Active ingredients: Ketoprofen
ORUDIS 50 mg hard capsules
Orudis package inserts are available for pack sizes:- ORUDIS 50 mg hard capsules
- ORUDIS 100 mg prolonged-release hard capsules, ORUDIS 200 mg prolonged-release hard capsules
- ORUDIS 100 mg / 2 ml solution for injection for intramuscular use
- ORUDIS 100 mg suppositories
- ORUDIS 5% gel
Indications Why is Orudis used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Orudis, 2- (3-benzoyl-phenyl) -propionic acid or ketoprofen, is a non-steroidal anti-inflammatory drug with strong anti-inflammatory, analgesic and antipyretic activity.
THERAPEUTIC INDICATIONS
Rheumatoid arthritis, ankylosing spondylitis, acute gout, osteoarthritis of various localization, sciatica, radiculitis, myalgia, bursitis, tendonitis, tenosynovitis, synovitis, capsulitis, contusions, sprains, dislocations, muscle tears, phlebitis, painful lymphoid lymphitis, superficial thrombophlebitis dentistry, urology and pneumology.
Contraindications When Orudis should not be used
Orudis is contraindicated in patients with a history of hypersensitivity reactions, such as bronchospasm, asthma attacks, rhinitis, urticaria or other allergic-type reactions, to ketoprofen, acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs (NSAIDs). severe, rarely fatal anaphylactic reactions have been reported in these patients (see also Side Effects).
Orudis is also contraindicated in the following cases:
- hypersensitivity to any of the excipients;
- during the third trimester of pregnancy
- during intensive diuretic therapy;
- severe renal failure;
- severe forms of liver failure (liver cirrhosis, severe hepatitis);
- leukopenia and thrombocytopenia;
- subjects with ongoing bleeding
- hemorrhagic diathesis;
- severe heart failure;
- active peptic ulcer, or a history of gastrointestinal bleeding, ulceration or perforation.
- Orudis is generally contraindicated in pregnancy, during lactation (see also Special Warnings) and in pediatric age.
Precautions for use What you need to know before taking Orudis
Orudis 50 mg capsules contain lactose; Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
Renal function should be carefully monitored at the initiation of treatment in patients with heart failure, cirrhosis and nephrosis, in patients on diuretic therapy, with chronic renal failure particularly if elderly. In such patients, administration of ketoprofen may cause decreased blood flow. kidney blood, caused by the inhibition of prostaglandins, and lead to renal alterations.
Caution should be exercised in patients with a history of hypertension and / or heart failure as fluid retention and edema have been reported in association with NSAID therapy.
As with other non-steroidal anti-inflammatory drugs, in the presence of infection, the anti-inflammatory, analgesic and antipyretic effects of ketoprofen may mask the symptoms of progression of the infection such as fever.
In patients with impaired liver function tests or with previous liver disease, transaminases should be evaluated regularly, particularly during long-term therapy. Rare cases of jaundice and hepatitis have been reported with ketoprofen.
The use of NSAIDs may impair female fertility and is not recommended in women intending to become pregnant. In women who have fertility problems or who are undergoing investigation of fertility, discontinuation of treatment should be considered.
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 medicinal product may cause asthma attacks or bronchospasm. particularly in subjects allergic to aspirin or NSAIDs (see also Contraindications).
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, 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).
If visual disturbances such as blurred vision occur, treatment should be discontinued
Interactions Which drugs or foods may change the effect of Orudis
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
ASSOCIATIONS NOT RECOMMENDED
Other non-steroidal anti-inflammatory drugs (including selective cyclo-oxygenase-2 inhibitors) and high-dose salicylates: increased risk of gastrointestinal ulcers and bleeding.
Anticoagulants (heparin and warfarin) and antiplatelet agents (eg ticlopidine and clopidogrel): increased risk of bleeding (see Precautions for use). If concomitant administration cannot be avoided, patients should be followed closely.
Lithium: risk of increased plasma lithium levels, which can sometimes reach toxic levels due to reduced renal excretion of lithium. Where necessary, plasma lithium levels should be monitored with possible dosage adjustment during and after NSAID therapy.
