Okitask 30 sachets granules 40 mg.

In compliance with article 118 "authorization of advertising to the public" of the legislative decree of 24 April 2006, number 219

INDICATIONS

Pain of different origins and nature, and in particular: headache, toothache, neuralgia, menstrual pain, muscular and osteoarticular pain.

CONTRAINDICATIONS

Okitask 40 mg granules must not be administered in the following cases: • hypersensitivity to the active substance, to other non-steroidal anti-inflammatory drugs (NSAIDs) or to any of the excipients, listed in paragraph 6.1; • asthma, bronchospasm, acute rhinitis, urticaria, skin rashes, nasal polyps, angioneurotic edema or other allergic reactions caused by ketoprofen, or by medicines with a similar mechanism of action (for example acetylsalicylic acid, other NSAIDs and selective cyclo-oxygenase 2 inhibitors), see section 4.8; • previous bronchial asthma; • severe heart failure; • gastritis; • active peptic ulcer/haemorrhage or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of demonstrated ulceration or haemorrhage); • previous history of gastrointestinal bleeding, ulceration or perforation, or chronic dyspepsia; • history of gastrointestinal bleeding or perforation following previous therapy with NSAIDs; • Crohn's disease or ulcerative colitis; • severe liver failure (liver cirrhosis, severe hepatitis); • severe renal failure; • leukopenia and thrombocytopenia; • haemorrhagic diathesis and other coagulation disorders, haemostatic disorders; • use of a high dosage of diuretics; • third trimester of pregnancy; • children under 15 years old.

WARNINGS AND 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 sections below on gastrointestinal and cardiovascular risks). The concomitant use of Okitask 40 mg granules with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided. Gastrointestinal reactions: Gastrointestinal haemorrhage, ulceration and perforation: Gastrointestinal haemorrhage, ulceration and perforation, which may be fatal, have been reported at any time during treatment with all NSAIDs, with or without warning symptoms or previous history of serious gastrointestinal events. In patients with a history of ulcer, especially if complicated by haemorrhage or perforation (see section 4.3), the risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment at the lowest possible dose. The concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients concomitantly taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5). Patients with a history of gastrointestinal toxicity, especially the elderly, should report any abdominal symptoms and/or signs (including gastrointestinal bleeding) even at the start of treatment. Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or haemorrhage, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see section 4.5). Elderly people: Elderly people have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2). Patients with current or previous gastrointestinal disease should be carefully monitored for the appearance of digestive disorders, especially gastrointestinal bleeding. When gastrointestinal bleeding or ulceration occurs in patients taking Okitask 40 mg granules, treatment should be suspended. Patients with active or previous peptic ulcer: Some epidemiological evidence suggests that ketoprofen may be associated with a high risk of serious gastrointestinal toxicity compared to other NSAIDs, especially at high doses (see sections 4.2 and 4.3). Skin reactions: 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). At the beginning of treatment patients appear to be at higher risk. Okitask 40 mg granules should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Precautions. Cardiovascular, renal and hepatic dysfunction: In patients with impaired renal function, the administration of ketoprofen must be carried out with particular caution given the essentially renal elimination of the drug. 