Active ingredients: Ketoprofen, Sucralfate
KETODOL 25 mg + 200 mg modified release tablets
Why is Ketodol used? What is it for?
WHAT IS IT
KETODOL is an NSAID (non-steroidal anti-inflammatory drug).
KETODOL contains two active ingredients: ketoprofen, in the central core of the tablet, with pain relieving - anti-inflammatory activity; and sucralfate, in the lining of the tablet, with protective activity of the mucous membrane of the stomach (gastric).
First the sucralfate is released, which protects the gastric mucosa, and immediately after the ketoprofen, which carries out its pain relieving and anti-inflammatory activity.
WHY IT IS USED
You can use KETODOL in case of pain of various origins and nature (headache, toothache, neuralgia, osteo-joint and muscle pain, menstrual pain).
Contraindications When Ketodol should not be used
KETODOL should not be used in the following cases:
- allergy (hypersensitivity) to the active substances, or to any of the excipients;
- patients with a history of hypersensitivity reactions such as bronchospasm, asthma attacks, rhinitis, urticaria or in whom substances with a similar mechanism of action (for example acetylsalicylic acid or other NSAIDs) have previously caused allergic-type reactions; severe anaphylactic reactions, rarely fatal, have been observed in these patients (see "Undesirable Effects");
- in the third trimester of pregnancy, during breastfeeding and in pediatric age (see "What to do during pregnancy and" breastfeeding ");
- severe heart failure;
- active peptic ulcer or previous history of gastrointestinal bleeding, ulceration or perforation;
- history of gastrointestinal bleeding or perforation following previous NSAID therapy;
- easy tendency to bleed;
- severe liver failure;
- severe kidney failure;
- during intensive diuretic therapy;
- chronic functional digestive difficulties;
- gastritis;
- low number of white blood cells and platelets (leukopenia and thrombocytopenia);
- congenital changes in hemoglobin formation (porphyria);
- cirrhosis of the liver;
- during antibiotic treatments with tetracyclines, as the latter may be ineffective.
Precautions for use What you need to know before taking Ketodol
Do not use for prolonged treatments. After a short period of treatment without appreciable results, consult your doctor.
Avoid using KETODOL with other NSAIDs, including selective cyclooxygenase-2 inhibitors.
NSAIDs should be used with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may worsen (see "Undesirable effects").
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.
Some epidemiological evidence suggests that the active substance ketoprofen may be associated with a higher risk of serious gastrointestinal side effects, compared to other NSAIDs, especially at high doses.
Elderly: Elderly patients have an increased frequency of side effects resulting from the use of NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see "How to use this medicine").
When gastrointestinal bleeding or ulceration occurs in patients taking ketoprofen the treatment should be discontinued.
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see "When it should not be used"), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increased doses of NSAIDs.
These patients should start treatment with the lowest available dose. In these patients and in patients taking low doses of aspirin or other drugs that may increase the risk of gastrointestinal events, concomitant use of stomach protective drugs (misoprostol or proton pump inhibitors) should be considered (see "Which ones?" medicines or foods can change the 'effect of the medicine').
Patients with a history of gastrointestinal toxicity, particularly the elderly, should inform the physician of any abdominal symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.
Caution is also required from patients taking concomitant medications that may increase the risk of ulceration or bleeding such as: oral corticosteroids, anticoagulants such as warfarin, antidepressants of the selective serotonin reuptake inhibitor class or antiplatelet agents such as "aspirin (see" Which medicines or foods can change the 'effect of the medicine').
Patients with asthma associated with chronic rhinitis, chronic sinusitis and / or nasal polyps are at greater risk of allergy to acetylsalicylic acid and / or NSAIDs than the rest of the population. The use of this drug can contribute to trigger seizures. asthmatics or bronchospasms, especially in people allergic to acetylsalicylic acid or NSAIDs (see "When it should not be used").
Patients with high blood pressure and / or congestive heart failure should seek medical attention for adequate monitoring and appropriate instructions as fluid retention and edema have been reported.