Methotrexate at doses above 15 mg / week: increased risk of haematological toxicity from methotrexate, particularly when administered in high doses (> 15 mg / week); possibly due to protein binding shift of methotrexate and reduced renal clearance. In patients already being treated with ketoprofen, therapy should be stopped at least 12 hours before methotrexate administration. If ketoprofen is to be administered at the end of methotrexate therapy, it is necessary to wait 12 hours before administration.
ASSOCIATIONS THAT REQUIRE CAUTION
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see also Special Warnings).
Diuretics: patients who are taking diuretics and among them, particularly dehydrated patients have a high risk of developing renal insufficiency following a decrease in renal blood flow caused by inhibition of prostaglandins. These patients must be rehydrated before the start of co-administration. and their renal function should be monitored when treatment is started.
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 cyclo-oxygenase system may lead to further deterioration of renal function, which includes possible acute renal failure. These interactions should be considered in patients taking Orudis 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 (see Precautions for use).
Methotrexate at doses below 15 mg / week: A complete blood count should be performed every week during the first few weeks of combination therapy. In the presence of impaired renal function or in elderly patients, monitoring should be more frequent.
Pentoxifylline: it determines an increased risk of bleeding. Closer clinical monitoring and bleeding time monitoring is required.
ASSOCIATIONS TO CONSIDER
Antihypertensives (beta-blockers, angiotensin converting enzymes, diuretics): risk of decreased antihypertensive activity (inhibition of prostaglandin vasodilation caused by NSAIDs).
Thrombolytics: increased risk of bleeding.
Probenecid: Concomitant administration of probenecid can significantly reduce the plasma clearance of ketoprofen. Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see Precautions for use).
Gemeprost: reduced efficacy of gemeprost.
Intrauterine contraceptive devices (IUDs): the effectiveness of the device may be reduced resulting in pregnancy.
Warnings It is important to know that:
Medicines such as Orudis may be associated with a small increased risk of heart attack ('myocardial infarction') or stroke. Any risk is more likely with high doses and prolonged treatments. Do not exceed the recommended dose or duration of treatment.
Concomitant use of Orudis with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Gastrointestinal bleeding, ulceration or 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 also Contraindications), 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. 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 Interactions).
Patients with a history of gastrointestinal toxicity, particularly the 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 Interactions).
When gastrointestinal bleeding or ulceration occurs in patients taking Orudis 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 also Side Effects)
Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see also Dose, Method and time of administration).
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 Undesirable Effects). be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Orudis should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
If you have heart problems, or stroke problems, or if you have a risk for these conditions (for example, high blood pressure, diabetes or high cholesterol or smoking), discuss your treatment with your doctor or pharmacist.
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 Dose, method and time of administration and Contraindications).
Pregnancy
The administration of ketoprofen, even if experimentally did not observe embryo-fetal toxicity for posologies comparable to those foreseen for clinical use, is not advisable in pregnancy, during lactation and in infancy.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Results of epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor. in the early stages of pregnancy. The absolute risk of cardiac malformations was increased from less than 1% to approximately 1.5%. The risk has been estimated to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the first and second trimester of pregnancy, Orudis should only be used as needed. If Orudis is used by women who are trying to have a baby or during the first and second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
The use of the drug close to childbirth can cause changes in the haemodynamics of the small circulation of the unborn child with serious consequences for breathing.
Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.
Feeding time
Since no data are available on the secretion of ketoprofen in breast milk, its use during lactation is not recommended.
Ask your doctor or pharmacist for advice before taking any medicine.
Effects on ability to drive and use machines
Patients should be informed of the potential for somnolence, dizziness or seizures and should avoid driving or engaging in activities that require special vigilance if such symptoms occur.
Dosage and method of use How to use Orudis: Dosage
In adults, the dose is 150-200 mg once a day (equal to 3-4 capsules a day) divided with meals.
In the treatment of elderly patients, the posology must be carefully established by the physician, who will have to evaluate a "possible reduction of the dosages indicated above. Although clinical and pharmacokinetic data have not revealed phenomena of increased secondary manifestations, it is appropriate, as with other drugs, to start treatment with Orudis hard capsules at the lowest recommended dose, and maintenance therapy with the lowest effective dose.
The maximum daily dose is 200 mg. The risk and benefit balance should be carefully considered before starting treatment with the 200 mg daily dose, and higher doses are not recommended (see also Precautions for use).