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 patients are elderly. In these patients, administration of ketoprofen may cause a decrease in renal blood flow caused by inhibition of prostaglandins and lead to renal decompensation (see section 4.3). Caution is also required in patients subject to diuretic therapy or likely to be hypovolemic because the risk of nephrotoxicity is increased. As with all NSAIDs, Okitask 40 mg granules can increase plasma urea nitrogen and creatinine. As with other prostaglandin synthesis inhibitors, Okitas 40 mg granules may be associated with adverse effects on the renal system which may lead to glomerular nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure (see section 4.8). In patients with abnormal liver function values ​​or a history of liver disease, transaminase levels should be evaluated periodically. As with other NSAIDs, Okitask 40 mg granules can cause increases in some hepatic parameters and also significant increases in SGOT and SGPT (see section 4.8). In case of significant increase in these parameters, therapy must be interrupted. Cases of jaundice and hepatitis have been reported with the use of ketoprofen (see section 4.8). Elderly patients are more predisposed to reduced renal, cardiovascular or hepatic function. Cardiovascular and cerebrovascular effects: As with other NSAIDs, patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with ketoprofen only after careful consideration. Similar considerations must be made before starting treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking). Caution is required before starting treatment in patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and edema have been reported related to treatment with NSAIDs. Clinical studies and epidemiological data suggest that the use of some NSAIDs may be associated with an increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There are insufficient data to exclude a similar risk for Okitask 40 mg granules. An increased risk of atrial fibrillation associated with the use of NSAIDs has been reported. Hyperkalaemia may occur, especially in patients with underlying diabetes, renal insufficiency, and/or concomitant treatment with agents promoting hyperkalaemia (see section 4.5). In these circumstances potassium levels should be assessed periodically. Infections. Masking of symptoms of underlying infections: Okitask 40 mg granules may mask the symptoms of infection, which may delay the initiation of appropriate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When Okitask 40 mg granules are administered for the relief of fever or pain related to infection, monitoring of the infection is recommended. In non-hospital settings, the patient should seek medical attention if symptoms persist or worsen. Respiratory disorders: Like all non-steroidal drugs, the use of ketoprofen in patients with bronchial asthma or allergic diathesis can cause an asthma attack. Patients with asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyposis are more exposed to the risk of allergy to acetylsalicylic acid and/or NSAIDs than the rest of the population. The administration of this drug can cause asthmatic attacks or bronchospasm, shock and other allergic phenomena, especially in subjects allergic to acetylsalicylic acid or NSAIDs (see section 4.3). Due to the action on the metabolism of arachidonic acid, bronchospasm attacks and possibly shock and other allergic phenomena may arise in asthmatics and predisposed subjects. Administer with caution in patients with allergic manifestations or previous allergy. Visual disturbances: In case of visual disturbances, such as blurred vision, treatment should be stopped. Okitask 40 mg granules should be administered with caution in patients suffering from haematopoietic alterations, systemic lupus erythematosus or mixed connective tissue diseases. When Okitask 40 mg granules are administered to patients with hepatic porphyria, caution is required as it may trigger an attack. Important information about some excipients: Okitask 40 mg granules contains less than 1mmol (23 mg) sodium per sachet, i.e. essentially 'sodium-free'. Okitask 40 mg granules contains lemon flavoring and lime flavouring. The lemon flavor contains sucrose. Patients suffering from rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency should not take this medicine. The lime flavor contains glucose. Patients suffering from rare problems of glucose-galactose malabsorption should not take this medicine.