As with other NSAIDs, patients with uncontrolled hypertension, congestive heart failure, established ischemic cardiomyopathy, peripheral arterial disease and / or cerebrovascular disease should only be treated with ketoprofen after careful consideration. Patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking) should also consult their doctor before starting long-term treatment.
Drugs such as KETODOL may be associated with a modest increase in arterial thrombotic events (eg, myocardial infarction or stroke). Do not exceed the recommended dose or duration of treatment, as a modest increase in risk is more likely with high doses and prolonged treatments.
In patients with renal function problems the use of KETODOL requires particular caution since the drug is eliminated essentially by the kidney.
At the beginning of treatment, renal function should be carefully monitored in patients with heart failure, cirrhosis and nephrosis, in subjects receiving diuretic drugs or with chronic renal failure, especially if elderly. In these patients, the use of ketoprofen it can cause a reduction in blood flow in the kidneys and lead to kidney failure.
Serious skin reactions, some of them fatal, including red inflammation of the skin (exfoliative dermatitis), bullous rashes (Stevens-Johnson syndrome) and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see " Undesirable effects "). 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.
KETODOL should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
As with other NSAIDs, in the presence of an infection, it must be taken into account that the anti-inflammatory, analgesic and antipyretic properties of the active ingredient ketoprofen can mask the symptoms of the progressing infection, such as fever.
As with other NSAIDs, the drug can cause small transient increases in some liver parameters and also significant increases in transaminases seen in blood tests (see "Side Effects"). In the event of a significant increase in these parameters, therapy must be discontinued.
Patients with abnormal liver function values or with a history of liver disease should seek medical attention, especially during long-term therapy for periodic assessment of transaminase levels. Rare cases of jaundice and hepatitis have been reported with the use of the active ingredient ketoprofen.
The drug, therefore, requires special precautions, or requires its "exclusion from" use, when the following conditions are present in the patient: states of kidney hypoperfusion, kidney disease, heart failure, mild to moderate hepatic insufficiency, advanced age .
In case of visual disturbances, such as blurred vision, treatment should be stopped.
To avoid possible reactions of hypersensitivity or allergy to the sun it is advisable not to expose yourself to the sun during use. The treatment must be suspended in case of allergic reactions.
Administration of KETODOL should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
The medicine is not contraindicated for people with celiac disease.
Interactions Which drugs or foods can modify the effect of Ketodol
Combinations with other drugs not recommended:
- Other NSAIDs (including selective cyclo-oxygenase-2 inhibitors) and high doses of salicylates: increased risk of gastrointestinal ulcers and bleeding.
- Anticoagulants (heparin and warfarin): NSAIDs can amplify the effects of anticoagulants such as warfarin; increased risk of bleeding. If concomitant administration cannot be avoided, seek medical attention.
- Antiplatelet agents (eg ticlopidine, clopidogrel): increased risk of bleeding Several substances are involved in interactions due to their antiplatelet effects: tirofiban, eptifibatide, abcixiab and iloprost. The use of various antiplatelet drugs increases the risk of bleeding.
- Lithium: risk of increased plasma lithium levels which can reach toxic values. Tell your doctor if you are being treated with lithium.
- Methotrexate at doses greater than 15 mg / week: increased risk of blood toxicity of methotrexate, especially when administered in high doses (> 15 mg / week).
Associations requiring caution:
- Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.
- Pentoxifylline: increased risk of bleeding. Inform your doctor if you are being treated with this drug.
- Diuretics: Patients treated with diuretics, particularly those who are dehydrated, have a higher risk of developing renal failure due to decreased renal blood flow. Contact your doctor if you are being treated with diuretic drugs. NSAIDs may reduce the effect of diuretics.
- ACE inhibitors, angiotensin II antagonists: In patients with renal insufficiency (e.g. dehydrated patients or elderly patients) the concomitant administration of an ACE inhibitor or an angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may further worsen kidney function, including possible acute kidney failure. Therefore, the combination should be administered with caution, especially in elderly patients. Contact your doctor if you are being treated with these drugs.
