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DICLOFENAC TABLETS BP 25MG

Active substance(s): DICLOFENAC SODIUM / DICLOFENAC SODIUM

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Diclofenac Tablets BP 25 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each enteric-coated tablet contains Diclofenac Sodium 25 mg.
For excipients, see 6.1.

3

PHARMACEUTICAL FORM
Gastro-resistant tablet.
Yellowish-mustard film coated biconvex tablet.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Adults:
Relief of all grades of pain and inflammation in a wide range of conditions,
including:
(i)

arthritic conditions: rheumatoid arthritis, osteoarthritis, ankylosing
spondylitis, acute gout,

(ii)

acute musculo-skeletal disorders such as periarthritis (for example
frozen shoulder), tendinitis, tenosynovitis, bursitis,

(iii)

other painful conditions resulting from trauma, including fracture, low
back pain, sprains, strains, dislocations, orthopaedic, dental and other
minor surgery.

Children (aged 1-12 years): Juvenile chronic arthritis.

Children aged 9 yrs and above:

The short term treatment of fever related to infections of the ear, nose or throat
(ENT), e.g. pharyngotonsillitis, otitis media.
As monotherapy or as adjunct therapy with morphine or other opiates (due to
its opiate-sparing effect) for the relief of acute post-operative pain.

4.2

Posology and method of administration
Undesirable effects may be minimised by using the lowest effective dose for
the shortest duration necessary to control symptoms (see section 4.4).
For oral administration.
To be taken preferably with or after food.
Adults: 75-150 mg daily in two or three divided doses.
The recommended maximum daily dose is 150 mg.
Special populations
Paediatric population
Children aged 1-12 years for juvenile chronic arthritis: 1-3 mg/kg per day in divided
doses.
Children aged 9 years and above: For the short term treatment of fever related to
infections of the ear, nose or throat (ENT) and post-operative pain the following
dosage should be given :
Children aged 9 years (min. 35 kg BW) or over and adolescents should be given up to
2 mg/kg body weight per day in 3 divided doses, depending on the severity of the
disorder.
Elderly
Although the pharmacokinetics of diclofenac are not impaired to any clinically
relevant extent in elderly patients, non steroidal anti-inflammatory drugs should be
used with particular caution in such patients who generally are more prone to adverse
reactions. In particular it is recommended that the lowest effective dosage be used in
frail elderly patients or those with a low body weight (see also section 4.4) and the
patient should be monitored regularly for GI bleeding during NSAID therapy.
Renal impairment
Diclofenac is contraindicated in patients with severe renal impairment (see section
4.3). No specific studies have been carried out in patients with renal impairment,
therefore, no specific dose adjustment recommendations can be made. Caution is
advised when administering diclofenac to patients with mild to moderate renal
impairment (see section 4.3 and 4.4).
Hepatic impairment
Diclofenac is contraindicated in patients with severe hepatic impairment (see section
4.3). No specific studies have been carried out in patients with hepatic impairment,
therefore, no specific dose adjustment recommendations can be made. Caution is

advised when administering diclofenac to patients with mild to moderate hepatic
impairment (see section 4.3 and 4.4).

4.3

Contraindications

Known hypersensitivity to the active substance or to any of the excipients.
Active gastric or intestinal ulcer, bleeding or perforation.
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of
proven ulceration, perforation or bleeding).

Last trimester of pregnancy (see section 4.6)
Severe hepatic, renal or cardiac failure (see section 4.4).
Like other non-steroidal anti-inflammatory drugs (NSAIDs), Diclofenac is also
contraindicated in patients in whom attacks of asthma, urticaria, acute rhinitis or angioedema
are precipitated by ibuprofen, acetylsalicylic acid or other NSAIDs.
Established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial
disease and/or cerebrovascular disease.

4.4

Special warnings and precautions for use

General
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 concomitant use of diclofenac with systemic NSAIDs including cyclooxygenase2 selective inhibitors should be avoided due to the absence of any evidence
demonstrating synergistic benefits and the potential for additive undesirable effects
(see section 4.5).
Caution is indicated in the elderly on basic medical grounds. In particular, it is
recommended that the lowest effective dose be used in frail elderly patients or those
with a low body weight (see section 4.2).
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid
reactions, can also occur in rare cases with diclofenac without earlier exposure to the
drug (see section 4.8).
Like other NSAIDs, Diclofenac may mask the signs and symptoms of infection due to
its pharmacodynamic properties.

