Okitask - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Ketoprofen (ketoprofen lysine salt)

OKITASK 40 mg granules

Indications Why is Okitask used? What is it for?

WHAT IS IT

OKITASK 40 mg granules belongs to the category of anti-inflammatory and antirheumatic drugs.

WHY IT IS USED

OKITASK 40 mg granules is used for pain of different origins and nature, and in particular: headache, toothache, neuralgia, menstrual pain, muscle and bone and joint pain.

Contraindications When Okitask should not be used

Hypersensitivity to ketoprofen or to substances with a similar mechanism of action (for example acetylsalicylic acid or other NSAIDs) or to any of the excipients.

The product should not be administered to subjects in whom the use of other non-steroidal anti-inflammatory drugs has led to hypersensitivity reactions such as bronchospasm, asthma attacks, acute rhinitis, urticaria, skin rashes. . Severe, rarely fatal, anaphylactic reactions have been observed in these patients.

The product should not be used in patients with gastric or duodenal ulcer, with active peptic ulcer / bleeding or a history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding), gastritis and chronic digestive disorders (dyspepsia), or in patients with a history of gastrointestinal bleeding, ulceration or perforation following previous NSAID therapy.

The product should not be administered to subjects with leukopenia (reduction in the number of white blood cells) or thrombocytopenia (reduction in the number of platelets), with ongoing bleeding or haemorrhagic diathesis (predisposition to haemorrhage), during treatment with anticoagulants, in patients with severe renal, hepatic or cardiac insufficiency. It is not recommended to administer it together with other anti-inflammatory drugs and acetylsalicylic acid.

Do not administer in the third trimester of known or suspected pregnancy and during lactation: (see What to do during pregnancy and lactation).

Pediatrics, geriatrics and specific clinical pictures: the drug should not be administered to children and young people under the age of 15. Patients undergoing major surgery.

Precautions for use What you need to know before taking Okitask

In asthmatic patients the product should be used with caution, consulting your doctor before taking it, as well as in patients with active or previous peptic ulcer, or inflammatory bowel disease (ulcerative colitis, Crohn's disease), heart disease (heart failure), hypertension, liver disease or nephropathy.

The product should be used with caution in patients taking concomitant medications that could increase the risk of ulceration or bleeding (oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin, see What medicines or foods can change the effect of the medicine).

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 Undesirable effects).

Interactions Which drugs or foods can modify the effect of Okitask

Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.

As the protein binding of ketoprofen is high, it may be necessary to reduce the dosage of diphenylhydantoin or sulfonamides that should be administered concurrently. During therapy with lithium-based drugs, the simultaneous administration of non-steroidal anti-inflammatory drugs causes an increase in plasma lithium levels. Probenecid can increase plasma concentrations of ketoprofen.

Corticosteroids can increase the risk of gastrointestinal ulceration or bleeding. Pentoxifylline, thrombolytics, antiplatelet drugs such as aspirin, ticlopidine or clopidogrel, and other NSAIDs (including selective cyclo oxygenase 2 inhibitors), may increase the risk of bleeding. Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of gastrointestinal bleeding (see Important to know). NSAIDs may amplify the effects of anticoagulants, such as warfarin or heparin (see Precautions for use). Patients who are taking diuretics and among them, those who are particularly dehydrated are most at risk of developing renal insufficiency secondary to reduced renal blood flow caused by prostaglandin inhibition. These patients should be rehydrated before starting co-administration and closely monitoring the kidney function after starting treatment.

Other NSAIDs, (including selective cyclooxygenase 2 inhibitors) and high doses of salicylates: increased risk of gastrointestinal ulcers.

Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the effect of diuretics and other antihypertensives. In some patients with impaired renal function (eg dehydrated patients or elderly patients) co-administration of an ACE inhibitor or an angiotensin II antagonist and non-steroidal anti-inflammatory agents can lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These changes should be considered in patients taking OKITASK 40 mg granules concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, and only after consultation with the physician, especially in elderly patients.

Any interactions with the following drugs should be kept in mind: oral hypoglycemic agents (sulfonylureas), anti-inflammatories and methotrexate. Patients being treated with such drugs should consult their doctor before taking the product.

Warnings It is important to know that:

Do not use for prolonged treatments. After a short period of treatment with no appreciable results, consult your doctor.

