Rheumatoid arthritis

Osteoarthrosis

Low back pain

Migraine attacks

Acute musculo-skeletal disorders and trauma such as periarthritis (especially frozen shoulder),

tendinitis, tenosynovitis, bursitis, sprains, strains and dislocations; relief of pain in fractures

Ankylosing spondylitis

Acute gout

Control of pain and inflammation in orthopaedic, dental and other minor surgery

Pyrophosphate arthropathy and associated disorders

For oral administration.

To be taken preferably with or after food.

The tablets should be swallowed whole with liquid

Undesirable effects may be minimised by using the lowest effective dose for the

shortest duration necessary to control symptoms (see section 4.4)

Adults

The recommended daily dose is 100 – 150 mg in two or three divided doses. For milder

cases, 75 – 100 mg daily in two or three divided doses is usually sufficient.

In migraine an initial dose of 50 mg should be taken at the first signs of an impending

attack. In cases where relief 2 hours after the first dose is not sufficient, a further dose of

50 mg may be taken. If needed, further doses of 50 mg may be taken at intervals of 4 – 6

hours, not exceeding a total dose of 200 mg per day.

Pediatric population

For children over 14 years of age, the recommended daily dose is 75 – 100 mg in two or

three divided doses. Diclofenac Potassium 25 mg tablets are not recommended for children

under 14 years of age. The use of Diclofenac Potassium 50 mg tablets in migraine attacks

has not been established in children.

Elderly

The elderly are at increased risk of the serious consequences of adverse reactions. If an

NSAID is considered necessary, the lowest effective dose should be used and for the

shortest possible duration. The patient should be monitored regularly for GI bleeding

during NSAID therapy.

Renal impairment

No adjustment of the starting dose is required for renally impaired patients (see section

4.4).

Hepatic impairment

No adjustment of the starting dose is required for hepatically impaired patients (see section

4.4).

- Hypersensitivity to the active substance or any of the excipients. - Active, gastric or intestinal ulcer, bleeding or perforation. - Active, or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding). - NSAIDs are contraindicated in 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. - Established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease. - Severe heart failure, hepatic failure and renal failure (see section 4.4). - History of gastro-intestinal bleeding or perforation, relating to previous NSAID therapy. - During the last trimester of pregnancy (see section 4.6).

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 use of Diclofenac potassium with concomitant 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 (see section 4.5).

Elderly

Caution is indicated in the elderly on basic medical grounds. The elderly have increased

frequency of adverse reactions to NSAIDs especially gastro intestinal bleeding and perforation

which may be fatal. 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). 

Gastrointestinal

Close medical surveillance is imperative in patients with symptoms indicative of gastrointestinal

disorders, with a history suggestive of gastric or intestinal ulceration, bleeding or perforation,

with ulcerative colitis, or with Crohn's disease as these conditions may be exacerbated (see

section 4.8).

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.

GI bleeding (haematemesis, melaena), ulceration or perforation, which can be fatal, has been

reported with all NSAIDs at any time during treatment, with or without warning symptoms or a

previous history of serious GI events. They generally have more serious consequences in the

elderly.

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. These patients should commence and maintain treatment on the

lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton

pump inhibitors) should be considered for these patients, and also for patients requiring

concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below

and section 4.5).

Caution should be advised in patients receiving concomitant medications which 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 potassium, the treatment

should be withdrawn.

NSAID

Hypersensitivity reactions

As with other non-steroidal anti-inflammatory drugs, allergic reactions, including

anaphylactic/anaphylactoid reactions, can occur without earlier exposure to the drug (see section

4.8).

Infection

Like other NSAIDs, Diclofenac Potassium tablets may mask the signs and symptoms of

infection due to their pharmacodynamic properties.

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).

Cardiovascular, Renal and Hepatic Impairment:

The administration of an NSAID may cause a dose dependent reduction in prostaglandin

formation and precipitate renal failure.

As fluid retention and oedema have been reported in association with NSAIDs 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 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 therapy is usually followed by recovery to the

pre-treatment state.

