Lodine SR

Lodine SR Tablets 600mg.

Etodolac 600mg.

Lodine SR Tablets are for oral administration. Each tablet is capsular, oval shaped light grey film coated, impressed on one side with Lodine SR600 and contains etodolac 600mg in a sustained release formulation.

Lodine (etodolac) is indicated for acute or long-term use in rheumatoid arthritis and osteoarthritis.

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

Adults: Lodine SR Tablets 600mg

One tablet daily, swallowed whole with a tumblerful of water. If a lower dose is sufficient, conventional Lodine capsules or tablets may be used.

The safety of doses in excess of 600mg per day has not been established.

No occurrence of tolerance or tachyphylaxis has been reported.

Elderly: No change in initial dosage is generally required in the elderly (see precautions).

The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.

Children: Not recommended.

Lodine should not be used in patients who have previously shown hypersensitivity to etodolac or to any of the excipients.

Lodine should not be used in patients with severe heart failure.

Lodine should not be used in patients with active or history of recurrent peptic ulceration or a history of peptic ulcer disease (with two or more distinct episodes of proven ulceration or bleeding).

NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis angioedema or urticaria) during therapy with ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs.

Severe heart failure, hepatic failure and renal failure

During the last trimester of pregnancy

History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

).

The use of Lodine with concomitant NSAIDs including cyclooxygenase-2-selective inhibitors should be avoided

Elderly:

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal

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 Lodine.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Lodine 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).

Respiratory disorders:

Caution is required if Lodine is administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.

Cardiovascular, Renal and Hepatic Impairment:

). Caution is required since the use of NSAIDs may result in a dose dependent reduction in prostaglandin formation and precipitate renal failure. The dose should be kept as low as possible. However, impairment of renal or hepatic functions due to other causes may alter drug metabolism; patients receiving concomitant long term therapy, especially the elderly, should be observed for potential side effects and their drug doses adjusted as needed, or the drug discontinued.

Gastrointestinal bleeding, ulceration and perforation:

Serious gastrointestinal adverse effects such as bleeding, ulceration and perforation, which can be fatal, has been reported and can occur at any time with or without warning symptoms in patients treated with NSAIDs or a previous history of serious GI events. If any sign of gastrointestinal bleeding occurs, Lodine should be stopped immediately.

Platelets:

Although non-steroidal anti-inflammatory drugs do not have the same direct effects on platelets as does aspirin, all drugs which inhibit the biosynthesis of prostaglandins may interfere, to some extent, with platelet function.)

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.

When GI bleeding or ulceration occurs in patients receiving Etodolac, 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

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematous (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.

Dermalogical:

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. 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. Lodine should be discontinued at the first appearance of the skin rash, mucosal lesions, or any other sign of hypersensitivity.

Impaired female fertility:

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

Lodine can cause dizziness, drowsiness, fatigue or abnormal vision. Patients need to be aware of how they react to this medicine before driving or operating machines.

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) .

Gastrointestinal: Reported side effects include nausea, epigastric pain, diarrhoea, indigestion, heartburn, flatulence, abdominal pain, constipation, vomiting, ulcerative stomatitis, dyspepsia, haematemesis, melaena, rectal bleeding, exacerbation of colitis, vasculitis, headaches, dizziness, abnormal vision, pyrexia, drowsiness, tinnitus, rash, pruritus, fatigue, depression, insomnia, confusion, paraesthesia, tremor, weakness/malaise, dyspnoea, palpitations, bilirubinuria, hepatic function abnormalities and jaundice, urinary frequency, dysuria, angioedema, anaphylactoid reaction, photosensitivity, urticaria and Stevens-Johnson syndrome and Crohn's disease have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consists of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Cardiovascular and cerebrovascular:

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).

Renal: Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

Hepatic: abnormal liver function, hepatitis and jaundice

Neurological and special senses: Visual disturbances, optic neuritis, headaches, paraethesia, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematous, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomitiong, fever or disorientation , depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Haematological: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Dermatological: Bullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity.

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, Website: www.mhra.gov.uk/yellowcard.

(a) Symptoms

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointaestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, occasionally convulsions. In cases of significant poisoning acute renal failure and liver damage are possible.

(b) Therapeutic measure

Patients should be treated symptomatically as required.

Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of indigestion of a potentially life-threatening overdose.

Good urine output should be ensured.

Renal and liver function should be closely montored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam.

Other measures may be indicated by the patient's clinical condition.

The standard practices of gastric lavage, activated charcoal administration and general supportive therapy should be undertaken.

Inhibition of prostaglandin synthesis and COX-2 selectivity: All non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit the formation of prostaglandins. It is this action which is responsible both for their therapeutic effects and some of their side-effects. The inhibition of prostaglandin synthesis observed with etodolac differs from that of other NSAIDs. In an animal model at an established anti-inflammatory dose, cytoprotective PGE concentration in the gastric mucosa have been shown to be reduced to a lesser degree and for a shorter period than other NSAIDs. This finding is consistent with subsequent in-vitro studies which have found etodolac to be selective for induced cyclo-oxygenase 2 (COX-2, associated with inflammation) over COX-1 (cytoprotective).

Furthermore, studies in human cell models have confirmed that etodolac is selective for the inhibition of COX-2.

The clinical benefit of preferential COX-2 inhibition over COX-1 has yet to be proven.

Anti-inflammatory effects: Experiments have shown etodolac to have marked anti-inflammatory activity, being more potent than several clinically established NSAIDs.

In man, etodolac is well absorbed following oral administration.

Etodolac is highly bound to serum proteins.

The elimination half-life averages seven hours in man. The primary route of excretion is in the urine, mostly in the form of metabolites.

In subjects receiving daily doses of Lodine SR 400mg or 600mg to steady state levels over a three day period, the peak plasma concentrations were 7.5µg/ml at 7.9 hours and 11.9µg/ml at 7.8 hours.

Nothing of note to the prescriber.

Hydroxypropyl Methylcellulose USP

Dibasic Sodium Phosphate USP

Ethylcellulose USNF

Lactose Ph Eur

Magnesium Stearate Ph Eur

Hydroxypropyl Cellulose

Macrogol 400

Macrogol 6000

Colourings - Titanium Dioxide (E171), Iron Oxide (E172)

None.

Lodine SR Tablets may be stored for up to 3 years.

Store at room temperature, below 25^oC.

Vinyl Aclar or PVdC/PVC/Aluminium foil blister packs of 2, 28 or 30 tablets.

HDPE bottle with child resistant closures of 28 or 30 tablets.

Polypropylene securitainers with polyethylene caps of 28 or 30 tablets.

None.

Almirall, S.A.

Ronda General Mitre 151

08022 Barcelona

Spain

PL 16973/0021

1 September 2000

July 2014