Indocid

'Indocid' Capsules 25 mg

'Indocid' Capsules 25 mg contain 25 mg of indomethacin.

'Indocid' Capsules 25 mg are ivory, opaque capsules marked 'MSD 25'.

Non-steroidal anti-inflammatory agent indicated for the active stages of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute musculoskeletal disorders, degenerative joint disease of the hip, low-back pain, and acute gouty arthritis.

Also indicated in inflammation, pain and oedema following orthopaedic procedures; and the treatment of pain and associated symptoms of primary dysmenorrhoea.

The dosage of 'Indocid' should be carefully adjusted to suit the needs of the individual patient.

In order to reduce the possibility of gastro-intestinal disturbances, 'Indocid' Capsules should always be taken with food or an antacid.

In chronic conditions, starting therapy with a low dosage, increasing this gradually as necessary, and continuing a trial of therapy for an adequate period (in some cases, up to one month) will give the best results with a minimum of unwanted reactions. The recommended oral dosage range is 50 mg to 200 mg daily in divided doses. Paediatric dosage not established.

Dosage in dysmenorrhoea: Up to 75 mg a day, starting with onset of cramps or bleeding, and continuing for as long as the symptoms usually last.

Dosage in acute gouty arthritis: 150 mg to 200 mg daily in divided doses until all symptoms and signs subside.

Use in the elderly: 'Indocid' should be used with particular care in older patients who are more prone to adverse reactions.

A history of peptic ulcer or active peptic ulcer; a recurrent history of gastro-intestinal lesions; in patients who have nasal polyps associated with angioneurotic oedema, who show sensitivity to indomethacin or any of the ingredients in this product, or who have experienced acute asthmatic attacks, urticaria or rhinitis as a result of therapy with aspirin or other non-steroidal anti-inflammatory drugs.

Safety for use in children has not been established.

<'Pregnancy and lactation').

Headache, sometimes accompanied by dizziness and light-headedness, may occur, usually early in treatment. Starting therapy with a low dosage and increasing it gradually will usually minimise the incidence of headache. These symptoms frequently disappear on continuing therapy or reducing the dosage, but if headache persists despite dosage reduction, 'Indocid' should be withdrawn. Patients should be warned that they may experience dizziness and, if they do, should not drive a car or undertake potentially dangerous activities needing alertness.

'Indocid' should be used cautiously in patients with a history of bronchial asthma and in patients with psychiatric disorders, epilepsy, or parkinsonism, as indomethacin may tend to aggravate these disorders.

NSAIDs should only be given with care to patients with a history of gastro-intestinal disease.

Gastro-intestinal disturbances may be minimised by giving 'Indocid' orally with food or an antacid. They usually disappear on reducing the dosage; if not, the risks of continuing therapy should be weighed against the possible benefits. If gastro-intestinal bleeding does occur, 'Indocid' should immediately be discontinued.

Single or multiple ulcerations, including perforation and haemorrhage of the oesophagus, stomach, duodenum or small or large intestine, have been reported to occur with 'Indocid'. Fatalities have been reported in some instances. Rarely, intestinal ulceration has been associated with stenosis and obstruction.

Gastro-intestinal bleeding without obvious ulcer formation and perforation of pre-existing sigmoid lesions (diverticulum, carcinoma, etc.) have occurred. Increased abdominal pain in ulcerative colitis patients or the development of ulcerative colitis and regional ileitis have been reported to occur rarely.

Fluid retention and peripheral oedema have been observed in some patients taking 'Indocid'. 'Indocid' should therefore be used with caution in patients with cardiac dysfunction, hypertension or other conditions predisposing to fluid retention.

'Indocid' may mask the signs and symptoms of infection. 'Indocid' should be used with caution in patients with existing but controlled infection.

In patients with rheumatoid arthritis, eye changes may occur which may be related to the underlying disease or to the therapy. Therefore, in chronic rheumatoid disease, ophthalmological examinations at periodic intervals are recommended. Discontinue therapy if eye changes are observed.