- Methotrexate at doses below 15mg / week: If you are being treated with methotrexate at doses below 15mg / week, please inform your doctor.
- Oral hypoglycemic agents Sulfonylureas: KETODOL may interact with these drugs. Contact your doctor if you are being treated with these drugs.
Associations that need to be considered:
- Diphenylhydantoin and sulfonamides: the dosage of these drugs may need to be reduced, consult your doctor before using KETODOL.
- Thrombolytics: increased risk of bleeding.
- Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
- Antihypertensives (beta-blockers, angiotensin converting enzyme inhibitors, diuretics): NSAIDs may reduce the effect of antihypertensive drugs. Risk of reduced antihypertensive potency (NSAIDs inhibit vasodilating prostaglandins).
- Probenecid: Simultaneous administration of probenecid can markedly reduce the elimination of ketoprofen from the blood.
- Ciclosporin, tacrolimus: risk of increased renal toxicity, especially in the elderly. If you are using other medicines ask your doctor or pharmacist for advice.
Warnings It is important to know that:
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
For the interaction of the drug with the metabolism of arachidonic acid, bronchospasm crises and possibly shock and other allergic phenomena may arise in asthmatics and predisposed subjects.
Due to the presence of sucralfate, the bioavailability of other drugs may be altered, therefore an interval of at least two hours must be interposed between the intake of the product and that of another drug. For these reasons it is advisable for patients undergoing any other treatment to consult the doctor before taking the product.
Cases of bezoar formation associated with sucralfate administration have been reported. The majority of these were represented by ICU patients. Therefore, extreme caution should be exercised in the treatment of ICU patients especially if they are receiving enteral nutrition, or in patients with predisposing factors such as delayed gastric emptying.
After three days of treatment without appreciable results, consult your doctor.
If your doctor has diagnosed you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
WHAT TO DO DURING PREGNANCY AND BREASTFEEDING
Use in pregnancy
Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breastfeeding.
Some scientific studies suggest an increased risk of miscarriage and cardiac and gastric malformations in the early stages of pregnancy after the use of prostaglandin synthesis inhibitor drugs.
The use of KETODOL is not recommended in women who intend to become pregnant.
Furthermore, KETODOL should not be used during the first and second trimester of pregnancy unless strictly necessary. If KETODOL is used in women who wish to become pregnant or during the first and second trimester of pregnancy, the dosage should be kept as low as possible for the shortest possible duration of treatment. KETODOL should not be used during the third trimester of pregnancy.
During the third trimester of pregnancy, all medicines of the KETODOL class can expose the fetus to:
- cardiopulmonary toxicity;
- 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.
Use while breastfeeding
KETODOL should not be used during breastfeeding.
DRIVING VEHICLES AND USE OF MACHINERY
In case of drowsiness, dizziness or convulsions, avoid driving, using machines or carrying out activities that require particular vigilance (see "Undesirable effects").
Dosage and method of use How to use Ketodol: Dosage
In adults and children over 15 years: 1 tablet in single or repeated dose 2-3 times a day, in painful forms of greater intensity, to be swallowed with a little water, preferably on a full stomach.
Use the lowest effective dose, particularly in elderly patients.
Do not exceed the indicated doses and do not use the medicine for prolonged periods of time without medical advice.
Overdose What to do if you have taken too much Ketodol
If you have taken too much medicine, the following symptoms may appear: headache, dizziness, confusion and loss of consciousness, pain, nausea and vomiting. Hypotension, respiratory depression, and cyanosis can also occur.
In cases of suspected overdose, notify your doctor immediately or go to the nearest hospital.
Side Effects What are the side effects of Ketodol
Like all medicines, KETODOL can cause side effects, although not everybody gets them.
