Active ingredients: Ketoprofen (Ketoprofen lysine salt)
Ketoprofen lysine salt ratiopharm 80 mg granules for oral solution
Why is Ketoprofen Sachets used - Generic Drug? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Anti-inflammatory, antirheumatic, non-steroidal drugs. Derivatives of propionic acid
THERAPEUTIC INDICATIONS
Adults: symptomatic treatment of inflammatory states associated with pain, including: rheumatoid arthritis, ankylosing spondylitis, painful arthrosis, extraarticular rheumatism, post-traumatic inflammation, painful inflammatory diseases in dentistry, otolaryngology, urology and pneumology.
In pediatrics: symptomatic and short-term treatment of inflammatory states associated with pain, also accompanied by pyrexia, such as those affecting the osteoarticular system, post-operative pain and ear infections.
Contraindications When should not be used Ketoprofen Sachets - Generic Drug
Ketoprofen is contraindicated in patients who have a "history of hypersensitivity reactions" such as bronchospasm, asthma attacks, rhinitis, nasal polyps, urticaria, angioneurotic edema or other allergic-type reactions to ketoprofen, acetylsalicylic acid or other NSAIDs.
Serious, rarely fatal, anaphylactic reactions have been reported in these patients (see section "UNDESIRABLE EFFECTS").
Ketoprofen is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients of this drug.
Ketoprofen is also contraindicated in the third trimester of pregnancy. Ketoprofen is contraindicated in the following cases:
- severe heart failure
- active peptic ulcer, or a history of gastrointestinal bleeding, ulceration or perforation
- severe hepatic insufficiency
- severe renal insufficiency
- previous bronchial asthma
- haemorrhagic diathesis and other coagulation disorders, or patients subject to anticoagulant therapy
- children under the age of 6.
Precautions for use What you need to know before taking Ketoprofen Sachets - Generic Drug
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 "UNDESIRABLE EFFECTS").
At the start of treatment, renal function should be carefully monitored in patients with heart failure, cirrhosis and nephrosis, in patients on diuretic therapy, in patients with chronic renal failure, particularly if the patient is elderly. In these patients, the administration of ketoprofen can induce a reduction in renal blood flow caused by the inhibition of prostaglandins and which can lead to renal decompensation.
Patients with a history of mild to moderate hypertension and / or congestive heart failure should be treated with caution, as fluid retention and edema have been reported with NSAID therapy.
As with other NSAIDs, it should be borne in mind that, in the presence of an infectious disease, the anti-inflammatory, analgesic and antipyretic properties of ketoprofen may mask the characteristic symptoms of progression of the infection, such as fever.
In patients with abnormal liver function tests 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 observed with ketoprofen.
The use of NSAIDs can impair fertility in women and therefore their use is not recommended in women desiring a child. In women who have difficulty conceiving, or who are undergoing fertility testing, discontinuation of NSAIDs should be considered.
Patients with asthma associated with chronic rhinitis, chronic sinusitis and / or nasal polyposis have a higher risk of being allergic to aspirin and / or NSAIDs than the rest of the population. Administration of this drug may cause asthma attacks or bronchospasm, particularly in subjects allergic to aspirin or NSAIDs (see "CONTRAINDICATIONS" section).
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ketoprofen lysine salt after careful consideration, as with all other NSAIDs. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg hypertension, hyperlipidaemia, diabetes mellitus, smoking). If visual disturbances such as blurred vision occur, treatment should be discontinued.
Administer with caution in patients with allergic manifestations or previous allergy.
In some pediatric patients treated with ketoprofen lysine salt, gastrointestinal bleeding, occasionally even serious, and ulcer have been reported (see section "UNDESIRABLE EFFECTS"); therefore the product must be administered under strict supervision of the physician who will have to evaluate the necessary dosage schedule each time.
As with all NSAIDs, the drug can increase plasma urea nitrogen and creatinine.
As with other prostaglandin synthesis inhibitors, the drug may be associated with adverse events on the renal system which can lead to glomerular nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure.
As with other NSAIDs, the drug can cause small transient increases in some liver parameters and also significant increases in SGOT and SGPT (see section "UNDESIRABLE EFFECTS"). In the event of a significant increase in these parameters, therapy must be discontinued.