INTERACTIONS

Associations not recommended. - Other NSAIDs (including selective cyclooxygenase 2 inhibitors) and high doses of salicylates (> 3 g/day): the simultaneous administration of several NSAIDs may increase the risk of gastrointestinal ulcers and bleeding, due to a synergistic effect. - Anticoagulants (heparin and warfarin): NSAIDs can amplify the effects of anticoagulants. If coadministration cannot be avoided, the patient should be closely monitored. - Platelet aggregation inhibitors (ticlopidine and clopidogrel): concomitant administration of an NSAID may increase the risk of bleeding due to inhibition of platelet function and damage to the gastrointestinal mucosa (see section 4.4). If coadministration cannot be avoided, the patient should be closely monitored. - Lithium: the simultaneous administration of several NSAIDs can increase plasma levels of lithium, which can reach toxic values, due to reduced renal excretion. Plasma lithium levels should be carefully monitored and the lithium dosage should be adjusted during and after discontinuation of treatment with ketoprofen and other NSAIDs. - Methotrexate, at doses higher than 15 mg/week: the simultaneous administration of an NSAID may increase the risk of blood toxicity of methotrexate, especially if administered at high doses, probably due to a displacement of plasma protein binding and a decrease in renal clearance. The intake of the two medicines must be spaced at least 12 hours apart. - Hydantoins and sulphonamides: the toxic effects of these substances may be increased; since the protein binding of ketoprofen is high, it may be necessary to reduce the dosage of diphenylhydantoin or sulphonamides, in case of concomitant administration. Associations requiring precaution. - Drugs or therapeutic categories that can promote hyperkalemia: potassium salts, potassium-sparing diuretics, inhibitors of enzyme converters (ACE inhibitors), angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), ciclosporin, tacrolimus and trimethoprim. The occurrence of hyperkalemia may depend on the presence of cofactors. The risk is increased in case of simultaneous administration of the above-mentioned drugs. - Tenofovir: concomitant administration of tenofovir disoproxil fumarate and NSAIDs may increase the risk of renal failure. - Diuretics: subjects treated with diuretics, especially in case of dehydration, are at greater risk of developing renal failure secondary to the reduction in renal blood flow caused by the inhibition of prostaglandins. Hydration before starting concomitant therapy and close monitoring of renal function after initiation of treatment are recommended (see section 4.4). NSAIDs can reduce the effect of diuretics. - ACE inhibitors and angiotensin II antagonists: coadministration with cyclo-oxygenase inhibitors may lead to a further deterioration of renal function and possible acute renal failure, especially in dehydrated and elderly subjects. Caution, hydration and monitoring of renal function are recommended in case of combined therapy. -Methotrexate at doses lower than 15 mg/week: anti-inflammatories cause a decrease in the renal clearance of methotrexate with a consequent increase in blood toxicity. In case of impaired renal function or advanced age, monitoring must be more frequent. - Corticosteroids: concomitant administration of NSAIDs may increase the risk of gastrointestinal ulceration or bleeding (see section 4.4). - Pentoxifylline: co-administration may cause an increased risk of bleeding: monitoring of bleeding time is recommended. - Zidovudine: the combination with NSAIDs increases the risk of toxicity on reticulocytes, with severe anemia occurring one week after starting treatment with NSAIDs. Complete blood cell count and reticulocyte count should be checked one week after starting treatment with the NSAID. - Sulfonylureas: NSAIDs can increase the hypoglycemic effect of sulfonylureas by displacing them from the binding sites with plasma proteins. Possible interactions with other oral hypoglycemics should also be kept in mind. - Cardiac glycosides: NSAIDs can exacerbate heart failure, reduce the glomerular filtration rate and increase levels of cardiac glycosides; however, the pharmacokinetic interaction between ketoprofen and active glycosides has not been demonstrated. Associations that need to be taken into consideration. - Antihypertensive agents (Beta-blockers, ACE inhibitors diuretics): treatment with an NSAID can reduce the effect of antihypertensive drugs by inhibiting the synthesis of vasodilatory prostaglandins. - Mifepristone: the effectiveness of the contraceptive method may, theoretically, be reduced due to the antiprostaglandin properties of NSAIDs including acetylsalicylic acid. There is some evidence to suggest that co-administration of NSAIDs on the day of administration of the prostaglandin dose does not unfavorably influence the effects of mifepristone or prostaglandin on cervical maturation or uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy. - Intrauterine contraceptive devices (IUDs): the effectiveness of the device may be reduced resulting in pregnancy. - Ciclosporin and tacrolimus: simultaneous treatment with NSAIDs may lead to a greater risk of nephrotoxicity, especially in elderly subjects. - Thrombolytics: concomitant administration with NSAIDs may increase the risk of bleeding. - Anti-aggregating agents (ticlopidine and clopidogrel) and selective serotonin reuptake inhibitors (SSRIs): NSAIDs may increase the risk of gastrointestinal bleeding (see section 4.4). - Probenecid: the concomitant administration of probenecid can markedly reduce the plasma clearance of ketoprofen due to inhibition of tubular secretion and glucuronide conjugation, therefore an adaptation of the dose of ketoprofen is necessary. - Quinolone antibiotics: animal data indicate that NSAIDs may increase the risk of convulsions related to quinolone use. Patients being treated with NSAIDs and quinolones may have an increased risk of developing seizures. - Diphenylhydantoin and sulphonamides: since the protein binding of ketoprofen is high, it may be necessary to reduce the dosage of diphenylhydantoin or sulphonamides in case of co-administration. - Gemeprost: combined use with an NSAID may reduce its effectiveness. Alcohol intake during treatment should be avoided.