Stop taking KETODOL and contact your doctor immediately if any of the following symptoms occur:
Gastric ulcers (continuous stomach pain, which gets worse on an empty stomach).
Gastro-intestinal bleeding (vomiting of blood, blood in the stool).
Swelling of the throat (Edema of the larynx and / or edema of the glottis), difficulty in breathing (dyspnoea), palpitation.
All side effects related to KETODOL are listed below:
Common side effects (may affect up to 1 in 10 people) include:
- Nausea, vomiting, heartburn, abdominal pain, stomach pain.
Uncommon side effects (may affect up to 1 in 100 people) include:
- Headache, dizziness, sleepiness.
- Diarrhea, constipation (constipation), flatulence (gas), inflammation of the stomach (gastritis).
- Inflammation of the skin, itching.
- Swelling, fatigue.
Rare side effects (may affect up to 1 in 1000 people) include:
- Hemorrhage anemia (seen on blood tests).
- Sensation of tingling, involuntary movements of the muscles.
- Blurred vision.
- Ringing in the ears, loss of balance (vertigo).
- Wheezing and difficulty breathing (asthma).
- Oral ulcerations.
- Inflammation of the liver, increased transaminases, elevated bilirubin (seen in blood tests).
- Rash.
- Generalized weakness.
- Weight gain.
Very rare side effects (may affect up to 1 in 10,000 people) include:
- Allergic hypersensitivity reactions (including anaphylactic shock).
- Presence of a mass of foreign material at the level of the stomach (bezoar).
During the marketing of Ketoprofen, the following side effects have been reported with an unknown frequency (frequency cannot be estimated from the available data):
- Significant reduction in white blood cells, reduction in the number of platelets, bone marrow failure (seen in the blood test).
- Changes in mood, insomnia.
- Involuntary muscle contraction (convulsions), altered sense of taste.
- Insufficient heart function.
- Increased blood pressure (hypertension), decreased blood pressure.
- Bronchospasm (particularly in patients with known hypersensitivity to acetylsalicylic acid and NSAIDs).
- Internal inflammation of the nose (rhinitis).
- Worsening of colitis and Crohn's disease.
- Sun allergy reactions (photosensitivity), hair loss (alopecia), hives, swollen diffuse urticaria, bullous rashes (including Steven-Johnson syndrome and toxic epidermal necrolysis), inflammation and redness of the skin (dermatitis, eczema).
- Difficulty urinating, decreased kidney function, interstitial inflammation of the kidneys, kidney damage (nephrotoxic syndrome), abnormal kidney function tests (seen in blood tests).
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. In this case, ask for and fill in the undesirable effects report form available at the pharmacy.
Expiry and Retention
EXPIRY: SEE THE EXPIRY DATE ON THE PACKAGE.
THE EXPIRY DATE INDICATED REFERS TO THE PRODUCT IN INTACT PACKAGING, CORRECTLY STORED.
CAUTION: DO NOT USE THE MEDICINAL PRODUCT AFTER THE EXPIRY DATE STATED ON THE PACKAGE.
THE MEDICINES SHOULD NOT BE DISPOSED OF INTO WASTE WATER AND HOUSEHOLD WASTE. ASK YOUR PHARMACIST HOW
DISPOSE OF MEDICINES YOU NO LONGER USE. THIS WILL HELP PROTECT THE ENVIRONMENT.
KEEP THE MEDICINE OUT OF THE VIEW AND REACH OF CHILDREN
It is important to always have the information on the medicine available, so keep both the box and the package leaflet.
Composition and pharmaceutical form
COMPOSITION
One modified-release tablet contains:
Active ingredients: Ketoprofen (core) 25 mg; Sucralfate (coating) 200 mg.
Excipients: Corn starch; Lactose; Carboxymethyl starch; Povidone; Talc; Magnesium stearate; Cochineal Red (E 120).
PHARMACEUTICAL FORM AND CONTENT
modified-release tablets 10 or 20 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
KETODOL 25 MG + 200 MG MODIFIED RELEASE TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One modified-release tablet contains:
Active ingredients: Core: ketoprofen 25 mg.
