Flurbiprofen

Avoid concomitant use of two or more NSAIDs, including Cox-2 inhibitors, as this may increase the risk of adverse effects.

NSAIDs may enhance the effects of anticoagulants such as warfarin.

Increased risk of gastrointestinal ulceration or bleeding with NSAIDs.

Increased risk of gastrointestinal bleeding with NSAIDs.

Increased risk of gastrointestinal bleeding.

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. Diuretics can also increase the risk of nephrotoxicity of NSAIDs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. These interactions should be considered in patients taking flurbiprofen concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in the elderly.

Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

As with other products containing NSAIDs, concomitant administration of flurbiprofen and aspirin is not generally recommended because of the potential of increased adverse effects.

Increased risk of nephrotoxicity.

Decreased elimination of lithium.

Caution is advised in the concomitant administration of flurbiprofen and methotrexate since NSAIDs may increase methotrexate levels.

NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV haemophiliacs receiving concurrent treatment with zidovudine and other NSAIDs.

Bronchospasm may be precipitated in patients suffering from, or with a previous history of bronchial asthma or allergic disease. Flurbiprofen should be used with caution in these patients.

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with flurbiprofen administration and NSAID therapy.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke. There are insufficient data to exclude such a risk for flurbiprofen.

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

Caution should be used when initiating treatment with NSAIDs such as flurbiprofen in patients with considerable dehydration.

There may be an increased risk of aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation).

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, flurbiprofen should not be given unless clearly necessary. If flurbiprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

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

• the foetus to:
  • cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
  • renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;
• the mother and the neonate, at the end of pregnancy, to:
  • possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.
  • inhibition of uterine contractions resulting in delayed or prolonged labour.

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

Flurbiprofen is excreted into human breast milk; however, the amount secreted is only a small fraction of the maternal dose. Flurbiprofen is not recommended for use in nursing mothers.

In the limited studies so far available, NSAIDs can appear in the breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

Impaired female fertility

The use of flurbiprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of flurbiprofen should be considered.

Labour and Delivery

The onset of labour may be delayed and the duration increased with a greater bleeding tendency in both mother and child.

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

Transient blurred vision can result after instillation into the conjuctival sac. If this occurs, the patient should wait until the vision clears before driving or using machinery.