Ibuprofen TZF

• Hypersensitivity to the active substance, other non-steroidal anti-inflammatory drugs (NSAIDs) or any of the excipients listed in section 6.1.
• Active or recurrent peptic ulcer, or gastrointestinal bleeding (two or more distinct episodes of proven ulceration or bleeding).
• Severe hepatic impairment.
• Severe heart failure (NYHA class IV).
• Severe renal impairment (glomerular filtration rate below 30 mL/min).
• Bleeding disorders.
• History of gastrointestinal perforation or bleeding related to previous NSAID treatment.
• Third trimester of pregnancy.
• Do not use in patients with a history of any allergy symptoms in the form of bronchial asthma, urticaria or rhinosinusitis during treatment with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).

Side effects can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, as well as “Bleeding, ulceration or perforation of the gastrointestinal tract” and “Effects on the circulatory system and cerebral vessels” – below).

Masking the symptoms of an underlying infection

Ibuprofen TZF may mask the symptoms of an infection, which may lead to a delayed onset of appropriate treatment and thus worsen the effects of the infection. This phenomenon has been observed in out-of-hospital bacterial pneumonia and bacterial complications of chickenpox.

If Ibuprofen TZF is used to counter fever or pain associated with an infection, it is recommended to control the course of the infection. In the out-patient setting, the patient should consult a doctor if symptoms persist or worsen. During long-term treatment with high doses of analgesics, headaches may occur which should not be treated with increased doses of the medicinal product. Alcohol consumption should be avoided as it may exacerbate the adverse effects of NSAIDs, especially if the gastrointestinal tract or central nervous system is affected.

There is evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis impair female fertility by affecting ovulation. This effect is transient and disappears after the end of treatment.

Cardiovascular and cerebrovascular effects

Patients with a history of hypertension and/or mild to moderate cardiac failure with fluid retention and oedema should be adequately controlled and appropriate recommendations made. Fluid retention and oedema have been reported in association with NSAID treatment.

Clinical studies indicate that the use of ibuprofen, especially at a high dose (2400 mg per day), may be associated with a small increase in the risk of arterial embolic events (for example, myocardial infarction or stroke). Overall epidemiological studies do not indicate that taking ibuprofen in low doses (e.g. 1200 mg per day) is associated with an increased risk of arterial embolic-thrombotic incidents.

Cases of Kounis syndrome have been reported in patients treated with Ibuprofen TZF. Kounis syndrome is defined as cardiovascular symptoms occurring secondary to an allergic or hypersensitivity reaction, associated with coronary artery spasm and which may lead to myocardial infarction.

In patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), known ischaemic heart disease, peripheral vascular disease and/or cerebrovascular disease, ibuprofen treatment should be used after careful consideration, while avoiding high doses (2400 mg per day). The inclusion of long-term treatment for patients with risk factors for cardiovascular incidents (hypertension, hyperlipidaemia, diabetes mellitus, smoking) should also be carefully considered, especially if high doses of ibuprofen (2400 mg per day) are required.

Gastrointestinal bleeding, ulceration or perforation

There is an association between the dose used and the occurrence of severe gastrointestinal bleeding. Avoid concomitant use of ibuprofen and other NSAIDs, including selective cyclooxygenase-2 inhibitors. Elderly patients have an increased risk of adverse effects during use of NSAIDs, particularly gastrointestinal bleeding and perforation, which can be fatal. Cases of bleeding, ulceration, or gastrointestinal perforation that can cause death have been reported following use of all NSAIDs at any time during treatment, with or without warning symptoms, or in the history of previous serious gastrointestinal events. The risk of gastrointestinal bleeding, ulceration, or perforation is increased when high doses of NSAIDs are used in patients with a history of gastrointestinal ulceration, especially complicated bleeding or perforation (see section 4.3) and in the elderly. If such risk factors are present, patients should start treatment with the lowest possible dose. Combination treatment with protective drugs (e.g. misoprostol or proton pump inhibitors) should be considered in these patients as well as in patients requiring low doses of acetylsalicylic acid or other drugs that increase the risk of gastrointestinal disorders (see below and section 4.5). Patients with a history of gastrointestinal disorders, especially if they are elderly patients, should be advised to look out for any unusual abdominal symptoms (especially gastrointestinal bleeding), especially at the start of treatment. If any such symptoms occur, the patient should seek medical advice. Caution is advised in patients taking concomitant medications that may increase the risk of gastrointestinal ulcers or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors and antiplatelet drugs such as acetylsalicylic acid (see section 4.5). If patients using ibuprofen experience bleeding or ulceration of the gastrointestinal tract, this product should be discontinued. In patients with a history of gastrointestinal diseases (e.g. ulcerative colitis, Crohn’s disease), NSAIDs should be used with caution as these diseases may be exacerbated.

Effects on the kidneys

Caution should be exercised in patients with significant dehydration. There is a risk of renal dysfunction especially in dehydrated children, adolescents and the elderly. As with other NSAIDs, long-term administration of ibuprofen has caused necrosis of the renal papillae and other pathological changes in the kidneys. Renal toxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining normal renal perfusion. In these patients, the administration of NSAIDs may cause a dose-dependent decrease in prostaglandin formation and secondarily, a decrease in local renal blood flow, which may cause renal failure. Patients most at risk of this reaction are those with renal impairment, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors, and the elderly. After discontinuation of NSAID treatment, there is usually a return to the pre-treatment state. In patients with impaired renal, hepatic or cardiac function, the lowest effective dose should be used for the shortest possible time, especially in patients on long-term treatment (see also section 4.3).

Effects on the haematological system

Ibuprofen may inhibit platelet aggregation resulting in prolonged bleeding time.

Effects on the respiratory system

In patients with active or a history of bronchial asthma, chronic rhinitis, or allergic diseases, ibuprofen may induce bronchospasm, urticaria, or angioedema.

Severe cutaneous adverse reactions (SCAR)

Severe cutaneous adverse reactions (SCAR) including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) and acute generalised exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in association with the use of ibuprofen (see section 4.8). The majority of these reactions occurred within the first month. If the physical and subjective symptoms are indicative of these reactions, ibuprofen should be discontinued immediately and alternative treatment considered (as appropriate).

Infections and parasitic infections

In exceptional cases, chickenpox can cause severe complicated infections of the skin and soft tissues. At present, the impact of NSAIDs on the severity of these infections cannot be ruled out. Thus, it is recommended that Ibuprofen TZF should be avoided in case of chickenpox.

Sterile meningitis

In isolated cases, aseptic meningitis has been observed in patients treated with ibuprofen. However, this is more likely in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease. In patients with gastrointestinal diseases, systemic lupus erythematosus, haematological or coagulation disorders and asthma, NSAIDs should be used with caution, and patients taking NSAIDs should be closely monitored as these diseases may be exacerbated.

Lactose monohydrate

Ibuprofen TZF medicinal product contains lactose monohydrate. The medicinal product should not be used in patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Sodium

The medicinal product Ibuprofen TZF contains less than 1 mmol (23 mg) of sodium per tablet, i.e. the product is considered ‘sodium free’