Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Aventis Pharma Limited, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK Trading as: Sanofi, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below). Patients treated with NSAIDs long-term should undergo regular medical supervision to monitor for adverse events.
The use of Surgam with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).
Tiaprofenic acid should be used with caution in:
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Tiaprofenic acid may cause sodium and water retention with oedema. At the start of therapy, urine volume and renal function should be carefully monitored in patients with a history of hypertension, cardiac insufficiency, liver cirrhosis, or nephrotic syndrome, and in patients on diuretics.
Urinary symptoms and cystitis have been reported with tiaprofenic acid and other NSAIDs. Tiaprofenic acid appears to have a greater propensity than other NSAIDs to generate reports of cystitis. Tiaprofenic acid can cause cystitis which may become severe if the treatment is continued after the onset of urinary symptoms. Non-recognition has led to extensive investigations and even surgical intervention, in some patients. If urinary symptoms such as frequency, urgency, dysuria, nocturia or haematuria occur, tiaprofenic acid should be stopped immediately and urinalysis and urine culture performed, and complete recovery is the rule.
Before starting treatment with tiaprofenic acid, the patient should be asked to inform his/her physician of any urinary symptom, even if the physician is familiar with these symptoms from the patient’s medical history (see Adverse Reactions). Patients should be warned about the onset of urinary symptoms which may suggest cystitis and are advised to stop taking the drug and seek medical advice if these occur.
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, 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 commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors, anti-platelet agents such as aspirin, or nicorandil (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving Surgam, the treatment should be withdrawn.
NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated (see section 4.8).
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 NSAIDSs. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Surgam should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
The use of Surgam 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 Surgam should be considered.
There is a risk of cross-sensitivity among aspirin and NSAIDs, including the group to which tiaprofenic acid belongs. These pseudo-allergic reactions may include rash, urticaria and angioedema or more potentially severe manifestations (e.g. laryngeal oedema, bronchoconstriction and shock). The risk of pseudo-allergic reactions is greater in patients with recurrent rhino-sinusitis, nasal polyposis or chronic urticaria. Asthmatic patients are particularly at risk of dangerous reactions. Therefore, tiaprofenic acid must not be administered to patients with a history of asthma.
As NSAIDs can interfere with platelet function, they should be used with caution in patients with intracranial haemorrhage and bleeding diathesis.
The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3).
Cases of acute renal failure after initiation of high dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs) have been reported in patients treated with tenofovir disoproxil fumarate and with risk factors for renal dysfunction. If tenofovir disoproxil fumarate is co-administered with an NSAID, renal function should be monitored adequately.
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 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 (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for tiaprofenic acid.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with tiaprofenic acid after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
An increased risk for arterial thrombotic events has been reported in patients treated with non-aspirin NSAIDS (e.g. parecoxib and valdecoxib) for perioperative pain in the setting of coronary artery bypass surgery (CABG). This effect has not been observed with tiaprofenic acid
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8).
Since Surgam is highly protein-bound, it is not recommended for co-administration with other highly protein-bound drugs such as heparin. Modification of the dosage may be necessary with hypoglycaemic agents, phenytoin and diuretics. With oral hypoglycaemic agents, an inhibition of metabolism of sulphonylurea drugs, prolonged half-life and increased risk of hypoglycaemia has been reported.
It is considered unsafe to take NSAIDs in combination with anticoagulants due to increased risk of bleeding.
If co-administration is unavoidable, patient should be closely monitored.
Concomitant use of Surgam with other NSAIDs (including cyclooxygenase-2 selective inhibitors) and high-dose salicylates should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.
Caution must be exercised when Surgam is administered with corticosteroids due to increased risk of gastrointestinal ulceration or bleeding.
In patients concomitantly receiving nicorandil and NSAIDs, there is an increased risk for severe complications such as gastrointestinal ulceration, perforation and hemorrhage (see section 4.4).
Caution should be exercised when Surgam is administered with cardiac glycosides and sulphonamides. With cardiac glycosides, NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.
Concomitant use of Surgam with methotrexate causes a decreased elimination of methotrexate. Concomitant use with high dose methotrexate should be avoided. Use with caution with low dose methotrexate.
Concomitant administration of tenofovir disoproxil fumarate and NSAIDs may increase the risk of renal failure.
