1. Name Of The Medicinal Product
Mobiflex Tablets 20mg
2. Qualitative And Quantitative Composition
Each tablet contains 20mg tenoxicam
For a full list of excipients, see section 6.1
3. Pharmaceutical Form
Film-coated tablet.
A greyish yellow, film-coated oval tablet imprinted “Roche” 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
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 orally, 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
As with other non-steroidal anti-inflammatory drugs, Mobiflex should be used with special caution in elderly patients since they may be less able to tolerate side-effects than younger patients. They are also more likely to be receiving concomitant medication or to have impaired hepatic, renal or cardiovascular function. The lowest dose should be used in elderly patients and 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
|
|
|
|
|
|
Because of the high plasma protein-binding of tenoxicam, caution is required when plasma albumin concentrations are markedly reduced (e.g. in nephritic 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
1. Active peptic ulceration and a past history of peptic ulceration, gastrointestinal bleeding (melaena, haematemesis) or severe gastritis.
2. Hypersensitivity to Mobiflex. Mobiflex should also be avoided in cases where the patient has suffered a hypersensitivity reaction (symptoms of asthma, rhinitis, angioedema or urticaria) to other nonsteroidal anti-inflammatory drugs, including aspirin, as the potential exists for cross-sensitivity to Mobiflex.
3. Severe heart failure
4.4 Special Warnings And Precautions For Use
NSAIDs should only be given with care to patients with a history of gastrointestinal disease.
Any patient being treated with Mobiflex who presents with symptoms of gastrointestinal disease should be closely monitored. If peptic ulceration or gastro-intestinal bleeding occurs, Mobiflex should be withdrawn immediately.
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), nephritic syndrome, volume depletion, hepatic disease, congestive cardiac failure and those patients receiving concomitant therapy with diuretics or potentially nephrotoxic drugs. Such patients should have their renal, hepatic and cardiac functions carefully monitored, and the dose should be kept as low as possible in patients with renal, hepatic or cardiac impairment. NSAIDs should be given with care to patients with a history of heart failure or hypertension since oedema has been reported in association with ibuprofen administration.
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.
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 nonsteroidal anti-inflammatory drugs.
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.
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).
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).
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
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. In healthy subjects no clinically relevant interaction between Mobiflex and low molecular weight heparin has been observed.
Tenoxicam is highly bound to serum albumin, and can, as with all NSAIDs, enhance the anticoagulant effect of warfarin and other anticoagulants. 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.
Mobiflex and other NSAIDs can reduce the effects of anti-hypertensive drugs. NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides.
As with all NSAIDs caution is advised when cyclosporin is co-administered because of the increased risk of nephrotoxicity.
Concomitant use of two or more NSAIDs should be avoided.
Patients taking quinolones may have an increased risk of developing convulsions.
Salicylates can displace tenoxicam from protein-binding sites and so increase the clearance and volume of distribution of Mobiflex. Concurrent treatment with salicylates or other non-steroidal anti-inflammatory drugs should therefore be avoided because of the increased risk of adverse reactions (particularly gastro-intestinal).
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.
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.
No clinically relevant interaction was found in small numbers of patients receiving treatment with penicillamine or parenteral gold.
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.
NSAIDs should not be used for 8 – 12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.
As with all NSAIDs, caution should be taken when co-administering corticosteroids because of the increased risk of GI bleeding.
4.6 Pregnancy And Lactation
The safety of Mobiflex during pregnancy and lactation has not been established and the drug should therefore not be given in these conditions. Congenital abnormalities have been reported in association with ibuprofen administration in man; however, these are low in frequency and do not appear to follow any discernible pattern.
Although no teratogenic effects were seen in animal studies, Mobiflex, like other non-steroidal anti-inflammatory drugs, is associated with prolonged and delayed parturition and an adverse influence on neonatal viability when administered to animals in late pregnancy. Non-steroidal anti-inflammatory agents are also known to induce closure of the ductus arteriosus in infants, therefore use in late pregnancy should be particularly avoided.
In the limited studies available so far, ibuprofen appears in the breast milk in very low concentrations and is unlikely to adversely affect the breast fed infant.
No information is available on penetration of Mobiflex into milk in humans; animal studies indicate that significant levels may be achieved.
4.7 Effects On Ability To Drive And Use Machines
None
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 non-thrombocytopenic 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).
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 anti-inflammatory 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 hydroxymetabolites.
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 And Other Handling
No special requirements.
7. Marketing Authorisation Holder
Meda Pharmaceuticals Ltd
249 West George Street
Glasgow
G2 4RB
Trading as:
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
10th August 1988/11th November 2009
10. Date Of Revision Of The Text
15th December 2009
No comments:
Post a Comment