced number of red blood cells), agranulocytosis (reduced number of granulocytes, a type of white blood cell, in the blood), pancytopenia (reduced number of all cells in the blood).
Elevation of serum alanine aminotransferase (ALT) may occur during administration of therapeutic doses of paracetamol.
Nervous system disorders:
- dizziness;
- drowsiness.
Hepatobiliary disorders (liver, biliary bladder and biliary tract):
- impaired liver function;
- hepatitis;
- dose-dependent liver failure, liver necrosis (the destruction of liver cells) life-threatening (see "Warnings and precautions" and "If you take more Saridon than you should").
Renal and urinary disorders:
- acute renal failure (rapid decrease in kidney function);
- interstitial nephritis (inflammation of the kidneys);
- hematuria (presence of blood in the urine);
- anuria (the absence of urine output).
Gastrointestinal disorders
The most commonly observed adverse events are gastrointestinal in nature:
- peptic ulcers (damage to the lining of the stomach), gastrointestinal perforation or haemorrhage, sometimes fatal, particularly in the elderly (see "Warnings and precautions"). In the elderly and in patients with a history of ulcer, especially if complicated with haemorrhage or perforation ( see section 4.3), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs. In this case, treatment should be started with the lowest available dose.
- nausea;
- He retched;
- diarrhea;
- flatulence (air in the intestine);
- constipation;
- dyspepsia (difficulty digesting);
- abdominal pain;
- melaena (presence of blood in the stool);
- hematemesis (vomiting of blood);
- ulcerative stomatitis (inflammation of the oral mucosa);
- exacerbation of colitis;
- Crohn's disease (see "Warnings and Precautions");
- gastritis (less frequently).
Thoracic and mediastinal disorders:
- bronchospasm and asthma (breathing disorders), including analgesic asthma syndrome.
Ear and labyrinth disorders:
- dizziness.
Edema (swelling caused by excessive accumulation of fluid in cells or tissues), hypertension (high blood pressure) and heart failure (the inability of the heart to pumping the adequate amount of blood needed by the body's needs.) Medicines such as Saridon may be associated with a modest increased risk of arterial thrombotic events such as heart attack ("myocardial infarction") or stroke (cerebrovascular accident).
Continued use of paracetamol, especially in combination with other analgesics, can lead to permanent kidney damage and kidney failure (analgesic nephropathy). High or prolonged doses of the product can cause a high risk liver disease and even serious alterations to the blood.Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. These side effects are usually transient. However, when they occur, it is advisable to consult your doctor or pharmacist.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children. Do not store above 30 ° C
Do not use this medicine after the expiry date which is stated on the package. The expiry date refers to the last day of that month. The expiry date refers to the product in intact packaging, correctly stored.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Saridon contains
- The active ingredients are: paracetamol, propiphenazone and caffeine. 1 tablet contains: paracetamol 250 mg, propiphenazone 150 mg, caffeine 25 mg.
- The other ingredients are: microgranular cellulose, povidone, maize starch, hypromellose, talc, magnesium stearate, precipitated silica.
What Saridon looks like and contents of the pack
Saridon comes in the form of tablets for oral use. The contents of the pack are 5,10 or 20 tablets.
Not all pack sizes may be marketed.
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
SARIDON TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains: paracetamol 250 mg, propiphenazone 150 mg, caffeine 25 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablet.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Symptomatic treatment of acute painful states (headache; toothache; neuralgia; menstrual pains) and of feverish states.
04.2 Posology and method of administration
Adults: 1-2 tablets, up to 4 tablets in 24 hours, with a generous sip of water. Do not exceed the recommended doses: in particular elderly patients should follow the minimum dosages indicated above.
The oral analgesic preparations must be taken on a full stomach.
Do not take for more than 3 consecutive days without consulting your doctor.
04.3 Contraindications
• Hypersensitivity to the active ingredients, to other closely related substances from a chemical point of view and / or to any of the excipients.
• History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
• Haemopathies such as granulocytopenia and intermittent porphyrias.
• Paracetamol-based products are contraindicated in patients with manifest insufficiency of glucose-6-phosphate dehydrogenase and in those suffering from severe haemolytic anemia.
- Severe hepatic insufficiency (Child-Pugh> 9).
- Severe renal insufficiency
- Severe heart failure.
- Due to the presence of caffeine, the product should not be given to children under 12 years of age.
- Pregnancy and breastfeeding.
04.4 Special warnings and appropriate precautions for use
Do not take for more than 3 consecutive days without consulting your doctor.
High or prolonged doses of the product can cause a high risk liver disease and even serious alterations to the blood.
An increase in serum alanine aminotransferase (ALT) may occur during administration of therapeutic doses of paracetamol.