Patients with rare hereditary problems of galactose intolerance, the LAPP lactase deficiency
or glucose-galactose malabsorption should not take this medicine as it contains lactose.
The tablets contain tartrazine aluminium lake which may cause allergic reactions.
The tablets contain methyl and propyl parahydroxybenzoate which may cause allergic
reactions (possibly delayed).

Gastrointestinal effects
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with
all NSAIDs, including diclofenac, and may occur at any time during treatment, with or
without warning symptoms or a previous history of serious gastrointestinal events. They
generally have more serious consequences in the elderly. If gastrointestinal bleeding or
ulceration occurs in patients receiving diclofenac, the medicinal product should be withdrawn.
As with all NSAIDs, including diclofenac, close medical surveillance is imperative and
particular caution should be exercised when prescribing diclofenac in patients with symptoms
indicative of gastrointestinal (GI) disorders or with a history suggestive of gastric or intestinal
ulceration, bleeding or perforation (see section 4.8).

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID
doses and in patients with a history of ulcer, particularly if complicated with
haemorrhage or perforation. The elderly have an increased frequency of adverse
reactions to NSAIDs especially gastrointestinal bleeding and perforation which may
be fatal (see section 4.2).
To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if
complicated with haemorrhage or perforation, and in the elderly, the treatment should
be initiated and maintained at the lowest effective dose.
Combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol)
should be considered for these patients, and also for patients requiring concomitant use of
medicinal products containing low-dose acetylsalicylic acid (ASA)/aspirin, or other medicinal
products likely to increase gastrointestinal risk (see section 4.5).
Patients with a history of GI toxicity, particularly the elderly, should report any unusual
abdominal symptoms (especially GI bleeding).
Caution is recommended in patients receiving concomitant medications which could increase
the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants such as
warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see
section 4.5).

Close medical surveillance and caution should also be exercised in patients with
ulcerative colitis or Crohn’s disease, as their condition may be exacerbated (see
section 4.8).
Hepatic effects
Close medical surveillance is required when prescribing diclofenac to patients with
impaired hepatic function, as their condition may be exacerbated.

As with other NSAIDs, including diclofenac, values of one or more liver enzymes
may increase. During prolonged treatment with diclofenac, regular monitoring of
hepatic function is indicated as a precautionary measure. If abnormal liver function
tests persist or worsen, if clinical signs or symptoms consistent with liver disease
develop or if other manifestations occur (eosinophilia, rash), diclofenac should be
discontinued. Hepatitis may occur with use of diclofenac without prodromal
symptoms. Caution is called for when using Diclofenac in patients with hepatic
porphyria, since it may trigger an attack.
Renal effects
As fluid retention and oedema have been reported in association with NSAID therapy,
including diclofenac, particular caution is called for in patients with impaired cardiac or renal
function, history of hypertension, the elderly, patients receiving concomitant treatment with
diuretics or medicinal products that can significantly impact renal function, and in those
patients with substantial extracellular volume depletion from any cause, e.g. before or after
major surgery (see section 4.3). Monitoring of renal function is recommended as a
precautionary measure when using Diclofenac in such cases. Discontinuation of therapy is
usually followed by recovery to the pre-treatment state.
Skin effects
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson
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. Diclofenac should be discontinued at the first appearance
of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Cardiovascular and cerebrovascular effects
Patients with significant risk factors for cardiovascular events (e.g. hypertension,
hyperlipidaemia, diabetes mellitus, smoking) should only be treated with diclofenac
after careful consideration.
As the cardiovascular risks of diclofenac may increase with dose and duration of
exposure, the shortest duration possible and the lowest effective daily dose should be
used. The patient's need for symptomatic relief and response to therapy should be reevaluated periodically.
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 consistently point towards an increased risk of
arterial thrombotic events (for example myocardial infarction or stroke) associated
with the use of diclofenac, particularly at high dose (150mg daily) and in long term
treatment.
Patients with uncontrolled hypertension, should only be treated with diclofenac after
careful consideration.