The concomitant use of OKITASK 40 mg granules with other NSAIDs should be avoided, (including selective cyclooxygenase-2 inhibitors).

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see paragraphs below on gastrointestinal and cardiovascular risks).

Caution is required when the product is administered to patients with hepatic porphyria as the drug could trigger an attack.

Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see How to use this medicine).

Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation which can be fatal have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.

Some epidemiological evidence suggests that ketoprofen may be associated with a higher risk of severe gastrointestinal toxicity, compared to other NSAIDs, especially at high doses (see How to use this medicine and When it should not be used).

Elderly patients are more prone to decreased renal, cardiovascular or hepatic function.

In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see When it should not be used), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest available dose.

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 Which medicines or foods can change the effect of the medicine).

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.

When gastrointestinal bleeding or ulceration occurs in patients taking OKITASK 40 mg granules the treatment should be discontinued.

Serious skin reactions, some of them fatal (exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis), have been reported very rarely with the use of NSAIDs (see Undesirable effects). The onset of the reaction occurs in most patients. cases in the early stages of treatment. OKITASK 40 mg granules should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.

Medicines such as OKITASK 40 mg granules 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.

Like other NSAIDs, in the presence of an infection, the anti-inflammatory, analgesic and antipyretic properties of ketoprofen can mask common symptoms of infection progression such as fever.

In case of visual disturbances, such as blurred vision, treatment should be stopped.

The use of OKITASK 40 mg granules, as with any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.

Administration of OKITASK 40 mg granules should be discontinued in women who have fertility problems or who are undergoing fertility investigations.

OKITASK 40 mg granules does not affect low-calorie or controlled diets.

When it can be used only after consulting your doctor

In asthmatic patients the product should be used with caution, consulting your doctor before taking it, as well as in patients with previous (previous) peptic ulcer, liver disease or nephropathy, chronic obstructive pulmonary disease, allergic and chronic rhinitis as well as in patients with a history of heart disease or stroke or risk factors for these conditions.

It is also advisable to consult your doctor in cases where these disorders have occurred in the past.

What to do during pregnancy and breastfeeding

Ask your doctor or pharmacist for advice before taking any medicine. OKITASK 40 mg granules should not be used during pregnancy and breastfeeding. Use should also be avoided if you suspect pregnancy or plan to maternity leave.

Some scientific studies suggest an increased risk of miscarriage and cardiac and gastric malformations in the early stages of pregnancy after the use of prostaglandin synthesis inhibitor drugs.

The use of OKITASK 40 mg is not recommended in women intending to become pregnant. Furthermore OKITASK 40 mg should not be used during the first and second trimester of pregnancy unless strictly necessary. If OKITASK 40 mg is used in women who wish to have a pregnancy or during the first and second trimester of pregnancy, the dosage should be kept as low as possible for the shortest possible duration of treatment OKITASK 40 mg should not be used during the third trimester of pregnancy.

During the third trimester of pregnancy, all medicines of the OKITASK 40 mg class can expose the fetus to:

  • cardiopulmonary toxicity;
  • renal dysfunction, which can progress to renal failure with oligo-hydroamnios;

the mother and the newborn, at the end of pregnancy, to:

  • possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
  • inhibition of uterine contractions resulting in delayed or prolonged labor.

Use while breastfeeding

OKITASK 40 mg should not be used during breastfeeding

Driving and using machines

In case of drowsiness, dizziness or convulsions, avoid driving, using machines or carrying out activities that require special vigilance. (see "Undesirable Effects").

Important information about some of the ingredients

Aspartame

The aspartame present in the product is a source of phenylalanine and makes the medicine unsuitable for people with phenylketonuria.

Dosage and method of use How to use Okitask: Dosage

How many

Warning: do not exceed the indicated doses without medical advice.

Adults and children over 15 years: 1 sachet.

In case of asthma, past (previous) peptic ulcer, heart disease, liver disease or nephropathy, you should contact your doctor.

When and for how long

Once, or repeated 2-3 times a day, in the painful forms of greater intensity.

It is advisable to take the medicine after meals.

Do not use for extended periods of time without medical advice.

Consult your doctor if the disorder occurs repeatedly or if you have noticed any recent changes in its characteristics.