Special populations
Patients with renal insufficiency and elderly patients It is recommended to reduce the starting dose and to practice maintenance therapy with the lowest effective dose. Individualized adjustments can be considered only after establishing good tolerability of the drug
Patients with hepatic insufficiency
Such patients should be followed closely and treated with the lowest effective daily dose.
Children
The safety and efficacy of ketoprofen have not been studied in children
Overdose What to do if you have taken too much Orudis
Cases of overdose have been reported with doses up to 2.5 g of ketoprofen. In most cases, the symptoms observed were benign in nature and limited to lethargy, somnolence, nausea, vomiting and epigastric pain.
There is no specific antidote to ketoprofen overdose. In case of suspicion of severe overdose, gastric lavage and the institution of supportive and symptomatic therapies are recommended to compensate for dehydration, to monitor renal function and to correct acidosis if present.
In case of renal insufficiency, hemodialysis may be useful to remove the drug from the circulation.
In case of accidental intake of an excessive dose of ORUDIS, notify your doctor immediately or go to the nearest hospital.
IF YOU HAVE ANY DOUBTS ABOUT USING ORUDIS, CONTACT YOUR DOCTOR OR PHARMACIST.
Side Effects What are the side effects of Orudis
Like all medicines, ORUDIS can cause side effects, although not everybody gets them.
Classification of expected frequencies: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10000 to <1 / 1000), very rare (<1/10000), not known (cannot be estimated from the available data).
Gastrointestinal disorders:
The most commonly observed adverse events are gastrointestinal in nature.
Common: dyspepsia, nausea, abdominal pain, vomiting
Uncommon: constipation, diarrhea, flatulence, gastritis
Rare: ulcerative stomatitis, peptic ulcers
Not known: exacerbation of colitis and Crohn's disease, gastrointestinal perforation or haemorrhage, sometimes fatal, particularly in the elderly (see Special Warnings). Melena, hematemesis.
Skin and subcutaneous tissue disorders:
Uncommon: rash, pruritus
Not known: photosensitization, alopecia, urticaria, angioedema, bullous reactions including Stevens-Johnson and Lyell syndrome and toxic epidermal necrolysis (very rarely)
Respiratory thoracic and mediastinal disorders:
Rare: asthma attacks
Not known: bronchospasm (particularly in patients with known hypersensitivity to acetylsalicylic acid ASA and other NSAIDs), rhinitis.
Nervous system disorders:
Uncommon: headache, dizziness, somnolence
Rare: paraesthesia
Not known: convulsions, dysgeusia
Eye disorders:
Rare: blurred vision (see also Special Warnings and Precautions for use)
Ear and labyrinth disorders
Rare: tinnitus
Renal and urinary disorders:
Not known: renal function test abnormalities, acute renal failure, interstitial tubular nephritis, nephrotic syndrome.
Hepatobiliary disorders:
Rare: hepatitis, increased transaminase levels, increased serum bilirubin due to liver disease.
Disorders of the blood and lymphatic system:
Rare: anemia due to bleeding
Not known: agranulocytosis, thrombocytopenia, bone marrow aplasia.
Disorders of the immune system
Not known: anaphylactic reactions (including shock).
Psychiatric disorders:
Not known: mood changes.
Cardiac disorders:
Not known: heart failure
Vascular disorders:
Not known: hypertension, vasodilation.
General disorders and administration site conditions:
Uncommon: edema, fatigue
Diagnostic tests:
Rare: weight gain
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In any case, the appearance of an important secondary reaction requires the immediate suspension of the treatment.
Expiry and Retention
Expiry: see the expiry date indicated on the package. The expiry date indicated refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date indicated on the package.
Store at a temperature not exceeding 30 ° C.
Keep in the outer carton to protect the medicine from light
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
COMPOSITION
ORUDIS 50 mg hard capsules
One capsule contains:
Active ingredient: ketoprofen 50 mg.
Excipients: Magnesium stearate, lactose. Shell components: iron oxide (E172), titanium dioxide (E171), gelatin.
PHARMACEUTICAL FORM AND CONTENT
Hard capsules. "50 mg hard capsules" 30 capsules
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
ORUDIS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
ORUDIS 50 mg hard capsules
One capsule contains:
Active principle: ketoprofen 50 mg.