Ketoprofen lysine salt should be administered with caution in patients with haematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disorders.
Caution should be exercised in the event of impaired hepatic, renal (see section "DOSE, METHOD AND TIME OF ADMINISTRATION") or cardiac function as well as in the presence of other conditions predisposing to fluid retention. In these cases, the use of NSAIDs can cause deterioration of renal function and fluid retention. Caution is also required in patients undergoing diuretic therapy or likely hypovolaemic because the risk of nephrotoxicity is increased.
Elderly patients are more prone to decreased renal, cardiovascular or hepatic function.
Interactions Which drugs or foods can modify the effect of Ketoprofen Sachets - Generic Drug
Combinations of medicines not recommended:
- Other NSAIDs, including selective cyclooxygenase-2 inhibitors and high dose salicylates: Increased risk of gastrointestinal ulcers and bleeding.
- Anticoagulants (heparin, warfarin) and platelet aggregation inhibitors (eg ticlopidine, clopidogrel): increased risk of bleeding (see section "SPECIAL WARNINGS"). If co-administration is unavoidable, patients should be carefully monitored.
- Lithium: risk of increased plasma lithium levels which can reach toxic values, due to decreased renal excretion of lithium. When necessary, plasma lithium levels should be closely monitored and the lithium dose adjusted during and following NSAID treatment.
- Hydantoins and sulphonamides: the toxic effects of these substances can be increased.
- Methotrexate at doses above 15 mg / week: Increased risk of haematological toxicity of methotrexate, particularly when administered at high doses (> 15 mg / week), possibly related to the shift of protein bound methotrexate and its reduced renal clearance .
Combinations of medicines requiring precautions for use:
- Diuretics: Patients, particularly those who are dehydrated on treatment with diuretics, are at increased risk of developing renal failure secondary to decreased renal blood flow due to inhibition of prostaglandin formation. These patients must be rehydrated before starting combination therapy and their renal function monitored at the start of treatment (see "SPECIAL WARNINGS" section).
- ACE inhibitors and angiotensin II antagonists: in patients with impaired renal function (e.g. dehydrated patients or elderly patients) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit cyclo-oxygenase may lead to further deterioration of renal function, which includes possible acute renal failure.
- Methotrexate at doses below 15 mg / week: During the first few weeks of combination treatment, a complete blood count should be performed weekly. In the event of impaired renal function or if the patient is elderly, monitoring should be performed more frequently.
- Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section "SPECIAL WARNINGS").
- Pentoxifylline: there is an increased risk of bleeding. Increase clinical monitoring and check bleeding time more frequently.
- Zidovudine: risk of increased toxicity on the red cell line by action on reticulocytes, with severe anemia occurring one week after starting treatment with the NSAID, Check the complete blood count and reticulocyte count one or two weeks later having started treatment with the NSAID.
- Sulfonylureas: NSAIDs can increase the hypoglycemic effect of sulfonylureas by displacing them from plasma protein binding sites.
Combinations of medicines to be evaluated:
- Antihypertensive agents (Beta-blockers, angiotensin converting enzyme inhibitors, diuretics): treatment with an NSAID may decrease their antihypertensive effect by inhibiting the synthesis of vasodilating prostaglandins.
- Thrombolytics: increased risk of bleeding.
- Probenecid: Concomitant administration of probenecid may result in a significant reduction in the plasma clearance of ketoprofen. Plasma concentrations of ketoprofen lysine salt may be increased; this interaction may be due to an inhibitory mechanism at the site of renal tubular secretion and glucuronide conjugation and requires dose adjustment of the ketoprofen lysine salt.
- Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section "SPECIAL WARNINGS").
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
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.
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 "INTERACTIONS").
The concomitant use of Ketoprofen lysine salt ratiopharm with other NSAIDs should be avoided, including selective cyclooxygenase-2 inhibitors (see section "INTERACTIONS")
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 than other NSAIDs, especially at high doses (see also "CONTRAINDICATIONS").
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section "CONTRAINDICATIONS"), the risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest available dose. The concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section "INTERACTIONS" ).
