VOLTAROL PAIN-EZE TABLETS

Active substance: DICLOFENAC POTASSIUM

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Voltarol Pain-eze Tablets
Or
Voltarol Joint Pain 12.5mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 12.5mg diclofenac potassium.
For a full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM
White capsule-shaped film-coated tablet

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Short term relief of headache, dental pain, period pain, rheumatic pain,
muscular pain and backache and the symptoms of colds and flu, including
fever.

4.2.

Posology and method of administration
Adults and children aged 14 years and over:
Initially two tablets, followed by one or two tablets every 4 to 6 hours as
needed. No more than 6 tablets (75 mg) should be taken in any 24 hour
period.
Voltarol Pain-eze Tablets should not be used for longer than 3 days.
symptoms persist or worsen consult your doctor.

If

The tablets should be swallowed whole with a drink of water.
Children and Adolescents:
Voltarol Pain-eze Tablets are not to be used in children and adolescents under
14 years of age.
Undesirable effects may be minimised by using the lowest effective dose for
the shortest duration necessary to control symptoms (see section 4.4 Special
warnings and precautions for use).

4.3.

Contraindications





Gastric or intestinal ulcer, bleeding or perforation.



Pregnancy or breastfeeding (see section 4.6 Pregnancy and lactation).



Severe hepatic or renal failure (see section 4.4 Special warnings and special
precautions for use).



Established congestive heart failure (NYHA II-IV), ischemic heart disease,
peripheral arterial disease and/or cerebrovascular disease



Concomitant use of anticoagulants and antiplatelets (see section 4.5
Interactions)



4.4.

Known hypersensitivity to diclofenac or to any of the excipients. Patients in
whom attacks of asthma, urticaria, angioedema, or acute rhinitis are
precipitated by aspirin or other non-steroidal anti-inflammatory drugs such as
ibuprofen.

Use with concomitant NSAIDs including cyclo-oxygenase-2 specific
inhibitors (see section 4.5 Interactions)
Special warnings and precautions for use
Warnings
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, have
been reported with all NSAIDs 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 occur in patients receiving
diclofenac, the medicinal product should be withdrawn.
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, including diclofenac (see
section 4.8 Undesirable effects). Patients appear to be at highest risk of 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.
As
with
other
NSAIDs,
allergic
reactions,
including
anaphylactic/anaphylactoid reactions, can occur in rare cases without earlier
exposure to diclofenac.
In common with other NSAIDs, diclofenac may mask the signs and symptoms
of infection due to its pharmacodynamic properties.

Precautions
General
Undesirable effects may be minimised by using the lowest effective dose for
the shortest duration necessary to control symptoms (see GI and
Cardiovascular risks below).
The concomitant use of diclofenac with systemic NSAIDs, including
cyclooxygenase-2 selective inhibitors, should be avoided due to the absence of
any evidence demonstrating synergistic benefits and the potential for additive
undesirable effects.
Caution is indicated in the elderly. In particular, it is recommended that the
lowest effective dose be used in frail elderly patients or those with a low body
weight.
Voltarol Pain-eze Tablets contain lactose and therefore are not recommended
for patients with rare hereditary problems of galactose intolerance, of severe
lactase deficiency or of glucose-galactose malabsorption.
Caution (discussion with doctor or pharmacist) is required prior to starting
treatment in patients with a history of hypertension and/or heart failure as fluid
retention, hypertension and oedema have been reported in association with
NSAIDs therapy (see Renal effects below).
Pre-existing asthma
In patients with asthma, seasonal allergic rhinitis, swelling of nasal mucosa
(i.e. nasal polypus), chronic obstructive pulmonary disease or chronic
infection of the respiratory tract (especially if linked to allergic rhinitis-like
symptoms), reactions to NSAIDs such as asthma exacerbations (so-called
intolerance to analgesics / analgesics-asthma), angioedema or urticaria are
more frequent than in other patients.
Gastrointestinal effects
As with all NSAIDs, close medical surveillance is imperative and 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
Undesirable effects). The risk of GI bleeding is higher with increasing NSAID
doses and in patients with a history of ulcer, particularly if complicated with
haemorrhage or perforation and in the elderly.
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, anti-platelet agents or selective serotonin-reuptake inhibitors
(see section 4.5 Interaction with other medicinal products and other forms of
interaction).
Close medical surveillance should also be exercised in patients with ulcerative
colitis or Crohn's disease, as their condition may be exacerbated (see section
4.8 Undesirable effects).

