Ibifen - 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

IBIFEN 50 mg HARD CAPSULES
IBIFEN 100 mg HARD CAPSULES
IBIFEN 200 mg PROLONGED RELEASE TABLETS
IBIFEN 50 mg EFFERVESCENT GRANULATE
IBIFEN 25 mg / ml ORAL DROPS SOLUTION
IBIFEN 100 mg / 2.5 ml SOLUTION FOR INJECTION FOR INTRAMUSCULAR USE
IBIFEN 100 mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE

Why is Ibifen used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Non-steroidal anti-inflammatory and antirheumatic drugs, derivatives of propionic acid. ATC code: M01AE03.

THERAPEUTIC INDICATIONS

IBIFEN ORAL DROPS SOLUTION

Pain of various origins and nature (headache, toothache, neuralgia, osteoarticular and muscle pain, menstrual pain).

IBIFEN OTHER ORAL FORMS

Rheumatoid arthritis, ankylosing spondylitis, acute gout, osteoarthritis of various localization, sciatica, radiculitis, myalgia, bursitis, tendinitis, tenosynovitis, synovitis, capsulitis, contusions, sprains, dislocations, muscle tears, phlebitis, painful lymphoid lymphitis, superficial thrombophlebitis dentistry, otolaryngology, urology and pulmonology.

IBIFEN FOR INJECTABLE USE

Symptomatic treatment of acute painful episodes in the course of inflammatory diseases of the musculoskeletal system.

Contraindications When Ibifen should not be used

  • Ibifen is contraindicated in patients with hypersensitivity to the active substance (ketoprofen), to any of the excipients or to other closely related substances from a chemical point of view. In particular towards other non-steroidal anti-inflammatory drugs (see below).
  • Ibifen is contraindicated in patients with a history of hypersensitivity reactions such as bronchospasm, asthma attacks, rhinitis, urticaria or other allergic-type reactions to ketoprofen, ASA or other NSAIDs. Serious, rarely fatal, anaphylactic reactions have been reported in these patients ( Ibifen capsules, granules and drops).
  • Ketoprofen is also contraindicated in the third trimester of pregnancy, during lactation and in children (see Special warnings).

Ketoprofen is contraindicated in the following cases:

  • Severe heart failure
  • History of active or recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding)
  • History of gastrointestinal bleeding or perforation, related to previous NSAID therapy (Ibifen capsules, granules and drops)
  • Hemorrhagic diathesis
  • Severe liver failure (liver cirrhosis, severe hepatitis)
  • Severe renal insufficiency
  • During intensive diuretic therapy
  • Chronic dyspepsia, gastritis
  • Leukopenia and thrombocytopenia, subjects with ongoing bleeding and bleeding diathesis
  • During treatment with anticoagulants as it synergizes their action

There is a possibility of cross-hypersensitivity with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs; therefore Ketoprofen should not be administered to patients in whom acetylsalicylic acid or other non-steroidal anti-inflammatory drugs have caused asthma, rhinitis, urticaria.

Ibifen for intramuscular or intravenous use is contraindicated in cases of cerebrovascular haemorrhages, or any other ongoing bleeding.

Ibifen for intramuscular use is contraindicated in patients with haemostasis disorders or on anticoagulant therapy.

Precautions for use What you need to know before taking Ibifen

The use of Ibifen, like any prostaglandin synthesis and cyclooxygenase inhibitor drug, is not recommended in women intending to become pregnant. The use of NSAIDs may reduce female fertility and is not recommended in women intending to become pregnant. In women who have difficulty conceiving or who are being tested for infertility, discontinuation of NSAIDs should be considered.

Ibifen, like all non-steroidal anti-inflammatory drugs, interferes with the synthesis of prostaglandins and their important intermediates that participate in physiological functions. The drug, therefore, requires special precautions, or requires its exclusion from use, when the following conditions are present in the patient: states of kidney hypoperfusion, kidney disease, heart failure, mild to moderate hepatic insufficiency, advanced age . As with all NSAIDs, care should be taken when treating patients with ongoing uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebral vasculopathy, as well as, before starting long-term treatment in patients with risk factors for cardiovascular diseases (such as hypertension, hyperlipidemia, diabetes mellitus, smoking).

The concomitant use of Ibifen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided. Undesirable effects can be minimized by using the lowest effective dose for the shortest possible treatment duration that is needed to control the symptoms.

Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.

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.

In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see Contraindications section), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest dose available. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low dose aspirin or other drugs that may increase the risk of gastrointestinal events (see below and interactions section). Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.

Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin.

Caution should be exercised in patients with a history of active or previous peptic ulcer.

When gastrointestinal bleeding or ulceration occurs in patients taking Ibifen the treatment should be discontinued.

NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see side effects section).

Caution should be exercised in patients with a history of hypertension and / or heart failure as fluid retention and edema have been reported in association with NSAID therapy.

Medicines such as Ibifen 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.

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 side effects section). higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Ibifen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.

At the start of treatment, renal function should be carefully monitored in patients with heart failure, cirrhosis and nephrosis, in patients on diuretic therapy, in patients with chronic renal failure, particularly if the patient is elderly. administration of ketoprofen can induce a reduction in renal blood flow caused by inhibition of prostaglandins and lead to renal failure.

The patient should consult their doctor to be instructed on the most correct method of administering the medicine.

As with other NSAIDs, in the presence of an infectious disease, it should be noted that the anti-inflammatory, analgesic and antipyretic properties of ketoprofen may mask the usual signs of infection progression such as fever. In patients with abnormal liver function tests or with a history of liver disease, transaminase levels should be evaluated periodically, particularly during long-term therapy. Rare cases of jaundice and hepatitis have been described with ketoprofen (Ibifen capsules, tablets, granules or drops).

Patients with asthma associated with chronic rhinitis, chronic sinusitis, and / or nasal polyposis have a higher risk of aspirin and / or NSAID allergy than the rest of the population.

The administration of this medicine can cause asthma attacks or bronchospasm, particularly in subjects allergic to aspirin or NSAIDs.

