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INDOMETACIN CAPSULES 50MG

Active substance(s): INDOMETACIN

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Indometacin capsules 50mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Indometacin Ph. Eur. 50 mg
Also contains lactose. For full list of excipients see 6.1.

3

PHARMACEUTICAL FORM
Capsule

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Indometacin has Non-steroidal analgesic and anti-inflammatory properties.
It is indicated for the following conditions:


active stages of rheumatoid arthritis, osteo-arthritis, ankylosing spondylitis
degenerative joint disease of the hip, acute musculoskeletal disorders (such as
bursitis, tendinitis, synovitis, tenosynovitis and capsulitis), gout and lumbago.



inflammation, pain and oedema following orthopaedic procedures.



treatment of pain and associated symptoms of primary dysmenorrhoea.

Since indometacin is not a simple analgesic, its use should be limited to the above
conditions.

4.2

Posology and method of administration
Method of administration:
For oral administration.
To be taken preferably with or after food.

Posology:
The dosage should be carefully adjusted according to the needs of the individual
patient.
Indometacin capsules should always be given with or after food, milk or an antacid to
lessen the chance of gastro-intestinal disturbance, and in chronic conditions start the
therapy with a low dosage, increasing as required.
Undesirable effects may be minimised by using the lowest effective dose for the
shortest duration necessary to control symptoms (see section 4.4).
Adults: The recommended oral dosage range is 50-200 mg daily.
Chronic rheumatic disorders, including chronic rheumatoid arthritis, osteoarthritis and
ankylosing spondylitis:
Initial: 25 mg two to three times daily with food.
Adjustment: Where necessary, if response is inadequate, by a gradual increase of 25
mg per day. Adequate response is usually achieved with not more than 150 mg per
day, rarely more than 200 mg daily
Acute rheumatoid arthritis: Initial: 25 mg two or three times a day.
Sudden flare up of chronic condition: Increase if necessary, by 25 mg a day until a
satisfactory response is obtained, or a dosage of 150-200 mg a day is reached. (If this
causes any adverse effects dosage should be reduced to a tolerable level for two or
three days and then carefully increased, as tolerated).
Acute musculo-skeletal disorders: initially 50 mg two or three times daily, according
to severity for 10-14 days. Normally 150 mg daily, rarely 200 mg daily.
Lumbago: 50 mg two or three times daily, according to severity. Duration of
treatment is not normally more than five days, but may be continued for up to 10
days.
Gout: 50 mg three to four times daily until all signs and symptoms have subsided.
Following orthopaedic procedures: Normally 100-150 mg daily in divided doses
until symptoms subside.
Dysmenorrhoea: Up to 75 mg daily, taken at the onset of discomfort and continued
for a few days while symptoms persist.
Additional considerations: In conditions where patients require a dosage of 150-200
mg a day, it is often possible to reduce this gradually to a maintenance level of 75100 mg a day. In patients with persistent night pain and/or morning stiffness, a dose
of up to 100 mg at bed time may be helpful in affording relief. It is rarely necessary to
exceed a dosage of 200 mg a day.
Elderly: 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 gastro-intestinal bleeding during NSAID therapy.
Children: Safety for use in children has not been established.

4.3

Contraindications
NSAIDs are contra-indicated in patients who have:


previously shown hypersensitivity reactions (e.g. asthma. rhinitis, angioedema or
urticaria) in response to indometacin, ibuprofen aspirin or other non-steroidal

anti-inflammatory drugs. Hypersensitivity to indometacin or to any of the
excipients


active, or history of recurrent peptic ulceration / haemorrhage (two or more
distinct episodes of proven ulceration or bleeding)



history of gastro-intestinal bleeding or perforation, related to previous NSAIDs
therapy



nasal polyps



severe hepatic, renal and cardiac failure (See section 4.4 – Special warnings and
precautions for use).



during the last trimester of pregnancy (See section 4.6 – Pregnancy and lactation).

Safety for use in children has not been established.