Moderate alcohol intake in conjunction with paracetamol intake may increase the risk of liver toxicity.
Administer with caution in subjects with renal or hepatic insufficiency (Child-Pugh Gilbert's syndrome or haematopoietic dysfunction.
Patients suffering from kidney disorders should consult their doctor before taking the product as a dose adjustment may be required.
In general, continued use of paracetamol, especially in combination with other analgesics, can lead to permanent kidney damage and kidney failure (analgesic nephropathy).
Particular caution is required in patients with asthma, chronic rhinitis or chronic urticaria. There have been isolated reports of asthma attacks and anaphylactic shock associated with the intake of drugs containing propiphenazone and paracetamol in susceptible individuals. The erroneous intake of quantities greater than those recommended can cause convulsions.
If, during treatment, fever or angina resume, discontinue therapy and consult your doctor.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). In the early stages of therapy. patients appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Saridon should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
During therapy with oral anticoagulants it is recommended to reduce the doses.
During treatment with paracetamol, before taking any other drug, check that it does not contain the same active ingredient, as if paracetamol is taken in high doses, serious adverse reactions can occur.
The use of Saridon should be closely monitored by a physician in case of hyperthyroidism. Instruct the patient to contact the physician before combining any other medication.
See also section 4.5.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see below on gastrointestinal and cardiovascular risks).
Gastrointestinal Risks
The use of Saridon should be avoided in conjunction with NSAIDs, including selective COX-2 inhibitors.
Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially for gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), the risk of gastrointestinal bleeding, ulceration or perforation is higher with higher doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (see below and paragraph 4.5).
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking Saridon, the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).
The use of Saridon should be closely monitored by a physician in case of stomach or duodenal ulcers.
Cardiovascular and cerebrovascular effects
Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatments) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke). There are currently insufficient data to exclude a similar risk for propiphenazone when it is administered at a daily dose of 150-600 mg.
Caution is required before starting treatment in patients with a history of hypertension and / or heart failure, since fluid retention, hypertension and edema have been reported in association with treatment with NSAIDs.
04.5 Interactions with other medicinal products and other forms of interaction
Drugs that slow down gastric emptying (eg propanteline), can reduce the absorption rate of paracetamol, delaying its therapeutic effect.
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
Diuretics, ACE inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking Saridon concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in elderly patients. Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy.
The product can interact with alcohol; in case of alcohol abuse, the intake of paracetamol, even at low doses, can cause liver damage.
The product may interact with some hypoglycemic agents (acetohexamide, chlorpropamide, tolbutamide).
Probenecid causes the reduction of paracetamol clearance by at least 2-fold by inhibiting its conjugation with glucuronic acid. In case of concomitant treatment with probenecid a dose reduction of paracetamol should be considered.
Metoclopramide and domperidone (drugs that accelerate gastric emptying) can accelerate the absorption rate of paracetamol, while cholestyramine can "slow down the speed" and the degree of absorption.
Concomitant administration of chloramphenicol can induce a prolongation of the half-life of paracetamol, with the risk of elevating its toxicity.
It is not recommended to use the product if the patient is being treated with other anti-inflammatories.
Use with extreme caution and under strict control during chronic treatment with drugs that can determine the induction of hepatic mono-oxygenases or in case of exposure to substances that can have this effect (for example phenytoin, rifampicin, cimetidine, antiepileptics such as glutethimide, phenobarbital, carbamazepine).
The administration of paracetamol can interfere with the determination of uricaemia (by the phosphotungstic acid method) and with that of blood glucose (by the glucose-oxidase-peroxidase method).
The concomitant use of paracetamol and AZT (zidovudine) increases the tendency for a reduction in the white blood cell count (neutropenia). The product, therefore, should not be taken in combination with AZT (zidovudine) except by prescription.
The simultaneous administration of NSAIDs or opioids determines a reciprocal enhancement of the analgesic effect.
Paracetamol can reduce the effectiveness of lamotrigine.
Paracetamol (or its metabolites) interferes with the enzymes involved in the synthesis of coagulation factors dependent on vitamin K. The interaction between paracetamol and warfarin or coumarin derivatives can cause an increase in the international normalized ratio and an increased risk of bleeding Patients on oral anticoagulants should not take paracetamol for long periods without medical supervision.
Tropisetron and granisetron, serotonin 5-HT3 receptor antagonists, can completely inhibit the analgesic effect of paracetamol through a pharmacodynamic interaction.
04.6 Pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo-fetal development. The results of epidemiological studies suggest an increased risk of abortion, cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor. in the early stages of pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk has been considered 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. , an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
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 can occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
The use of Saridon is not recommended in case of presumed pregnancy.