With Ibifen capsules, tablets, granules or drops

  • If visual disturbances, such as blurred vision, occur, treatment should be stopped

With Ibifen for IV and IM use

  • Risk of gastrointestinal bleeding: the relative risk increases in subjects who have a low body weight. If gastrointestinal bleeding or ulcer occurs, treatment should be stopped immediately
  • Blood cell counts and liver and kidney function tests should be done during long-term treatment
  • Hyperkalaemia caused by diabetes or concomitant treatment with potassium-sparing agents (see Interactions). Potassium levels need to be checked regularly under these circumstances

With Ibifen for IV use

  • Ketoprofen can be used in combination with morphine derivatives if the pain is severe.

Ibifen for injectable use

This drug cannot be considered a simple pain reliever and requires to be used under close medical supervision. Furthermore, once the acute painful episode has been overcome, it is prudent to switch to the use of preparations for non-parenteral use which, although qualitatively giving the same side effects, are less prone to inducing severe reactions.

The possible use for prolonged periods of IBIFEN in injectable solution for intramuscular use is allowed only in hospitals and nursing homes.

The injectable solution must be used immediately after reconstitution and the injections must be performed in strict compliance with hygiene rules.

Solutions for intramuscular use should not be injected intravenously.

Interactions Which drugs or foods can modify the effect of Ibifen

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. During therapy with lithium-based drugs, the simultaneous administration of non-steroidal anti-inflammatory drugs causes an increase in the plasma levels of lithium itself. It is advisable not to combine Ketoprofen with acetylsalicylic acid or with other non-steroidal anti-inflammatory drugs.

Combinations with medicinal products are not recommended:

Lithium: risk of increased plasma lithium levels, which can sometimes reach toxic levels due to reduced renal excretion of lithium. Where necessary, plasma lithium levels should be closely monitored and the lithium dosage adjusted during and after NSAID therapy.

Other NSAIDs (including selective COX-2 inhibitors) and high-dose salicylates: increased risk of gastrointestinal ulcers and bleeding

Anticoagulants (heparin and warfarin) and platelet aggregation inhibitors (for example: ticlopidine clopidogrel): increased risk of bleeding. If concomitant administration is unavoidable, it should be carefully monitored.

Methotrexate at doses above 15 mg / week: Increased risk of haematological toxicity of methotrexate, particularly when administered at high doses (> 15 mg / week), possibly related to the shift in protein binding of methotrexate and its reduced renal clearance. At least 12 hours should elapse between stopping or starting ketoprofen treatment and administering methotrexate (last statement applies to IV / IM only).

Combinations of medicinal products requiring precautions for use:

Diuretics: Patients and particularly dehydrated patients taking diuretics are at increased risk of developing renal failure secondary to a reduction in renal blood flow caused by inhibition of prostaglandins. Such patients should be rehydrated prior to initiating therapy with concomitant administration and renal function monitored when treatment is initiated.

ACE inhibitors and angiotensin II antagonists: in patients with impaired renal function (e.g. dehydrated patients or elderly patients, concomitant administration of an ACE inhibitor or angiotensin II antagonists and agents that inhibit cyclo-oxygenase may lead to further deterioration of renal function, including possible acute renal failure.

Methotrexate at doses below 15 mg / week: During the first weeks of combined treatment, complete blood counts should be monitored weekly. If there is renal impairment or if the patient is elderly, monitoring should be done more often.

Ibifen tablets, capsules, granules and drops only:

Corticosteroids: increased risk of ulceration or bleeding (see special warnings section). Pentoxifylline: There is an increased risk of bleeding. More frequent clinical monitoring and bleeding time monitoring is required.

Combinations to consider:

Antihypertensive agents (beta-blockers, angiotensin converting enzyme inhibitors, diuretics): risk of decreased antihypertensive potency (inhibition of vasodilatory prostaglandins by NSAIDs).

Thrombolytics: increased risk of bleeding

Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see special warnings).

Ibifen tablets, capsules, granules and drops only:

Probenecid: Concomitant administration of probenecid can significantly reduce the plasma clearance of ketoprofen.

Ibifen IM and IV only

Risks associated with hyperkalaemia: some medicinal products or therapeutic categories capable of promoting hyperkalaemia, ie potassium salts, potassium-sparing diuretics, converting enzyme inhibitors, angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus and trimethoprim The occurrence of hyperkalaemia may depend on the presence of cofactors This risk is greater when the above drugs are administered concomitantly.

Risks associated with the antiplatelet effect: many substances are involved in the interactions due to their antiplatelet effects: tirofiban, eptifibarid, abcixiab and iloprost. The use of various antiplatelet drugs increases the risk of bleeding.

Combinations to consider:

Ciclosporin, tacrolimus: risk of additive nephrotoxic effects, particularly in elderly subjects Ibifen oral drops solution Its ethyl alcohol content can modify or increase the effect of other drugs taken at the same time.

Warnings It is important to know that:

For the interaction of the drug with the metabolism of arachidonic acid, bronchospasm crises and possibly shock and other allergic phenomena may arise in asthmatics and predisposed subjects.

Use in pregnancy and during lactation

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Results of epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early stages of 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. During the first and second trimester of pregnancy, ketoprofen should not be administered unless strictly necessary. If ketoprofen is used by a woman trying to conceive, or during the first and second trimester of pregnancy, the dosage should be kept as low and the duration of treatment as short as possible.

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

  • cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension)
  • renal dysfunction, which can progress to renal failure with oligo-hydroamnios; the mother and the newborn, at the end of pregnancy, to:
  • possible prolongation of bleeding time, an anti-aggregating effect which can occur even at very low doses
  • inhibition of uterine contractions resulting in delayed or prolonged labor.

Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.

Feeding time

There are no data on the secretion of ketoprofen in breast milk. Ketoprofen is not recommended for breastfeeding women.

Effects on ability to drive and use machines

Patients should be warned of the potential for somnolence, dizziness or seizures and advised not to drive or operate machinery if such symptoms occur.