4.4

Special warnings and precautions for use
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).
The use of indometacin with concomitant NSAIDs including cyclooxygenase 2 specific
inhibitors should be avoided (See section 4.5 Interactions).
Patients should be carefully observed to detect any unusual manifestations of drug
sensitivity.
Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs especially
gastrointestinal bleeding and perforation, which may be fatal (See section 4.2 –
Posology and administration).
Respiratory disorders:
Caution is required if administered to patients suffering from, or with a previous
history of, bronchial asthma since NSAIDs have been reported to precipitate
bronchospasm in these patients.
Headache:
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 minimise the incidence of headache. These symptoms frequently
disappear on continuing therapy or reducing the dosage, but if headache persists
despite dosage reduction, indometacin should be withdrawn.
Indometacin should be used cautiously in patients with impaired renal function,
bleeding disorders, psychiatric disorders, epilepsy or Parkinsonism, as it may tend to
aggravate these disorders.
Gastrointestinal bleeding, ulceration and perforation:
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all
NSAIDs at any time during treatment, with or without warning symptoms or a
previous history of serious GI events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID
doses, in patients with a history of ulcer, particularly if complicated with
haemorrhage or perforation (see section 4.3), and in the elderly. These patients should
commence treatment on the lowest dose available. Combination therapy with
protective agents (e.g.misoprostol or proton pump inhibitors) should be considered
for these patients, and also for patients requiring concomitant low dose aspirin, or
other drugs likely to increase gastrointestinal risk (see below and section 4.5).
NSAIDs should only be given with care to patients with a history of gastrointestinal
disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated
(See section 4.8 – Undesirable effects).
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 antiplatelet agents such as aspirin (See section 4.5 Interactions).
Gastro-intestinal disturbances may be minimised by giving indometacin orally with
food, milk or an antacid. These usually disappear on reducing the dosage; if not, the
risks of continuing therapy should be weighed against the possible benefits.
Single or multiple ulcerations, including perforation and haemorrhage of the
oesophagus, stomach, duodenum or small or large intestine have been reported to
occur with indometacin. Fatalities have been reported in some instances. Rarely,
intestinal ulceration has been associated with stenosis and obstruction. Gastrointestinal bleeding without obvious ulcer formation and perforation of pre-existing
sigmoid lesions (diverticulum, carcinoma, etc.) have occurred.
Increased abdominal pain in ulcerative colitis and regional ileitis has been reported to
occur rarely.
When GI bleeding or ulceration occurs in patients receiving indometacin, the
treatment should immediately be discontinued.
Tenesmus and irritation of the rectal mucosa (sigmoidoscopic examination of a
number of patients showed no mucosal changes) have been reported with existing,
but controlled infection.
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 indometacin.
Patients with uncontrolled hypertension, congestive heart failure, established
ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease
should only be treated with indometacin 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).
Cardiovascular, Renal and Hepatic Impairment:

In patients with renal, cardiac, hepatic impairment, hypertension, heart failure or
conditions predisposing to fluid retention caution is required since the use of NSAIDs
may result in deterioration of renal function (see section 4.8 - Undesirable effects).
The dose should be kept as low as possible and renal function should be monitored.
NSAIDs may also cause fluid retention which may further aggravate these conditions.
The administration of an NSAID may cause a dose dependent reduction in
prostaglandin formation and precipitate renal failure as renal prostaglandins play a
major role in maintaining renal perfusion. Patients at greatest risk of this reaction are
those with impaired renal or hepatic function, cardiac impairment, liver dysfunction,
the elderly and those taking diuretics or any nephrotoxic drug. Indometacin should be
given with caution and renal function should be monitored in these patients. (See also
section 4.3 – Contraindications), a lower daily dosage should be used to avoid
excessive drug accumulation. Discontinuation of non-steroidal anti-inflammatory
therapy is usually followed by recovery to the pre-treatment state.
Patients should be periodically observed to allow early detection of any unwanted
effects on peripheral blood (anaemia), liver function (see section 4.8 – Undesirable
effects) or gastro-intestinal tract especially during prolonged therapy.
Indometacin can inhibit platelet aggregation. The effect usually disappears within 24
hours of discontinuing indometacin. Caution is required in post-operative patients as
bleeding time is prolonged (but within normal range in normal adults). Because this
effect may be exaggerated in patients with underlying haemostatic defects,
indometacin 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 and renal failure, in patients receiving long-term administration of
indometacin.
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 hyporeninaemichypoaldosteronism state.
Eye changes:
In patients with rheumatoid arthritis, eye changes may occur which may be related to
the underlying disease or to the therapy. During prolonged therapy, ophthalmological
examinations at periodic intervals are recommended, as corneal deposits and retinal
disturbances have been reported. Discontinue therapy if eye changes are observed
SLE and mixed connective tissue disease:
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue
disorders there may be an increased risk of aseptic meningitis (See section 4.8 –
Undesirable effects).
Impaired Female fertility:
The use of indometacin may impair female fertility and is not recommended in
women attempting to conceive. In women who have difficulties conceiving or who
are undergoing investigation of infertility, withdrawal of indometacin should be
considered.
Dermatological:
Serious skin reactions, some of them fatal, including exfoliative dermatitis, StevensJohnson syndrome and toxic epidermal necrolysis have been reported very rarely in
association with the use of NSAIDs (see section 4.8). 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.
Indometacin should be discontinued at the first appearance of skin rash, mucosal
leisions or any other sign of hypersensitivity.
Infections:
Indometacin may mask the signs and symptoms of an infection, so antibiotic therapy
should be initiated promptly if an infection occurs during therapy with indometacin. It
should be used with caution in patients with existing but controlled infections.
Caution is advised with concomitant use of live vaccines.
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% 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 eosinophilla occur, indometacin should be stopped.
Adverse reactions:
NSAIDs have been reported to cause nephrotoxicity in various forms and their use
can lead to interstitial nephritis, nephrotic syndrome and renal failure.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption should not take this medicine.