Like

OKITASK 40 mg granules can be placed directly on the tongue. It dissolves with saliva; this allows it to be used without water.

It is preferable to take the product on a full stomach.

Do not exceed the recommended doses: in particular elderly patients should follow the minimum dosages indicated above.

Overdose What to do if you have taken an overdose of Okitask

Cases of overdose have been reported with doses up to 2.5 g of ketoprofen. In most cases, benign symptoms were observed and limited to: lethargy, drowsiness, headache, dizziness, confusion and loss of consciousness, as well as pain, nausea, vomiting and epigastric pain. Gastrointestinal bleeding, hypotension, respiratory depression and cyanosis can also occur

There is no specific antidote to ketoprofen overdose. In cases of suspected massive overdose, gastric lavage is recommended and symptomatic and supportive treatment instituted to compensate for dehydration, monitor urinary excretion and correct acidosis, if present.

In cases of kidney failure, hemodialysis can be helpful in removing the drug from the bloodstream.

In case of accidental ingestion / intake of an excessive dose of OKITASK 40 mg granules, notify your doctor immediately or go to the nearest hospital.

Side Effects What are the side effects of Okitask

Like all medicines, OKITASK 40 mg granules can cause side effects, although not everybody gets them.

The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur, particularly in the elderly (see It is important to know that).

The frequency and extent of these effects are significantly reduced by taking the drug on a full stomach. In exceptional cases, the manifestations of hypersensitivity can take the character of severe systemic reactions (edema of the larynx, edema of the glottis, dyspnoea, palpitations) up to shock anaphylactic. In these cases immediate medical assistance is required.

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 / 10,000), not known (frequency cannot be estimated from the available data).

The following adverse reactions have been observed with the use of ketoprofen in adults:

Disorders of the blood and lymphatic system

  • Rare: haemorrhagic anemia
  • Not known: thrombocytopenia, agranulocytosis, bone marrow failure

Disorders of the immune system

  • Not known: anaphylactic reactions (including shock), hypersensitivity

Psychiatric disorders

  • Not known: mood alterations Nervous system disorders
  • Uncommon: headache, dizziness, somnolence,
  • Rare: paraesthesia
  • Not known: convulsions, dysgeusia Eye disorders
  • Rare: blurred vision (see IT IS IMPORTANT TO KNOW) 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 (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnoea, larynx edema, glottal edema.

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, ulcerative stomatitis, melaena, haematemesis, duodenal ulcer and perforation

Hepatobiliary disorders

  • Rare: hepatitis, increased transaminases, elevated serum bilirubin levels due to liver disorders

Skin and subcutaneous tissue disorders

  • Uncommon: rash, pruritus
  • Not known: photosensitivity reactions, alopecia, urticaria, angioedema, bullous eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis, edema, exanthema

Renal and urinary disorders:

  • Not known: acute renal failure, interstitial tubular nephritis, nephritic syndrome, renal function test abnormal

General disorders and administration site conditions

  • Uncommon: edema, fatigue Investigations
  • Rare: weight increased

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 inform your doctor or pharmacist.

Expiry and Retention

Expiry: see the expiry date indicated 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.

Store at a temperature not exceeding 30 ° C

Keep this medicine out of the sight and reach of children.

It is important to always have the information about the medicine available, so keep both the box and the package leaflet.

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 and pharmaceutical form

COMPOSITION

One sachet contains:

Active ingredient: ketoprofen lysine salt 40 mg (corresponding to 25 mg of ketoprofen) Excipients: povidone, colloidal silica, hydroxypropylmethylcellulose, eudragit EPO, sodium dodecyl sulfate, stearic acid, magnesium stearate, aspartame, mannitol, xylitol, lime, talc lemon aroma, fresh aroma

HOW IT LOOKS

OKITASK 40 mg granules come in the form of granules for oral use. The contents of the package are 10 sachets or 20 sachets

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.

More information about Okitask can be found in the "Summary of Features" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the primary packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER CIO 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

OKITASK 40 MG GRANULES

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each sachet contains:

Active principle: ketoprofen lysine salt 40 mg (corresponding to 25 mg of ketoprofen)

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Granules for oral use

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Pain of different origin and nature, and in particular:

headache, toothache, neuralgia, menstrual pain, muscle and bone pain.