Important information about some of the ingredients

The hard capsules contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

The effervescent granules contain sucrose and lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product

Ibifen oral drops solution

Warning: the product contains 23.6% of ethyl alcohol 96 °. Each dose contains 0.236 g (20 drops) to 0.354 g (30 drops) of alcohol. Ibifen oral drops solution is contraindicated in patients suffering from liver disease, alcoholism, epilepsy, brain damage or disease, as well as in pregnant women and children under the age of 15. It can modify or increase the effect of other medicines, administered at the same time. For those who carry out sports activities, the use of medicines containing ethyl alcohol can determine positive doping tests in relation to the alcohol concentration limits indicated by some sports federations.

Ibifen for injectable use

The solution for injection should not be mixed with solvents having an acidic pH, such as, for example, solutions containing lidocaine.

Dosage and method of use How to use Ibifen: Dosage

Adults and children over 15 years

The maximum daily dose is 200 mg.

IBIFEN 50 mg HARD CAPSULES

2 - 4 capsules a day divided with meals.

IBIFEN 100 mg HARD CAPSULES

1 - 2 capsules a day divided with meals.

IBIFEN 200 mg PROLONGED RELEASE TABLETS

1 tablet a day immediately after meals.

IBIFEN 50 mg EFFERVESCENT GRANULATE

3 sachets per day.

IBIFEN 25 mg / ml ORAL DROPS SOLUTION

20 - 30 drops, 3-4 times a day (20 drops = 1 ml)

The drops should be taken in a little water preferably during meals.

IBIFEN 100 mg / 2.5 ml SOLUTION FOR INJECTION FOR INTRAMUSCULAR USE

100 mg 1-2 times a day.

IBIFEN 100 mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE

100 mg 1-2 times a day

In the treatment of elderly patients and patients with renal insufficiency, the dosage must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above.

Before administration, injectable drugs must be checked to exclude the presence of particles in suspension or other alterations of the normal appearance that could make the product unsuitable for use. The solution should be injected immediately after reconstitution; any residues must be eliminated.

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

Ibifen tablets, capsules and granules

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 are no specific antidotes for ketoprofen overdose. If massive overdose is suspected, gastric lavage is advised and symptomatic and supportive treatment should be instituted to compensate for dehydration, to monitor urinary excretion, and to correct acidosis, if present. In renal insufficiency, hemodialysis can be helpful in removing the circulating medicine.

Ibifen drops

In the event of a massive overdose, the patient should be immediately transferred to the hospital. Gastric contents must be rapidly eliminated. Symptomatic treatment should be instituted.

Ibifen IV and IM

In adults, the main signs of overdose are headache, dizziness, drowsiness, nausea, vomiting, diarrhea and abdominal pain. During severe intoxication, hypotension, respiratory depression and gastrointestinal bleeding were observed. The patient should be immediately transferred to a specialized hospital where symptomatic treatment can begin. There is no specific antidote.

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

If you have any questions about the use of Ibifen, ask your doctor or pharmacist.

Side Effects What are the side effects of Ibifen

Like all medicines, Ibifen 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, particularly in the elderly (see special warnings section). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Ibifen (see special warnings section). Gastritis has been observed less frequently.

More rarely, transient dysuria, asthenia, headache, dizziness, somnolence, skin rash, edema and thrombocytopenia have been reported; photosensitivity reactions, rare in case of systemic administration. Although extremely rare, severe systemic hypersensitivity reactions are possible, such as edema of the larynx, edema of the glottis, dyspnoea, palpitation, up to anaphylactic shock. In such cases immediate medical assistance is required.

Edema, hypertension and heart failure have been reported in association with NSAID treatment. Medicines such as Ibifen may be associated with a modest increased risk of heart attack ("myocardial infarction") or stroke.

Bullous reactions including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (very rarely).

Ibifen drops

Reactions of vomiting, diarrhea and hypersensitivity have been reported in clinical studies in infants and children.

Classification of expected frequencies: Very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (1 / 1,000 to <1/100), rare (≥1 / 10,000 to <1 / 1,000), very rare (<1 / 10,000), not known (cannot be estimated from the available data).

Ibifen tablets, capsules, granules, drops, IM and IV

The following adverse reactions have been reported in adults:

Disorders of the blood and lymphatic system

  • Rare: haemorrhagic anemia
  • Not known: agranulocytosis, thrombocytopenia, bone marrow failure (the latest adverse event applies only to Ibifen capsules, tablets, granules and drops)

Disorders of the immune system

  • Not known: anaphylactic reactions (including shock)

Psychiatric disorders

  • Not known: mood alterations

Nervous system disorders

  • Uncommon: headache, dizziness, somnolence
  • Rare: paraesthesia (only for Ibifen capsules, tablets, granules and drops)
  • Not known: seizures, dysgeusia (the latest adverse event only applies to Ibifen capsules, tablets, granules and drops)

Eye disorders

  • Rare: blurred vision

Ear and labyrinth disorders

  • Rare: tinnitus

Cardiac pathologies

  • Not known: heart failure

Vascular pathologies

  • Not known: hypertension, vasodilation (the latest adverse event only applies to Ibifen capsules, tablets, granules and drops)

Respiratory, thoracic and mediastinal disorders

  • Rare: asthma
  • Not known: bronchospasm (particularly in patients with known hypersensitivity to ASA and other NSAIDs), rhinitis

Gastrointestinal disorders

  • Common: dyspepsia (only for Ibifen capsules, tablets, granules and drops), nausea, abdominal pain (abdominal pain only applies to Ibifen capsules, tablets, granules and drops), vomiting
  • Uncommon: constipation, diarrhea, flatulence (flatulence only applies to Ibifen capsules, tablets, granules and drops), gastritis
  • Rare stomatitis, peptic ulcer
  • Not known: exacerbation of colitis and Crohn's disease, (Ibifen tablets, capsules, granules and drops), gastrointestinal bleeding and perforation

Pathologies of the hepatobiliary system

  • Rare: hepatitis, increased transaminases, elevated serum bilirubin levels caused by hepatitis

Skin and subcutaneous tissue disorders

  • Uncommon: rash, pruritus
  • Not known: photosensitivity reactions, alopecia, urticaria, aggravation of chronic urticaria (IV and IM only), angioedema, bullous eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis

Renal and urinary disorders

  • Not known: acute renal failure, tubulointerstitial nephritis, nephritic syndrome, changes in renal function tests (the latest adverse event only applies to Ibifen capsules, tablets, granules and drops)

General disorders and administration site conditions

  • Uncommon: edema, fatigue (fatigue only applies to Ibifen capsules, tablets, granules and drops)

Diagnostic tests

  • Rare: weight gain (only for Ibifen capsules, tablets, granules and drops) Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and long-term treatments) may be associated with an increased risk of events. arterial thrombotics (for example myocardial infarction or stroke).