Haematological effects
During prolonged treatment with Diclofenac, as with other NSAIDs, monitoring of
the blood count is recommended.
Like other NSAIDs, Diclofenac may temporarily inhibit platelet aggregation (see
anticoagulants in section 4.5). Patients with defects of haemostasis, bleeding diathesis
or haematological abnormalities should be carefully monitored.
Pre-existing asthma
In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e.
nasal polyps), chronic obstructive pulmonary diseases or chronic infections of the
respiratory tract (especially if linked to allergic rhinitis-like symptoms), reactions on
NSAIDs like asthma exacerbations (so-called intolerance to analgesics/analgesicsasthma), Quincke’s oedema or urticaria are more frequent than in other patients.
Therefore, special precaution is recommended in such patients (readiness for
emergency). This is applicable as well for patients who are allergic to other
substances, e.g. with skin reactions, pruritus or urticaria.
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 such patients.
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).

Impaired female fertility
The use of diclofenac 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 diclofenac should be considered (see section 4.6).

Long-term treatment
All patients who are receiving non-steroidal anti-inflammatory agents should be
monitored as a precautionary measure e.g. renal function, hepatic function (elevation
of liver enzymes may occur) and blood counts. This is particularly important in the
elderly.
4.5

Interaction with other medicinal products and other forms of interaction
The following interactions include those observed with Diclofenac gastro-resistant
tablets and/or other pharmaceutical forms of diclofenac.
Lithium: If used concomitantly, diclofenac may raise plasma concentrations of
lithium. Monitoring of serum lithium level is recommended.

Digoxin: If used concomitantly, diclofenac may raise plasma concentrations of
digoxin. Monitoring of the serum digoxin level is recommended.
Diuretics and antihypertensive agents: Like other NSAIDs, concomitant use of
diclofenac with diuretics or antihypertensive agents (e.g. beta-blockers, angiotensin
converting enzyme (ACE) inhibitors) may cause a decrease in their antihypertensive
effect via inhibition of vasodilatory prostaglandin synthesis. Therefore the
combination should be administered with caution and patients, especially the elderly,
should have their blood pressure periodically monitored. Patients should be
adequately hydrated and consideration should be given to monitoring of renal
function after initiation of concomitant therapy and periodically thereafter,
particularly for diuretics and ACE inhibitors due to the increased risk of
nephrotoxicity.
Drugs known to cause hyperkalemia: Concomitant treatment with potassiumsparing diuretics, ciclosporin, tacrolimus or trimethoprim may be associated with
increased serum potassium levels, which should therefore be monitored frequently
(see section 4.4).
Other NSAIDs including cyclooxygenase-2 selective inhibitors and
corticosteroids: Concomitant administration of diclofenac and other systemic
NSAIDs (including aspirin) or corticosteroids may increase the frequency of
gastrointestinal undesirable effects bleeding or ulceration (see section 4.4). Avoid
concomitant use of two or more NSAIDs (see section 4.4).
Anticoagulants and anti-platelet agents: Caution is recommended since
concomitant administration could increase the risk of bleeding. Although clinical
investigations do not appear to indicate that diclofenac affects the action of
anticoagulants, there are reports of an increased risk of haemorrhage in patients
receiving diclofenac and anticoagulants concomitantly. Close monitoring of such
patients is therefore recommended.
Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of
systemic NSAIDs, including diclofenac, and SSRIs may increase the risk of
gastrointestinal bleeding (see section 4.4).
Antidiabetics: Clinical studies have shown that Diclofenac can be given together
with oral antidiabetic agents without influencing their clinical effect. However there
have been isolated reports of both hypoglycaemic and hyperglycaemic effects
necessitating changes in the dosage of the antidiabetic agents during treatment with
diclofenac. For this reason, monitoring of the blood glucose level is recommended as
a precautionary measure during concomitant therapy.
Methotrexate: Diclofenac can inhibit the tubular renal clearance of methotrexate
hereby increasing methotrexate levels. Caution is recommended when NSAIDs,
including diclofenac, are administered less than 24 hours before or after treatment
with methotrexate, since blood concentrations of methotrexate may rise and the
toxicity of this substance be increased. Cases of serious toxicity have been reported
when methotrexate and NSAIDs are given within 24 hours of each other. This
interaction is mediated through accumulation of methotrexate resulting from
impairment of renal excretion in the presence of the NSAID.
Ciclosporin: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of
ciclosporin due to the effect on renal prostaglandins. Therefore, it should be given at
doses lower than those that would be used in patients not receiving ciclosporin.

Quinolone antibacterials: Animal data indicate that NSAIDs can increase the risk of
convulsions associated with quinolone antibiotics. There have been isolated reports of
convulsions which may have been due to concomitant use of quinolones and
NSAIDs. Patients taking NSAIDs and quinolones may have an increased risk of
developing convulsions. Convulsions may occur in patients with or without a
previous history of epilepsy or convulsions. Therefore, caution should be exercised
when considering the use of a quinolone in patients who are already receiving an
NSAID.