04.2 Posology and method of administration

Adults and children over 15 years: 1 sachet, in a single dose, or repeated 2-3 times a day, in the painful forms of greater intensity.

The contents of the sachet can be placed directly on the tongue. It dissolves with saliva: this allows it to be used without water.

It is preferable to take the product on a full stomach.

Do not exceed the recommended doses: in particular elderly patients should follow the minimum dosages indicated above.

The duration of the therapy must be limited to the overcoming of the painful episode.

04.3 Contraindications

The drug should not be administered in the following cases:

• patients with a history of hypersensitivity reactions such as bronchospasm, asthma attacks, acute rhinitis, hives, skin rashes or other allergic-type reactions to ketoprofen, or substances with a similar mechanism of action (for example acetylsalicylic acid or other NSAIDs) .

Serious, rarely fatal, anaphylactic reactions have been observed in these patients (see section 4.8).

• patients with hypersensitivity to any of the excipients;

• third trimester of pregnancy, known or presumed pregnancy, during lactation (see section 4.6 - pregnancy and lactation) and in children under 15 years;

• severe heart failure

• patients with gastric or duodenal ulcer, gastritis and chronic dyspepsia;

• subjects with leukopenia or thrombocytopenia, with ongoing bleeding or haemorrhagic diathesis, undergoing treatment with anticoagulants;

• patients with severe renal or hepatic insufficiency;

• patients undergoing major surgery.

Furthermore, concomitant administration with other anti-inflammatory drugs and acetylsalicylic acid is not recommended.

Active peptic ulcer / haemorrhage or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or haemorrhage).

Previous history of gastrointestinal bleeding, ulceration or perforation related to previous NSAID treatment.

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 below on gastrointestinal and cardiovascular risks).

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 - Interactions with other medicinal products. and other forms of interaction).

Concomitant use of OKITASK 40 mg granules with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.

In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3 - Contraindications), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest possible dose. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking concomitantly low dose aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5 - Interactions with other medicines and other forms of interaction).

Patients with a history of gastrointestinal toxicity, especially when 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 (see section 4.2 - Posology and method of administration).

When gastrointestinal bleeding or ulceration occurs in patients taking OKITASK 40 mg granules 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 association with the use of NSAIDs (see section 4.8 - Undesirable effects).In the early stages of therapy, patients appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. OKITASK 40 mg granules 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 an increased risk of arterial thrombotic events (eg myocardial infarction or stroke). Sufficient data are currently available to exclude a similar risk for ketoprofen when it is administered as a daily dose of one sachet, as a single dose, or repeated 2-3 times a day.

OKITASK 40 mg granules contains aspartame as a sweetener: this substance is contraindicated in subjects suffering from phenylketonuria.

OKITASK 40 mg granules does not affect low-calorie or controlled diets and can also be administered to diabetic patients.

Precautions

Patients with active peptic ulcer or with a history of 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 diuretic therapy, in patients with chronic renal impairment, particularly if the patients are elderly. In these patients, the administration of ketoprofen can cause a decrease in renal blood flow caused by the inhibition of prostaglandins and lead to renal decompensation.

Caution is required before starting treatment in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention, hypertension and edema have been reported in association with treatment with NSAIDs.

As with other NSAIDs, in the presence of an infection, it must be taken into account that the anti-inflammatory, analgesic and antipyretic properties of ketoprofen can mask the common symptoms of the progression of the infection such as fever.

In patients with abnormal liver function values ​​or with a history of liver disease, transaminase levels should be evaluated periodically, especially during long-term therapy.

Rare cases of jaundice and hepatitis have been reported with the use of ketoprofen.

The use of NSAIDs can reduce female 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.

Patients presenting with asthma associated with chronic and allergic rhinitis, chronic sinusitis and / or nasal polyposis are at greater risk of allergies to acetylsalicylic acid and / or NSAIDs than the rest of the population. Administration of this drug may cause a seizure. asthma or bronchospasm, especially in subjects allergic to acetylsalicylic acid or NSAIDs (see section 4.3 - Contraindications). Therefore in these subjects, as well as in case of chronic obstructive pulmonary disease or nephropathy, the product should only be used under medical supervision.

As with other 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 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).