ORUDIS 100 mg prolonged-release hard capsules
One capsule contains:
Active principle: ketoprofen 100 mg.
ORUDIS 200 mg prolonged-release hard capsules
One capsule contains:
Active principle: ketoprofen 200 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsules.
Prolonged-release hard capsules.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Orudis 50 mg hard capsules it is indicated in the treatment of rheumatoid arthritis, ankylosing spondylitis, acute gout, osteoarthritis of various localization, sciatica, radiculitis, myalgia, bursitis, tendinitis, tenosynovitis, synovitis, capsulitis, contusions, sprains, dislocations, muscle tears, lymphbitis, superficial thrombophlebitis , painful inflammatory diseases in dentistry, otolaryngology, urology and pulmonology.
Orudis 100 mg and 200 mg prolonged-release hard capsules it is indicated in the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute joint and periarticular manifestations (bursitis, capsulitis, synovitis, tendonitis); cervical spondylitis, lumbar pain (tearing, lumbago, sciatica, fibrositis), musculoskeletal pain syndromes and dysmenorrhea.
04.2 Posology and method of administration
The use of the medicinal product is reserved for adult patients only.
Hard capsules : the dose is 150-200 mg per day (equal to 3 - 4 capsules per day) divided with meals;
Prolonged-release hard capsules : the dose is 100-200 mg once a day, depending on the weight of the subject and the severity of the symptoms. Orudis extended-release hard capsules are to be taken orally after a meal.
The maximum daily dose is 200 mg. The benefit and risk balance should be carefully considered before starting treatment with the 200 mg daily dose and higher doses are not recommended (see also section 4.4).
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.4).
Special populations
Patients with renal insufficiency and the elderly
It is advisable to reduce the starting dose and practice maintenance therapy with the lowest effective dose. Individualized adjustments can only be considered after establishing good tolerability of the drug (see section 5.2).
Patients with hepatic insufficiency
Such patients should be followed closely and treated with the lowest effective daily dose (see sections 4.6 and 5.2).
Children
The safety and efficacy of ketoprofen have not been studied in children.
04.3 Contraindications
Orudis is contraindicated in patients with a history of hypersensitivity reactions, such as bronchospasm, asthma attacks, rhinitis, urticaria or other allergic-type reactions, to ketoprofen, acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs (NSAIDs). severe, rarely fatal, anaphylactic reactions have been reported in these patients (see section 4.8).
Orudis is also contraindicated in the following cases:
• hypersensitivity to any of the excipients;
• during the third trimester of pregnancy
• undergoing intensive diuretic therapy;
• severe renal insufficiency;
• severe forms of liver failure (liver cirrhosis, severe hepatitis);
• leukopenia and thrombocytopenia;
• subjects with ongoing bleeding
• hemorrhagic diathesis;
• severe heart failure;
• active peptic ulcer, or a history of gastrointestinal bleeding, ulceration or perforation.
Orudis is generally contraindicated in pregnancy, during lactation (see section 4.6) and in pediatric age.
04.4 Special warnings and appropriate precautions for use
Orudis 50 mg capsules contain lactose; Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Orudis prolonged-release capsules contain sucrose: patients with rare problems of fructose intolerance, glucose / galactose malabsorption or sucrase isomaltase insufficiency should not take this medicine.
Warnings
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and below).
Concomitant use of Orudis with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Gastrointestinal bleeding, ulceration or 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 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 the 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).
When gastrointestinal bleeding or ulceration occurs in patients taking Orudis 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).
Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
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. Orudis 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 sufficient data to exclude a similar risk for ketoprofen.
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 also sections 4.2 and 4.3).
Precautions
Renal function should be carefully monitored at the start of treatment in patients with heart failure, with cirrhosis and nephrosis, in patients on diuretic therapy, with chronic renal failure particularly if elderly. In such patients the administration of ketoprofen may cause a reduction in blood flow. renal blood, caused by the inhibition of prostaglandins and lead to renal alterations.
Caution is 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 non-steroidal anti-inflammatory drugs, in the presence of infection, the anti-inflammatory, analgesic and antipyretic effects of ketoprofen can mask the symptoms of progression of the infection such as fever.