SIDE EFFECTS

The most commonly observed adverse events are gastrointestinal in nature. 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). The following adverse reactions have been observed with the use of ketoprofen in adults:

MedDRA system organ class | Very common (≥1/10) | Common (≥1/100, <1/10) | Uncommon (≥1/1,000, <1/100) | Rare (≥1/10,000, <1/1,000) | Very rare (<1/10,000) | Frequency not known

Pathologies of the blood and lymphatic system | Rare (≥1/10,000, <1/1,000): hemorrhagic anemia | Frequency not known: thrombocytopenia, agranulocytosis, bone marrow failure, hemolytic anemia, leukopenia, neutropenia, aplastic anemia, leukocytosis, thrombocytopenic purpura.

Immune system disorders | Frequency not known: anaphylactic reaction (including shock), hypersensitivity

Gastrointestinal disorders | Common (≥1/100, <1/10): dyspepsia, nausea, abdominal pain, vomiting | Uncommon (≥1/1,000, <1/100) : constipation, diarrhea, flatulence, gastritis | Rare (≥1/10,000, <1/1,000): stomatitis, peptic ulcer | Frequency not known: exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage, gastrointestinal perforation (sometimes fatal, particularly in the elderly - see section 4.4), gastric ulcer, mouth ulceration, duodenal ulcer, duodenal perforation, melena, haematemesis, abdominal discomfort, colitis, heartburn, mouth edema, pancreatitis, hyperchlorhydria, gastric pain, erosive gastritis, tongue edema

Skin and subcutaneous tissue disorders | Uncommon (≥1/1,000, <1/100) : rash, itching | Very rare (<1/10,000): erythema | Frequency not known: photosensitivity reaction, alopecia, urticaria, angioedema, bullous dermatitis including Stevens-Johnson syndrome and toxic epidermal necrolysis, edema, exanthema, Lyell's syndrome, maculopapular exanthema, purpura, acute generalized exanthematous pustulosis, dermatitis

Systemic disorders and conditions relating to the administration site | Uncommon (≥1/1,000, <1/100) : fatigue, | Very rare (<1/10,000): edema of the face | Frequency not known: peripheral edema, chills, asthenia

Nervous system disorders | Uncommon (≥1/1,000, <1/100) : headache, dizziness, drowsiness | Rare (≥1/10,000, <1/1,000): paresthesia | Frequency not known: seizure, dysgeusia, dizziness, dyskinesia, syncope, tremor, hyperkinesia

Eye diseases | Rare (≥1/10,000, <1/1,000): blurred vision (see section 4.4) | Frequency not known: periorbital edema

Ear and labyrinth disorders | Rare (≥1/10,000, <1/1,000): tinnitus

Hepatobiliary disorders | Rare (≥1/10,000, <1/1,000): hepatitis, increased transaminases, increased blood bilirubin | Frequency not known: jaundice

Respiratory, thoracic and mediastinal disorders | Rare (≥1/10,000, <1/1,000): asthma | Frequency not known: bronchospasm (especially in patients with proven hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, dyspnoea, laryngeal edema, laryngospasm, acute respiratory failure (one case with fatal outcome was reported in an asthmatic patient sensitive to acetylsalicylic acid).

Renal and urinary disorders: | Frequency not known: acute renal failure, tubulointerstitial nephritis, nephritic syndrome, evidence of abnormal renal function, hematuria, nephritis, nephrotic syndrome, glomerulonephritis, sodium/water retention with possible edema, acute tubular necrosis, renal papillary necrosis, oliguria

Psychiatric disorders | Frequency not known: altered mood, depression, hallucination, confusional state, agitation, insomnia

Cardiac disorders | Frequency not known: heart failure, atrial fibrillation, palpitations, tachycardia

Vascular pathologies | Frequency not known: hypertension, vasodilation, hypotension, vasculitis (including leukocytoclastic vasculitis)

Metabolism and nutrition disorders | Frequency not known: hyperkalemia, hyponatremia

Infections and infestations | Frequency not known: aseptic meningitis, lymphangitis

Diagnostic tests | Rare (≥1/10,000, <1/1,000): Increased weight

Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatments) may be associated with an increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section 4.4). Reporting of suspected adverse reactions. Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.