INDOCID CAPSULES 25MG

Active substance: INDOMETHACIN

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
‘Indocid’ Capsules 25 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
‘Indocid’ Capsules 25 mg contain 25 mg of indomethacin.

3

PHARMACEUTICAL FORM
‘Indocid’ Capsules 25 mg are ivory, opaque capsules marked ‘MSD 25’.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
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.

4.2

Posology and method of administration
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.

4.3

Contraindications
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: ‘Indocid’ should not be used during pregnancy or
lactation (see section 4.6 ‘Pregnancy and lactation’).

4.4

Special warnings and precautions for use
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 gastrointestinal 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.

4.5

Interaction with other medicinal products and other forms of interaction
Aspirin: the use of ‘Indocid’ with aspirin or other salicylates is not
recommended.
Controlled clinical studies have shown no enhanced
therapeutic effect, and one study showed a significant increase in the incidence
of gastro-intestinal side effects. A study in normal volunteers showed that
chronic administration of 3.6 g aspirin with indomethacin lowered the
indomethacin blood levels by approximately 20%.
Diflunisal: co-administration of diflunisal with ‘Indocid’ increases the plasma
level of indomethacin by about a third, with a concomitant decrease in renal
clearance. Fatal gastro-intestinal haemorrhage has occurred. The combination
should not be used.
Other NSAIDS: the concomitant use of ‘Indocid’ with other NSAIDs is not
recommended due to the increased possibility of gastro-intestinal toxicity, with
little or no increase in efficacy.
Anticoagulants: although clinical studies suggest that ‘Indocid’ does not
influence the hypoprothrombinaemia induced by anticoagulants, patients also
receiving anticoagulants should be closely observed for alterations of the
prothrombin time.
Probenecid: co-administration of probenecid may increase plasma levels of
indomethacin.

Methotrexate: caution should be exercised with simultaneous use of ‘Indocid’
with methotrexate. ‘Indocid’ has been reported to decrease the tubular
secretion of methotrexate and to potentiate toxicity.
Cyclosporin:
administration of non-steroidal anti-inflammatory drugs
concomitantly with cyclosporin has been associated with an increase in
cyclosporin-induced toxicity, possibly due to decreased synthesis of renal
prostacyclin. NSAIDs should be used with caution in patients taking
cyclosporin, and renal function should be monitored carefully.
Lithium: indomethacin 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
concentrations. This effect has been attributed to inhibition of prostaglandin
synthesis. As a consequence, when indomethacin 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.
Diuretics: in some patients, the administration of ‘Indocid’ can reduce the
diuretic and antihypertensive effects of loop, potassium-sparing and thiazide
diuretics. Therefore, when ‘Indocid’ and diuretics are used concomitantly, the
patient should be observed closely to determine if the desired effect of the
diuretic is obtained.
‘Indocid’ reduces basal plasma renin activity (PRA), as well as those
elevations of PRA induced by frusemide 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 ‘Indocid’ resulted in reversible acute renal failure in two of four healthy
volunteers. ‘Indocid’ and triamterene should not be administered together.
‘Indocid’ and potassium-sparing diuretics each may be associated with
increased plasma potassium levels. The potential effects of ‘Indocid’ 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
‘Indocid’.
Cardiac glycosides/Digoxin: ‘Indocid’ given concomitantly with digoxin has
been reported to increase the serum concentration and prolong the half-life of
digoxin. Therefore, when ‘Indocid’ and digoxin are used concomitantly,
serum digoxin levels should be closely monitored.

Antihypertensive medications: co-administration of ‘Indocid’ and some
antihypertensive agents may attenuate acutely the hypotensive effect of the
latter, due partly to indomethacin’s inhibition of prostaglandin synthesis.
Therefore, caution should be exercised when considering the addition of
‘Indocid’ to the regimen of a patient taking any of the following
antihypertensive agents: alpha-adrenergic blocking agents, ACE inhibitors,
beta-adrenergic blocking agents, diuretics, hydralazine, or losartan (an
angiotensin II receptor antagonist).
Phenylpropanolamine: hypertensive crises have been reported due to oral
phenylpropanolamine alone and, rarely, to phenylpropanolamine given with
‘Indocid’. This additive effect is probably due partly to indomethacin’s
inhibition of prostaglandin synthesis. Caution should be exercised when
‘Indocid’ and phenylpropanolamine are administered concomitantly.
Corticosteroids:
the risk of gastro-intestinal bleeding and ulceration
associated with NSAIDs is increased when used with corticosteroids.
Mifepristone: NSAIDs and aspirin should be avoided until at least 8 to 12
days after administration of mifepristone.
Quinolone antibiotics: there have been reports that 4-quinolones may induce
convulsions in patients with or without a history of convulsions; taking
NSAIDs at the same time may also induce them.

4.6

Pregnancy and lactation
Use in pregnancy: ‘Indocid’ should be used during the first two trimesters of
pregnancy only if the potential benefit justifies the potential risk to the foetus.
The known effects of indomethacin and other drugs of this class on the human
foetus during the third trimester of pregnancy include: constriction of the
ductus arteriosus prenatally, tricuspid incompetence, and pulmonary
hypertension; non-closure of the ductus arterisosus postnatally which may be
resistant to medical management; myocardial degenerative changes, platelet
dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or
failure, renal injury/dysgenesis which may result in prolonged or permanent
renal failure, oligohydramnios, gastro-intestinal bleeding or perforation and
increased risk of necrotising enterocolitis. Use of ‘Indocid’ during the third
trimester of pregnancy is not recommended.
Use in breast-feeding: administration of ‘Indocid’ is not recommended in
breast-feeding mothers. Indomethacin is excreted in breast milk.

4.7

Effects on ability to drive and use machines
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.

4.8

Undesirable effects
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. 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.

4.9

Overdose
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.

5

PHARMACOLOGICAL PROPERTIES

5.1

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

5.2

Pharmacokinetic properties
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.

5.3

Preclinical safety data
No relevant information.

6

PHARMACEUTICAL PARTICULARS

6.1

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

6.2

Incompatibilities
None known.

6.3

Shelf life
36 months

6.4

Special precautions for storage
Do not store above 25°C. Keep in original package.

6.5

Nature and contents of container
‘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.

6.6

Special precautions for disposal
‘Indocid’ Capsules should always be taken with food or an antacid.

7.

MARKETING AUTHORISATION HOLDER
Aspen Pharma Trading Limited
3016 Lake Drive
Citywest Business Campus

Dublin 24
Ireland

8

MARKETING AUTHORISATION NUMBER(S)
PL 39699/012

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Licence first granted 12 June 1981.

10

DATE OF REVISION OF THE TEXT
19/12/2013

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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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