4.5

Interaction with other medicinal products and other forms of interaction
Indometacin is an NSAID so care should be taken in patients treated with any of the
following drugs as interactions have been reported in some patients.
Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid
concomitant use of two or more NSAIDs (including aspirin and keterolac) as this may
increase the risk of adverse effects (See section 4.4 – Special warnings and
precautions for use).
Aspirin and other salicylates: The use of indometacin with aspirin or other
salicylates is not recommended because there is no enhancement of therapeutic effect
while the incidence of gastro-intestinal side-effects is increased. A study in normal
volunteers showed that chronic administration of 3.6 g aspirin with indometacin
lowered the indometacin blood levels by approximately 20%.
Diflunisal: avoid concomitant use. Co-administration of diflunisal with indometacin
increases the plasma level of indometacin by about a third with a concomitant decrease
in renal clearance. Fatal gastro-intestinal haemorrhage has occurred. The combination
should not be used.
Antihypertensives: Reduced antihypertensive effect. Because indometacin may
reduce the antihypertensive effect of beta-blockers due partly to indometacin’s
inhibition of prostaglandin synthesis, patients receiving dual therapy should have the
antihypertensive effect of their therapy reassessed. Therefore, caution should be
exercised when considering the addition of indometacin to the regimen of a patient
taking any of the following antihypertensive agents: alpha-adrenergic blocking
agents, ACE inhibitors, beta-adrenergic blocking agents, angiotensin-2-receptor
antagonists, hydralazine or nifedipine. An increased risk of hyperkalaemia has also
been reported when NSAIDs are taken with ACE inhibitors.

Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity
of NSAIDs. In some patients, the administration of indometacin can reduce the
diuretic and antihypertensive effects of loop, potassium-sparing, and thiazide
diuretics. Therefore, when indometacin and diuretics are used concomitantly, the
patient should be observed closely to determine if the desired effect of the diuretic is
obtained.
Indometacin reduces basal plasma renin activity (PRA), as well as those elevations of
PRA induced by furosemide administration, or salt or volume depletion. These facts
should be considered when evaluating plasma renin activity in hypertensive patients.
It has been reported that the addition of triamterene to a maintenance schedule of
indometacin resulted in reversible acute renal failure in two of four healthy
volunteers. Indometacin and triamterene should not be administered together.
Indometacin and potassium-sparing diuretics each may be associated with increased
plasma potassium levels. The potential effects of indometacin and potassium-sparing
diuretics on potassium kinetics and renal function should be considered when these
agents are administered concurrently.
Most of the above effects concerning diuretics have been attributed, at least in part, to
mechanisms involving inhibition of prostaglandin synthesis by indometacin.
Cardiac glycosides (e.g. digoxin): NSAIDs may exacerbate cardiac failure, reduce
GFR and increase plasma glycoside levels.
Lithium: Decreased elimination of lithium. Indometacin 50 mg three times a day
produced a clinically relevant elevation of plasma lithium and reduction in renal
lithium clearance in psychiatric patients and normal subjects with steady state plasma
lithium prostaglandin synthesis. As a consequence, when indometacin and lithium are
given concomitantly, the patient should be observed carefully for signs of lithium
toxicity. In addition the frequency of monitoring serum lithium concentrations should
be increased at the outset of such combination drug treatment.
Cytotoxics: Indometacin may decrease the tubular secretion of methotrexate thus
potentiating toxicity; simultaneous use should be undertaken with caution.
Ciclosporin: Increased risk of nephrotoxicity. Administration of NSAIDs
concomitantly with ciclosporin has been associated with an increase in ciclosporininduced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs
should be used with caution in patients taking ciclosporin, and renal function should
be monitored carefully.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone
administration as NSAIDs can reduce the effect of mifepristone.
Muscle Relaxants: increased risk of baclofen toxicity due to reduced rate of
excretion.
Pentoxifylline: possible increased risk of bleeding when taken with NSAIDs.
Corticosteroids: Increased risk of gastro-intestinal ulceration or bleeding (See section
4.4 – Special warnings and precautions for use).
Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of
convulsions associated with quinolone antibiotics. Patients taking NSAIDs and
quinolones may have an increased risk of developing convulsions.
Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as
warfarin (See section 4.4 – Special warnings and precautions for use). Although
clinical studies suggest that indometacin does not influence the hypoprothrombinaemia