Patients should be periodically observed to allow early detection of any unwanted effects on peripheral blood (anaemia), liver function, or gastro-intestinal tract.

'Indocid' can inhibit platelet aggregation. This effect usually disappears within 24 hours of discontinuing 'Indocid'. Bleeding time is prolonged (but within normal range) in normal adults. Because this effect may be exaggerated in patients with underlying haemostatic defects, 'Indocid' should be used cautiously in patients with coagulation defects.

As with other non-steroidal anti-inflammatory drugs, there have been reports of acute interstitial nephritis with haematuria, proteinuria, and occasionally nephrotic syndrome in patients receiving long-term administration of indomethacin.

In patients with reduced renal blood flow where renal prostaglandins play a major role in maintaining renal perfusion, administration of a non-steroidal anti-inflammatory agent may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with renal or hepatic dysfunction, diabetes mellitus, advanced age, extracellular volume depletion, congestive heart failure, sepsis, or concomitant use of any nephrotoxic drug. A non-steroidal anti-inflammatory drug should be given with caution and renal function should be monitored in any patient who may have reduced renal reserve. Discontinuation of non-steroidal anti-inflammatory therapy is usually followed by recovery to the pretreatment state.

Increases in plasma potassium concentration, including hyperkalaemia, have been reported, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninaemic-hypoaldosteronism state (see 4.5 'Interaction with other medicaments and other forms of interaction').

Since 'Indocid' is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored; a lower daily dosage should be used to avoid excessive drug accumulation.

Patients should be warned that they may experience dizziness, drowsiness, visual disturbances or headaches and if they do, should not drive or undertake activities requiring alertness.

CNS reactions - headaches, dizziness, light-headedness, depression, vertigo, and fatigue (including malaise and listlessness). Reactions reported infrequently include mental confusion, anxiety, syncope, drowsiness, convulsions, coma, peripheral neuropathy, muscle weakness, involuntary muscle movements, insomnia, psychiatric disturbances such as hallucinations, depersonalisation; and, rarely, paraesthesia, dysarthria, aggravation of epilepsy and Parkinsonism. These are often transient and disappear frequently with continued treatment or with reduced dosage. However, occasionally, severe reactions require stopping therapy.

Gastro-intestinal - the more frequent reactions are nausea, anorexia, vomiting, epigastric distress, abdominal pain, constipation, and diarrhoea. Others which may develop are ulceration - single or multiple - of oesophagus, stomach, duodenum or small or large intestine, including perforation and haemorrhage with a few fatalities having been reported; gastro-intestinal tract bleeding without obvious ulcer formation; and increased abdominal pain when used in patients with pre-existing ulcerative colitis. Reactions occurring infrequently are stomatitis; gastritis; flatulence; bleeding from the sigmoid colon - occult or from a diverticulum - and perforation of pre-existing sigmoid lesions (diverticula, carcinoma). Rarely, intestinal strictures (diaphragms) and intestinal ulceration followed by stenosis and obstruction has been reported. With suppositories, tenesmus and irritation of the rectal mucosa have occasionally been reported. Pancreatitis has been reported with an unknown frequency. Other gastro-intestinal side effects which may or may not be caused by indomethacin include: ulcerative colitis and regional ileitis.

Hepatic - rarely, hepatitis and jaundice. (Some fatalities reported.)

Cardiovascular/Renal - oedema, increased blood pressure, tachycardia, chest pain, arrhythmia, palpitation, hypotension, congestive heart failure, blood urea elevation, and haematuria (all infrequent).

Dermatological/Hypersensitivity - pruritus, urticaria, angioneurotic oedema, angiitis, erythema nodosum, skin rash and photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, loss of hair, rapid fall in blood pressure resembling a shock-like state, acute anaphylaxis, acute respiratory distress including sudden dyspnoea, asthma and pulmonary oedema (all infrequent). Bronchospasm may be precipitated in patients suffering from, or with a history of, bronchial asthma or allergic disease.

