Mobiflex Tablets 20mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Mobiflex Tablets 20mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 20mg tenoxicam For excipients, see 6.1
3. PHARMACEUTICAL FORM
Film-coated tablet.
A greyish yellow, film-coated oval tablet imprinted “20” on one face with a break line on the other.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Mobiflex is indicated for the relief of pain and inflammation in osteoarthritis and rheumatoid arthritis. It is also indicated for the short term management of acute musculoskeletal disorders including strains, sprains and other soft-tissue injuries. IV, IM tenoxicam is also available for these indications in those patients considered unable to take oral tenoxicam
4.2 Posology and method of administration
For oral administration.
To be taken preferably with or after food.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Adults
A single daily dose of 20mg Mobiflex should be taken at the same time each day. Mobiflex Tablets are for oral administration with water or other fluid.
Higher doses should be avoided as they do not usually achieve significantly greater therapeutic effect but may be associated with a higher risk of adverse events.
In acute musculoskeletal disorders treatment should not normally be required for more than 7 days, but in severe cases it may be continued up to a maximum of 14 days.
Elderly
The elderly are at increased risk of the serious consequences of adverse reactions. They are also more likely to be receiving concomitant medication or to have impaired hepatic, renal or cardiovascular function. If an NSAID is considered necessary the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored for GI bleeding for 4 weeks following initiation of NSAID therapy.
Children
There are insufficient data to make a recommendation for administration of Mobiflex to children.
Use in renal and hepatic insufficiency
|
Creatinine clearance |
Dosage regimen |
|
Greater than 25ml/min |
Usual dosage but monitor patients carefully (see section 4.4) |
|
Less than 25ml/min |
Insufficient data to make dosage recommendations |
Because of the high plasma protein-binding of tenoxicam, caution is required when plasma albumin concentrations are markedly reduced (e.g. in nephrotic syndrome) or when bilirubin concentrations are high.
There is insufficient information to make dosage recommendations for Mobiflex in patients with pre-existing hepatic impairment.
4.3 Contraindications
Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
History of gastro-intestinal bleeding (melaena, haematemesis), perforation related to previous NSAID therapy or severe gastritis.
Hypersensitivity to tenoxicam or to any of the excipients.
NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (symptoms of asthma, rhinitis, angio-oedema or urticaria) in response to ibuprofen, aspirin or other non-steroidal antiinflammatory drugs.
Severe renal, hepatic or heart failure (see section 4.4).
Mobiflex is contraindicated during the last trimester of pregnancy (see section 4.6).
4.4 Special warnings and precautions for use
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).
The use of Mobiflex with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).
Gastrointestinal bleeding, ulceration and perforation
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime 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 or anti-platelet agents such as aspirin (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving tenoxicam, 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 these conditions may be exacerbated (see section 4.8).
SLE and mixed connective tissue disease:
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).
Dermatological:
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). Patients appear to be at highest risk for 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. Mobiflex should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Cardiovascular, renal and hepatic impairment
In rare cases, non-steroidal anti-inflammatory drugs may cause interstitial nephritis, glomerulonephritis, papillary necrosis and the nephrotic syndrome. Such agents inhibit the synthesis of renal prostaglandin which plays a supportive role in the maintenance of renal perfusion in patients whose renal blood flow and blood volume are decreased. In these patients, administration of a non-steroidal anti-inflammatory drug may precipitate overt renal decompensation, which returns to the pre-treatment state upon withdrawal of the drug. Patients at greatest risk of such a reaction are those with pre-existing renal disease (including diabetics with impaired renal function), nephrotic syndrome, volume depletion, hepatic disease, congestive cardiac failure, patients receiving concomitant therapy with diuretics or potentially nephrotoxic drugs and the elderly. Such patients should have their renal, hepatic and cardiac functions carefully monitored (see also section 4.3), and the dose should be kept as low as possible in patients with renal, hepatic or cardiac impairment.
Respiratory disorders
Caution is required if administered to patients suffering from, or with a previous history of bronchial asthma since ibuprofen has been reported to cause bronchospasm in such patients.
Occasional elevations of serum transaminases or other indicators of liver function have been reported. In most cases these have been small and transient increases above the normal range. If the abnormality is significant or persistent, Mobiflex should be stopped and follow-up tests carried out. Particular care is required in patients with pre-existing hepatic disease.
Mobiflex reduces platelet aggregation and may prolong bleeding time. This should be borne in mind for patients who undergo major surgery (e.g. joint replacement) and when bleeding time needs to be determined.