Applies to Ibifen IV and IM

Gastrointestinal disorders

  • Gastrointestinal upset, stomach pains, and rare cases of colitis

Renal and urinary disorders:

  • Water / sodium retention with possible edema, hyperkalaemia.
  • Organic renal damage which could cause acute renal failure: Isolated cases of acute tubular necrosis and renal papillary necrosis have been reported.

Disorders of the blood and lymphatic system

  • Rare cases of leukopenia General disorders and administration site conditions
  • A few cases of pain and a burning sensation at the injection site have been reported.

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

Check the expiration date indicated on the package.

The expiry date refers to the product in intact packaging, correctly stored.

Warning: do not use the medicine after this date.

IBIFEN FOR INJECTABLE USE

Store below 25 ° C

Keep this medicine out of the reach of children

Composition and pharmaceutical form

COMPOSITION

IBIFEN 50 mg HARD CAPSULES

Each hard capsule contains:

Active principle

Ketoprofen 50 mg

Excipients

Lactose, magnesium stearate, polyvinylpyrrolidone, titanium dioxide, red iron oxide, yellow iron oxide, gelatin

IBIFEN 100 mg HARD CAPSULES

Each hard capsule contains:

Active principle

Ketoprofen 100 mg

Excipients

Lactose, magnesium stearate, polyvinylpyrrolidone, gelatin, titanium dioxide

IBIFEN 200 mg PROLONGED RELEASE TABLETS

Each tablet contains:

Active principle

Ketoprofen 200 mg

Excipients

Hydroxypropylmethylcellulose, mannitol, polyvinylpyrrolidone, colloidal silica, magnesium stearate, Eudragit L100-55, triacetin.

IBIFEN 50 mg EFFERVESCENT GRANULATE

Each sachet contains

Active principle

Ketoprofen 50 mg

Excipients

Sodium bicarbonate, tartaric acid, citric acid, sodium chloride, tribasic sodium citrate dihydrate, sucrose, lactose, sodium carbonate, ammonium glycyrrhizin, tetrarome orange flavor, E110.

IBIFEN 25 mg / ml ORAL DROPS SOLUTION

One 20ml bottle contains

Active principle

Ketoprofen 500 mg

Excipients

Diethanolamine, propylene glycol, ethyl alcohol 96 °, methyl p-hydroxybenzoate, glycyrrhizinated ammonium, currant flavor, water

IBIFEN 100 mg / 2.5 ml SOLUTION FOR INJECTION FOR INTRAMUSCULAR USE

Each vial contains:

Active principle

Ketoprofen 100 mg

Excipients

Sodium hydrate, citric acid, glycine, benzyl alcohol, water p.p.i ..

IBIFEN 100 mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE

Each vial contains:

Active principle

Ketoprofen 100 mg

Excipients

Sodium hydrate, citric acid, glycine, water p.p.i.

PHARMACEUTICAL FORM AND CONTENT

Hard capsules of 50 mg in packs of 30 units

Hard capsules of 100 mg in packs of 30 units

Prolonged-release tablets of 200 mg in packs of 30 units

Effervescent granules of 50 mg in packs of 30 sachets

Oral drops solution of 25 mg / ml in 20 ml bottle

Solution for injection for intramuscular use of 100 mg in packs of 6 ampoules of 2.5 ml

100 mg solution for injection for intravenous use in packs of 6 x 5 m ampoules

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.

Further information on Ibifen can be found in the "Summary of Characteristics" 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 the 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 immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER 09 .0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS AND QUALITY CONTROLS

01.0 NAME OF THE MEDICINAL PRODUCT

IBIFEN

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

IBIFEN 50 mg HARD CAPSULES

Each hard capsule contains:

Ketoprofen 50 mg

IBIFEN 100 mg HARD CAPSULES

Each hard capsule contains:

Ketoprofen 100 mg

IBIFEN 200 mg PROLONGED RELEASE TABLETS

Each tablet contains:

Ketoprofen 200 mg

IBIFEN 50 mg EFFERVESCENT GRANULATE

Each sachet contains

Ketoprofen 50 mg

IBIFEN 25 mg / ml ORAL DROPS SOLUTION

One 20ml bottle contains

Ketoprofen 500 mg

IBIFEN 100 mg / 2.5 ml SOLUTION FOR INJECTION FOR INTRAMUSCULAR USE

Each vial contains:

Ketoprofen 100 mg

IBIFEN 100 mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE

Each vial contains:

Ketoprofen 100 mg

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Hard capsules

Prolonged-release tablets

Effervescent granules

Oral drops solution

Injectable solution

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

IBIFEN ORAL DROPS SOLUTION

Pain of various origins and nature (headache, toothache, neuralgia, osteoarticular and muscle pain, menstrual pain).

IBIFEN OTHER ORAL FORMS

Rheumatoid arthritis, ankylosing spondylitis, acute gout, osteoarthritis of various localization, sciatica, radiculitis, myalgia, bursitis, tendinitis, tenosynovitis, synovitis, capsulitis, contusions, sprains, dislocations, muscle tears, phlebitis, painful lymphoid lymphitis, superficial thrombophlebitis dentistry, otolaryngology, urology and pulmonology.

IBIFEN FOR INJECTABLE USE

Symptomatic treatment of acute painful episodes in the course of inflammatory diseases of the musculoskeletal system.