Coating: sucralfate 200 mg.
Excipients: lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Modified-release tablet.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Pain of various origins and nature (headache, toothache, neuralgia, osteo-joint and muscle pain, menstrual pain).
04.2 Posology and method of administration
Adults and children over 15 years: 1 tablet in single or repeated dose 2 - 3 times a day, in painful forms of greater intensity, preferably on a full stomach (with a glass of water).
Do not exceed the recommended doses: in particular elderly patients should follow the minimum dosages indicated above.
04.3 Contraindications
Ketodol is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients.
Ketodol is contraindicated in patients with a history of hypersensitivity reactions such as bronchospasm, asthma attacks, rhinitis, urticaria or in whom substances with a similar mechanism of action (eg acetylsalicylic acid or other NSAIDs) cause other allergic-type reactions.
Serious anaphylactic reactions, rarely fatal, have been reported in these patients (see section 4.8).
Ketodol is also contraindicated in the third trimester of pregnancy, during lactation and in pediatric age (see section 4.6).
Ketodol is contraindicated in the following cases:
- severe heart failure
- active peptic ulcer or a previous history of gastrointestinal bleeding, ulceration or perforation
- history of gastrointestinal bleeding or perforation following previous NSAID therapy
- hemorrhagic diathesis
- severe hepatic insufficiency
- severe renal insufficiency
- during intensive diuretic therapy
- chronic dyspepsia
- gastritis
- porphyria, leukopenia and thrombocytopenia,
- cirrhosis of the liver
- do not administer during antibiotic treatments with tetracyclines to avoid the formation of complex salts with inactivation of the antibiotic itself in contact with sucralfate.
04.4 Special warnings and appropriate precautions for use
Warnings
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
The concomitant use of ketoprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
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.
Some epidemiological evidence suggests that ketoprofen may be associated with a higher risk of severe gastrointestinal toxicity, compared to other NSAIDs, especially at high doses (see sections 4.2 and 4.3).
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 increasing doses of NSAIDs.
These patients should begin treatment at the lowest possible dose. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low dose aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5).
Patients with a history of gastrointestinal toxicity, especially if elderly, should report any abdominal 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 aspirin (see section 4.5).
Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal. When gastrointestinal bleeding or ulceration occurs in patients taking ketoprofen the treatment should be discontinued.
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 an increased risk of arterial thrombotic events (eg, myocardial infarction or stroke). there are sufficient data to exclude a similar risk for ketoprofen.
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. Ketodol should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
For the interaction of the drug with the metabolism of arachidonic acid, bronchospasm crises and possibly shock and other allergic phenomena may arise in asthmatics and predisposed subjects.
Precautions
Patients with active or previous peptic ulcer.
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).
At the start of treatment, renal function should be carefully monitored in patients with heart failure, cirrhosis and nephrosis, in patients receiving diuretic therapy, in patients with chronic renal impairment, particularly if the patients are elderly. administration of ketoprofen can cause a decrease in renal blood flow caused by the inhibition of prostaglandins and lead to renal failure.
Adequate monitoring and instruction are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment.
As with other NSAIDs, in the presence of an infection, it must be taken into account that the anti-inflammatory, analgesic and antipyretic properties of ketoprofen may mask the symptoms of the progressing infection such as fever.
In patients with abnormal liver function values or with a history of liver disease, transaminase levels should be evaluated periodically, especially during long-term therapy. Rare cases of jaundice and hepatitis have been reported with the use of ketoprofen.
As with other NSAIDs, patients with uncontrolled hypertension, congestive heart failure, established ischemic cardiomyopathy, peripheral arterial disease and / or cerebrovascular disease should only be treated with ketoprofen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg hypertension, hyperlipidaemia, diabetes mellitus, smoking).
The product, like all non-steroidal anti-inflammatory drugs, interferes with the synthesis of prostaglandins and their important intermediates that participate in physiological functions.
