Active ingredients: Ketoprofen (Ketoprofen lysine salt)
OKi 30 mg suppositories
Oki package inserts are available for packs:- OKi 30 mg suppositories
- OKi 60 mg suppositories
- OKi 160 mg suppositories
- OKi 80 mg / ml oral drops, solution
- OKi 80 mg granules for oral solution
- OKi 160 mg / 2 ml solution for injection for intramuscular use
Indications Why is Oki used? What is it for?
OKI belongs to the category of non-steroidal anti-inflammatory drugs.
Symptomatic and short-term treatment of inflammatory states associated with pain such as those affecting the osteoarticular system, post-operative pain and ear infections.
Contraindications When Oki should not be used
OKi 30 mg suppositories is contraindicated in patients with hypersensitivity to ketoprofen or to any of the excipients.
Ketoprofen is contraindicated in patients with a history of hypersensitivity reactions such as bronchospasm, asthma attacks, rhinitis, urticaria or other allergic reactions to ketoprofen, acetyl salicylic acid (ASA) or other NSAIDs. Serious, rarely fatal, anaphylactic reactions have been observed in these patients (see side effects section).
Ketoprofen is contraindicated in the following cases:
- severe heart failure
- active peptic ulcer / haemorrhage or history of haemorrhage / recurrent peptic ulcer (two or more known episodes of bleeding or ulceration);
- history of gastrointestinal perforation or bleeding following previous NSAID therapy;
- hemorrhagic diathesis
- severe hepatic insufficiency
- severe renal insufficiency
- leukopenia or thrombocytopenia
- severe bleeding disorders
- Ulcerative colitis
- gastritis
- a history of gastrointestinal bleeding, ulceration or perforation or chronic dyspepsia
- third trimester of pregnancy (see section "Pregnancy and lactation") Ketoprofen is contraindicated in cases of proctitis or a history of proctorrhagia. Children under the age of 6.
Precautions for use What you need to know before taking Oki
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, including
including oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as acetyl salicylic acid (see section "Interactions").
The concomitant use of OKi 30 mg suppositories with other NSAIDs should be avoided, including selective cyclooxygenase-2 inhibitors.
Gastrointestinal ulceration, perforation or bleeding: There have been reports of gastrointestinal ulceration, perforation or bleeding, which may be fatal 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 also section "Contraindications").
The risk of gastrointestinal ulcer, perforation or bleeding is higher with increased doses of NSAIDs, in patients with a history of ulcer, particularly if aggravated by haemorrhage or perforation and in the elderly (see section "Contraindications"). These patients should start treatment at the lowest possible dose. Combination therapy with protective drugs (e.g. misoprostol or proton pump inhibitors) should be considered for these patients and for those who have to take concomitantly low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events ( see below and section "Interactions").
Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual 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 (see "Dose, method and time of administration").
When gastrointestinal bleeding or ulceration occurs in patients taking OKi 30 mg suppositories the treatment should be discontinued.
Serious skin reactions, some of them fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome and epidermal necrolysis have been reported very rarely in association with the use of NSAIDs (see section "Undesirable effects"). Patients appear to have an increased risk to develop these reactions early in treatment, with the onset of reactions in most cases within the first month of treatment.
Stop taking ketoprofen at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Several clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatments) may be associated with an increased risk of arterial thrombo-embolic events (eg myocardial infarction or stroke). there are sufficient data to exclude that ketoprofen is also associated with these risks.
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 "Undesirable effects").
At the start of treatment, renal function should be carefully monitored in patients with heart failure, cirrhosis and nephrosis, in subjects on diuretic therapy or with chronic renal failure, especially if elderly. In these patients, administration of ketoprofen may induce a reduction of renal blood flow caused by the inhibition of prostaglandins and lead to renal decompensation.
Caution is advised in patients with a history of mild to moderate hypertension and / or congestive heart failure as there have been reports of fluid retention and edema associated with NSAID therapy.
Like other NSAIDs, in the presence of an infectious disease, the anti-inflammatory, analgesic and antipyretic properties of ketoprofen can mask common symptoms of the progression of the infection, such as fever.
In patients with liver function test abnormalities or with a history of liver disease, transaminase levels should be checked periodically, especially with long-term treatment. Rare cases of jaundice and hepatitis have been reported with the use of ketoprofen.
In patients with impaired renal function the administration of ketoprofen should be carried out with particular caution in consideration of the essentially renal elimination of the drug.