Hepatic

Close medical surveillance is required when prescribing diclofenac to patients with impairment

of 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, clinical signs or

symptoms consistent with liver disease develop or if other manifestations occur (eosinophilia,

rash), Diclofenac Potassium tablets should be discontinued.

Hepatitis may occur without prodromal symptoms.

Use of Diclofenac Potassium tablets in patients with hepatic porphyria may trigger an attack.

Haematological

Diclofenac Potassium tablets may reversibly inhibit platelet aggregation (see section 4.5).

Patients with defects of haemostasis, bleeding diathesis or haematological abnormalities should

be carefully monitored.

Long term treatment

All patients who are receiving long term treatment with non-steroidal, anti-inflammatory agents

should be monitored as a precautionary measure eg renal function, hepatic function (elevation of

liver enzymes may occur) and blood counts. This is particularly important in the elderly.

Respiratory disorders

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 / analgesics asthma), 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.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other

NSAIDs can precipitate bronchospasm if administered to patients suffering from, or with a

previous history of bronchial asthma.

Cardiovascular and cerebrovascular effects

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 suggest that 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).

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart

disease, peripheral arterial disease, and/or cerebrovascular disease and with significant risk

factors for cardiovascular events (e.g.,, 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 re-evaluated periodically.

Dermatological

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 potassium should be discontinued at the first appearance of skin

rash, mucosal lesions, or any other sign of hypersensitivity.

Impaired female fertility

The use of Diclofenac Potassium tablets may impair female fertility and is not recommended in

women attempting to conceive. In women who may have difficulties conceiving or who are

undergoing investigation of infertility, withdrawal of Diclofenac Potassium tablets should be

considered (see section 4.6).

Other NSAIDs including cyclooxygenase-2 selective inhibitors and corticosteroids:

Co-administration of diclofenac with other systemic NSAIDs or corticosteroids may increase the

risk of gastrointestinal bleeding or ulceration. Avoid concomitant use of two or more NSAIDs

(see section 4.4).

Diuretics and antihypertensive agents: Like other NSAIDs, concomitant use of diclofenac with

diuretics and 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 periodically thereafter, particularly for diuretics and ACE inhibitors due to

the increased risk of nephrotoxicity.(see section 4.4)

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma

glycoside levels.

Lithium: If used concomitantly, diclofenac may increase plasma concentrations of lithium

Monitoring of the serum lithium level is recommended.

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 treatment with methotrexate, since blood

concentrations of methotrexate may rise and the toxicity of this substance be increase. Cases of

serious toxicity have been reported when methotrexate and NSAIDs including diclofenac 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.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as

NSAIDs can reduce the effect of mifepristone.

Anti-coagulants and anti-platelet agents: Caution is recommended since concomitant

administration could increase the risk of bleeding (see section 4.4). Although clinical

investigations do not appear to indicate that diclofenac has an influence on the effect of

anticoagulants, there are reports of an increased risk of haemorrhage in patients receiving

diclofenac and anticoagulant concomitantly (see section 4.4). Therefore, to be certain that no

change in anticoagulant dosage is required, close monitoring of such patients is required. As with

other nonsteroidal anti-inflammatory agents, diclofenac in a high dose can reversibly inhibit

platelet aggregation.NSAID

Digoxin: If used concomitantly, diclofenac may raise plasma concentrations of digoxin.

Monitoring of the serum digoxin level is recommended. 

Selective serotonin reuptake inhibitors (SSRls): lncreased risk of gastrointestinal bleeding (see

section 4.4).

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

This might be mediated through renal antiprostagladin effects of both NSAID and calcineurin

inhibitor.

Quinolone antibacterials: Convulsions may occur due to an interaction between quinolones and

NSAIDs. This 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.

Zidovudine: lncreased 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.

Antidiabetic agents: Clinical studies have shown that Diclofenac Potassium tablets can be given

together with oral antidiabetic agents without influencing their clinical effect. However there

have been isolated reports of hypoglycaemic and hyperglycaemic effects which have required

adjustment to the dosage of hypoglycaemic agents. For this reason, monitoring of the blood

glucose level is recommended as a precautionary measure during concomitant therapy.