The drug, therefore, requires special precautions, or requires its exclusion from use, when the following conditions are present in the patient: states of kidney hypoperfusion, kidney disease, heart failure, mild to moderate hepatic insufficiency, advanced age .
To avoid any phenomena of hypersensitivity or photosensitization, it is advisable not to expose yourself to the sun during use.
The use of ketoprofen, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended for women intending to become pregnant.
The administration of ketoprofen should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
Patients with asthma associated with chronic rhinitis, chronic sinusitis and / or nasal polyps have a higher risk of allergies to aspirin and / or NSAIDs than the rest of the population. Administration of this medicine may cause asthma attacks or bronchospasm, especially in subjects allergic to aspirin and / or NSAIDs (see section 4.3).
Treatment should be discontinued if visual disturbances such as blurred vision appear.
The medicine is not contraindicated for people with celiac disease.
Due to the presence of sucralfate, the bioavailability of other drugs may be altered, therefore an interval of at least two hours must be interposed between the intake of the product and that of another drug. For these reasons it is advisable for patients undergoing any other treatment to consult the doctor before taking the product.
Cases of bezoar formation associated with sucralfate administration have been reported. The majority of these were represented by ICU patients. Therefore, extreme caution should be exercised in the treatment of ICU patients especially if they are receiving enteral nutrition, or in patients with predisposing factors such as delayed gastric emptying.
After three days of treatment without appreciable results, consult your doctor.
Excipients Warnings: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
04.5 Interactions with other medicinal products and other forms of interaction
Associations to avoid:
Lithium: risk of increased plasma lithium levels which may reach toxic values due to decreased renal excretion of lithium. If necessary, plasma lithium levels should be carefully monitored and the lithium dosage adjusted. during and after NSAID therapy.
Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates: it is advisable not to combine Ketodol with acetylsalicylic acid or with other non-steroidal anti-inflammatory drugs (including selective cyclooxygenase-2 inhibitors): it may increase the risk of gastrointestinal ulceration and bleeding.
Methotrexate at doses above 15mg / week: Increased risk of methotrexate blood toxicity, especially when administered at high doses (> 15mg / week), possibly related to shift from methotrexate binding proteins and decreased renal clearance.
Anticoagulants (heparin and warfarin): NSAIDs can amplify the effects of anticoagulants such as warfarin; increased risk of bleeding (see section 4.4).
If concomitant administration cannot be avoided, patients should be carefully monitored.
Antiplatelet agents (e.g. ticlopidine, clopidogrel): increased risk of gastrointestinal bleeding (see section 4.4).
Several substances are involved in interactions due to their antiplatelet effects: tirofiban, eptifibatide, abcixiab and iloprost. The use of various antiplatelet drugs increases the risk of bleeding.
Associations requiring caution:
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Pentoxifylline: increased risk of bleeding. More frequent clinical checks and monitoring of bleeding time.
Diuretics: Patients on diuretic therapy, particularly those who are dehydrated, have a higher risk of developing renal failure due to decreased renal blood flow caused by prostaglandin inhibition. These patients should be adequately hydrated prior to initiation of concomitant therapy and Monitoring of renal function after initiation of treatment should be considered (see section 4.4).
NSAIDs may reduce the effect of diuretics.
ACE inhibitors and angiotensin II antagonists: In patients with impaired renal function (e.g. dehydrated patients or elderly patients) co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cycle system -oxygenase can lead to further deterioration of renal function, which includes possible acute renal failure. 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.
Methotrexate at doses lower than 15mg / week: carry out a weekly monitoring of the hemocytometric test during the first weeks of the combination. Increase the frequency of monitoring in the presence of even a slight deterioration in renal function, as well as in the elderly.
Sulfonylureas: furthermore, any interactions with oral hypoglycemic agents should be kept in mind
Associations that need to be considered:
Diphenylhydantoin and sulfonamides: Since the protein binding of ketoprofen is high, it may be necessary to reduce the dosage of diphenylhydantoin or sulfonamides that should be administered simultaneously.