Haematological - infrequently, blood dyscrasias may occur, including leucopenia, petechiae or ecchymosis, purpura, aplastic and haemolytic anaemia, agranulocytosis, bone-marrow depression, disseminated intravascular coagulation, and particularly thrombocytopenia. Because some patients may develop anaemia secondary to obvious or occult gastro-intestinal bleeding, appropriate blood determinations are recommended.

Ocular - infrequently, blurred vision, diplopia, and orbital and peri-orbital pain. Corneal deposits and retinal disturbances, including those of the macula, have been reported in patients with rheumatoid arthritis on prolonged therapy, but similar changes may also be expected in patients with rheumatoid arthritis who have not received indomethacin.

Aural - tinnitus, hearing disturbances (rarely deafness).

Genito-urinary - proteinuria, nephrotic syndrome, interstitial nephritis, and renal insufficiency including renal failure (all rare).

Miscellaneous - vaginal bleeding, hyperglycaemia, glycosuria, hyperkalaemia, flushing and sweating, epistaxis, breast changes including enlargement and tenderness, gynaecomastia, and ulcerative stomatitis (all rare).

Laboratory tests

Borderline elevations of one or more liver tests may occur, and significant elevations of ALT (SGPT) or AST (SGOT) have been seen in less than 1% of patients receiving therapy with non-steroidal anti-inflammatory drugs in controlled clinical trials. If abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations such as rash or eosinophilia occur, 'Indocid' should be stopped.

False-negative results in the dexamethasone suppression test (DST) in patients being treated with 'Indocid' have been reported. Thus, results of this test should be used with caution in these patients.

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

The following symptoms may be observed following overdosage: nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. There have been reports of paraesthesia, numbness, and convulsions.

Treatment is symptomatic and supportive. The stomach should be emptied as quickly as possible if the ingestion is recent and correction of severe electrolyte abnormalities may need to be considered.

If vomiting has not occurred spontaneously, the patient should be induced to vomit with syrup of ipecac. If the patient is unable to vomit, gastric lavage should be performed. Once the stomach has been emptied, 25 or 50 g of activated charcoal may be given. Depending on the condition of the patient, close medical observation and nursing care may be required. The patient should be followed for several days because gastro-intestinal ulceration and haemorrhage have been reported as adverse reactions of indomethacin. Use of antacids may be helpful.

The plasma elimination of indomethacin is biphasic with the half-life of the terminal plasma half-life phase between 2.6 and 11.2 hours.

Indomethacin has anti-inflammatory, antipyretic, and analgesic effects, it is an inhibitor of prostaglandin synthetase.

Indomethacin is rapidly and almost completely absorbed on oral administration, and peak plasma levels are reached in ½ to 2 hours. Absorption is slowed but remains virtually complete when taken with food. About 90% is bound to plasma proteins. It appears to undergo enterohepatic cycling. It is metabolised partly by O-demethylation, partly by N-deacylation, and unchanged drug and metabolites are partly conjugated with glucoronic acid, in man, it is excreted unchanged and as it metabolites in both urine and faeces.

No relevant information.

Colloidal silicon dioxide, lactose, liquid lecithin concentrate, and magnesium stearate E572. Capsule shells: gelatin, titanium dioxide E171 and yellow ferric oxide E172.

None known.

36 months

Do not store above 25°C. Keep in original package.

'Indocid' Capsules 25 mg: high density bottles with high density polyethylene cap-to-cap closures containing 100 or 500 capsules. Opaque 250 micron PVC blisters with 20 micron aluminium lid. Each blister contains 10 capsules. Each pack contains 90 capsules.

'Indocid' Capsules should always be taken with food or an antacid.

Aspen Pharma Trading Limited

3016 Lake Drive

Citywest Business Campus

Dublin 24

Ireland

PL 39699/012

Licence first granted 12 June 1981.

June 2016