1. Name Of The Medicinal Product
Diclofenac potassium 12.5mg Tablets
Double Action Pain Relief 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
Film coated Tablet
White round, unscored biconvex film coated tablet, 5mm diameter, with 'I' marked on one side.
4. Clinical Particulars
4.1 Therapeutic Indications
Short term relief of headache, dental pain, period pain, rheumatic pain, muscular pain, 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.
Double Action Pain Relief 12.5mg Tablets should not be used for longer than 3 days. If symptoms persist or worsen consult your doctor.
To be taken preferably with or after food, swallowed whole with a drink of water.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to relieve symptoms (see section 4.4).
Children and Adolescents:
Double Action Pain Relief 12.5mg Tablets are not to be used in children and adolescents under 14 years of age.
4.3 Contraindications
Known hypersensitivity to diclofenac or to any of the excipients.
Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes) of proven ulceration or bleeding.
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.
Severe heart failure, hepatic failure or renal failure (see section 4.4).
Use with concomitant NSAIDs including cyclooxygenase-2-selective inhibitors should be avoided (see section 4.5).
Concomitant use of anticoagulants and antiplatelets (see section 4.5).
Pregnancy or breastfeeding (see section 4.6).
This product contains soya. If you are allergic to peanut or soya, do not use this medicinal product.
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 elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Cardiovascular and cerebrovascular effects
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 NSAID therapy.
Clinical trial and epidemiological data suggest that use of diclofenac, particularly at high doses (150 mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). 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.
Gastrointestinal
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.
Although diclofenac is usually well tolerated, there have been reported incidences of gastro-intestinal bleeding. Therefore, patients with a history of gastro-intestinal disease should not take diclofenac without being closely monitored by their doctor (see section 4.3).
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 anti-platelet agents such as aspirin (see section 4.5).
When GI bleeding or ulceration occurs in patients receiving diclofenac, the treatment should be withdrawn.
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.
NSAIDs should 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).
Respiratory disorders:
Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease.
Renal:
Renal impairment, as the use of NSAIDs may result in further deterioration of renal function (see sections 4.3 and 4.8).
Patients with impaired renal or cardiac function, particularly the elderly, and patients receiving concomitant treatment with diuretics or medicinal products that can significantly impact renal function should only consider use of diclofenac with great caution and always only under their doctor's supervision, who will need to monitor renal function.
Hepatic:
As with other NSAIDs, values of one or more liver enzymes may increase. In the case of diclofenac being prescribed for a prolonged period, close medical surveillance is needed and regular monitoring of hepatic function is indicated as a precautionary measure (see sections 4.3 and 4.8).
Caution is called for when using diclofenac in patients with hepatic porphyria, since it may trigger an attack.
Haematological effects:
Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Patients with defects of haemostasis should be carefully monitored.
Anaphylactic (anaphylactoid) reactions:
As with other non-steroidal anti-inflammatory drugs, allergic reactions, including anaphylactic/anaphylactoid reactions, can occur in rare cases without earlier exposure to diclofenac.
SLE and mixed connective tissue disease:
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease there may be increase risk of aseptic meningitis (see section 4.8).
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 including diclofenac (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. Double Action Pain Relief 12.5mg Tablets should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Impaired female fertility:
There is limited evidence that drugs which inhibit cyclo-oxygenase / prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.
In common with other NSAIDs, diclofenac potassium may mask the signs and symptoms of infection due to its pharmacodynamic properties.
The label will state:
Read the enclosed leaflet before taking this medicine.
Do not take if you:
• have (or have had two or more episodes of) a stomach ulcer, perforation or bleeding
• are allergic to diclofenac or any other ingredient of the product, aspirin, ibuprofen or other related painkillers
• are taking other NSAID painkillers, or aspirin
• are taking medicines that thin the blood
• 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 allergic to peanut or soya
• 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
Diclofenac should be avoided in combination with:
Aspirin: Unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, as this may increase the risk of adverse reactions (see section 4.4).
Other NSAIDs: including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse effects (see section 4.3).
Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.3).
Diclofenac should be used with caution in combination with:
Antihypertensive and diuretics: NSAIDs may diminish the effect of these drugs. Diclofenac and other non-steroidal anti-inflammatory drugs may increase the risk of renal impairment associated with the use of ACE-inhibitors. Diuretics can increase the risk on nephrotoxity of NSAIDs.
Concomitant treatment with potassium-sparing diuretics may be associated with increased serum potassium levels, which should therefore be monitored frequently under medical supervision (see section 4.4 Special warnings and special precautions for use).
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Selective serotonin reuptake inhibitors (SSRIs) and anti-platelet agents: Increased risk of gastrointestinal bleeding (see section 4.4).
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increased plasma glycoside levels.
Lithium: There is evidence for potential increases in plasma levels of lithium, due to decreased elimination of lithium.
Methotrexate: There is a potential for an increase in plasma methotrexate, due to decreased elimination of methotrexate.
Ciclosporin: Increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthoroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
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.
Antidiabetics: Clinical studies have shown that diclofenac potassium 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.
4.6 Pregnancy And Lactation
Pregnancy
The use of diclofenac in pregnant women has not been studied. Therefore, Double Action Pain Relief 12.5mg 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, Double Action Pain Relief 12.5mg 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 (see section 4.4).
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 drug reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (
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.
Gastro-intestinal: the most commonly-observed adverse events are gastrointestinal in nature.
Common - Nausea, vomiting, diarrhoea, flatulence, dyspepsia, abdominal pain.