Phenytoin: When using phenytoin concomitantly with diclofenac, monitoring
of phenytoin plasma concentrations is recommended due to an expected
increase in exposure to phenytoin.
Colestipol and cholestyramine: These agents can induce a delay or decrease in
absorption of diclofenac. Therefore, it is recommended to administer diclofenac at
least one hour before or 4 to 6 hours after administration of colestipol/cholestyramine.

Potent CYP2C9 inhibitors: Caution is recommended when co-prescribing
diclofenac with potent CYP2C9 inhibitors (such as voriconazole), which could
result in a significant increase in peak plasma concentrations and exposure to
diclofenac due to inhibition of diclofenac metabolism.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone
administration, as NSAIDs can reduce the effect of mifepristone.
Cardiac glycosides: Concomitant use of cardiac glycosides and NSAIDs in patients
may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Tacrolimus: possible increased risk of nephrotoxicity when NSAIDs are given with
tacrolimus. This might be mediated through renal antiprostaglandin effects of both
NSAID and calcineurin inhibitor.
Zidovudine: 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 (a NSAID).

4.6

Fertility, pregnancy and lactation

Pregnancy
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the
embryo/foetal development. Data from epidemiological studies suggest an increased risk of
miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin
synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformation was
increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with
dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor
has been shown to result in increased pre- and post-implantation loss and embryo-foetal
lethality.
In addition, increased incidences of various malformations, including cardiovascular, have
been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic

period. If diclofenac is used by a woman attempting to conceive, or during the first trimester
of pregnancy, the dose should be kept as low and duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the
foetus to:
- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary
hypertension);
- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;
the mother and the neonate, at the end of pregnancy, to:
- possible prolongation of bleeding time, an anti-aggregating effect which may occur even at
very low doses.
- inhibition of uterine contractions resulting in delayed or prolonged labour.
Consequently, diclofenac is contraindicated during the third trimester of pregnancy.
Lactation
Like other NSAIDs, diclofenac passes into the breast milk in small amounts. Therefore
diclofenac should not be administered during breastfeeding in order to avoid undesirable
effects in the infant (see section 5.2).
Fertility
As with other NSAIDs, the use of diclofenac 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 diclofenac should be
considered (see also section 4.4).

4.7

Effects on ability to drive and use machines
Patients experiencing visual disturbances, dizziness, drowsiness, fatigue,
vertigo, somnolence or other central nervous disturbances while taking
diclofenac, should refrain from driving or using machines.

4.8

Undesirable effects
If serious side-effects occur, Diclofenac should be withdrawn.
Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent
first, using the following convention: very common: (>1/10); common (>1/100,
<1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1/1,000); very rare
(<1/10,000); not known: cannot be estimated from the available data.
The following undesirable effects include those reported with either short-term or
long-term use.
Table 1
Blood and lymphatic system disorders
Very rare

Immune system disorders
Rare

Thrombocytopenia, neutropenia,
leucopenia, anaemia (including
haemolytic and aplastic anaemia),
agranulocytosis
Hypersensitivity, anaphylactic and
anaphylactoid reactions (including

Very rare
Psychiatric disorders
Very rare

Nervous system disorders
Common
Rare
Very rare

Not known
Eye disorders
Very rare
Not known
Ear and labyrinth disorders
Common
Very rare
Cardiac disorders
Very rare
Vascular disorders
Very rare
Respiratory, thoracic and mediastinal
disorders
Rare
Very rare
Not known
Gastrointestinal disorders
Common

Rare

Very rare

hypotension and shock)
Angioneurotic oedema (including face
oedema).
Disorientation, depression, insomnia,
nightmares, irritability, psychotic
disorder.
Headache, dizziness.
Somnolence.
Paraesthesia, memory impairment,
convulsion, anxiety, tremor, 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), taste disturbances,
cerebrovascular accident.
Disturbances of sensation, confusion,
hallucinations, malaise, fatigue,
drowsiness.
Visual disturbance, vision blurred,
diplopia.
Optic neuritis.
Vertigo.
Tinnitus, hearing impaired.
Palpitations, chest pain, cardiac failure,
myocardial infarction.
Hypertension, vasculitis, hypotension.

