Emflex Capsules

Each capsule contains Acemetacin 60mg

Gelatine capsule

Rheumatoid arthritis, osteoarthritis, low back pain, and post-operative pain and inflammation.

The recommended starting dose is 120mg/day in divided doses, increasing to 180mg/day in divided doses, depending on patient response.

For the treatment of elderly patients, adjustment of dosage is not normally required. However, non-steroidal anti-inflammatory drugs should be used with particular care in older patients who may be more prone to adverse reactions.

Emflex should be taken with food, milk or an antacid to reduce the possibility of gastro-intestinal disturbance.

Active peptic ulcer; history of recurrent ulceration; known hypersensitivity to acemetacin or indomethacin. Patients who have experienced asthma attacks, urticaria or acute rhinitis resulting from treatment with aspirin or non-steroidal anti-inflammatory drugs. Patients with nasal polyps associated with angioneurotic oedema. Safety in children is not established.

As rare instances of peptic ulceration have been reported administration should be closely supervised in patients with a history of upper gastrointestinal disease. Treatment should be discontinued if peptic ulceration or gastrointestinal bleeding occurs.

Inhibition of platelet aggregation may occur.

Aggravation of psychiatric disorders, epilepsy or parkinsonism may occur.

Signs and symptoms of infection may be masked.

Emflex should be used with caution in patients with reduced renal blood flow where renal perfusion may be maintained by prostaglandins. In patients at particular risk - renal or hepatic dysfunction, congestive heart failure, electrolyte or fluid imbalance, sepsis, concomitant use of nephrotoxic drugs, the dose should be kept as low as possible and renal function should be monitored.

Patients receiving long-term treatment should be periodically screened for renal and hepatic function and blood counts. Borderline elevation of renal and hepatic function test parameters may occur. If this persists or worsens, treatment should be stopped.

Eye changes may occur in chronic rheumatoid disease and patients should receive periodic ophthalmological examinations and therapy discontinued if changes occur.

Hyperkalaemia has been reported with use of indomethacin and this should be considered when administration with potassium sparing diuretics is proposed.

Emflex is highly protein bound and it may therefore be necessary to modify the dosage of other highly protein bound drugs e.g. anti-coagulants. As there is a possibility of either a pharmacokinetic or pharmacodynamic interaction with aspirin or other salicylates, diflusinal, probenecid, lithium, triamterene, ACE inhibitors, haloperidol and methotrexate, patients receiving such combinations should be carefully monitored and dosages adjusted as necessary. Non-steroidal anti-inflammatory drugs may reduce the anti-hypertensive effects of beta-blockers, although clinical studies showed no propensity for Emflex to antagonise the effects of propranolol. Likewise the reduction of diuretic effects of thiazides and frusemide may occur with non-steroidal anti-inflammatory drugs and this should be borne in mind when treating patients with compromised cardiac function or hypertension.

The safety of this product for use in human pregnancy and lactation has not been established. Animal reproduction studies do not provide reassurance regarding the lack of reproductive toxicity/ teratogenicity. Due to maternal toxicity, the studies were conducted at doses below the therapeutic dose or a very low multiple of the therapeutic dose. It should not therefore be used in pregnancy or lactation in women of childbearing age unless they are taking adequate contraceptive precautions.

The ability to drive a car or operate machinery may be affected.

The following side effects have been either reported with Emflex or could possibly occur as they are common to a number of NSAIDs:

Gastro-intestinal: Gastro-intestinal discomfort/pain, anorexia, nausea, vomiting, indigestion, diarrhoea and constipation, peptic ulceration, gastrointestinal perforation and haemorrhage.

Central Nervous System: Symptoms most frequently encountered are headache, dizziness, vertigo and insomnia. Rarely, confusion, depressed mood, irritability.

Hepatic: Occasional elevation of liver function test parameters without overt clinical symptomatology. Very rarely, symptoms of cholestasis.

Cardiovascular/renal: Rarely, oedema, chest pain, palpitations, blood urea elevation. NSAIDs have been reported to cause nephrotoxicity in various forms and their use can lead to interstitial nephritis, nephrotic syndrome and renal failure.

Dermatological/hypersensitivity: Pruritus, urticaria, erythema, skin rash, alopecia, angio-neurotic oedema and excessive sweating have been reported.

Haematological: Rarely, thrombocytopenia, leucopenia and reduced haemoglobin levels. Very rarely, reversible agranulocytosis, bone marrow depression.

Ocular/auditory: Infrequently, tinnitus, blurred vision and rarely, eye pain.

Symptomatic and supportive therapy is indicated. If ingestion is recent, vomiting should be induced or gastric lavage should be performed. Progress should be followed for several days as gastrointestinal ulceration and haemorrhage have been reported with overdosage of other NSAIDs. Antacids may be helpful.

Acemetacin is a glycolic acid ester of indomethacin and the pharmacological activity resulting from acemetacin administration in man is derived from the presence of both acemetacin and indomethacin. The precise pharmacological mode of action of acemetacin is not known. However, unlike other NSAIDs, acemetacin is only a relatively weak inhibitor of prostaglandin synthetase.

Prostaglandins are known to have an antisecretory and cytoprotective effect on the gastric mucosa. Acemetacin shows activity in many of the established in vitro tests of anti-inflammatory activity, including inhibition of the release of a number of mediators of inflammation.

Acemetacin is well absorbed after oral administration. Its major metabolite is indomethacin which, after repeated administration, is present at levels in excess of those of acemetacin. Acemetacin is bound to plasma protein to a slightly lesser extent than indomethacin and has a relatively short plasma elimination half-life. It is eliminated by both hepatic and renal mechanisms. The pharmacokinetics appear to be linear at recommended therapeutic doses, unaffected by moderate renal or hepatic impairment, and unchanged in the elderly.

Emflex Capsules show similar toxicity to other non-steroidal anti-inflammatory drugs.

Gelatine capsule (colourings: Ferric oxide red E172, Ferric oxide yellow E172 and titanium dioxide E171), lactose, magnesium stearate, silicon dioxide, talc and sodium dodecylsulphate.

None known.

Five years

Store below 25 degree C.

White polypropylene bottles with polypropylene screw caps.

Pack sizes: 90, 56, 60 and 30 capsules.

PVC/PVDC foil blister packs in cartons:

Pack sizes: 90, 60, 56, 30, 10, and 6 capsules

To be taken with food.

Merck Serono Ltd

Bedfont Cross, Stanwell Road

Feltham, Middlesex

TW14 8NX, UK

PL 11648/0083

26 November 1990/25 March 1996

25 September 2009

POM