Patients with a history of gastrointestinal toxicity, particularly if elderly, should report any abdominal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
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 lysine salt the treatment should be discontinued.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in conjunction with the use of NSAIDs (see section "UNDESIRABLE EFFECTS"). In the early stages of therapy i patients appear to be at higher risk for these reactions: the onset of the reaction occurs in most cases within the first month of treatment.
Treatment with ketoprofen lysine salt should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
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). There are insufficient data to exclude a similar risk for ketoprofen lysine salt.
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 has been considered 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 of 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, ketoprofen should not be administered except in strictly necessary cases. If ketoprofen 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 oligohydroamnios;
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, ketoprofen is contraindicated during the third trimester of pregnancy.
Use while breastfeeding
There are no data on the secretion of ketoprofen in human milk. Administration of ketoprofen is not recommended during breastfeeding. Ask your doctor or pharmacist for advice before taking any medicine
Driving and using machines
Patients should be advised of the possibility of somnolence, dizziness or seizures and should be advised not to drive or operate machinery if these symptoms occur.
With ketoprofen 12.5 mg lozenges, at the recommended doses and duration of therapy, none of these symptoms are expected.
Dosage and method of use How to use Ketoprofen Sachets - Generic Drug: Dosage
Adults: one 80 mg sachet (full dose) three times a day with meals.
Children aged between 6 and 14: half a 40 mg sachet (half dose) three times a day with meals.
Senior citizens: the posology must be carefully established by the doctor who will have to evaluate a "possible reduction of the dosages indicated above (see paragraph" PRECAUTIONS FOR USE ").
Patients with hepatic insufficiency: it is advisable to start therapy at the minimum daily dosage (see paragraph "PRECAUTIONS FOR USE").
Patients with mild or moderate renal insufficiency: it is advisable to monitor the volume of diuresis and renal function (see section "PRECAUTIONS FOR USE").
Instructions on the use of the sachet: opening the sachet along the line indicated "half dose" gives a dose of 40 mg. Opening the sachet along the line marked "full dose" gives a dose of 80 mg. Pour the contents of a sachet or half a sachet into half a glass of water and mix.
Overdose What to do if you have taken an overdose of Ketoprofen Sachets - Generic Drug
Cases of overdose have been reported with ketoprofen doses up to 2.5 mg. In most cases, the symptoms observed were benign and limited to lethargy, drowsiness, nausea, vomiting and epigastric pain.
There is no specific antidote for the treatment of ketoprofen overdose. If massive overdose is suspected, it is recommended that gastric lavage be performed and symptomatic and supportive therapy instituted to compensate for dehydration, to monitor urinary excretion and to correct acidosis, if present.
In the presence of renal insufficiency, hemodialysis can be useful to remove the circulating drug.
In case of accidental ingestion / intake of an excessive dose of KETOPROFENE LYSINE SALT RATIOPHARM, notify your doctor immediately or contact the nearest hospital.
If in doubt about the use of KETOPROFENE LYSINE SALT RATIOPHARM, contact your doctor or pharmacistSide Effects What are the side effects of Ketoprofen Sachets - Generic Drug
Like all medicines, KETOPROFENE LYSINE SALT RATIOPHARM can cause side effects, although not everybody gets them. Classification of expected frequencies: Very common (≥1 / 10); common (≥ 1/100,
The following side effects have been reported following the use of ketoprofen in adults:
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 shock)
Psychiatric disorders
- not known: mood alteration
Nervous system disorders
- uncommon: headache, dizziness, somnolence
- rare: paraesthesia
- not known: convulsions, dysgeusia
Eye disorders
- rare: blurred vision (see "SPECIAL WARNINGS" section)
Ear and labyrinth disorders
- rare: tinnitus
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 ASA and other NSAIDs), rhinitis
Gastrointestinal disorders
- common: dyspepsia, nausea, abdominal pain, vomiting
- uncommon: constipation, diarrhea, flatulence, gastritis
- rare: stomatitis, peptic ulcer
- not known: exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage and perforation
Hepatobiliary disorders
- rare: hepatitis, increased transaminases, increased serum bilirubin due to liver disorders
Skin and subcutaneous tissue disorders
- uncommon: rash, pruritus
- not known: photosensitivity reaction, alopecia, urticaria, angioedema, bullous eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis
Renal and urinary disorders
- not known: acute renal failure, tubulointerstitial nephritis, nephritic syndrome, impaired renal function test
General disorders and administration site conditions
- uncommon: edema
- not known: fatigue
Diagnostic tests
- rare: weight gain
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 episodes (eg myocardial infarction or stroke) ( see paragraph "SPECIAL WARNINGS").