Asthma (including dyspnoea).
Pneumonitis.
Aggravated asthma, bronchospasm
Nausea, vomiting, diarrhoea, dyspepsia,
abdominal pain or cramps, flatulence,
anorexia.
Gastritis, gastrointestinal haemorrhage,
haematemesis, diarrhoea haemorrhagic,
melaena, gastrointestinal ulcer (with or
without bleeding or perforation),
sometimes fatal, particularly in the
elderly, may occur (see section 4.4).
Colitis (including haemorrhagic colitis
and exacerbation of ulcerative colitis or
Crohn’s disease), constipation, stomatitis
(including ulcerative stomatitis),

Not known
Hepatobiliary disorders
Common
Rare
Very rare
Not known
Skin and subcutaneous tissue
disorders
Common
Rare
Very rare

Renal and urinary disorders
Very rare

General disorders
Rare
Reproductive system and breast
disorders
Not known

glossitis, oesophageal disorder,
oesophageal lesions, diaphragm-like
intestinal strictures, pancreatitis, colonic
damage.
Ischaemic colitis
Transaminases increased.
Hepatitis, jaundice, liver disorder.
Fulminant hepatitis, hepatic necrosis,
hepatic failure
Abnormal liver function.

Rash
Urticaria
Bullous eruptions, eczema, erythema,
erythema multiforme, Stevens Johnson
Syndrome, toxic epidermal necrolysis
(Lyell’s syndrome), dermatitis
exfoliative, loss of hair, photosensitivity
reaction, purpura, allergic purpura,
pruritis.
Acute renal failure, haematuria,
proteinuria, nephrotic syndrome,
interstitial nephritis, renal papillary
necrosis. Acute renal insufficiency.
Oedema

Impotence (association with diclofenac
intake is doubtful)

Clinical trial and epidemiological data consistently point towards an increased
risk of arterial thrombotic events (for example myocardial infarction or stroke)
associated with the use of diclofenac, particularly at high dose (150mg daily)
and in long term treatment (see section 4.3 and 4.4).
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 at:
www.mhra.gov.uk/yellowcard.
4.9

Overdose
Symptoms
There is no typical clinical picture resulting from diclofenac over dosage. Over
dosage can cause symptoms such as headache, nausea, vomiting, epigastric pain,

gastrointestinal haemorrhage, diarrhoea, disorientation, excitation, coma, drowsiness,
dizziness, tinnitus, fainting or convulsions. In the event of significant poisoning, acute
renal failure and liver damage are possible.
Therapeutic measures
Management of acute poisoning with NSAIDs, including diclofenac, essentially
consists of supportive measures and symptomatic treatment. Supportive measures and
symptomatic treatment should be given for complications such as hypotension, renal
failure, convulsions, gastrointestinal disorder, and respiratory depression.
Special measures such as forced diuresis, dialysis or haemo-perfusion are probably of
no help in eliminating NSAIDs, including diclofenac, due to high protein binding and
extensive metabolism.
Activated charcoal may be considered after ingestion of a potentially toxic overdose,
and gastric decontamination (e.g. vomiting, gastric lavage) after ingestion of a
potentially life threatening overdose.

5.1

Pharmacodynamic properties
Pharmacotherapeutic Group: Antiinflammatory and Antirheumatic products, Nonsteroids; Acetic Acid Derivatives and Related Substances
ATC Code: M01AB05
Diclofenac is a non-steroidal agent with marked analgesic and anti-inflammatory
properties. It is an inhibitor of prostaglandin synthetase, (cyclo-oxygenase).
Diclofenac sodium in-vitro does not suppress proteoglycan biosynthesis in cartilage at
concentrations equivalent to the concentrations reached in human beings.
There is limited clinical trial experience of the use of diclofenac in JRA/JIA
paediatric patients. In a randomised, double-blind, 2-week, parallel group study in
children aged 3-15 years with JRA/JIA, the efficacy and safety of daily 2-3 mg/kg
BW diclofenac was compared with acetylsalicylic acid (ASS, 50-100 mg/kg BW/d)
and placebo - 15 patients in each group. In the global evaluation, 11 of 15 diclofenac
patients, 6 of 12 aspirin and 4 of 15 placebo patients showed improvement with the
difference being statistically significant (p < 0.05). The number of tender joints
decreased with diclofenac and ASS but increased with placebo. In a second
randomised, double-blind, 6-week parallel group study in children aged 4-15 years
with JRA/JIA, the efficacy of diclofenac (daily dose 2-3 mg/kg BW, n=22) was
comparable with that of indometacin (daily dose 2-3 mg/kg BW, n=23).