Feeding time:
The medicine is contraindicated in breastfeeding.
04.7 Effects on ability to drive and use machines
Due to the possible onset of dizziness or somnolence, Saridon may impair the ability to drive and use machines.
04.8 Undesirable effects
The adverse reactions listed below derive from spontaneous reports and therefore it is not possible to organize them by frequency categories.
Skin and subcutaneous tissue disorders
Skin reactions of various types and severities have been reported, including rash, pruritus, urticaria, allergic edema and angioedema, acute generalized exanthematous pustulosis, fixed erythema, erythema multiforme, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rarely and with possible fatal outcome).
Disorders of the immune system.
Hypersensitivity reactions such as dyspnoea, sweating, nausea, hypotension, asthma, laryngeal edema, anaphylactoid reaction, anaphylactic reaction, anaphylactic shock have been reported.
Disorders of the blood and lymphatic system
Changes in the count of corpuscle elements in the blood, such as thrombocytopenia, thrombocytopenic purpura, leukopenia, anemia, agranulocytosis, pancytopenia.
Nervous system disorders
Dizziness, sleepiness.
Hepatobiliary disorders
Hepatic impairment, hepatitis, dose-dependent hepatic failure, life-threatening hepatic necrosis (see sections 4.4 and 4.9).
Renal and urinary disorders:
Acute renal failure, interstitial nephritis, haematuria, anuria.
Gastrointestinal disorders:
The most commonly observed adverse events are gastrointestinal in nature. Serious adverse events such as peptic ulcers, gastrointestinal perforation or haemorrhage (sometimes fatal, particularly in the elderly, may occur in association with the use of non-steroidal anti-inflammatory drugs (see section 4.4).
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Saridon (see section 4.4).
Gastritis has been observed less frequently.
Thoracic and mediastinal disorders
Bronchospasm and asthma, including analgesic asthma syndrome.
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke) (see paragraph 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. http://www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
In case of overdose, contact a doctor or poison control center immediately. Prompt medical intervention is important for both adults and children even if there are no obvious signs or symptoms.
Acute toxicity
Acute paracetamol intoxication has been associated with hepatocellular toxicity, caused by binding of the paracetamol metabolites to hepatic cell proteins. At therapeutic doses these metabolites are bound to glutathione and form non-toxic conjugates. In the event of a high overdose, the liver's supply of SH-donors (which promote the formation of glutathione) is depleted, toxic metabolites accumulate, and liver cell necrosis occurs, resulting in liver failure which can progressively lead to hepatic coma. Acute kidney injury with acute tubular necrosis may also occur (see Symptoms of Intoxication).
The threshold for paracetamol overdose may be reduced in patients who are taking certain types of drugs or alcohol, or are severely undernourished.
Chronic toxicity
Chronic toxicity includes liver changes of various kinds (see Symptoms of Intoxication). The data relating to the chronic toxicity and in particular to the nephrotoxicity of paracetamol are controversial. Attention should be paid to the possible influence on peripheral cell count.
Symptoms of intoxication
The onset of acute paracetamol intoxication is characterized by nausea, vomiting, abdominal pain, sweating and general malaise. The patient's condition may improve after 24-48 hours, although symptoms may not disappear completely.
Due to the presence of caffeine, always for high doses, hyperstimulation with excitement, insomnia, muscle tremor, nausea, vomiting, increased diuresis, tachycardia, ectopic beats may occur.
The size of the liver increases rapidly, the transaminases and bilirubin are elevated, the prothrombin time becomes pathological, the urinary flow is reduced, a slight azotemia may develop. Hypokalaemia and metabolic acidosis (including lactic acidosis) may also develop from acute and / or chronic overdose. Frequent clinical manifestations after 3-5 days are jaundice,
fever, hepatic stench, haemorrhagic diathesis, hypoglycemia, and liver damage. Liver damage can progress to all stages of hepatic encephalopathy, cerebral edema and death.
Acute renal injury with acute tubular necrosis may also occur, strongly suggested by low back pain, haematuria and proteinuria in the absence of severe hepatic injury.
Treatment of overdose
Intensive medical therapy with close monitoring of vital signs, laboratory parameters and circulatory conditions.
Gastric lavage is useful within the first 6 hours. Hemodialysis and haemoperfusion promote elimination of the substance. It is recommended that the plasma concentration of paracetamol be monitored.
In case of suspected paracetamol intoxication, within 10 hours of ingestion it is useful to administer sources of SH-groups, which conjugate reactive metabolites and accelerate detoxification. N-acetylcysteine can have a certain protective effect up to 48 hours after "ingestion.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: analgesic and antipyretic; paracetamol, combinations except psycholeptics.