A single case of anxiety, visual hallucinations, hyperexcitability and altered behavior was reported in a pediatric patient who received twice the dose recommended in the CPR. Symptoms disappeared spontaneously within 1-2 days.
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
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.
KEEP OUT OF THE SIGHT AND REACH OF CHILDREN
Medicines should not be disposed of via wastewater or household waste. Ask the pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
COMPOSITION
A bipartite sachet contains:
active ingredient: ketoprofen 80 mg lysine salt (equivalent to 50 mg of ketoprofen)
Excipients: Mannitol, povidone, colloidal silica, sodium chloride, sodium saccharin, mint flavor (maltodextrin, gum arabic, sulfur dioxide, pulegone).
PHARMACEUTICAL FORM AND CONTENT
Granules for oral solution. Lithographed cardboard box containing 30 bipartite sachets of 80 mg of ketoprofen lysine salt.
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
KETOPROFENE LYSINE SALT RATIOPHARM 80 MG GRANULES FOR ORAL SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
A bipartite sachet contains:
active principle: ketoprofen 80 mg lysine salt (equivalent to 50 mg ketoprofen)
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Granules for oral solution
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Adults: symptomatic treatment of inflammatory states associated with pain, including: rheumatoid arthritis, ankylosing spondylitis, painful arthrosis, extra-articular rheumatism, post-traumatic inflammation, painful inflammatory diseases in dentistry, otolaryngology, urology and pneumology.
In pediatrics: symptomatic and short-term treatment of inflammatory states associated with pain, also accompanied by pyrexia, such as those affecting the osteoarticular system, post-operative pain and ear infections.
04.2 Posology and method of administration
Dosage
Adults: one 80 mg sachet (full dose) three times a day with meals.
Children aged between 6 and 14: half a 40 mg sachet (half dose) three times a day with meals.
Senior citizens: the posology must be carefully established by the physician who will have to evaluate a "possible reduction of the dosages indicated above (see section 4.4). Patients with hepatic insufficiency: it is recommended to initiate therapy at the minimum daily dosage (see section 4.4).
Patients with mild or moderate renal insufficiency: monitoring of urine output and renal function is advised (see section 4.4).
Method of administration
Instructions on the use of the sachet: opening the sachet along the line marked "half dose" gives a dose of 40 mg. Opening the sachet along the line marked "full dose" gives a dose of 80 mg. Pour the contents of a sachet or half a sachet into half a glass of water and mix.
04.3 Contraindications
Ketoprofen is contraindicated in patients who have a "history of hypersensitivity reactions" such as bronchospasm, asthma attacks, rhinitis, nasal polyps, urticaria, angioneurotic edema or other allergic-type reactions to ketoprofen, acetylsalicylic acid (ASA) or others NSAIDs.
Serious, rarely fatal, anaphylactic reactions have been reported in these patients (see section 4.8).
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Ketoprofen is also contraindicated in the third trimester of pregnancy.
Ketoprofen is contraindicated in the following cases:
• severe heart failure
• active peptic ulcer, or a previous history of gastrointestinal bleeding, ulceration or perforation
• severe liver failure
• severe renal failure, previous bronchial asthma
• bleeding diathesis and other coagulation disorders, or patients subject to anticoagulant therapy
• children under the age of 6.
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.
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).
The concomitant use of Ketoprofen lysine salt ratiopharm with other NSAIDs should be avoided, including selective cyclooxygenase-2 inhibitors (see section 4.5).
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 than other NSAIDs, especially at high doses (see also section 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 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 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, particularly if elderly, should report any abdominal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
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 lysine salt the treatment should be discontinued.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in conjunction with the use of NSAIDs (see section 4.8). In the early stages of therapy, patients appear to be at highest risk for these reactions: the onset of the reaction occurs in most cases within the first month of treatment.