Elderly
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2). Particular care should be taken to regularly monitor elderly patients to detect possible interactions with concomitant therapy and to review renal, hepatic and cardiovascular function which may be potentially influenced by non-steroidal anti-inflammatory drugs.
Ocular effects
Adverse eye findings have been reported with non-steroidal anti-inflammatory drugs, therefore it is recommended that patients who develop visual disturbances during treatment with Mobiflex have ophthalmic evaluation.
Cardiovascular and cerebrovascular effects
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 tenoxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with tenoxicam 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).
Impaired female fertility
The use of Mobiflex may impair 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 Mobiflex should be considered.
4.5 Interaction with other medicaments and other forms of interaction
Other analgesics including cyclooxygenase-2 selective inhibitors
Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.4).
Acetylsalicylate and salicylates
Salicylates can displace tenoxicam from protein-binding sites and so increase the clearance and volume of distribution of Mobiflex. Concurrent treatment with salicylates should therefore be avoided because of the increased risk of adverse reactions (particularly gastro-intestinal).
Antacids and H2-receptor antagonists
Antacids may reduce the rate, but not the extent, of absorption of Mobiflex. The differences are not likely to be of clinical significance. No interaction has been found with concomitantly administered cimetidine.
Anticoagulants
Tenoxicam is highly bound to serum albumin, and can, as with all NSAIDs, enhance the effects of anticoagulants such as warfarin (see section 4.4). Close monitoring of the effects of anticoagulants and oral glycaemic agents is advised, especially during the initial stages of treatment with Mobiflex. No interaction with digoxin has been observed. In healthy subjects no clinically relevant interaction between Mobiflex and low molecular weight heparin has been observed.
Anti-hypertensives
Mobiflex and other NSAIDs can reduce the effects of anti-hypertensive drugs. Cardiac glycosides
NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides.
Ciclosporin
As with all NSAIDs caution is advised when ciclosporin is co-administered because of the increased risk of nephrotoxicity.
Quinolone antibiotics
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.
Lithium
Non-steroidal anti-inflammatory drugs have been reported to decrease elimination of lithium. If tenoxicam is prescribed for a patient receiving lithium therapy, the frequency of lithium monitoring should be increased, the patient warned to maintain fluid intake and to be aware of symptoms of lithium intoxication.
Diuretics
Non-steroidal anti-inflammatory drugs may cause sodium, potassium and fluid retention and may interfere with the natriuretic action of diuretic agents, which can increase the risk of nephrotoxicity of NSAIDs. These properties should be kept in mind when treating patients with compromised cardiac function or hypertension since they may be responsible for a worsening of those conditions.
Methotrexate
Caution is advised where methotrexate is given concurrently because of possible enhancement of its toxicity, since NSAIDs have been reported to decrease elimination of methotrexate.
Mifepristone
NSAIDs should not be used for 8 - 12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.
Corticosteroids
As with all NSAIDs, caution should be taken when co-administering corticosteroids because of the increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs)
There is an increased risk of gastrointestinal bleeding (see section 4.4) when anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs.
Tacrolimus
There is a possible risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine
There is an 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.
Gold/penicillamine
No clinically relevant interaction was found in small numbers of patients receiving treatment with penicillamine or parenteral gold.
4.6 Pregnancy and lactation
Pregnancy
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 sysnthesis 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, tenoxicam should not be given unless clearly necessary. If tenoxicam 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-hydramniosis;
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 low doses.
- inhibition of uterine contractions resulting in delayed or prolonged
labour.
Consequently, tenoxicam is contraindicated during the third trimester of pregnancy.
Lactation
In the limited studies available so far, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.
See section 4.4 regarding female fertility.
4.7 Effects on ability to drive and use machines
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
4.8 Undesirable effects
For most patients, any side-effects are transient and resolve without discontinuation of treatment.
The most common side-effects relate to the gastro-intestinal tract. They include dyspepsia, nausea, abdominal pain and discomfort, constipation, diarrhoea, flatulence, indigestion, epigastric distress, stomatitis and anorexia. As with other non-steroidal anti-inflammatory drugs, there is a risk of peptic ulceration and gastro-intestinal bleeding, both of which have been reported with Mobiflex. Should this occur, Mobiflex is to be discontinued immediately and appropriate treatment instituted.