In patients with impaired liver function tests or with previous liver disease, transaminases should be evaluated regularly, particularly during long-term therapy.Cases of jaundice and hepatitis have been reported with ketoprofen.
The use of NSAIDs can compromise female fertility and is not recommended for women intending to become pregnant.
In women who have fertility problems or who are undergoing fertility investigations, discontinuation of treatment should be considered.
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 medicinal product 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 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).
If visual disturbances such as blurred vision occur, treatment should be discontinued.
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.
04.5 Interactions with other medicinal products and other forms of interaction
ASSOCIATIONS NOT RECOMMENDED
Other non-steroidal anti-inflammatory drugs (including selective cyclooxygenase-2 inhibitors ) And salicylates in high doses : increased risk of gastrointestinal ulcers and bleeding.
Anticoagulants (heparin and warfarin) and antiplatelet agents (e.g. ticlopidine and clopidogrel) : increased risk of bleeding (see section 4.4). If concomitant administration cannot be avoided, patients should be followed closely
Lithium : risk of increased plasma lithium levels, which can sometimes reach toxic levels due to reduced renal excretion of lithium. Where necessary, plasma lithium levels should be monitored with possible dosage adjustment during and after NSAID therapy.
Methotrexate at doses above 15 mg / week: increased risk of haematological toxicity from methotrexate, particularly when administered in high doses (> 15 mg / week); possibly due to protein binding shift of methotrexate and reduced renal clearance. In patients already being treated with ketoprofen, therapy should be stopped at least 12 hours before methotrexate administration. If ketoprofen is to be administered at the end of methotrexate therapy, it is necessary to wait 12 hours before administration.
ASSOCIATIONS THAT REQUIRE CAUTION
Corticosteroids : increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Diuretics : patients who are taking diuretics and, among them, particularly dehydrated patients have a high risk of developing renal insufficiency following a decrease in renal blood flow caused by inhibition of prostaglandins. These patients must be rehydrated before the start of co- administration and their renal function should be monitored when treatment is initiated (see section 4.4).
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 the cyclo-oxygenase system may lead to further deterioration of the renal function, including possible acute renal failure These interactions should be considered in patients taking Orudis 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 (see section 4.4).
Methotrexate at doses below 15 mg / week: a weekly blood count should be performed during the first few weeks of combination therapy. In the presence of impaired renal function or in elderly patients, monitoring should be more frequent.
Pentoxifylline : there is an increased risk of bleeding. Closer clinical monitoring and bleeding time monitoring is required.
ASSOCIATIONS TO CONSIDER
Antihypertensives (beta-blockers, angiotensin converting enzymes, diuretics): risk of decreased antihypertensive activity (inhibition of prostaglandin vasodilation caused by NSAIDs).
Thrombolytics: increased risk of bleeding.
Probenecid: concomitant administration of probenecid can significantly reduce the plasma clearance of ketoprofen.
Selective Serotonin Reuptake Inhibitors (SSRIs) : increased risk of gastrointestinal bleeding (see section 4.4).
Gemeprost: reduced efficacy of gemeprost.
Intrauterine contraceptive devices (IUDs): the effectiveness of the device may be reduced resulting in pregnancy.
04.6 Pregnancy and lactation
The administration of ketoprofen, even if experimentally did not observe embryo-fetal toxicity for posologies comparable to those foreseen for clinical use, is not advisable in pregnancy, during lactation and in infancy.
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 was increased from less than 1% to to approximately 1.5%. The risk has been estimated to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the first and second trimester of pregnancy, Orudis should only be used as needed. If Orudis is used by women who are trying to have a baby or during the first and second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
• renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
• possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
• inhibition of uterine contractions resulting in delayed or prolonged labor.
The use of the drug close to childbirth can cause changes in the haemodynamics of the small circulation of the unborn child with serious consequences for breathing.
Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.
Feeding time
Since no data are available on the secretion of ketoprofen in breast milk, its use during lactation is not recommended.
04.7 Effects on ability to drive and use machines
Patients should be informed of the potential for somnolence, dizziness or seizures and should avoid driving or engaging in activities that require special vigilance if such symptoms occur.
04.8 Undesirable effects
Like all medicines, ORUDIS can cause side effects, although not everybody gets them.