5.2

Pharmacokinetic properties
Absorption
Absorption is complete but onset is delayed until passage through the stomach, which
may be affected by food which delays stomach empyting. The mean peak plasma
diclofenac concentration reached at about 2 hours (50mg dose produces 1.48 ±
0.65µg/ml (1.5µg/ml ≡ 5µmol/l)).
Bioavailability

About half of the administered diclofenac is metabolised during its first passage
through the liver (“first pass” effect), the area under the concentrations curve (AUC)
following oral administration is about half that following an equivalent parenteral
dose.
Pharmacokinetic behaviour does not change on repeated administration.
Accumulation does not occur, provided the recommended dosage intervals are
observed.
Distribution
The active substance is 99.7% protein bound, mainly to albumin (99.4%).
Diclofenac enters the synovial fluid, where maximum concentrations are measured 24 hours after the peak plasma values have been attained. The apparent half life for
elimination from the synovial fluid is 3-6 hours. Two hours after reaching the peak
plasma values, concentrations of the active substance are already higher in the
synovial fluid than they are in the plasma and remain higher for up to 12 hours.
Diclofenac was detected in a low concentration (100 ng/mL) in breast milk in one
nursing mother. The estimated amount ingested by an infant consuming breast milk is
equivalent to a 0.03 mg/kg/day dose (see section 4.6).
Metabolism
Biotransformation of diclofenac takes place partly by glucuronidation of the intact
molecule, but mainly by single and multiple hydroxylation and methoxylation,
resulting in several phenolic metabolites, most of which are converted to glucuronide
conjugates. Two phenolic metabolites are biologically active, but to a much lesser
extent than diclofenac.
Elimination
The total systemic clearance of diclofenac in plasma is 263 ± 56 mL/min (mean value
± SD). The terminal half-life in plasma is 1-2 hours. Four of the metabolites,
including the two active ones, also have short plasma half-lives of 1-3 hours.
About 60% of the administered dose is excreted in the urine in the form of the
glucuronide conjugate of the intact molecule and as metabolites, most of which are
also converted to glucuronide conjugates. Less than 1% is excreted as unchanged
substance. The rest of the dose is eliminated as metabolites through the bile in the
faeces.
Characteristics in patients
Elderly: No relevant age-dependant differences in the drug’s absorption, metabolism,
or excretion have been observed, other than finding that in five elderly patients, a 15
minute iv infusion resulted in 50% higher plasma concentrations than expected with
young healthy subjects.
Patients with renal impairment: In patients suffering from renal impairment, no
accumulation of the unchanged active substance can be inferred from the single-dose
kinetics when applying the usual dosage schedule. At a creatinine clearance of <10
mL/min, the calculated steady-state plasma levels of the hydroxy metabolites are

about 4 times higher than in normal subjects. However, the metabolites are ultimately
cleared through the bile.
Patients with hepatic disease: In patients with chronic hepatitis or nondecompensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in
patients without liver disease.

5.3

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

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Core ingredients:
Sodium starch glycollate
Microcrystalline cellulose
Lactose
Maize starch
Magnesium stearate
Purified talc
Coating ingredients:
Methacrylic Acid-Ethyl Acrylate Copolymer (1:1) Dispersion 30 per
cent
Hypromellose
Tartrazine Lake (E102)
Red Iron Oxide (El72)
Titanium Dioxide (E171)
Sodium Hydroxide
Hydroxybenzoate esters (E216, E218)
Disodium Edetate (E385).

6.2

Incompatibilities
None known

6.3

Shelf life
2 years.

6.4

Special precautions for storage
Store in container provided. Do not store above 25°C

6.5

Nature and contents of container
Aluminium foil/ PVC blisters packs in a cardboard carton containing 28, 50,
84 and 100 tablets.
Polypropylene container with a polyurethane foam insert and tamper-evident
cap containing 50 and 100 tablets.

6.6

Special precautions for disposal
None.

7

MARKETING AUTHORISATION HOLDER
Crescent Pharma Ltd
Units 3 and 4, Quidhampton Business Units
Polhampton Lane
Overton
Hampshire
RG25 3ED
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 20416/0219

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of first authorisation: 28 June 2004
Date of last renewal: 2 February 2009

10

DATE OF REVISION OF THE TEXT
01/07/2016

Expand Transcript

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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