04.2 Posology and method of administration

Adults and children over 15 years:

The maximum daily dose is 200 mg. The risk and benefit balance must be carefully considered before starting treatment with the 200 mg daily dose, and higher doses are not recommended (see also section 4.4).

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.4).

IBIFEN 50 mg HARD CAPSULES

2 - 4 capsules a day divided with meals.

IBIFEN 100 mg HARD CAPSULES

1 - 2 capsules a day divided with meals.

IBIFEN 200 mg PROLONGED RELEASE TABLETS

1 tablet a day immediately after meals.

IBIFEN 50 mg EFFERVESCENT GRANULATE

3 sachets per day.

IBIFEN 25 mg / ml ORAL DROPS SOLUTION

20 - 30 drops, 3-4 times a day (20 drops = 1 ml)

The drops should be taken in a little water preferably during meals.

IBIFEN 100 mg / 2.5 ml SOLUTION FOR INJECTION FOR INTRAMUSCULAR USE

100 mg 1-2 times a day

IBIFEN 100 mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE

100 mg 1-2 times a day

In the treatment of elderly patients and patients with renal insufficiency, the dosage must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above.


04.3 Contraindications

- Ibifen is contraindicated in patients who have a history of hypersensitivity reactions such as bronchospasm, asthma attacks, rhinitis, urticaria or other allergic-type reactions to ketoprofen, ASA or other NSAIDs. Serious anaphylactic reactions have been reported rarely in these patients. fatal (applies to Ibifen capsules, tablets, granules and drops) (see section 4.8)

- Hypersensitivity to the active substance, to any of the excipients or to other closely related substances from a chemical point of view. Specifically to other non-steroidal anti-inflammatory drugs (see below)

- Ketoprofen is also contraindicated in the third trimester of pregnancy, during lactation and in pediatric age (see section 4.6).

Ketoprofen is contraindicated in the following cases:

- Severe heart failure

- History of active or recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding)

- History of gastrointestinal bleeding or perforation, related to previous NSAID therapy (applies to Ibifen capsules, tablets, granules and drops).

- Hemorrhagic diathesis

- Severe liver failure (liver cirrhosis, severe hepatitis)

- Severe renal insufficiency

- During intensive diuretic therapy

- Chronic dyspepsia, gastritis

- Leukopenia and thrombocytopenia, subjects with ongoing bleeding

- During treatment with anticoagulants as it synergizes their action

There is a possibility of cross-hypersensitivity with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs; therefore Ketoprofen should not be administered to patients in whom acetylsalicylic acid or other non-steroidal anti-inflammatory drugs have caused asthma, rhinitis, urticaria.

Ibifen is contraindicated in cases of cerebrovascular haemorrhage, or other active bleeding (applies to Ibifen IV and IM).

Ibifen is contraindicated in patients with haemostatic disorders or current anticoagulant therapy (applies to Ibifen IM).


04.4 Special warnings and appropriate precautions for use

Warnings

For the interaction of the drug with the metabolism of arachidonic acid, bronchospasm crises and possibly shock and other allergic phenomena may arise in asthmatics and predisposed subjects.

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.

Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see section 4.5).

The concomitant use of ketoprofen with other NSAIDs, including selective cyclo-oxygenase-2 inhibitors, should be avoided.

Some epidemiological evidence suggests that ketoprofen may be associated with a higher risk of severe gastrointestinal toxicity, compared to other NSAIDs, especially at high doses (see also sections 4.2 and 4.3).

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.

The risk of gastrointestinal bleeding, ulceration or perforation is higher with increased doses of NSAIDs in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3) and in the elderly.

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 section 4.5). Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.

Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.

When gastrointestinal bleeding or ulceration occurs in patients taking Ibifen 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). 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. Ibifen should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.

Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg, myocardial infarction or stroke). There are insufficient data to exclude such a risk for ketoprofen.

Precautions for use

Patients with a history of 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).

At the start of treatment, renal function should be carefully monitored in patients with heart failure, cirrhosis and nephrosis, in patients on diuretic therapy, in patients with chronic renal failure, particularly if the patient is elderly. administration of ketoprofen can induce a reduction in renal blood flow caused by inhibition of prostaglandins and lead to renal failure.

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 other NSAIDs, in the presence of an infectious disease, it should be noted that the anti-inflammatory, analgesic and antipyretic properties of ketoprofen may mask the usual signs of infection progression such as fever.

In patients with abnormal liver function tests or with a history of liver disease, transaminase levels should be evaluated periodically, particularly during long-term therapy. Rare cases of jaundice and hepatitis have been described with ketoprofen (applies to Ibifen capsules, tablets, granules and drops).

The use of Ibifen, as well as any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.

The use of NSAIDs may reduce female fertility and is not recommended for women intending to become pregnant.

The administration of NSAIDs should be discontinued in women who have fertility problems or who are undergoing investigation of fertility.

Patients with asthma associated with chronic rhinitis, chronic sinusitis, and / or nasal polyposis, have a greater risk of allergy to aspirin and / or NSAIDs than the rest of the population. The administration of Ibifen could cause asthma attacks or bronchospasm, especially in subjects allergic to aspirin or NSAIDs (see section 4.3).

Ibifen, like all non-steroidal anti-inflammatory drugs, interferes with the synthesis of prostaglandins and their important intermediates that participate in physiological functions. The drug, therefore, requires special precautions, or requires its "exclusion from" use, when the following conditions are present in patients: states of kidney hypoperfusion, kidney disease, heart failure, mild to moderate hepatic insufficiency, advanced age .

Precautions only for Ibifen capsules, tablets, granules and drops

Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ketoprofen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking).

If visual disturbances, such as blurred vision, occur, treatment should be stopped.

Precautions for Ibifen IV and IM only

Risk of gastrointestinal bleeding: the relative risk increases in subjects who have a low body weight. If gastrointestinal bleeding or ulcer occurs, treatment should be stopped immediately

Blood cell counts and liver and kidney function tests should be done during long-term treatment

Hyperkalaemia caused by diabetes or concomitant treatment with potassium-sparing agents (see Interactions). Potassium levels need to be checked regularly under these circumstances.

