Document: spc-doc_PL 00030-0054 change

• spc-doc_PL 00030-0054
• spc-doc_PL 44673-0161

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Voltarol Pain-eze Extra Strength 25mg Tablets

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each tablet contains diclofenac potassium 25mg.

Chemical name: potassium-[o-[(2,6-dichlorophenyl)-amino]-phenyl] -acetate. For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Pale red, round biconvex sugar-coated tablets.

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:

Take one tablet every 4 to 6 hours as needed. No more than 3 tablets (75 mg) should be taken in any 24 hour period.

Voltarol Extra Strength 25mg Tablets should not be used for longer than 3 days. If symptoms persist or worsen consult your doctor.

The tablets should be swallowed whole with a drink of water.

Children and Adolescents:

Voltarol Extra Strength 25mg 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

• 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.

•    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)

•    Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors (see section 4.5 Interactions)

4.4 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.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

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.

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 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 (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 patients 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 Extra Strength 25mg 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 Fertility, pregnancy and lactation Pregnancy

The use of diclofenac in pregnant women has not been studied. Therefore, Voltarol Pain-eze Extra Strength 25mg 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 Extra Strength 25mg 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

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: NSAID, ATC code: {M01 AB 05}

Voltarol Pain-eze Extra Strength 25mg Tablets contain the potassium salt of diclofenac, a non-steroidal anti-inflammatory drug with pronounced analgesic and anti-pyretic properties.

Voltarol Pain-eze Extra Strength 25mg 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 is a potent inhibitor of prostaglandin bio-synthesis and modulator of arachidonic acid release and uptake.

Diclofenac possesses clinically demonstrable analgesic, antipyretic and antiinflammatory effects.

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 50mg sugar-coated tablet was 3.9 mmol/l after 20-60 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 Voltarol Pain-eze Extra Strength 25mg Tablets for 8 days in daily doses of 50mg three times a day does not lead to accumulation of diclofenac in the plasma.

Approximately 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.

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.

Characteristics in patients:

The age of the patient has no influence on the absorption, metabolism, or excretion of diclofenac.

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 Voltarol Pain-eze Extra Strength 25mg Tablets is included in other sections of the Summary of Product Characteristics.

PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Core

Aerosil 200 (silica aerogel)

Calcium phosphate, tribasic Magnesium stearate Maize starch

Polyvinylpyrrolidone K30, PH Sodium carboxymethyl starch

Coating

Avicel PH 101 (cellulose)

Iron oxide, red 17266 Polyethylene glycol 8000 Polyvinylpyrrolidone K30, PH Sucrose, cryst Talc PH

Titanium dioxide, PH

6.2    Incompatibilities

None

6.3    Shelf life

30 months.

6.4    Special precautions for storage

Store below 30°C and protect from moisture.

6.5    Nature and contents of container

PVC/PE/PVdC blister strips containing 9 tablets.

6.6    Special precautions for disposal and other handling

Medicines should be kept out of the reach of children.

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 00030/0054.

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

03/12/2010

10 DATE OF REVISION OF THE TEXT

25/07/2014