Rare – Gastritis, melaena, haematemesis. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (See section 4.4).
Very rare - Constipation, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (See section 4.4) have been reported following administration, pancreatitis.
Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs.
These may consist of (a) non-specific allergic reactions and anaphylaxis – rare (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, - rare or (c) assorted skin disorders, including rashes of various types (common); urticaria (rare); purpura, angiodema pruritus, and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis, erythema multiforme – very rare.
Cardiovascular: Rare – Oedema.
Very rare - Hypertension, and cardiac failure, have been reported in association with NSAID treatment.
Clinical trial and epidemiological data suggest that the use of diclofenac, particularly at high dose (150mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events ( for example myocardial infarction or stroke) (see section 4.4).
Renal: Very rare- Nephrotoxicity in various forms, interstitial nephritis, nephrotic syndrome and renal failure.
Hepatic: Rare - Abnormal liver function, hepatitis and jaundice.
Neurological and special senses: Common - Headache, dizziness, vertigo. Very rare - Visual disturbances, optic neuritis, paraesthesia, depression, confusion, hallucinations, tinnitus, malaise, fatigue and drowsiness.
Aseptic meningitis (especially in patients with existing autoimmune 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).
Haematological: Very rare - Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia, haemolytic anaemia.
Dermatological: Very rare - Photosensitivity, bullous reactions including Stevens Johnson syndrome and toxic epidermal necrolysis.
Other organ systems: Very rare – Impotence.
4.9 Overdose
Symptoms
Most patients who have ingested clinically important amounts of NSAIDs will develop no more than nausea, vomiting, epigastric pain, or more rarely diarrhoea. Tinnitus, headache and gastrointestinal bleeding are also possible. In more serious poisoning, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation and disorientation or coma. Occasionally patients develop convulsions.
In serious poisoning metabolic acidosis may occur and the prothrombin time / INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur.
Exacerbation of asthma is possible in asthmatics.
Management
Management should be symptomatic and supportive and include the maintainance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents with 1 hour of ingestion of a potentially toxic amount if frequent of prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.
Renal and liver function should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: NSAID, ATC code: {M01 AB 05}
Diclofenac potassium tablets contain the potassium salt of diclofenac, a non-steroidal compound with pronounced and clinically demonstrable analgesic, anti-inflammatory and anti-pyretic properties.
Diclofenac is a potent inhibitor of prostaglandin bio-synthesis and modulator of arachidonic acid release and uptake.
Diclofenac potassium tablets have a rapid onset of action and are, therefore, suitable for the treatment of acute episodes of pain and inflammation.
In migraine attacks Diclofenac potassium has been shown to be effective in relieving the headache and in improving the accompanying symptom of nausea.
Diclofenac in vitro does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent to the concentrations reached in human beings.
5.2 Pharmacokinetic Properties
Absorption
Diclofenac is rapidly and completely absorbed from sugar-coated tablets. Food intake does not affect absorption.
Peak plasma concentration after one 12.5 mg tablet was 0.944 μmol/l after 54 minutes. The plasma concentrations show a linear relationship to the size of the dose.
Diclofenac undergoes first-pass metabolism and is extensively metabolised.
Distribution
Diclofenac is highly bound to plasma proteins (99.7%), chiefly albumin (99.4%)
Elimination
The total systemic clearance of diclofenac in plasma is 263 ± 56 ml/min (mean ± SD).
The terminal half-life in plasma is 1-2 hours.
Repeated oral administration of Diclofenac Potassium for 8 days in daily doses of 50 mg t i d does not lead to accumulation of diclofenac in the plasma.
Approx. 60% of the dose administered is excreted in the urine in the form of metabolites, and less than 1% as unchanged substance. The remainder of the dose is eliminated as metabolites through the bile in the faeces.
Biotransformation
The biotransformation of diclofenac involves partly glucuronidation of the intact molecule but mainly single and multiple hydroxylation followed by glucuronidation.
Characteristics in patients
The age of the patient has no influence on the absorption, metabolism, or excretion of diclofenac.
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 theoretical steady-state plasma levels of metabolites are about four times higher than in normal subjects. However, the metabolites are ultimately cleared through the bile.
In the presence of impaired hepatic function (chronic hepatitis, non-decompensated cirrhosis) the kinetics and metabolism are the same as for patients without liver disease.
5.3 Preclinical Safety Data
Relevant information on the safety of Diclofenac potassium is included in other sections of the Summary of Product Characteristics.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Tablet core:
Silica colloidal anhydrous
Sodium starch glycollate
Povidone
Starch maize
Calcium hydrogen phosphate anhydrous
Magnesium stearate
Film coating:
Polyvinyl alcohol partially hydrolysed
Titanium dioxide E171
Talc
Lecithin soya E322
Xanthan gum E415
6.2 Incompatibilities
Not applicable
6.3 Shelf Life
36 months
6.4 Special Precautions For Storage
Do not store above 25°C.
6.5 Nature And Contents Of Container
Blister pack. Pack size: 18 tablets
6.6 Special Precautions For Disposal And Other Handling
No special requirements
7. Marketing Authorisation Holder
Actavis Group PTC ehf
Reykjavíkurvegi 76-78
220 Hafnarfjordur
Iceland.
8. Marketing Authorisation Number(S)
PL 30306/0243
9. Date Of First Authorisation/Renewal Of The Authorisation
3rd March 2009
10. Date Of Revision Of The Text
24th June 2010
11 DOSIMETRY
(IF APPLICABLE)
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
(IF APPLICABLE)
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