Precautions for Ibifen IV only

Ketoprofen can be used in combination with morphine derivatives if the pain is severe.

Ibifen Oral Drops Solution

Warning: the product contains 23.6% of ethyl alcohol 96 °. Each dose contains 0.236 g (20 drops) to 0.354 g (30 drops) of alcohol. Ibifen oral drops solution is contraindicated in patients suffering from liver disease, alcoholism, epilepsy, brain damage or disease, as well as in pregnant women and children under the age of 15.

Ibifen Hard Capsules

The hard capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Ibifen Effervescent Granules

The effervescent granules contain sucrose and lactose. Patients with rare hereditary problems of fructose or galactose intolerance, glucose / galactose malabsorption syndrome, sucrase-isomaltase deficiency or the Lapp lactase deficiency should not take this medicine.

Ibifen For Injectable Use

This drug cannot be considered a simple pain reliever and requires to be used under close medical supervision. Furthermore, once the acute painful episode has been overcome, it is prudent to switch to the use of preparations for non-parenteral use which, although qualitatively giving the same side effects, are less prone to inducing severe reactions.

The possible use for prolonged periods of Ibifen in injectable solution for intramuscular use is only allowed in hospitals and nursing homes.

The injectable solution must be used immediately after reconstitution and the injections must be performed in strict compliance with hygiene rules.

Solutions for intramuscular use should not be injected intravenously.


04.5 Interactions with other medicinal products and other forms of interaction

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.

Combinations of medicinal products not recommended

Other NSAIDs (including selective cyclo-oxygenase-2 inhibitors) and high doses of salicylates: increased risk of gastrointestinal ulcer and bleeding.

Anticoagulants (heparin and warfarin) and antiplatelet agents (e.g. ticlopidine, clopidogrel): increased risk of haemorrhage (see section 4.4). If co-administration is unavoidable, the patient should be closely monitored.

Lithium: risk of increased plasma lithium levels, which can sometimes reach toxic levels due to reduced renal excretion of lithium. Where necessary, plasma lithium levels should be closely monitored and the lithium dosage adjusted during and after NSAID therapy.

Methotrexate at doses above 15 mg / week: Increased risk of haematological toxicity of methotrexate, particularly when administered at high doses (> 15 mg / week), possibly related to the displacement of methotrexate from binding proteins and its reduced renal clearance. At least 12 hours should elapse between stopping or starting treatment with ketoprofen and administering methotrexate (only for Ibifen IV / IM).

Combinations of medicinal products requiring precautions for use

Diuretics: Patients and particularly dehydrated patients taking diuretics are at increased risk of developing renal failure secondary to decreased renal blood flow caused by prostaglandin inhibition. Such patients should be rehydrated prior to initiating therapy with concomitant administration and renal function monitored when treatment is initiated (see section 4.4).

ACE inhibitors and angiotensin II antagonists: in patients with impaired renal function (e.g. dehydrated patients or elderly patients) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of the renal function, which includes possible acute renal failure.

Methotrexate at doses below 15 mg / week: During the first few weeks of combined treatment, complete blood counts should be monitored weekly. If there is renal impairment or if the patient is elderly, monitoring should be done more often.

Combinations of medicinal products to be considered

Antihypertensive agents (beta-blockers, angiotensin converting enzyme inhibitors, diuretics): risk of decreased antihypertensive potency (inhibition of vasodilatory prostaglandins by NSAIDs).

Thrombolytics: increased risk of bleeding

Selective Serotonin Reuptake Inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).

It applies only to Ibifen capsules, tablets, granules and drops:

Combinations of medicinal products requiring precautions for use

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Pentoxifylline: increased risk of bleeding. More frequent clinical monitoring and bleeding time monitoring is required.

Combinations of medicinal products to be considered

Probenecid: Concomitant administration of probenecid can significantly reduce the plasma clearance of ketoprofen.

Applies only for Ibifen IM and IV

Combinations of medicinal products to be considered

Risks associated with hyperkalemia: some medicinal products or therapeutic categories capable of promoting hyperkalaemia, ie potassium salts, potassium-sparing diuretics, converting enzyme inhibitors, angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or not fractionated), cyclosporine, tacrolimus and trimethoprim The occurrence of hyperkalaemia may depend on the presence of cofactors This risk is greater when the above drugs are administered concomitantly.

Risks associated with the antiplatelet effect: several substances are involved in the interactions due to their antiplatelet effects: tirofiban, eptifibarid, abcixiab and iloprost. The use of various antiplatelet drugs increases the risk of bleeding.

Combinations to consider:

Ciclosporin, tacrolimus: risk of additive nephrotoxic effects, particularly in elderly subjects.

Ibifen Oral Drops Solution

Its ethyl alcohol content can modify or increase the effect of other drugs taken at the same time.


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 believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and embryo-fetal mortality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.

During the first and second trimester of pregnancy, ketoprofen should not be administered unless strictly necessary. If ketoprofen is used by a woman trying to conceive, or during the first and second trimester of pregnancy, the dosage should be kept as low and the duration of treatment as short as possible.

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

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

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

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

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

- inhibition of uterine contractions resulting in delayed or prolonged labor

Consequently, ketoprofen is contraindicated during the third trimester of pregnancy.

Feeding time There are no data on the secretion of ketoprofen in breast milk. Ibifen is not recommended in women who are breastfeeding.


04.7 Effects on ability to drive and use machines

Patients should be warned of the potential for somnolence, dizziness or seizures and advised not to drive or operate machinery if such symptoms occur.

Only for Ibifen IV and IM

Patients should be warned of any visual disturbances. If this occurs, patients should not drive or operate machinery.


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).

After administration of Ibifen the following have been reported: nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4 - special warnings and precautions for use) Gastritis has been observed less frequently.