Classification of expected frequencies: very common (≥1 / 10), common (≥1 / 100,
The following reactions have been reported with the use of ketoprofen in adults
Gastrointestinal disorders
The most commonly observed adverse events are gastrointestinal in nature.
Common: dyspepsia, nausea, abdominal pain, vomiting.
Uncommon: constipation, diarrhea, flatulence, gastritis
Rare: ulcerative stomatitis, peptic ulcers
Not known: exacerbation of colitis and Crohn's disease, gastrointestinal perforation or haemorrhage, sometimes fatal, particularly in the elderly (see section 4.4). Melena, hematemesis.
Skin and subcutaneous tissue disorders:
Uncommon: rash, pruritus
Not known: photosensitization, alopecia, urticaria, angioedema, bullous reactions including Stevens-Johnson and Lyell syndrome and toxic epidermal necrolysis (very rarely).
Respiratory thoracic and mediastinal disorders:
Rare: asthma attacks,
Not known: bronchospasm (particularly in patients with known hypersensitivity to acetylsalicylic acid ASA and other NSAIDs), rhinitis.
Nervous system disorders:
Uncommon: headache, dizziness, somnolence
Rare: paraesthesia
Not known: convulsions, dysgeusia.
Pathology of the eye:
Rare: blurred vision (see section 4.4).
Pathology of the ear and labyrinth:
Rare: tinnitus.
Renal and urinary disorders:
Not known: renal function test abnormalities, acute renal failure, interstitial tubular nephritis, nephrotic syndrome.
Hepatobiliary disorders:
Rare: hepatitis, increased transaminase levels, increased serum bilirubin due to liver disease.
Disorders of the blood and lymphatic system:
Rare: anemia due to bleeding
Not known: agranulocytosis, thrombocytopenia, bone marrow aplasia.
Disorders of the immune system:
Not known: anaphylactic reactions (including shock).
Psychiatric disorders:
Not known: mood changes.
Cardiac pathologies:
Not known: heart failure
Vascular pathologies:
Not known: hypertension, vasodilation.
General disorders and administration site conditions:
Uncommon: edema, 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 a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke) (see paragraph 4.4).
04.9 Overdose
Cases of overdose have been reported with doses up to 2.5 g of ketoprofen. In most cases, the symptoms observed were benign in nature and limited to lethargy, somnolence, nausea, vomiting and epigastric pain.
There is no specific antidote to ketoprofen overdose. If severe overdose is suspected, gastric lavage and the institution of supportive and symptomatic therapies are recommended to compensate for dehydration, to monitor renal function and to correct acidosis if present.
In case of renal insufficiency, hemodialysis may be useful to remove the drug from the circulation.
Since Orudis prolonged-release hard capsules are a regulated take-away preparation, it is plausible to assume that ketoprofen will continue to be absorbed for 16 hours from the time of intake.
If the patient is brought to the doctor's observation within a short time after the ingestion of excessive doses, a gastric lavage should be performed in order to recover the granules still present in the stomach, which are recognizable in the gastric contents. However, the treatment is symptomatic and supportive.
Administration of activated carbon should also be considered in an attempt to reduce the absorption of slow release ketoprofen.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-steroidal anti-inflammatory / antirheumatic drugs.
ATC code: M01AE03.
Ketoprofen is a drug with anti-inflammatory and analgesic activity belonging to the pharmacotherapeutic group of NSAIDs.
The anti-inflammatory activity is related to four well documented mechanisms of action: stabilization of the lysosomal membrane; inhibition of prostaglandin synthesis; antibradykinin activity; antiplatelet activity.
Pharmacological studies conducted on animals and partly also on healthy volunteers, suggest that the analgesic activity is doubly articulated.
It is in fact probable that alongside the now known peripheral activity, mediated mainly by the inhibitory effect on prostaglandin synthesis, ketoprofen also exerts its analgesic activity through a central mechanism. non-opioid in which supraspinal structures are involved such as NMDA-like glutamate receptors inducing central sensitization in which various biochemical mediators are involved, such as substance P, 5-HT, in addition to the prostaglandins themselves present in the CNS.
This peculiar analgesic profile would explain the rapidity of the analgesic effect of ketoprofen observed in the clinic in various acute painful conditions, otherwise not explainable with the only peripheral mechanism known to date.