In case of visual disturbances, such as blurred vision, treatment should be stopped.

After a few days of treatment without appreciable results, consult your doctor.

Administer with caution in patients with allergic manifestations or previous allergy.

Patients with current or previous gastrointestinal disease should be carefully monitored for the appearance of digestive disorders, especially gastrointestinal bleeding.

Caution is required when the product is administered to patients with hepatic porphyria as the drug could trigger an attack.

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).

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 not recommended

Other NSAIDs, (including selective cyclooxygenase 2 inhibitors) and high doses of salicylates: increased risk of gastrointestinal ulceration and bleeding.

Anticoagulants (heparin and warfarin) and platelet aggregation inhibitors (ticlopidine, 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, which may reach toxic levels due to decreased renal excretion of lithium. If necessary, plasma lithium levels should be closely monitored and lithium dosage adjusted during and after therapy with NSAIDs.

Methotrexate, at doses above 15 mg / week: Increased risk of haematic toxicity of methotrexate, especially when administered at high doses (> 15 mg / week), possibly related to shift from methotrexate-binding proteins and decreased renal clearance.

Therefore, patients undergoing treatment with such drugs should consult their doctor before taking the product.

Associations 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 closely monitoring the renal function (see Section 4.4) 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) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents capable of inhibiting cyclo-oxygenase may lead to further deterioration of function. kidney, 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 below 15 mg / week:

Perform weekly monitoring of the complete blood count during the first weeks of the combination. Increase the frequency of monitoring in the presence of even a slight deterioration in renal function, as well as in the elderly.

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.

Any interactions with the following drugs should be taken into account: oral hypoglycemic agents

Associations that need to be considered:

Antihypertensive drugs (Beta-blockers, ACE inhibitors and angiotensin II antagonists, diuretics): treatment with an NSAID can reduce the effect of antihypertensive drugs by inhibiting the synthesis of vasodilating prostaglandins.

Thrombolytics and anti-aggregating agents: increased risk of bleeding. Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4 - Special warnings and precautions for use).

Probenecid: Concomitant administration of probenicid may markedly reduce the plasma clearance of ketoprofen.

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.

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 has been considered to increase with dose and duration of therapy.

In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and embryo-fetal mortality.

In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.

Therefore ketoprofen should not be administered during the first and second trimester of pregnancy unless strictly necessary.

If ketoprofen is used by a woman conceiving, or during the first and second trimester of pregnancy, the dosage should be kept as low as possible for the shortest possible duration of treatment.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose

the fetus to:

• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);

• renal dysfunction, which can progress to renal failure with oligo-hydroamnios;

the mother and the newborn, at the end of pregnancy, to:

• possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;

• inhibition of uterine contractions resulting in delayed or prolonged labor.

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 contraindicated during lactation.

04.7 Effects on ability to drive and use machines

Patients should be warned of the possibility of drowsiness, dizziness or convulsions and to avoid driving, operating machinery if these symptoms appear.

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, particularly in the elderly (see section 4.4 - Special warnings and precautions for use). The frequency and extent of these effects are significantly reduced by taking the drug on a full stomach.

In exceptional cases, the manifestations of hypersensitivity can take the character of severe systemic reactions (edema of the larynx, edema of the glottis, dyspnoea, palpitation) up to anaphylactic shock. In these cases immediate medical assistance is required.

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 / 10,000), not known (frequency cannot be estimated from the available data).

The following adverse reactions have been observed with the use of ketoprofen in adults:

Disorders of the blood and lymphatic system

• Rare: haemorrhagic anemia

• Not known: thrombocytopenia, agranulocytosis, modullary insufficiency hypoplasia

Disorders of the immune system

• Not known: anaphylactic reactions (including shock), hypersensitivity

Psychiatric disorders

• Not known: mood changes

Nervous system disorders

• Uncommon: headache, dizziness, somnolence,

• Rare: paraesthesia

• Not known: convulsions, dysgeusia

Eye disorders

• Rare: blurred vision (see section 4.4 - Special warnings and precautions for use)

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 (especially in patients with known hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnoea, larynx edema, glottal edema.