Antihypertensives (beta-blockers, angiotensin converting enzyme inhibitors, diuretics): NSAIDs can reduce the effect of antihypertensive drugs. Risk of reduced antihypertensive potency (NSAIDs inhibit vasodilating prostaglandins).
Thrombolytics: increased risk of bleeding.
Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding
Probenecid: Concomitant administration of probenecid can significantly reduce the plasma clearance of ketoprofen.
Ciclosporin, tacrolimus: risk of additional nephrotoxic effects, particularly in the elderly.
04.6 Pregnancy and lactation
Use in pregnancy
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 increased from less than 1% to approximately 1.5%.
The risk was 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.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
Therefore ketoprofen should not be administered during the first and second trimester of pregnancy unless strictly necessary. If ketoprofen is used in women who wish to become pregnant or during the first and second trimester of pregnancy, the dosage should be kept as low as possible for the shortest possible duration of treatment.
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.
Ketodol is therefore contraindicated during the third trimester of pregnancy.
Use while breastfeeding
There are no data on the excretion of ketoprofen in human milk.
Ketodol is contraindicated during breastfeeding.
04.7 Effects on ability to drive and use machines
Patients should be advised of the possibility of drowsiness, dizziness or convulsions and to avoid driving, operating machinery or carrying out activities requiring special vigilance if these symptoms appear (see section 4.8).
04.8 Undesirable effects
The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4).
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, heartburn, gastralgia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Ketodol (see section 4.4).
Gastritis has been observed less frequently.
The frequency and extent of these effects are significantly reduced by taking the drug on a full stomach (during meals or with milk).
Although extremely rare, severe systemic hypersensitivity reactions are possible, such as edema of the larynx, edema of the glottis, dyspnoea, palpitation, up to anaphylactic shock. In such cases immediate medical assistance is required.
Adverse reactions that have been observed following administration of ketoprofen in adults are listed by system organ class and by frequency: very common (≥1 / 10); common (≥1 / 100 to
Disorders of the blood and lymphatic system
Rare: haemorrhagic anemia.
Not known: agranulocytosis, thrombocytopenia, bone marrow failure.
Disorders of the immune system
Not known: anaphylactic reactions (including anaphylactic shock).
Psychiatric disorders
Not known: mood changes, insomnia.
Nervous system disorders
Uncommon: headache, dizziness, somnolence.
Rare: paraesthesia, dyskinesia.
Not known: convulsions, dysgeusia.
Eye disorders
Rare: blurred vision (see section 4.4).
Ear and labyrinth disorders
Rare: tinnitus, dizziness.
Cardiac pathologies
Not known: heart failure.
Vascular pathologies
Not known: hypertension, vasodilation.
Respiratory, thoracic and mediastinal disorders
Rare: asthma.
Not known: bronchospasm (particularly in patients with known hypersensitivity to acetylsalicylic acid and NSAIDs), rhinitis.
Gastrointestinal disorders
Common: dyspepsia, nausea, abdominal pain, gastralgia, vomiting.
Uncommon: constipation, diarrhea, flatulence, gastritis.
Rare: stomatitis, peptic ulcer.
Not known: exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage and perforation, melaena, haematemesis.
Hepatobiliary disorders
Rare: hepatitis, increased transaminases, elevated bilirubin due to liver disorders.
Skin and subcutaneous tissue disorders
Uncommon: rash, pruritus.
Rare: rash.
Not known: photosensitivity reactions, alopecia, urticaria, angioedema, bullous eruptions including Steven-Johnson syndrome and toxic epidermal necrolysis, dermatitis, contact eczema.
Renal and urinary disorders
Not known: acute renal failure, interstitial nephritis, nephrotoxic syndrome, renal function test abnormal, dysuria.
General disorders and administration site conditions
Uncommon: edema, fatigue.
