Etofenamate

There is a particularly increased possibility of increasing the incidence of gastrointestinal disorders with concomitant use of etophenamate with corticosteroids or other non-steroidal anti-inflammatory drugs or alcohol.

Hepatic, kidney or cardiac impairment. If porphyria is likely, etofenamate should be given after weighed carefully the risks and benefits.

The action of various diuretics (eg furosemide, thiazides) and antihypertensives (eg β-blockers) can be reduced by the etofenamate.

Concomitant use of anti-uremic, probenecid and sulphopyrazone with etophenamate results in delayed elimination of etophenamate.

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 including diclofenac.

Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high dose (150mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with diclofenac after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, and smoking).

Particularly careful medical monitoring is necessary when administering etophenamate to patients with a history of bowel inflammation (ulcerative colitis, Crohn’s disease).

Etofenamate and some of its metabolites have been shown to cross the placenta in rats (oral and cutaneous) and rabbits (cutaneous). After 10, 30 and 100mg/kg BW per day (rabbits up to the 18th day of gestation) the concentrations in the placentas, uteri, foetuses, organs and bile decreased rapidly after stopping administration; they were below the per mille limit.

Elimination with the milk has been studied in goats and humans. After 65 mg/kg BW i.m., goats excreted 20-60 microg of etofenamate plus metabolites per litre of milk. After oral administration of 300 mg etofenamate the milk of lactating women contained no etofenamate but only main metabolite flufenamic acid. In total 1-14 microg flufenamic acid was excreted within 2 days. These concentrations have no practical meaning, since they are orders of magnitude below the therapeutic dose.

Not applicable.

The following undesirable effects have been reported through post-marketing use.

Undesirable effects listed below are grouped by MedDRA System Organ Classes and are ranked under heading of frequency, using the following convention, when applicable: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10, 000); not known (cannot be estimated from the available data).

Skin and subcutaneous tissue disorder

Rare: Contact dermatitis