Decreased elimination of lithium. NSAIDs have been reported to increase steady state plasma levels of lithium and it is, therefore, recommended that these levels are monitored in patients receiving Surgam therapy.
Aspirin and other NSAIDs should not be used for at least 8–12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Caution must be exercised when Surgam is administered with diuretics. It reduces both the diuretic and antihypertensive effect of diuretics and increase risk of renal impairment and/or hyperkalemia. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
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 ibuprofen.
Further deterioration of renal function, including possible acute renal failure, in patients with compromised renal function (e.g. dehydrated patients or elderly patients).
The possibility of interaction must be taken into account with:
The possibility of interaction must be taken into account with selective serotonin reuptake inhibitors (SSRIs), increased risk of gastrointestinal bleeding.
Increased risk of bleeding
The risk of nephrotoxicity may be increased if NSAIDs are given with ciclosporins.
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.
Care should also be taken if Surgam is concomitantly administered with aminoglycosides or probenecid. Aminoglycosides may interact with NSAIDs to cause a reduction in renal function in susceptible individuals, decreased elimination of aminoglycoside and increased plasma concentrations. A reduction in metabolism and elimination of NSAID and metabolites has been observed with probenecid.
Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. Tiaprofenic acid crosses the placental barrier. Although animal studies have not revealed evidence of teratogenicity, safety in human pregnancy and lactation cannot be assumed and, in common with other NSAIDs, Surgam should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus.
In view of the known effects of NSAIDs on the foetal cardiovascular system (a closure of ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (see section 4.3).
The level of Surgam in mother’s milk has been studied and the total daily exposure is very small; approximately 0.2% of the administered dose and is unlikely to be of pharmacological significance. Breast feeding or treatment of the mother should be stopped as necessary.
See section 4.4 regarding female fertility.
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention: very common (≥10%), common (≥1% and <10%); uncommon (≥0.1% and <1%); rare (≥0.01% and <0.1%), very rare (<0.01%), not known (cannot be estimated from the available data).
Very common: abdominal pain upper
Common: nausea, vomiting, dyspepsia, diarrhoea
Not known: melaena, haematemesis, anorexia, indigestion, heartburn, flatulence, constipation, gastritis, ulcerative stomatitis, pancreatitis, colitis and Crohn’s disease (see section 4.4).
Peptic ulcers, gastrointestinal haemorrhage and perforation have occasionally been reported, particularly in the elderly, and in exceptional case may have been associated with fatalities.
Not known: Rash, pruritis, urticaria, purpura, alopecia and erythema and dermatitis bullous (Stevens-Johnson Syndrome or toxic epidermal necrolysis), photosensitivity reaction, angioedema
Common: Non-specific allergic reactions, bronchospasm, dyspnea
Not known: Hypersensitivity reactions have been reported following treatment with NSAIDs, anaphylactic shock, asthma, especially in subjects allergic to aspirin and other NSAIDs
Not known: Thrombocytopenia, anaemia due to bleeding may occur.
Not known: Vertigo, tinnitus and drowsiness.
Common: dizziness
Not known: Headaches
Not known: bladder pain, dysuria, and pollakiuria, hematuria may occur
After continuous, prolonged treatment with tiaprofenic acid in presence of urinary symptoms, urinary tract inflammation, have been observed.
NSAIDs have been reported to cause nephrotoxicity in various forms. As with other NSAIDs, isolated cases of tubulo-interstitial nephritis, nephrotic syndrome and renal failure have also been reported with tiaprofenic acid.
Not known: sodium and fluid retention (see section 4.4).
Not known: Hepatitis, jaundice.
Common: cystitis
Not known: bleeding time prolonged, abnormal liver function test
Other side-effects that have been reported with NSAIDS but not specifically with Surgam are:
Nervous system disorders: optic neuritis
Eye disorders: visual disturbances
Musculoskeletal and connective tissue disorders: paraesthesia
Psychiatric disorders: depression, confusion, hallucinations
General disorders and administration site conditions: fatigue, malaise
Blood and lymphatic system disorders: neutropenia, agranulocytosis, aplastic anaemia, haemolytic anaemia
Nervous disorders: reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4)
Vascular and cardiac disorders: oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
None known.
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