Patients with asthma associated with chronic rhinitis, chronic sinusitis and / or nasal polyposis are at greater risk of allergy to acetylsalicylic acid and / or NSAIDs than the rest of the population.
The administration of this drug can contribute to triggering asthma attacks or bronchospasms, especially in subjects allergic to acetylsalicylic acid or NSAIDs (see section "Contraindications").
In some pediatric patients treated with ketoprofen lysine salt, gastrointestinal haemorrhages, occasionally even severe, and peptic ulcer have been reported; therefore the product must be administered under strict supervision of the physician who will have to evaluate the necessary dosage schedule each time.
It is not known that the drug gives rise to addiction and dependence phenomena.
Interactions Which drugs or foods can change the effect of Oki
"Please inform your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription"
Combinations not recommended
- Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates: increased risk of gastrointestinal bleeding and ulceration.
- Anticoagulants (heparin and warfarin): NSAIDs can amplify the effects of anticoagulants such as warfarin; increased risk of bleeding (see section "Precautions for use"). If concomitant administration cannot be avoided, patients should be carefully monitored.
- Platelet aggregation inhibitors (ticlopidine, clopidogrel): increased risk of bleeding (see section "Precautions for use"). If co-administration is unavoidable, patients should be closely monitored.
- Lithium: Risk of increased plasma lithium levels, sometimes up to toxicity levels due to decreased renal excretion of lithium. If necessary, plasma lithium levels should be closely monitored and the lithium dosage adjusted during and after NSAID therapy.
- Methotrexate, at doses greater than 15 mg / week or more: increased risk of haematological toxicity to methotrexate, especially when administered at high doses (> 15 mg / week), possibly related to shift from methotrexate-binding proteins and decreased renal clearance .
Combinations with other drugs requiring precaution:
- Diuretics: patients who are taking diuretics and among them, those who are particularly dehydrated are most at risk of developing renal failure secondary to reduced renal blood flow caused by prostaglandin inhibition. These patients should be rehydrated before starting co-administration and monitoring should be done. renal function (see "Precautions for use") after initiation of treatment. NSAIDs may reduce the effect of diuretics.
- ACE inhibitors and angiotensin II antagonists: in patients with impaired renal function (e.g. dehydrated patients and elderly patients) co-administration of an ACE inhibitor or angiotensin II antagonist and agents capable of inhibiting cycle oxygenase can lead to further deterioration of this 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 15 mg / week: during the first weeks of the combination, perform a weekly monitoring of the complete blood count. Increase the frequency in the presence of even a slight worsening of renal function or as in the elderly.
- Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see "Precautions for use").
- Pentoxifylline: increased risk of bleeding. More frequent clinical checks and monitoring of bleeding time.
- Probenecid: co-administration of probenecid may markedly reduce the plasma clearance of ketoprofen.
Combinations with other drugs to be considered
- Antihypertensive drugs (beta-blockers, ACE inhibitors, diuretics): NSAIDs may reduce the effect of antihypertensive drugs. Risk of reduced antihypertensive potency (NSAIDs inhibit vasodilator prostaglandins).
- Thrombolytic drugs: increased risk of bleeding.
- Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see "Precautions for use").
- Diphenylhydantoin and Sulfonamides: Since the protein binding of ketoprofen is high, it may be necessary to reduce the dosage of diphenylhydantoin or sulfonamides that must be administered simultaneously.
- Ciclosporin, tacrolimus: risk of additional nephrotoxic effects, particularly in the elderly.
Warnings It is important to know that:
The use of NSAIDs can compromise fertility and is not recommended in women intending to become pregnant as well as the use of any drug that inhibits prostaglandin synthesis and cyclooxygenase. Administration of NSAIDs should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
As with all non-steroidal anti-inflammatory drugs, the use of ketoprofen in patients with bronchial asthma or with allergic diathesis can cause an asthmatic crisis.
In patients with impaired renal function the administration of ketoprofen should be carried out with particular caution in consideration of the essentially renal elimination of the drug.
Medicines such as OKi 30 mg suppositories may be associated with a modest 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.
If you have heart problems, have a history of stroke or think you may be at risk for these conditions (for example if you have high blood pressure, diabetes or high cholesterol or smoke) you should discuss your treatment with your doctor or pharmacist.
In case of visual disturbances, such as blurred vision, treatment should be stopped.
Pregnancy and breastfeeding
"Ask your doctor and pharmacist for advice before taking any medicine".
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Data from 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 cardiovascular malformations is increased by less than 1%, to approximately 1.5%. The risk is believed to increase with dosage and duration of therapy. In animal studies, 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 ones, was observed in animals administered 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 who wishes to become pregnant, or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor
Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.