More rarely, transient dysuria, asthenia, headache, dizziness, somnolence, skin rash, edema and thrombocytopenia have been reported; photosensitivity reactions, rare in case of systemic administration. Although extremely rare, severe systemic hypersensitivity reactions are possible, such as edema of the larynx, edema of the glottis, dyspnoea, palpitation, up to anaphylactic shock. In such cases immediate medical assistance is required.

Bullous reactions including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (very rarely).

Edema, hypertension and heart failure have been reported in association with NSAID treatment.

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).

Only for the Ibifen drops formulation

Reactions of vomiting, diarrhea and hypersensitivity have been reported in clinical studies in infants and children.

Classification of expected frequencies:

Very common (≥ 1/10), common (≥ 1/100 a

For Ibifen formulations capsules, tablets, granules and drops, IV and IM

The following adverse reactions have been reported in adults:

Disorders of the blood and lymphatic system

- Rare: haemorrhagic anemia

- Not known: agranulocytosis, thrombocytopenia, bone marrow failure (the latest adverse event only applies to Ibifen capsules, tablets, granules and drops)

Disorders of the immune system

- Not known: anaphylactic reactions (including shock)

Psychiatric disorders

- Not known: mood alterations

Nervous system disorders

- Uncommon: headache, dizziness, somnolence

- Rare: paraesthesia (just for Ibifen capsules, tablets, granules and drops)

- Not known: convulsions, dysgeusia (the last adverse event only applies to Ibifen capsules, tablets, granules and drops)

Eye disorders

- Rare: blurred vision (see section 4.4)

Ear disorders and the labyrinth

- Rare: tinnitus

Cardiac pathologies

- Not known: heart failure

Vascular pathologies

- Not known: hypertension, vasodilation (the latest adverse event only applies to Ibifen capsules, tablets, granules and drops)

Respiratory, thoracic and mediastinal disorders

- Rare: asthma

- Not known: bronchospasm (particularly in patients with known hypersensitivity to ASA and other NSAIDs), rhinitis

Gastrointestinal disorders

- Common: dyspepsia (only for Ibifen capsules, tablets, granules and drops), nausea, abdominal pain (abdominal pain only applies to Ibifen capsules, tablets, granules and drops), He retched

- Uncommon: constipation, diarrhea, flatulence (flatulence only applies to Ibifen capsules, tablets, granules and drops), gastritis

- Rare stomatitis, peptic ulcer

- Not known: exacerbation of colitis and Crohn's disease, (only applies to Ibifen capsules, tablets, granules and drops), gastrointestinal bleeding and perforation

Pathologies of the hepatobiliary system

- Rare: hepatitis, increased transaminases, elevated serum bilirubin levels caused by hepatitis

Skin and subcutaneous tissue disorders

- Uncommon: rash, pruritus

- Not known: photosensitivity reactions, alopecia, urticaria, aggravation of chronic urticaria (aggravation of chronic urticaria only applies to IV and IM), angioedema, bullous eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis

Renal and urinary disorders

- Not known: acute renal failure, tubulointerstitial nephritis, nephritic syndrome, renal function test abnormalities (the latest adverse event only applies to Ibifen capsules, tablets, granules and drops)

General disorders and administration site conditions

- Uncommon: edema, fatigue (fatigue only applies to Ibifen capsules, tablets, granules and drops)

Diagnostic tests

- Rare: weight gain (only for Ibifen capsules, tablets, granules and drops)

Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and long-term treatments) may be associated with an increased risk of arterial thrombotic events (eg myocardial infarction or stroke) (see section 4.4).

Applies to Ibifen IV and IM only

Gastrointestinal disorders

- Gastrointestinal disorders, stomach pains, and rare cases of colitis

Renal and urinary disorders

- Water / sodium retention with possible edema, hyperkalaemia (see sections 4.4 and 4.5)

- Organic renal damage which could lead to acute renal failure: isolated cases of acute tubular necrosis and renal papillary necrosis have been reported

Disorders of the blood and lymphatic system

- Rare cases of leukopenia

General disorders and administration site conditions

- A few cases of pain and a burning sensation at the injection site have been reported


04.9 Overdose

Ibifen capsules, tablets and granules

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 are no specific antidotes for ketoprofen overdoses. In the event of suspected cases of massive overdose, gastric lavage is recommended and symptomatic and supportive treatment should be instituted to compensate for dehydration, to monitor urinary excretion and to correct acidosis, if present. In renal insufficiency, hemodialysis can be helpful in removing circulating medicine.

Ibifen drops

In the event of a massive overdose, the patient should be immediately transferred to the hospital. Gastric contents must be rapidly evacuated.

Symptomatic treatment should be instituted.

Ibifen IV e IM

In adults, the main signs of overdose are headache, dizziness, drowsiness, nausea, vomiting, diarrhea and abdominal pain. During severe intoxication, hypotension, respiratory depression and gastrointestinal bleeding were observed.

The patient should be transferred immediately to a specialized hospital where symptomatic treatment can begin.

There is no specific antidote.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: non-steroidal anti-inflammatory / antirheumatic drugs.

ATC code: M01AE03.

Ketoprofen is a drug with anti-inflammatory and analgesic activity belonging to the pharmacotherapeutic group of NSAIDs.

The anti-inflammatory activity is related to four well documented mechanisms of action: stabilization of the lysosomal membrane; inhibition of prostaglandin synthesis; antibradykinin activity; antiplatelet activity.

Pharmacological studies conducted on animals and partly also on healthy volunteers, suggest that the analgesic activity is doubly articulated.

It is in fact probable that alongside the now known peripheral activity, mediated mainly by the inhibitory effect on prostaglandin synthesis, ketoprofen also exerts its analgesic activity through a central non-opioid mechanism in which supraspinal structures such as glutamate-type receptors are involved. NMDA inducing central sensitization in which various biochemical mediators are involved, such as substance P, 5-HT, in addition to the prostaglandins themselves present in the CNS.

This peculiar analgesic profile would explain the rapidity of the analgesic effect of ketoprofen observed in the clinic in various acute painful conditions, otherwise not explainable with the only peripheral mechanism known to date.