Rare: asthenia.
Diagnostic tests
Rare: weight gain.
Clinical studies and epidemiological data suggest that the use of 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 and stroke).
Very rare cases of bezoar formation associated with sucralfate administration have been reported.
04.9 Overdose
Symptoms of overdose may include: central nervous system disorders, such as headache, dizziness, confusion and loss of consciousness, as well as pain, nausea and vomiting. Hypotension, respiratory depression, and cyanosis can also occur.
Cases of overdose have been reported with ketoprofen doses above 2.5 g. In many cases the symptoms observed were benign and limited to lethargy, drowsiness, nausea, vomiting and epigastric pain.
There are no specific antidotes for ketoprofen intoxication. In cases of suspected massive overdose, gastric lavage is recommended and symptomatic and supportive therapy instituted to compensate for dehydration, to monitor urinary excretion and correct acidosis if of the case.
In the case of kidney failure, hemodialysis can be helpful in removing the medicine from the circulation.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-steroidal anti-inflammatory / antirheumatic drugs / propionic acid derivatives / ketoprofen combinations.
ATC code M01AE53.
The anti-inflammatory and analgesic activity of ketoprofen is related to four well-documented mechanisms of action: stabilization of the lysosomal membrane; inhibition of prostaglandin synthesis; antibradykinin activity; antiplatelet activity.
The anti-ulcer activity of sucralfate is determined by protecting the ulcerated area against further attacks by digestive juices. Sucralfate has a negligible capacity to neutralize acids and the anti-ulcer action cannot be attributed to the neutralization of gastric acidity. In particular clinical pharmacology studies have shown that sucralfate forms a complex adherent to ulceration with the protein exudate of the ulcerated site.
05.2 Pharmacokinetic properties
In humans the absorption of ketoprofen is very high. It reaches maximum plasma levels within 1 hour when administered orally or rectally.
Peak values are 3.5 mcg / ml after administration of 50 mg per os; of 7.5 mcg / ml after administration of 100 mg rectally. The administration of Ketodol (ketoprofen + sucralfate) causes a slower and more prolonged gastrointestinal absorption than that observed with the administration of ketoprofen alone; in particular, there is a lower maximum plasma concentration and a higher plasma half-life, while the other pharmacokinetic constants remain unchanged. The elimination of ketoprofen occurs essentially through the urine (> 50% in the form of metabolites) and minimally through the faeces (1%).
Sucralfate is absorbed from the gastrointestinal tract only in minimal quantities. Traces of sucralfate, absorbed from the gastrointestinal tract, are excreted via the urine.
05.3 Preclinical safety data
There is no further information on preclinical data on effects on mother, fetus and neonate other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).
The toxicological tests have shown the low toxicity and the high therapeutic index of ketoprofen. The LD50 in the rat per os is 165 mg / kg; in the mouse, by various routes of administration, it is between 365 and 662 mg / kg
Preclinical data also reveal no genotoxicity or carcinogenic potential.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Nucleus: lactose, carboxymethyl starch, povidone, magnesium stearate.
Coating: corn starch, carboxymethyl starch, povidone, talc, magnesium stearate, cochineal red (E120).
06.2 Incompatibility
Do not administer during antibiotic treatments with tetracyclines to avoid the formation of complex salts with inactivation of the antibiotic itself in contact with sucralfate.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions
06.5 Nature of the immediate packaging and contents of the package
Box of 10 or 20 modified-release tablets in blister packs.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Alfa Wassermann S.p.A.
Registered office: Via E. Fermi, n. 1 - Alanno (PE)
Administrative headquarters: Via Ragazzi del "99, n. 5 - Bologna
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 028561037 - "25 mg + 200 mg modified release tablets" - 20 tablets
AIC n. 028561049 - "25 mg + 200 mg modified release tablets" - 10 tablets
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
02.11.92 / 02.11.2012
10.0 DATE OF REVISION OF THE TEXT
AIFA resolution of 28 January 2013