Cardiovascular and cerebrovascular effects
Patients with significant risk factors for cardiovascular events (e.g.
hypertension, hyperlipidaemia, diabetes mellitus and 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 re-evaluated periodically. Patients should be advised to seek
further medical advice if symptoms persist or do not improve within the
recommended duration of treatment.
Clinical trial and epidiological 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 (150 mg daily)
and in long-term treatment. Available data do not suggest an increased risk
with use of low dose diclofenac (up to 75 mg/day) up to 3 days for relief of
pain or fever.
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, values of one or more liver enzymes may increase. In
the case of diclofenac being prescribed for a prolonged period, 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 (e.g.
eosinophilia, rash), diclofenac should be discontinued. Hepatitis may occur
without prodromal symptoms.
Caution is called for when using diclofenac in patients with hepatic porphyria,
since it may trigger an attack.
Renal effects
Caution is called for in patiens with impaired renal function, particularly the
elderly and patients receiving concomitant treatment with diuretics or
medicinal products that can significantly impact renal function and in those
patients with substantial extracellular volume depletion.
As fluid retention and oedema have been reported in association with NSAID
therapy, particular caution is called for in 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 Contraindications). 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 pretreatment state.

Haematological effects
Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation.
Patients with defects of haemostasis should be carefully monitored.
Dermatological 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. Voltarol Pain-eze Tablets should be discontinued at
the first appearance of skin rash, mucosal lesions, or any other sign of
hypersensitivity.
The label will state:
Read the enclosed leaflet before taking this medicine.
Do not take if you:


have or have ever had a stomach ulcer, perforation or bleeding



are allergic to diclofenac or any other ingredient of the product,
acetylsalicylic acid, ibuprofen or other related painkillers



are taking other NSAID painkillers, or aspirin



are pregnant or breastfeeding

Speak to a pharmacist or your doctor before taking this product if you:


have or have had asthma, diabetes, high cholesterol, high blood pressure, a
stroke, liver, heart, kidney or bowel problems



are intolerant to some sugars



are on a controlled potassium diet



are a smoker

If symptoms persist or worsen, consult your doctor.
4.5

Interaction with other medicinal products and other forms of interaction
Lithium and digoxin: Diclofenac may increase plasma concentrations of
lithium and digoxin.
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.
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.
Concomitant treatment with potassium-sparing diuretics may be associated
with increased serum potassium levels, which should therefore be monitored
frequently (see section 4.4 Special warnings and special precautions for use).
Other NSAIDs: including cyclooxygenase-2 selective inhibitors and
corticosteroids:
Co-administration of diclofenac with aspirin or corticosteroids may increase
the risk of gastrointestinal bleeding or ulceration. Avoid concomitant use of
two or more NSAIDs (see section 4.4 Special warnings and special
precautions for use).
Selective serotonin reuptake inhibitors (SSRIs) and anti-platelet agents:
Increased risk of gastrointestinal bleeding (see section 4.4 Special warnings
and special precautions for use).
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. Monitoring of the blood glucose
level is recommended as a precautionary measure during concomitant therapy.
Methotrexate: Caution is recommended when NSAIDs 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.
Ciclosporin and tacrolimus: 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 or tacrolimus.
Quinolone antibacterials: There have been isolated reports of convulsions
which may have been due to concomitant use of quinolones and NSAIDs.
4.6

Pregnancy and lactation
Pregnancy
The use of diclofenac in pregnant women has not been studied. Therefore,
Voltarol Pain-eze Tablets should not be used during pregnancy except on the
advice of a doctor.
Lactation
Like other NSAIDs, diclofenac passes into the breast milk in small amounts.
Therefore, Voltarol Pain-eze Tablets should not be administered during breast
feeding in order to avoid undesirable effects in the infant.
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.