Treatment with ketoprofen lysine salt should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
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 insufficient data to exclude a similar risk for ketoprofen lysine salt.
Precautions
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 on diuretic therapy, in patients with chronic renal failure, particularly if the patient is elderly. administration of ketoprofen can induce a reduction in renal blood flow caused by the inhibition of prostaglandins and which can lead to renal decompensation.
Patients with a history of mild to moderate hypertension and / or congestive heart failure should be treated with caution, as fluid retention and edema have been reported with NSAID therapy.
As with other NSAIDs, it should be borne in mind that, in the presence of an infectious disease, the anti-inflammatory, analgesic and antipyretic properties of ketoprofen may mask the characteristic symptoms of progression of the infection, such as fever.
In patients with abnormal liver function tests 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 observed with ketoprofen.
The use of NSAIDs can impair fertility in women and therefore their use is not recommended in women desiring a child. In women who have difficulty conceiving, or who are undergoing fertility testing, discontinuation of NSAIDs should be considered.
Patients with asthma associated with chronic rhinitis, chronic sinusitis and / or nasal polyposis have a higher risk of being allergic to aspirin and / or NSAIDs than the rest of the population. Administration of this drug may cause asthma attacks or bronchospasm, particularly in subjects allergic to aspirin or NSAIDs (see section 4.3).
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ketoprofen lysine salt after careful consideration, as with all other NSAIDs. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg hypertension, hyperlipidaemia, diabetes mellitus, smoking).
If visual disturbances such as blurred vision occur, treatment should be discontinued.
Administer with caution in patients with allergic manifestations or previous allergy.
Gastrointestinal haemorrhages, occasionally severe, and ulcer have been reported in some pediatric patients treated with ketoprofen lysine salt (see section 4.8); therefore the product must be administered under strict supervision of the physician who will have to evaluate the necessary dosage schedule each time.
As with all NSAIDs, the drug can increase plasma urea nitrogen and creatinine.
As with other prostaglandin synthesis inhibitors, the drug may be associated with adverse events on the renal system which can lead to glomerular nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure.
As with other NSAIDs, the drug may cause transient small increases in some liver parameters and also significant increases in SGOT and SGPT (see section 4.8). In the event of a significant increase in these parameters, therapy must be discontinued.
Ketoprofen lysine salt should be administered with caution in patients with haematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disorders.
Caution should be exercised in the event of impaired hepatic, renal (see section 4.2) or cardiac function as well as in the presence of other conditions predisposing to fluid retention. In these cases, the use of NSAIDs can cause deterioration of renal function and fluid retention. Caution is also required in patients undergoing diuretic therapy or likely hypovolaemic because the risk of nephrotoxicity is increased.
Elderly patients are more prone to decreased renal, cardiovascular or hepatic function.
04.5 Interactions with other medicinal products and other forms of interaction
Combinations of medicines not recommended:
• Other NSAIDs, including selective cyclooxygenase-2 inhibitors and high doses of salicylates: Increased risk of gastrointestinal ulcers and bleeding.
• Anticoagulants (heparin, warfarin), and platelet aggregation inhibitors (eg. Ticlopidine and clopidogrel): increased risk of bleeding (see section 4.4). If co-administration is unavoidable, patients should be carefully monitored.
• Lithium: risk of increased plasma lithium levels which may reach toxic values, due to decreased renal excretion of lithium. When necessary, plasma lithium levels should be closely monitored and the lithium dose adjusted during and following NSAID treatment.
• Hydantoins and sulfonamides: the toxic effects of these substances can be increased.
• Methotrexate at doses above 15 mg / week: Increased risk of haematological toxicity of methotrexate, particularly when administered at high doses (> 15 mg / week), possibly related to the shift of protein bound methotrexate and its reduced renal clearance.
Combinations of medicines requiring precautions for use:
• Diuretics: Patients, particularly those who are dehydrated on treatment with diuretics, are at increased risk of developing renal failure secondary to a reduction in renal blood flow due to inhibition of prostaglandin formation. These patients should be rehydrated prior to initiating combination therapy and their renal function monitored at initiation of treatment (see section 4.4).