Feeding time
- There is no information available on the excretion of ketoprofen in breast milk. Ketoprofen is not recommended during lactation.
Effects on ability to drive and use machines
- Should somnolence, dizziness or convulsions occur following administration of ketoprofen, the patient should avoid driving or operating machinery.
- Keep this medicine out of the reach of children
Dosage and method of use How to use Oki: Dosage
Since the recommended posology must be between 1 and 2 mg / kg per administration, the following dosage schedule is recommended:
children aged no less than 6 years with a body weight of less than 30 kg: 1 suppository 2-3 times a day.
Undesirable effects can be minimized with the use of the shortest possible duration of treatment that is needed to control symptoms (see section PRECAUTIONS FOR USE).
Overdose What to do if you have taken too much Oki
Cases of overdose have been reported with doses exceeding 2.5 g of ketoprofen. In most cases, the symptoms observed were benign and limited to lethargy, drowsiness, nausea, vomiting and epigastric pain.
There is no specific antidote to ketoprofen overdose. In the event of suspected massive overdose, gastric lavage is recommended and symptomatic and supportive treatment instituted to compensate for dehydration, control urinary excretion and correct acidosis if necessary.
In case of kidney failure, hemodialysis can be helpful in removing the drug from the body.
In case of accidental intake / ingestion of an overdose of OKi 30 mg suppositories, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of OKi 30 mg suppositories, ask your doctor or pharmacist.
Side Effects What are the side effects of Oki
Like all medicines, OKi 30 mg suppositories can cause side effects, although not everybody gets them.
Gastrointestinal system: the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal, may occur (see section "Precautions for use").
After administration of OKi 30 mg suppositories the following have been reported: melaena, haematemesis, ulcerative stomatitis (see section "Precautions for use").
Gastritis has been observed less frequently.
As with other non-steroidal anti-inflammatory drugs, disorders, usually transient, of the gastrointestinal tract, such as gastralgia, may be found. Only exceptionally have been reported: transient dyskinesia, asthenia, headache, sensation of dizziness, skin rash, allergic reactions, edema of the larynx, hematuria, hypotension, syncope, increased liver enzymes, purpura, dyspnoea.
Medicines such as OKi 30 mg suppositories may be associated with a modest increased risk of heart attack ("myocardial infarction") or stroke.
The following adverse reactions have been observed with the use of ketoprofen in adults:
Disorders of the blood and lymphatic system
thrombocytopenia, agranulocytosis, haemorrhagic anemia, bone marrow failure
Disorders of the immune system
anaphylactic reactions (including shock)
Psychiatric disorders
mood changes
Nervous system disorders
headache, dizziness, somnolence, paraesthesia, convulsions, dysgeusia
Eye disorders
blurred vision (see "Precautions for use")
Ear and labyrinth disorders
tinnitus
Cardiac pathologies
heart failure
Vascular pathologies
Hypertension, vasodilation
Respiratory, thoracic and mediastinal disorders
asthma, bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis.
Gastrointestinal disorders
dyspepsia, abdominal pain, nausea, vomiting, constipation, diarrhea, gastritis, flatulence, stomatitis, peptic ulcer, gastrointestinal haemorrhage and perforation, exacerbation of colitis and Crohn's disease.
Hepatobiliary disorders
hepatitis, increased transaminases, elevated serum bilirubin levels due to liver disorders
Skin and subcutaneous tissue disorders
rash, pruritus, photosensitivity reactions, alopecia, urticaria, angioedema, bullous rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis
Renal and urinary disorders:
acute renal failure, interstitial tubular nephritis, nephritic syndrome, abnormal kidney function tests
General disorders and administration site conditions
edema, fatigue
Diagnostic tests
Increased weight
Clinical studies and epidemiological data suggest that the use of some NSAIDs (particularly at high doses and for long periods of treatment) may be associated with an increased risk of arterial thrombotic events (eg myocardial infarction and stroke) (see "Precautions for "use").
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.
Expiry and Retention
The expiry date indicated refers to the intact product, correctly stored. Store at a temperature not exceeding 25 ° C.
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
OKI SUPPOSITORIES 30 MG - 60 MG
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
03.0 PHARMACEUTICAL FORM
Suppositories
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Symptomatic and short-term treatment of inflammatory states associated with pain such as those affecting the osteoarticular system, post-operative pain and ear infections.