induced by anticoagulants, patients also receiving anticoagulants should be closely
observed for alterations of the prothrombin time.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs):
increased risk of gastrointestinal bleeding (see section 4.4).
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with
tacrolimus.
Phenytoin: NSAIDs possibly enhance the effects of phenytoin.
Probenecid: Co-administration of probenecid may increase plasma levels of
indometacin. When increases in the dose of indometacin are made under these
circumstances, they should be made cautiously and in small increments.
Antidiabetics: NSAIDs possibly enhance effects of sulphonylureas.
Antipsychotics: Severe drowsiness is possible of indometacin is given with
haloperidol.
Tiludronic acid: The bioavailability of tiludronic acid is increased by indometacin.
Desmopressin: The effect of desmopressin is potentiated by indometacin.
Antivirals: Plasma concentration of NSAIDs is possibly increased by ritonavir, avoid
concomitant use.
Zidovudine: There is increased risk of haematological toxicity when NSAIDs are given
with zidovudine. There is evidence of an increased risk of haemarthroses and
haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine
and ibuprofen.
Laboratory tests: false-negative results in the dexamethasone suppression test (DST) in
patients being treated with indometacin have been reported. Thus, results of this test
should be used with caution in these patients.

4.6

Pregnancy and lactation
Indometacin should not be used during pregnancy or lactation (Indometacin is
secreted in breast milk).
Pregnancy:
Whilst no tetratogenic effects have been demonstrated in animal toxicology studies,
the use of indometacin during pregnancy should if possible be avoided. Congenital
abnormalities have been reported in association with NSAID administration in man;
however, these are low in frequency and do not appear to follow any discernible
pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system
(risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is
contraindicated. The onset of labour may be delayed and the duration increased with
an increased bleeding tendency in both mother and child (See section 4.3 –
Contraindications). NSAIDs should not be used during the first two trimesters of
pregnancy or labour unless the potential benefit to the patient outweighs the potential
risk to the foetus.
Lactation:
In limited studies so far available, NSAIDs can appear in breast milk in very low
concentrations. NSAIDs should, if possible, be avoided when breastfeeding. See
section 4.4 – Special warnings and precautions for use, regarding female fertility.

4.7

Effects on ability to drive and use machines
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are
possible after taking NSAIDs. If affected, patients should not drive a car or operate
mechanical equipment or undertake potentially dangerous activities needing alertness.