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, ulcerative stomatitis, melaena, haematemesis, duodenal ulcer and perforation

Hepatobiliary disorders

• Rare: hepatitis, increased transaminases, elevated serum bilirubin levels due to liver disorders

Skin and subcutaneous tissue disorders

• Uncommon: rash, itching

• Not known: photosensitivity reactions, alopecia, urticaria, angioedema, bullous eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis, edema, rash

Renal and urinary disorders:

• Not known: acute renal failure, interstitial tubular nephritis, nephritic syndrome, renal function test abnormal

General disorders and administration site conditions

• Uncommon: fatigue, edema

Diagnostic tests

• Rare: weight increased

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 section 4.4 - Special warnings and precautions for use).

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 and limited to lethargy, drowsiness, headache, dizziness, confusion and loss of consciousness, as well as pain, nausea, vomiting, epigastric pain. Gastrointestinal bleeding, hypotension, respiratory depression and cyanosis can also occur.

There is no specific antidote to ketoprofen overdose. In case of suspected massive overdose, gastric lavage is recommended and symptomatic and supportive treatment should be instituted to compensate for dehydration, monitor urinary excretion and correct acidosis, if present.

In cases of kidney failure, hemodialysis can be helpful in removing the drug from the bloodstream.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: anti-inflammatory / antirheumatic drugs, non-steroids - derivatives of propionic acid

ATC code: M01AE03.

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 enzyme cyclo oxygenase.

Specifically, there is an inhibition of the transformation of arachidonic acid into the cyclic endoperoxides, PGG2 and PGH2, precursors of the prostaglandins PGE1, PGE2, PGF2a and PGD2 and also of the prostacyclin PGI2 and thromboxanes (TxA2 and TxB2). 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.

Painful inflammatory manifestations are eliminated or attenuated by promoting joint mobility.

05.2 Pharmacokinetic properties

The ketoprofen lysine salt is rapidly and completely absorbed. Maximum plasma concentrations of ketoprofen are reached 20 minutes after administration.

The plasma half-life is approximately 1.5 hours. No accumulation was observed after repeated administration of ketoprofen.

Ketoprofen is 95-99% bound to plasma proteins (mainly albumin).

Plasma clearance values ​​are between 0.06 and 0.08 L / kg / h and the distribution value is 0.1-0.4 L / kg.

Ketoprofen is extensively metabolised by microsomal liver enzymes, mainly by conjugation and only in small amounts by hydroxylation. The products of this metabolism appear pharmacologically inactive. Elimination is rapid and occurs mainly via the kidney. 60-80% of a dose of OKITASK 40 mg granules is excreted in the urine as glucuronate metabolite in 24 hours. A pharmacokinetic study conducted on 69 subjects shows that at 5 "Plasma levels of 0.15 mcg / ml (SD 0.19 mcg / ml) are achieved.

After administration of ketoprofen, the product was identified in tonsillar tissue and synovial fluid.

05.3 Preclinical safety data

The LD50 of ketoprofen lysine salt in rats and mice by oral route was respectively 102 and 444 mg / kg, equal to 30-120 times the active dose as anti-inflammatory and analgesic in the animal. By endoperitoneal route 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 changes were found attributable 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.

Studies of teratogenesis, fertility and reproduction and peri-postnatal toxicity highlight the non-teratogenicity of ketoprofen and the absence of negative effects on reproductive function.

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.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Povidone, colloidal silica, hydroxypropylmethylcellulose, eudragit EPO, sodium dodecyl sulfate, stearic acid, magnesium stearate, aspartame, mannitol, xylitol, talc, lime flavor, lemon flavor, fresh flavor

06.2 Incompatibility

Not relevant.

06.3 Period of validity

3 years.

06.4 Special precautions for storage

Store at a temperature not exceeding 30 ° C

06.5 Nature of the immediate packaging and contents of the package

10 sachets of 40 mg granules

20 sachets of 40 mg granules

Not all pack sizes may be marketed.

06.6 Instructions for use and handling

No special instructions.

07.0 MARKETING AUTHORIZATION HOLDER

Dompé Pharmaceuticals S.p.A.

Via San Martino 12 - 20122 Milan

08.0 MARKETING AUTHORIZATION NUMBER

10 sachets A.I.C. n. 042028011

20 sachets A.I.C. n. 042028023

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

Date of first authorization: September 2012

10.0 DATE OF REVISION OF THE TEXT

January 2015

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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