04.2 Posology and method of administration
Since the recommended posology must be between 1 and 2 mg / kg per administration, the following dosage schedule is recommended:
children under the age of 6:
• body weight less than 30 kg: 1 suppository OKi 30 mg 2-3 times a day
• body weight over 30 kg: 1 suppository OKi 60 mg 2-3 times a day.
Undesirable effects can be minimized with the use of the shortest possible duration of treatment that is needed to control symptoms (see section 4.4).
04.3 Contraindications
OKi 60 and 30 mg suppositories is contraindicated in patients with hypersensitivity to ketoprofen or to any of the excipients.
Ketoprofen is contraindicated in patients with a history of hypersensitivity reactions such as bronchospasm, asthma attacks, rhinitis, urticaria or other allergic reactions to ketoprofen, acetyl salicylic acid (ASA) or other NSAIDs. Serious, rarely fatal, anaphylactic reactions have been observed in these patients (see section 4.8).
Ketoprofen is contraindicated in the following cases:
• severe heart failure
• active peptic ulcer / haemorrhage or history of haemorrhage / recurrent peptic ulcer (two or more known episodes of bleeding or ulceration)
• history of gastrointestinal perforation or bleeding following previous NSAID therapy
• bleeding diathesis
• severe hepatic insufficiency
• severe renal insufficiency
• leukopenia or thrombocytopenia
• severe bleeding disorders
• Ulcerative colitis
• gastritis
• a history of gastrointestinal bleeding, ulceration or perforation or chronic dyspepsia
• third trimester of pregnancy (see section 4.6 "." Pregnancy and lactation).
Ketoprofen is contraindicated in cases of proctitis or a history of proctorrhagia.
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 (see section 4.2 and the paragraphs below on gastrointestinal and cardiovascular risks).
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, including oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetyl salicylic acid (see section 4.5 Interactions with other medicinal products and other forms of interaction).
Concomitant use of OKi 60 mg suppositories and OKi 30 mg suppositories with other NSAIDs including selective cyclooxygenase-2 inhibitors should be avoided.
Gastrointestinal ulceration, perforation or bleeding: There have been reports of gastrointestinal ulceration, perforation or bleeding, which may be fatal, 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 also sections 4.2 - Posology and method of administration and 4.3 - Contraindications).
The risk of gastrointestinal ulcer, perforation or bleeding is higher with increased doses of NSAIDs, in patients with a history of ulcer, particularly if aggravated by haemorrhage or perforation and in the elderly (see section 4.3 - Contraindications). These patients should start treatment at the lowest possible dose. Combination therapy with protective drugs (e.g. misoprostol or proton pump inhibitors) should be considered for these patients and for those who have to take concomitantly low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events ( see below section 4.5 - Interactions with other medicinal products and other forms of interaction).
Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual 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 (see section 4.2 - Posology and method of administration).
In case of gastrointestinal bleeding or ulceration, discontinue treatment with ketoprofen.
Serious skin reactions, some of them fatal, such as 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 - Undesirable effects). Patients appear to have a major risk of developing these reactions early in treatment, with the onset of reactions in most cases within the first month of treatment.
Stop taking ketoprofen at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Several clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatments) may be associated with an increased risk of arterial thrombo-embolic events (eg myocardial infarction or stroke). there are sufficient data to exclude that ketoprofen is also associated with these risks.
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 - Undesirable effects).
At the start of treatment, renal function should be carefully monitored in patients with heart failure, cirrhosis and nephrosis, in patients receiving diuretics or with chronic renal failure, especially if elderly. In these patients, administration of ketoprofen may induce a reduction in renal blood flow caused by the inhibition of prostaglandins and lead to renal decompensation.
Like other NSAIDs, in the presence of an infectious disease, the anti-inflammatory, analgesic and antipyretic properties of ketoprofen can mask common symptoms of the progression of the infection, such as fever.
In patients with liver function test abnormalities or with a history of liver disease, transaminase levels should be checked periodically, especially with long-term therapy. Rare cases of jaundice and hepatitis have been reported with the use of ketoprofen.
In patients with impaired renal function the administration of ketoprofen should be carried out with particular caution in consideration of the essentially renal elimination of the drug.
The use of NSAIDs may reduce female fertility and is not recommended in women intending to become pregnant. NSAID administration 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 polyposis have a higher risk of allergy to acetylsalicylic acid and / or NSAIDs than the rest of the population.
Administration of this drug may cause asthma attacks or bronchospasm, especially in subjects allergic to acetylsalicylic acid or NSAIDs (see section 4.3 - Contraindications).