05.2 Pharmacokinetic properties
Orudis prolonged-release hard capsules are a pH controlled release ketoprofen preparation designed for once daily administration of the required therapeutic dose.
Absorption
Ketoprofen is rapidly and completely absorbed from the gastrointestinal tract. Maximum plasma levels are reached within 60 - 90 minutes after oral administration (45 - 60 minutes after rectal administration).
When administered with food, the absorption rate is reduced so as to have reduced and delayed peak plasma concentrations (Cmax); however, the total bioavailability is not altered.
With prolonged-release capsules, the peak plasma concentration occurs after 6-8 hours. A 13% reduction in bioavailability was observed with the administration of this formulation with high calorie foods.
Distribution
The drug is 99% bound to plasma proteins.
Ketoprofen spreads to synovial fluid and intraarticular, capsular, synovial and tendon tissues. Ketoprofen crosses the blood brain and placental barrier. The plasma elimination half-life is approximately 2 hours. The volume of distribution is approximately 7 L.
Prolonged-release formulation: After reaching the plateau (fifth and twelfth hours), ketoprofen levels decrease with an apparent half-life of 3-4 hours. No accumulation was observed after repeated administration.
Biotransformation
The biotransformation of ketoprofen is characterized by two main pathways, hydroxylation and conjugation with glucuronic acid, of which the second is the main pathway in man. Excretion in unchanged form is minimal (less than 1%). Almost all the drug is excreted unchanged in the urine, 65 - 85% of the administered dose is glucuronised.
Excretion
50% of the dose is excreted in the urine within 6 hours of administration. Within 5 days of administration approximately 75% - 90% of the dose is mainly excreted in the urine. The fecal elimination is minimal (1 to 8%).
Special populations
Elderly patients
Absorption of ketoprofen is not affected; there is a lengthening of the half-life (3 hours) and a reduction in renal and plasma clearance.
Patients with renal insufficiency
There is a reduction in renal and plasma clearance and an increase in half-life related to the severity of renal insufficiency.
Patients with hepatic insufficiency
There are no significant changes in plasma clearance and elimination half-life. However, the free fraction has roughly doubled.
05.3 Preclinical safety data
The toxicological tests have shown the low toxicity and the high therapeutic index of ketoprofen. The LD50 in rats, per os, is 165 mg / kg, in mice, by various routes of administration, is between 365 and 662 mg / kg.
There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
ORUDIS 50 mg hard capsules
Magnesium stearate, lactose.
Components of the enclosure: iron oxide (E172), titanium dioxide (E171), gelatin.
ORUDIS 100 mg prolonged-release hard capsules
sucrose, starch, colloidal silica, shellac, ethylcellulose, talc.
Components of the enclosure: erythrosine (E127), patent blue V (E131), titanium dioxide (E171), gelatin.
ORUDIS 200 mg prolonged-release hard capsules
sucrose, starch, colloidal silica, shellac, ethylcellulose, talc.
Components of the enclosure: erythrosine (E127), titanium dioxide (E171), gelatin.
06.2 Incompatibility
None reported.
06.3 Period of validity
2 years.
06.4 Special precautions for storage
ORUDIS 50 mg hard capsules
Store at a temperature not exceeding 30 ° C.
Keep in the outer carton to protect the medicine from light.
ORUDIS 100 mg prolonged-release hard capsules
ORUDIS 200 mg prolonged-release hard capsules
Store in the original package to protect the medicine from light.
06.5 Nature of the immediate packaging and contents of the package
Aluminum / PVC blister
"50 mg hard capsules" 30 capsules
"100 mg prolonged-release capsules, hard" 30 capsules
"200 mg prolonged-release capsules, hard" 30 capsules
06.6 Instructions for use and handling
None in particular.
07.0 MARKETING AUTHORIZATION HOLDER
Sanofi S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
50 mg hard capsules - 30 cps: A.I.C. n. 023183027
100 mg prolonged-release hard capsules - 30 cps: A.I.C. n. 023183181
200 mg prolonged-release hard capsules - 30 cps: A.I.C. n. 023183193
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
First authorization:
hard capsules February 1979
Prolonged-release hard capsules June 1998
Renewal of the Authorization: June 2010
10.0 DATE OF REVISION OF THE TEXT
October 2014