• ACE inhibitors and angiotensin II antagonists: in patients with impaired renal function (eg dehydrated patients or elderly patients) co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit cyclo-oxygenases may lead to further deterioration of renal function , which includes possible acute renal failure.
• Methotrexate at doses below 15 mg / week: During the first few weeks of combination treatment, a complete blood count should be performed weekly. In the event of impaired renal function or if the patient is elderly, monitoring should be performed more frequently.
• Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
• Pentoxifylline: c "is an increased risk of bleeding. Increase clinical monitoring and check bleeding time more frequently.
• Zidovudine: risk of increased toxicity on the red cell line by action on reticulocytes, with severe anemia occurring one week after starting treatment with the NSAID. Check the complete blood count and reticulocyte count one or two weeks after having started treatment with the NSAID.
• Sulfonylureas: NSAIDs can increase the hypoglycemic effect of sulfonylureas by displacing them from binding sites with plasma proteins.
Combinations of medicines to be evaluated:
• Antihypertensive agents (Beta-blockers, angiotensin converting enzyme inhibitors, diuretics): treatment with an NSAID may decrease their antihypertensive effect by inhibiting the synthesis of vasodilating prostaglandins.
• Thrombolytics: increased risk of bleeding.
• Probenecid: Concomitant administration of probenecid may result in a significant reduction in the plasma clearance of ketoprofen. Plasma concentrations of ketoprofen lysine salt may be increased; this interaction may be due to an inhibitory mechanism at the site of renal tubular secretion and glucuronide conjugation and requires dose adjustment of the ketoprofen lysine salt.
• Selective Serotonin Reuptake Inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
04.6 Pregnancy and lactation
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% up 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 loss of pre- and post-implantation and of 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, ketoprofen should not be administered except in strictly necessary cases. If ketoprofen 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 may 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, ketoprofen is contraindicated during the third trimester of pregnancy.
Feeding time
There are no data on the secretion of ketoprofen in human milk. Administration of ketoprofen is not recommended during lactation.
04.7 Effects on ability to drive and use machines
Patients should be advised of the possibility of somnolence, dizziness or seizures and should be advised not to drive or operate machinery if these symptoms occur.
With ketoprofen 12.5 mg lozenges, at the recommended doses and duration of therapy, none of these symptoms are expected.
04.8 Undesirable effects
List of adverse reactions
Classification of expected frequencies: very common (≥1 / 10); common (≥1 / 100,
The following side effects have been reported following the use of ketoprofen in adults:
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 shock)
Psychiatric disorders
- not known: mood alteration
Nervous system disorders
- uncommon: headache, dizziness, somnolence
- rare: paraesthesia
- not known: convulsions, dysgeusia
Eye disorders
- rare: blurred vision (see section 4.4)
Ear and labyrinth disorders
- rare: tinnitus
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 ASA and other NSAIDs), rhinitis
Gastrointestinal disorders
- common: dyspepsia, nausea, abdominal pain, vomiting
- uncommon: constipation, diarrhea, flatulence, gastritis
- rare: stomatitis, peptic ulcer
- not known: exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage and perforation
Hepatobiliary disorders
- rare: hepatitis, increased transaminases, increased serum bilirubin due to liver disorders
Skin and subcutaneous tissue disorders
- uncommon: rash, itching
- not known: photosensitivity reaction, alopecia, urticaria, angioedema, bullous eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis
Renal and urinary disorders
- not known: acute renal failure, tubulointerstitial nephritis, nephritic syndrome, impaired renal function test
General disorders and administration site conditions
- uncommon: edema
- not known: fatigue
Diagnostic tests
- rare: weight gain
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 episodes (eg myocardial infarction or stroke) ( see section 4.4).
A single case of anxiety, visual hallucinations, hyperexcitability and altered behavior was reported in a pediatric patient who received twice the dose recommended in the CPR. Symptoms disappeared spontaneously within 1-2 days.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
04.9 Overdose
Cases of overdose have been reported with ketoprofen doses up to 2.5 mg. In most cases, the symptoms observed were benign and limited to lethargy, drowsiness, nausea, vomiting and epigastric pain. There is no specific antidote for the treatment of ketoprofen overdose. If massive overdose is suspected, it is recommended that gastric lavage be performed and symptomatic and supportive therapy instituted to compensate for dehydration, to monitor urinary excretion and to correct acidosis, if present.