ATC code: N02BE51
Saridon exhibits analgesic and antipyretic properties.
Its marked therapeutic efficacy is also due to the balanced synergy of its components.
Paracetamol is a substance with analgesic and antipyretic properties which are attributed to a direct effect on the pain centers and thermoregulation probably through the inhibition of PG-synthetase. Propiphenazone, belonging to the class of pyrazolics, possesses analgesic, anti-inflammatory and antipyretic.
The analgesic effect can be both central and peripheral, and there is evidence that propiphenazone acts centrally on the hypothalamic center which regulates the temperature.
The analgesic and antipyretic effect occurs rapidly, lasts a few hours and slowly regresses.
05.2 "Pharmacokinetic properties
Propiphenazone
Absorption
Propiphenazone is readily absorbed and exhibits more prolonged plasma concentrations when administered concomitantly with caffeine.
The oral bioavailability is 90%.
Peak plasma concentrations are reached approximately 0.5-0.6 hours after administration.
Distribution
Plasma protein binding is approximately 10%. Propiphenazone has a volume of distribution of 0.4 L / kg.
Metabolism
Propiphenazone undergoes significant hepatic metabolism. In the liver there is first demethylation with the formation of N-2 demethyl-propiphenazone and subsequently glucuronidation with the formation of the main active metabolite N-2-demethyl propiphenazone enol-glucuronide. First pass metabolism eliminates approximately 25% of the dose.
Elimination
Elimination occurs mainly via the kidney with a half-life of between 2.1 and 2.4 hours.
Part of the drug is excreted as unchanged propiphenazone and small amounts of other metabolites are excreted in the urine.
Paracetamol
Absorption
Following oral administration, paracetamol is rapidly absorbed (peak plasma level is reached in 30-90 minutes) and completely.
Distribution
In the organism, paracetamol diffuses widely in the body fluids and overcomes the blood-brain barrier, reaching concentrations in the cerebrospinal fluid equal to about 40% of those in the plasma.
The percentage of paracetamol bound to plasma proteins is minimal, but may increase following overdose.
Metabolism
Metabolism occurs almost completely in the liver, mainly by glucuronation (42-60% of a dose) and sulfation (33-52%). Less than 10% of a dose is conjugated to cystine (3-4%) or subjected to hydroxylation and acetylation (up to 4%). The highly reactive N-acetylparabenzoquinone hydroxylated intermediate metabolite imine (NAPQI) is formed from CYP 2E1 (to a lesser extent CYP 1A2 and 3A4). Generally NAPQI is neutralized in hepatocytes by reduced glutathione and its inactive transformation products (mercapturic acid and cystine conjugates) are rapidly excreted in the urine.
Elimination
Elimination is completed within 24 hours and occurs mainly in the urine both as unchanged substance and in the form of conjugated metabolites (glucuronates and sulphates).
However, the overdose of paracetamol can cause an intracellular accumulation of NAPQI sufficient to exceed the reducing capacity of glutathione; the compound can therefore irreversibly bind to the sulfhydryl groups of proteins, causing hepatocellular necrosis (typically centrilobular). The glucuronated and sulfated metabolites of paracetamol are relatively unstable and can partially convert back to the parent compound.
In the presence of adequate renal function they are rapidly excreted in the urine by glomerular filtration and tubular secretion, together with a small amount of unchanged paracetamol (about 3% of an oral dose). Urinary pH does not influence the process.
Caffeine
Caffeine is easily absorbed, metabolized almost completely and then excreted through the renal emunctory. The plasma half-life is indicated in humans in about 3.5 hours.
05.3 Preclinical safety data
Acute toxicity in rats with oral administration of 0.5-1-2 mg / kg was found to be very modest, while sub-chronic toxicity with per-kg doses 10-20-40 times greater than the maximum doses used in therapy in humans, showed the appearance of serious toxic effects only in the group of animals treated with the maximum dose. There is no further information on preclinical data other than that already reported in other parts of this Summary of Product Characteristics (see section 4.6 ).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Microgranular cellulose, povidone, corn starch, hypromellose, talc, magnesium stearate, precipitated silica.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Do not store above 30 ° C
06.5 Nature of the immediate packaging and contents of the package
The product is packaged in blister packs of plastic material coupled with aluminum tape, contained in a cardboard box together with the package leaflet.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Bayer S.p.A. Viale Certosa 130, 20156 Milan
Dealership for sale
Bruno Farmaceutici S.p.A
Via delle Ande, 15 00144 Rome
08.0 MARKETING AUTHORIZATION NUMBER
20 tablets AIC n ° 004336107
10 tablets AIC n ° 004336044
5 tablets AIC n 004336083 (not marketed)
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal: June 2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination: 02/2016