4.7

Effects on ability to drive and use machines
Usually there is no effect at the recommended low-dose and short duration of
treatment. However patients experiencing visual disturbances, dizziness,
vertigo, somnolence or other central nervous system disturbances while taking
diclofenac should refrain from driving or using machines.

4.8.

Undesirable effects
Adverse reactions (Table 1) are ranked under heading of frequency, the most
frequent first, using the following convention: common (≥ 1/100, < 1/10);
uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (<
1/10,000), including isolated reports.
Available data do not suggest an increased risk with use of low dose
diclofenac (up to 75 mg/day) for up to 3 days treatment for the relief of pain or
fever.
Table 1
Blood and lymphatic system disorders
Very rare:
Thrombocytopenia, leukopenia, anaemia (including haemolytic
anaemia and aplastic anaemia), agranulocytosis.
Immune system disorders
Rare:
Hypersensitivity, anaphylactic and anaphylactoid reaction (including
hypotension and shock).
Very rare:
Angioneurotic oedema (including face oedema).
Psychiatric disorders
Very rare:
Disorientation, depression, insomnia, nightmare, irritability, psychotic
disorder.
Nervous system disorders
Common:
Headache, dizziness.
Rare:
Somnolence.
Very rare:
Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic
meningitis, taste disturbances, cerebrovascular accident.
Eye disorders
Very rare:
Visual disturbance, vision blurred, diplopia.
Ear and labyrinth disorders
Common:
Vertigo.
Very rare:
Tinnitus, hearing impaired.
Cardiac disorders
Very rare:
Palpitations, chest pain, cardiac failure, myocardial infarction.
Vascular disorders
Very rare:
Hypertension, vasculitis.
Respiratory, thoracic and mediastinal disorders
Rare:
Asthma (including dyspnoea).
Very rare:
Pneumonitis.
Gastrointestinal disorders
Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence,
Common:
anorexia.
Rare:
Gastritis, gastrointestinal haemorrhage, Haematemesis, diarrhoea,
hemorrhagic melaena, gastrointestinal ulcer (with or without bleeding
or perforation).

Very rare:

Colitis, (including haemorrhagic colitis and exacerbation of ulcerative
colitis or Crohn’s disease), constipation, stomatitis, glossitis,
oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders
Common:
Transaminases increased.
Rare:
Hepatitis, jaundice, liver disorder.
Very rare:
Fulminant hepatitis
Skin and subcutaneous tissue disorders
Common:
Rash.
Rare:
Urticaria.
Very rare:
Bullous eruptions, eczema, erythema, erythema multiforme, StevensJohnson syndrome, toxic epidermal necrolysis (Lyell's syndrome),
dermatitis exfoliative, loss of hair, photosensitivity reaction, purpura,
allergic purpura, pruritus.
Renal and urinary disorders
Very rare:
Acute renal failure, haematuria, proteinuria, nephrotic syndrome,
interstitial nephritis, renal papillary necrosis.
General disorders and administration site conditions
Rare:
Oedema.

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 for Contraindications and
Special warnings and special precautions for use).
4.9