4.8

Undesirable effects
Gastrointestinal disorders - The most commonly-observed adverse events are
gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal,
particularly in the elderly may occur (see section 4.4). If gastro-intestinal bleeding
does occur treatment with indometacin should be discontinued. Gastro-intestinal
disorders which occur can be reduced by giving indometacin with food, milk or
antacids. Nausea, anorexia, vomiting, epigastric distress, abdominal pain,
constipation, dyspepsia, melaena, haematemesis, flatulence, ulcerative stomatitis
diarrhoea, exacerbation of colitis and Crohn’s disease (or development of this
condition, see section 4.4 – Special warnings and precautions for use) have been
reported following administration.
Others are ulceration (single or multiple) of oesophagus, stomach, duodenum or
elsewhere in the small or large intestine, sometimes with haemorrhage and
perforation (a few fatalities have been reported); gastro-intestinal bleeding without
obvious ulcer formation; increased abdominal pain in patients with pre-existing
ulcerative colitis.
Reactions occurring infrequently are; gastritis, bleeding from the sigmoid colon
(occult or from a diverticulum); perforation of pre-existing sigmoid lesions such as
diverticula and carcinomata; ulcerative colitis, interstitial strictures and regional ileitis
(casual relationship not established). With suppositories, tenesmus and irritation of
the rectal mucosa have occasionally been reported, but sigmoidoscopic examination
in a number of cases has not revealed mucosal changes.
Rarely, intestinal ulceration followed by stenosis and obstruction has been reported.
Pancreatitis has been reported very rarely.
Hepatobiliary disorders: cholestasis, 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 NSAIDs 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, indometacin should be stopped. Abnormal liver function, hepatitis
and jaundice (some fatalities reported).
Musculoskeletal, connective tissue and bone disorders: muscle weakness and
acceleration of cartilage degeneration.
Renal and urinary disorders: haematuria, nephrotoxicity in various forms,
including interstitial nephritis, nephrotic syndrome and renal failure, renal
insufficiency, proteinuria have all been reported. In patients with renal, cardiac or
hepatic impairment, caution is required since the use of non-steroidal anti-

inflammatory drugs may result in deterioration of renal function. The dose should be
kept as low as possible and renal function should be monitored.
Reproductive system and breast disorders: vaginal bleeding, breast changes
(enlargement, tenderness, gynaecomastia)
Hypersensitivity – Hypersensitivty reactions have been reported following treatment
with NSAIDs. These may consist of (a) non-specific allergic reactions, rapid fall in
blood pressure resembling a shock-like state and anaphylaxis (b) respiratory tract
reactivity comprising asthma, aggravated asthma, bronchospasm, pulmonary oedema
or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritis,
urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses
(including epidermal necrolysis and erythema multiforme).
Cardiac disorder – 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). Oedema, hypertension, and cardiac failure have
been reported in association with NSAID treatment. Also increased blood pressure,
tachycardia, chest pain, arrhythmia, palpitation, hypotension, congestive heart failure,
blood urea elevation and haematuria (all infrequent).
Metabolism and nutrition disorders: Hyperglycaemia, glycosuria, hyperkalaemia
has been reported rarely.
Blood and lymphatic system disorders - blood dyscrasias may occur including
leucopenia, neutropenia, anaemia and haemolytic anaemia, petechiae or ecchymosis,
purpura, aplastic or haemolytic anaemia, agranulocytosis, bone-marrow depression,
thrombocytopenia and disseminated intravascular coagulation may occur
infrequently. Because some patients may develop anaemia secondary to obvious or
occult gastro-intestinal bleeding, appropriate blood determinations are recommended.
Hyperglycaemia has also been reported. Epistaxis has been reported rarely.
Nervous system disorders – Visual disturbances, optic neuritis, headaches, dizziness
and light-headedness are common side effects. Starting therapy with a low dose and
increasing gradually minimises the incidence of headache. These symptoms
frequently disappear on continued therapy or reducing the dosage, but if headache
persists despite dosage reduction, indometacin should be withdrawn. Other CNS
effects include paraesthesia, reports of aseptic meningitis (especially in patients with
existing auto-immune disorders, such as systemic lupus erythematosus, mixed
connective tissue disease) with symptoms such as stiff neck, headache, nausea,
vomiting, fever or disorientation (See section 4.4), depression, confusion,
hallucinations, tinnitus, vertigo, dizziness, malaise, dysarthia, fatigue and drowsiness.
Other reactions reported infrequently include mental confusion, anxiety, syncope,
drowsiness, convulsions, coma, cerebral oedema, nervousness, peripheral neuropathy,
muscle weakness, involuntary muscle movements, insomnia, psychiatric disturbances
such as depersonalisation and, rarely, paraesthesia, aggravation of epilepsy and
Parkinsonism. These are often transient and abate or disappear with reduced dosage
or stopping treatment. However, occasionally, severe reactions require stopping
therapy.
Eye disorders: blurred vision, diplopia, optic neuritis and orbital and peri-orbital
pain are seen infrequently. Corneal deposits and retinal disturbances including those
of the macula have been reported in patients with rheumatoid arthritis on prolonged
therapy with indometacin. Ophthalmic examinations are desirable in patients given
prolonged treatment.