The use of ketoprofen in patients with bronchial asthma or with allergic diathesis can cause an asthmatic crisis.
In some pediatric patients treated with ketoprofen lysine salt, gastrointestinal haemorrhages, occasionally even severe, and peptic ulcer have been reported; therefore the product must be administered under strict supervision of the physician who will have to evaluate the necessary dosage schedule each time.
It is not known that the drug gives rise to addiction and dependence phenomena.
Cardiovascular and cerebrovascular effects
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 all NSAIDs, 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. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
In case of visual disturbances, such as blurred vision, treatment should be stopped.
04.5 Interactions with other medicinal products and other forms of interaction
Associations not recommended:
• Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high-dose salicylates: increased risk of gastrointestinal bleeding and ulceration.
• 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.
• Platelet aggregation inhibitors (ticlopidine and clopidogrel): increased risk of bleeding (see section 4.4 - Special warnings and precautions for use). If co-administration is unavoidable, patients should be closely monitored.
• Lithium: risk of increased plasma lithium levels, sometimes up to toxicity levels due to decreased renal excretion of lithium. If necessary, plasma lithium levels should be closely monitored and the lithium dosage adjusted during and after NSAID therapy.
• Methotrexate, at doses above 15 mg / week: increased risk of haematological toxicity to methotrexate, especially when administered at high doses (> 15mg / week), possibly related to the shift from methotrexate-binding proteins and the decrease in its renal clearance .
Combinations with other drugs requiring precaution:
• Diuretics: patients who are taking diuretics and among them, those particularly dehydrated are at increased risk of developing renal failure secondary to the reduction in renal blood flow caused by the inhibition of prostaglandins. These patients must be rehydrated before the start of concomitant therapy and renal function should be closely monitored after initiation of treatment (see section 4.4 - Special warnings and precautions for use). NSAIDs may reduce the effect of diuretics.
• ACE inhibitors and angiotensin II antagonists: in patients with impaired renal function (eg dehydrated patients and elderly patients) co-administration of an ACE inhibitor or angiotensin II antagonist and agents capable of inhibiting cycle oxygenase can lead to further deterioration of this renal function, potentially causing even 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, in doses lower than 15 mg / week: during the first weeks of the association, carry out a weekly monitoring of the complete blood count. Increase the frequency of monitoring in the presence of even a slight deterioration in renal function as well as in the elderly.
• Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4 - Special warnings and precautions for use).
• Pentoxifylline: increased risk of bleeding. More frequent clinical checks and monitoring of bleeding time.
• Probenecid: co-administration of probenecid may markedly reduce the plasma clearance of ketoprofen.
Combinations with other drugs to be considered:
• Antihypertensive drugs (beta-blockers, ACE inhibitors, diuretics): NSAIDs can reduce the effect of antihypertensive drugs. Risk of reduced antihypertensive potency (NSAIDs inhibit vasodilator prostaglandins).
• Thrombolytic drugs: increased risk of bleeding.
• Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4 - Special warnings and precautions for use).
• 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.
• Ciclosporin, tacrolimus: risk of additional nephrotoxic effects, particularly in the elderly.
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% to approximately 1.5%. The risk is believed 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, ketoprofen should not be administered except in strictly necessary cases.
If ketoprofen is used by a woman who wishes to become pregnant, or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose
the fetus to:
• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
• renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
• possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
• inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.
Feeding time
There is no information available on the excretion of ketoprofen in breast milk. 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 convulsions and to avoid driving or operating machinery if these symptoms occur.
04.8 Undesirable effects
Gastrointestinal system: the most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur (see section 4.4 Special warnings and precautions for use).
After administration of OKi 60 mg suppositories and OKi 30 mg suppositories the following have been reported: melaena, haematemesis, ulcerative stomatitis (see section 4.4 - Special warnings and precautions for use).
Gastritis has been observed less frequently.
As with other non-steroidal anti-inflammatory drugs, disorders, usually transient, of the gastrointestinal tract, such as gastralgia, may be found. Only exceptionally have been reported: transient dyskinesia, asthenia, headache, sensation of dizziness, skin rash, allergic reactions, edema of the larynx, hematuria, hypotension, syncope, increased liver enzymes, purpura, dyspnoea.