As with other non-steroidal anti-inflammatory drugs, peripheral oedema of mild or moderate degree and without clinical sequelae occurred in a small proportion of patients and the possibility of precipitating congestive cardiac failure in elderly patients or those with compromised cardiac function should therefore be borne in mind.
Central nervous system reactions of headache and dizziness have been reported in a small number of patients. Somnolence, insomnia, depression, nervousness, dream abnormalities, mental confusion, paraesthesias and vertigo have been reported rarely.
Hypersensitivity reactions have been reported following treatment with NSAIDs, these include:
a) Non specific allergic reactions and anaphylaxis
b) Respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea
c) Skin reactions of rash, angiodema and pruritus have been reported. Nail disorders, alopecia, erythema, urticaria and photosensitivity reactions have been reported rarely.
As with other non-steroidal anti-inflammatory drugs, Lyell's syndrome and Stevens-Johnson syndrome may develop in rare instances. Vesiculo-bullous reactions and vasculitis have also been reported rarely. Reversible elevations of blood urea nitrogen and creatinine have been reported (see Special warnings and special precautions for use).
Decreases in haemoglobin, unrelated to gastro-intestinal bleeding, have occurred. Anaemia, aplastic anaemia, haemolytic anaemia, thrombocytopenia and nonthrombocytopenic purpura, leucopenia and eosinophilia have been reported. Epistaxis has been reported infrequently. Rare cases of agranulocytosis have been reported.
As with most other non-steroidal anti-inflammatory drugs, changes in various liver function parameters have been observed. Some patients may develop raised serum transaminase levels during treatment. Although such reactions are rare, if abnormal liver function tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur (e.g. eosinophilia, rash), Mobiflex should be discontinued. Hepatitis jaundice have also been reported.
Palpitations and dyspnoea have also been reported rarely. Metabolic abnormalities, such as weight decrease or increase and hyperglycaemia, have occurred rarely.
Swollen eyes, blurred vision and eye irritation have been reported. Ophthalmoscopy and slit-lamp examination have revealed no evidence of ocular changes. Malaise and tinnitus may occur.
Nephrotoxicity has been reported in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.
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 of suspected adverse reactions
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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
There is no reported experience of serious overdosage with Mobiflex. No specific measures are available; administration of H2-antagonist drugs may be of benefit. Gastric lavage should be carried out as soon as possible after drug ingestion and the patient should be closely observed and general supportive measures taken as necessary.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Mobiflex is a non-steroidal anti-inflammatory drug which has marked anti-inflammatory and analgesic activity and some antipyretic activity. As with other non-steroidal antiinflammatory drugs, the precise mode of action is unknown, though it is probably multifactorial, involving inhibition of prostaglandin biosynthesis and reduction of leucocyte accumulation at the inflammatory site.
5.2 Pharmacokinetic properties
Mobiflex is long-acting; a single daily dose is effective.
After oral administration, Mobiflex is rapidly and completely absorbed as unchanged drug. Concomitant food reduces the rate, but not the extent, of absorption of Mobiflex. Tenoxicam penetrates well into synovial fluid to give concentrations approximately half those in plasma. The mean plasma elimination half-life is approximately 72 hours.
With the recommended dosage regimen of 20mg once daily, steady-state plasma concentrations are reached within 10 -15 days, with no unexpected accumulation.
Mobiflex is strongly bound to plasma proteins.
Mobiflex is cleared from the body almost exclusively by metabolism. Approximately two-thirds of the administered dose is excreted in the urine, mainly as the pharmacologically inactive 5-hydroxypyridyl metabolite, and the remainder in the bile, much of it as glucuronide conjugates of hydroxy-metabolites.
No age-specific changes in the pharmacokinetics of Mobiflex have been found although inter-individual variation tends to be higher in elderly persons.
5.3 Preclinical safety data
None Stated.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose
maize starch magnesium stearate talc
hypromellose titanium dioxide E171 yellow iron oxide E172.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
5 years
6.4 Special precautions for storage
Do not store above 30°C.
6.5 Nature and contents of container
PVC/Aluminium foil blister pack containing 30 tablets.
6.6 Special precautions for disposal
No special requirements.
7. MARKETING AUTHORISATION HOLDER
Meda Pharmaceuticals Ltd Skyway House Parsonage Road Takeley
Bishop’s Stortford CM22 6PU
8 MARKETING AUTHORISATION NUMBER(S)
PL 15142/0112
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10 August 1988 / 01 December 1998
10 DATE OF REVISION OF THE TEXT
26/02/2014