In the presence of renal insufficiency, hemodialysis can be useful to remove the circulating drug.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory, antirheumatic, non-steroidal drugs. Derivatives of propionic acid. ATC code: M01AE03
Ketoprofen lysine salt is the lysine salt of 2- (3-benzoylphenyl) propionic acid, an analgesic, anti-inflammatory and antipyretic drug belonging to the class of NSAIDs (M01AE). Ketoprofen lysine salt is more soluble than acid ketoprofen.
the mechanism of action of NSAIDs is related to the reduction of prostaglandin synthesis by inhibiting the cyclooxygenase enzyme.
Specifically, there is an inhibition of the transformation of arachidonic acid into cyclic endoperoxides, PGG 2 and PGH 2, precursors of prostaglandins PGE 1, PGE 2, PGF 2a and PGD 2 and also of prostacyclin PGI 2 and thromboxanes (TxA 2 and TxB 2). Furthermore, the inhibition of prostaglandin synthesis can interfere with other mediators such as kinins, causing an indirect action that would add to the direct action.
Ketoprofen lysine salt possesses a marked analgesic effect, correlated both with its anti-inflammatory effect and with a central effect.
Ketoprofen lysine salt exerts an antipyretic activity without interfering with the normal thermoregulation processes.
Painful inflammatory manifestations are eliminated or attenuated by promoting joint mobility.
05.2 "Pharmacokinetic properties
The ketoprofen lysine salt possesses higher solubility than acid ketoprofen. The form for oral use allows the assumption of the active principle already in aqueous solution and therefore leads to a rapid increase in plasma levels and an early reaching of the peak value. This is manifested, clinically, with a more rapid onset and a greater intensity of the analgesic and anti-inflammatory effect.
The kinetic profile in the child does not differ from that in the adult. Repeated administration does not change the kinetics of the drug or produce accumulation. Ketoprofen is 95-99% bound to plasma proteins. Significant levels of ketoprofen have been found in the tonsillar tissue and in the synovial fluid after systemic administration. Elimination is rapid and essentially via the kidney: 50% of the product administered systemically is excreted in the urine in 6 hours. Ketoprofen is extensively metabolised: approximately 60-80% of the systemically administered product is found in the form of metabolites in the urine.
05.3 Preclinical safety data
The LD50 of ketoprofen lysine salt in rats and mice orally was respectively 102 and 444 mg / kg, equal to 30-120 times the active dose as anti-inflammatory and analgesic in the animal. Intraperitoneally the LD50 of ketoprofen lysine salt was found to be 104 and 610 mg / kg in the rat and mouse, respectively.
Prolonged treatment in rats, dogs and monkeys with oral ketoprofen lysine salt at doses equal to or higher than the prescribed therapeutic dosages did not cause the appearance of any toxic phenomenon. At high doses, gastrointestinal and renal alterations were found due to the known side effects caused in animals by non-steroidal anti-inflammatory drugs. In a prolonged toxicity study conducted in rabbits by the oral or rectal route, ketoprofen was shown to be better tolerated when administered orally. rectal versus oral In an intramuscular tolerability study in rabbits, ketoprofen lysine salt was well tolerated.
Ketoprofen lysine salt was found to be non-mutagenic in genotoxicity tests carried out "in vitro" and in "vivo". Carcinogenicity studies with ketoprofen in mice and rats showed the absence of carcinogenic effects.
As regards embryo-fetal toxicity and teratogenesis of NSAIDs in animals, please refer to section 4.6.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Mannitol, povidone, colloidal silica, sodium chloride, sodium saccharin, mint flavor (maltodextrin, gum arabic, sulfur dioxide, pulegone).
06.2 Incompatibility
Not relevant
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
Lithographed cardboard box containing 30 bipartite paper / aluminum / polythene sachets.
06.6 Instructions for use and handling
No special instructions.
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
ratiopharm GmbH - Graf-Arco Strasse n. 3 - Ulm (Germany)
08.0 MARKETING AUTHORIZATION NUMBER
Ketoprofen lysine salt ratiopharm 80 mg granules for oral solution - 30 bipartite sachets AIC: 039414014
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