The following adverse reactions have been observed with the use of ketoprofen in adults:
Disorders of the blood and lymphatic system
thrombocytopenia, agranulocytosis, haemorrhagic anemia, bone marrow failure
Disorders of the immune system
anaphylactic reactions (including shock)
Psychiatric disorders
mood changes
Nervous system disorders
headache, dizziness, somnolence, paraesthesia, convulsions, dysgeusia
Eye disorders
blurred vision (see section 4.4 - Special warnings and precautions for use)
Ear and labyrinth disorders
tinnitus
Cardiac pathologies
heart failure
Vascular pathologies
Hypertension, vasodilation
Respiratory, thoracic and mediastinal disorders
asthma, bronchospasm (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis.
Gastrointestinal disorders
dyspepsia, abdominal pain, nausea, vomiting, constipation, diarrhea, gastritis, flatulence, stomatitis, peptic ulcer, gastrointestinal haemorrhage and perforation, exacerbation of colitis and Crohn's disease.
Hepatobiliary disorders
hepatitis, increased transaminases, elevated serum bilirubin levels due to liver disorders
Skin and subcutaneous tissue disorders
rash, pruritus, photosensitivity reactions, alopecia, urticaria, angioedema, bullous rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis
Renal and urinary disorders
acute renal failure, interstitial tubular nephritis, nephritic syndrome, abnormal kidney function tests
General disorders and administration site conditions
edema, fatigue
Diagnostic tests
increased weight
Clinical studies and epidemiological data suggest that the use of some NSAIDs (particularly at high doses and for long periods of treatment) may be associated with an increased risk of arterial thrombotic events (eg myocardial infarction and stroke) (see section 4.4 - Special warnings and precautions for use).
04.9 Overdose
Cases of overdose have been reported with doses exceeding 2.5 g of ketoprofen. In most cases, the symptoms observed were benign and limited to lethargy, drowsiness, nausea, vomiting and epigastric pain.
There is no specific antidote for ketoprofen overdose. In the event of suspected massive overdose, gastric lavage is recommended and symptomatic and supportive therapy instituted to compensate for dehydration, monitor urinary excretion, and correct acidosis as appropriate.
In case of kidney failure, hemodialysis can be helpful in removing the drug from the body.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Ketoprofen lysine salt is a drug with anti-inflammatory, analgesic and antipyretic activity.
Ketoprofen lysine salt, like ketoprofen, owes its anti-inflammatory efficacy above all to the inhibition of the synthesis of prostaglandins from arachidonic acid, to the stabilization of the lysosomal membrane with inhibition of enzymatic release, to the antibradykinin activity and to the antiplatelet activity, these factors play an important role in the pathogenesis of inflammatory phenomena.
05.2 Pharmacokinetic properties
Ketoprofen lysine salt exhibits kinetics in children comparable to that of young adults. Ketoprofen lysine salt is rapidly absorbed in 45-60 minutes rectally.
The maximum serum level is reached after 1-2 hours. Repeated administration does not change the kinetics of the drug, nor does it produce accumulation.
Elimination is essentially urinary and massive: 50% of the product administered systemically is excreted in the urine in 6 hours. Metabolization is significant: about 55% of the product administered systemically is found in the form of metabolites in the urine.
Ketoprofen is 95% bound to serum proteins.
05.3 Preclinical safety data
The toxicological tests carried out on the active ingredient have shown the low toxicity of Ketoprofen lysine salt.
The LD50, depending on the route of administration, is on average 300 mg / kg, equal to 80-100 times the active dose as an anti-inflammatory and analgesic. The product is not teratogenic and is not chemically correlated with drugs known to have a "carcinogenic action".
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Semi-synthetic glycerides.
06.2 Incompatibility
None
06.3 Period of validity
OKi 60 mg suppositories and OKi 30 mg suppositories are valid for 3 years.
The expiry date indicated on the label refers to the product in intact packaging, correctly stored.
06.4 Special precautions for storage
Store at a temperature not exceeding 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
Valve in polythene aluminum, compliant with MinSan circular 84/1977.
OKi 60 mg suppositories: box of 10 suppositories
OKi 30 mg suppositories: box of 10 suppositories
06.6 Instructions for use and handling
To release the suppository, pull the edges of the aluminum socket in the opposite direction in correspondence with the invitation.
07.0 MARKETING AUTHORIZATION HOLDER
Dompé Pharmaceuticals S.p.A.
Via San Martino 12
20122 Milan
08.0 MARKETING AUTHORIZATION NUMBER
OKi 60 mg suppositories: AIC n. 028511071
OKi 30 mg suppositories: AIC n. 028511083
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 31.10.1994
Date of renewal of the authorization: 15.11.2009
10.0 DATE OF REVISION OF THE TEXT
January 2015