05.2 "Pharmacokinetic properties

In man the absorption of Ketoprofen is very high. It reaches maximum blood levels within one "hour when administered orally or rectally. Peak values ​​are 3.5 mcg / ml after administration of 50 mg per os; of 7.5 mcg / ml after administration of 100 mg per os. rectally. With the retard capsule form, the blood peak of 5.12 mcg / ml is reached between the 3rd and 6th hours and remains stable for a few hours, then decreasing slowly until the 12th hour. Administered intramuscularly it reaches maximum levels blood within half an hour; the mean peak value is 10.4 mcg / ml. The pharmacokinetics of ketoprofen in the synovial fluid are particularly interesting; in fact, concentrations below the blood levels are reached here, but they are far more persistent and this characteristic may explain the prolonged effect of the drug on the painful joint component.

Ketoprofen rapidly crosses the blood-brain barrier reaching concentrations in equilibrium with those in plasma, as early as 15 minutes after its intramuscular administration at a dose of 100 mg.

Relatively large amounts of free ketoprofen can be reached in the cerebrospinal fluid even when plasma levels of ketoprofen are still below peak values.

The elimination of Ketoprofen occurs essentially through the urine (> 50% in the form of metabolites) and minimally through the faeces (1%).


05.3 Preclinical safety data

The toxicological tests have shown the low toxicity and the high therapeutic index of IBIFEN. The LD50 in rats, per os, is 165 mg / kg; in mice, by various routes of administration, it is between 365 and 662 mg / kg.

After administration of non-steroidal anti-inflammatory drugs in pregnant rats, restriction of the fetal ductus arteriosus was observed.

There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

IBIFEN 50 mg HARD CAPSULES

Lactose, magnesium stearate, polyvinylpyrrolidone, titanium dioxide, red iron oxide, yellow iron oxide, gelatin.

IBIFEN 100 mg HARD CAPSULES

Lactose, magnesium stearate, polyvinylpyrrolidone, gelatin, titanium dioxide.

IBIFEN 200 mg PROLONGED RELEASE TABLETS

Hydroxypropylmethylcellulose, mannitol, polyvinylpyrrolidone, colloidal silica, magnesium stearate, Eudragit L100-55, triacetin.

IBIFEN 50 mg EFFERVESCENT GRANULATE

Sodium bicarbonate, tartaric acid, citric acid, sodium chloride, tribasic sodium citrate dihydrate, sucrose, lactose, sodium carbonate, glycyrizinated ammonium, tetrarome orange flavor, E110.

IBIFEN 25mg / ml ORAL DROPS SOLUTION

Diethanolamine, propylene glycol, 96 ° ethyl alcohol, methyl p-hydroxybenzoate, glycyrrhizinated ammonium, currant flavor, water.

IBIFEN 100 mg / 2.5 ml SOLUTION FOR INJECTION FOR INTRAMUSCULAR USE

Sodium hydrate, citric acid, glycine, benzyl alcohol, water p.p.i ..

IBIFEN 100 mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE

Sodium hydrate, citric acid, glycine, water p.p.i ..


06.2 Incompatibility

IBIFEN FOR INJECTABLE USE

The solution for injection should not be mixed with solvents having an acidic pH, such as, for example, solutions containing lidocaine.


06.3 Period of validity

IBIFEN 50 mg HARD CAPSULES

IBIFEN 100 mg HARD CAPSULES

5 years

IBIFEN 50 mg EFFERVESCENT GRANULATE

IBIFEN 25 mg / ml ORAL DROPS SOLUTION

IBIFEN 100 mg / 2.5 ml SOLUTION FOR INJECTION FOR INTRAMUSCULAR USE

IBIFEN 100 mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE

3 years

IBIFEN 200 mg PROLONGED RELEASE TABLETS

2 years


06.4 Special precautions for storage

IBIFEN FOR ORAL USE

No particular

IBIFEN FOR INJECTABLE USE

Store below 25 ° C


06.5 Nature of the immediate packaging and contents of the package

IBIFEN 50 mg HARD CAPSULES in packs of 30 capsules

IBIFEN 100 mg HARD CAPSULES in packs of 30 capsules

IBIFEN 200 mg PROLONGED-RELEASE TABLETS in packs of 30 tablets

IBIFEN 50 mg EFFERVESCENT GRANULATE in packs of 30 sachets

IBIFEN 25mg / ml ORAL DROPS SOLUTION in 20 ml bottle

IBIFEN 100mg / 2,5 ml INJECTABLE SOLUTION FOR INTRAMUSCULAR USE in pack of 6 ampoules

IBIFEN 100mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE in pack of 6 ampoules


06.6 Instructions for use and handling

IBIFEN FOR ORAL USE

No particular.

IBIFEN FOR INJECTABLE USE

Before administration, injectable drugs must be checked to exclude the presence of particles in suspension or other alterations of the normal appearance that could make the product unsuitable for use.

The solution should be injected immediately after reconstitution; any residues must be eliminated.

07.0 MARKETING AUTHORIZATION HOLDER

ITALIAN BIOCHEMICAL INSTITUTE GIOVANNI LORENZINI S.p.A. Via Fossignano, 2 - 04011 Aprilia (LT)

08.0 MARKETING AUTHORIZATION NUMBER

IBIFEN 50 mg HARD CAPSULES AIC No. 024994117

IBIFEN 100 mg HARD CAPSULES AIC No. 024994081

IBIFEN 200 mg PROLONGED RELEASE TABLETS AIC No. 024994168

IBIFEN 50 mg EFFERVESCENT GRANULATE AIC No. 024994170

IBIFEN 25 mg / ml ORAL DROPS SOLUTION AIC No. 024994220

IBIFEN 100mg / 2.5 ml SOLUTION FOR INJECTION FOR INTRAMUSCULAR USE AIC No 024994182

IBIFEN 100mg / 5 ml SOLUTION FOR INJECTION FOR INTRAVENOUS USE AIC No 024994194

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

Renewal August 2005

10.0 DATE OF REVISION OF THE TEXT

March 2013

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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