Overdose
Symptoms
There is no typical clinical picture resulting from diclofenac overdosage.
Overdose can cause symptoms such as vomiting, gastrointestinal
haemorrhage, diarrhoea, dizziness, tinnitus or convulsions. In the event of
significant poisoning, acute renal failure and liver damage are possible.
Therapeutic measures
Management of acute poisoning with NSAIDs essentially consists of
supportive measures and symptomatic treatment. These should be given for
complications such as hypotension, renal failure, convulsions, gastrointestinal
disorder, and respiratory depression.
Special measures such as forced diuresis, dialysis or haemoperfusion are
probably of no help in eliminating NSAIDs due to the high protein binding
and extensive metabolism.
Activated charcoal may be considered in case of a potentially toxic overdose,
and gastric decontamination (e.g. vomiting, gastric lavage) in case of a
potentially life-threatening overdose.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products,
non-steroids, acetic acid derivatives and related substances (ATC code M01A
B05).
Voltarol Pain-eze Tablets contain diclofenac potassium, a non-steroidal antiinflammatory drug (NSAID) with pronounced analgesic, anti-inflammatory
and antipyretic properties. Inhibition of prostaglandin biosynthesis is
considered fundamental to its mechanism of action. Prostaglandins play a
major role in causing inflammation, pain and fever.
Diclofenac potassium in vitro does not suppress proteoglycan biosynthesis in
cartilage at concentrations equivalent to those reached in humans.

5.2

Pharmacokinetic properties
Absorption
Diclofenac is rapidly and completely absorbed. Following ingestion of two
12.5 mg coated tablets, mean peak plasma concentrations of 2.15 μmol/L are
attained after approximately 30 minutes (median Tmax).
The amount absorbed is in linear proportion to the size of the dose.
Since about half of diclofenac is metabolised during its first passage through
the liver (“first pass” effect), the area under the concentration curve is about
half as large following oral administration as it is following a parenteral dose
of equal size.
Pharmacokinetic behaviour does not change after repeated administration. No
accumulation occurs provided the recommended dosage intervals are
observed.
Distribution
99.7% of diclofenac binds to serum proteins, mainly to albumin (99.4%). The
apparent volume of distribution is 0.12 to 0.17 L/kg.
Diclofenac enters the synovial fluid, where maximum concentrations are
measured 2 to 4 hours after peak plasma values have been reached. The
apparent half-life for elimination from the synovial fluid is 3 to 6 hours. Two
hours after reaching peak plasma levels, concentrations of the active substance
are already higher in the synovial fluid than in the plasma, and they remain
higher for up to 12 hours.
Biotransformation
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 of these phenolic metabolites are
biologically active, but to a much lesser extent than diclofenac.
Elimination
Total systemic clearance of diclofenac from plasma is 263 ± 56 mL/min. The
terminal half-life in plasma is 1 to 2 hours. Four of the metabolites, including
the two active ones, also have short plasma half-lives of 1 to 3 hours. A fifth

metabolite, 3’-hydroxy-4’-methoxy-diclofenac, has a much longer plasma
half-life. This metabolite is virtually inactive.
About 60% of the administered dose is excreted in the urine as 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
No relevant age-dependent differences in the drug’s absorption, metabolism,
or excretion have been observed.
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 less than 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.
In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics
and metabolism of diclofenac are the same as in patients without liver disease.
5.3

Preclinical safety data
Preclinical data from acute and repeated dose toxicity studies, as well as from
genotoxicity, mutagenicity, and carcinogenicity studies with diclofenac
revealed no specific hazard for humans at the intended therapeutic doses.
There was no evidence that diclofenac had a teratogenic potential in mice, rats
or rabbits.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Core: silica, lactose, maize starch, sodium starch glycolate, polyvidone,
microcrystalline cellulose, magnesium stearate.
Coating: hypromellose, titanium dioxide (E171), microcrystalline cellulose,
stearic acid.

6.2

Incompatibilities
Not applicable

6.3

Shelf life
3 years

6.4

Special precautions for storage
Do not store above 25°C.

6.5

Nature and contents of container
PVC/Polychlorotrifluoroethylene/PVC – Alu blister packs.
Polyamide/ALU/PVC – Alu blister packs.
Pack size: 10 or 18 tablets, not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling
No special requirements

7

MARKETING AUTHORISATION HOLDER
Novartis Consumer Health UK Limited
Park View, Riverside Way,
Watchmoor Park, Camberley,
Surrey GU15 3YL
Trading as: Novartis Consumer Health

8

MARKETING AUTHORISATION NUMBER(S)
PL 00030/0073

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION

10

DATE OF REVISION OF THE TEXT
25/07/2014

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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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