Ear and labyrinth disorders: tinnitus or hearing disturbances (rarely deafness) have
been reported.
Vascular disorders: flushing has been reported rarely.
Respiratory, thoracic and mediastinal disorders: pulmonary eosinophilia. There
may be bronchospasm in patients with a history of bronchial asthma or other allergic
disease.
Skin and subcutaneous tissue disorders: pruritus, urticaria, angioneurotic oedema,
angiitis, erythema nodosum, rash, photosensitivity, exfoliative dermatitis, bullous
reactions including Stevens Johnson syndrome and Toxic Epidermal Necrolysis have
been reported very rarely. Photosensitivity, erythema multiforme, loss of hair
(infrequent), sweating and exacerbation of psoriasis.
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 Yellow Card Scheme [www.mhra.gov.uk/yellowcard].

4.9

Overdose
Symptoms
The following symptoms may be observed following overdosage; nausea, vomiting,
intense headache, epigastric pain, gastrointestinal bleeding, dizziness, excitation,
coma, tinnitus, drowsiness, fainting, rarely diarrhoea, mental confusion, disorientation
or lethargy. There have been reports of paraesthesiae, numbness and convulsions. In
cases of significant poisoning acute renal failure and liver damage are possible.
Therapeutic measure
Treatment is symptomatic and supportive. The stomach should be emptied as quickly
as possible if the ingestion is recent. Within one hour of ingestion of potentially toxic
amount, 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.
Alternatively, in adults, gastric lavage should be performed within one hour of
ingestion of a potentially life-threatening overdose. The patient should be followed
for several days because gastro-intestinal ulceration and haemorrhage have been
reported as adverse reactions of indometacin. Use of antacids may be helpful.
Good urine output should be ensured. Renal and liver function should be closely
monitored. 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 patients’s clinical condition.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC CODE: M01A B01
Indometacin has prominent anti-inflammatory and analgesic-antipyretic properties.
Indometacin has analgesic properties distinct from its anti-inflammatory effects and
there is evidence for both a central and a peripheral effect.
Indometacin is one of the most potent inhibitors of the prostaglandin-forming cyclooxygenase. Like colchicine, it inhibits motility of polymorphonuclear leukocytes.
Like many other of the aspirin-like drugs, indometacin uncouples oxidative
phosphorylation in supratherapeutic concentrations and depresses the biosynthesis of
mucopolysaccharides.

5.2

Pharmacokinetic properties
Absorption: Indometacin is readily absorbed from the gastro-intestinal tract; peak
plasma concentrations are reached in ½ to 2 hours after a dose.
Distribution: More than 90% is bound to plasma proteins. It is distributed into
synovial fluid, CNS and placenta. Low concentrations have been found in breast
milk.
Metabolism: It is metabolised in the liver and kidneys primarily by demethylation
and deacetylation; it also undergoes glucuronidation and enterohepatic circulation.
Half-life is between 3 – 11 hours.
Excretion: Mainly excreted in the urine, approximately 60% (the pH of the urine can
affect this amount), and to a much lesser extent in the faeces. Indometacin is also
excreted in milk in small amounts.

5.3

Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to
that already included in other sections of the SPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose, sodium lauryl sulphate, anhydrous colloidal silica, magnesium stearate,
yellow iron oxide (E172), titanium dioxide (E171), black iron oxide (E172), gelatin.

6.2

Incompatibilities
None known.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Store below 25°C in a dry place. Keep container closed.

6.5

Nature and contents of container
High density polystyrene containers with polythene lids and/or polypropylene
containers with polypropylene or polythene lids and polyurethane/polythene inserts.
Pack sizes: 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000 capsules.
PVC/Aluminium blister packs.
Pack sizes: 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000 capsules.

6.6

Special precautions for disposal
None.

7

MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
11 Boumpoulinas Street,
3rd floor, 1060 Nicosia
Cyprus

8

MARKETING AUTHORISATION NUMBER(S)
PL 33414/0055

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION

10

DATE OF REVISION OF THE TEXT
10/01/2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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