Drugs known to cause hyperkalemia: Concomitant treatment with potassium-sparing diuretics,

ciclosporin, tacrolimus or trimethoprim may be associated with increased serum potassium

levels, which should therefore be monitored frequently (see section 4.4).

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.

Pregnancy Category C Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (see section 4.3). NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to foetus. Lactation Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore Diclofenac should not be administered during breast feeding 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 may have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of diclofenac should be considered. See section 4.4 regarding female fertility.

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are

possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

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.   Table1 Blood and lymphatic system disorders Very rare Thrombocytopenia, leukopenia, anaemia (including haemolytic and aplastic anaemia), Agranulocytosis. Immune system disorders Rare   Very rare Hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock). Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident Eye disorders   Visual disturbance, vision blurred, diplopia. Ear and labyrinth disorders Common Very rare Vertigo. 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 Very rare Asthma (including dyspnoea). Pneumonitis. Gastrointestinal disorders Common   Rare       Very rare Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, anorexia.   Gastritis, gastrointestinal haemorrhage, haematemesis, diarrhoea haemorrhagic, melaena, gastrointestinal ulcer (with or without bleeding or perforation).   Colitis (including haemorrhagic colitis   and exacerbation of ulcerative colitis or Crohn's disease), constipation, Stomatitis (including ulcerative stomatitis), glossitis, oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis. Hepatobiliary disorders Common Rare Very rare Transaminases increased. Hepatitis, jaundice, liver disorder. Fulminant hepatitis, hepatic necrosis, hepatic failure. Skin and subcutaneous tissue disorders Common Rare Very rare 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, 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 Reproductive system and breast disorders Very rare Impotence     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) (see 4.4). The following undesirable effects include those reported with either short-term or long-term use.

 

 

 

 

 

To report any side effects

·    Saudi Arabia

National Pharmacovigilance & Drug Safety Center (NPC)

Fax: +966-11-205-7662

Call NPC at: +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

Toll free phone: 8002490000

E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

·    Other GCC States:

Please contact the relevant competent authority

a) Symptoms

There is no typical clinical picture resulting from diclofenac over dosage. Symptoms include

headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhea, dizziness,

disorientation, excitation, coma, drowsiness, tinnitus, fainting, occasionally convulsions. In rare

cases of significant poisoning acute renal failure and liver damage are possible.

b) Therapeutic measure

Patients should be treated symptomatically as required.

Within one hour of ingestion of a potentially toxic amount, activated charcoal should be

considered. Alternatively, in adults, gastric lavage should be considered within one hour of

ingestion of a potentially life-threatening overdose.

Good urine output should be ensured. 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.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam. Supportive

measures should be given for complications such as hypotension, renal failure, gastrointestinal

disorder, and respiratory depression.

Other measures may be indicated by the patient's clinical condition.

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug (NSAID).

ATC code: M01A B05

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 biosynthesis and a 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 tablets have 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.

To report any side effect(s)

• Saudi Arabia:

National Pharmacovigilance and Drug Safety Center (NPC)

Fax: +966-11-205-7662

Call NPC at +966-11-2038222

Exts: 2317-2356-2353-2354-2334-2340

Toll free phone: 8002490000

E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

• Other GCC States:

Please contact the relevant competent authority.

Absorption

Diclofenac is rapidly and completely absorbed from sugar-coated tablets. Food intake does not

affect absorption.

Peak plasma concentration after one 50 mg sugar-coated tablet was 3.9 μmol/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%)

Diclofenac was detected in a low concentration (100ng/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).

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 tablets for 8 days in daily doses of 50 mg

t.d.s 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.

Relevant information on the preclinical safety of Diclofenac Potassium Tablets is included

in previous sections of this Summary of Product Characteristics.

Sodium Starch Glycolate

Talc

Colloidal Silicone Dioxide

Magnesium stearate

Methocel E6

plyethylene Glycol 4000

Titanium Dioxide

Ferric Oxide Red

Simethicone Emulsion

Copovidone

Dibasic Calcium Phosphate Anhydrous

Not applicable.

36 months.

Store below 30°C.

Two Aluminum-PVC/PVDC blisters of 10 tablets each, packed in printed carton with folded leaflet.

No special requirements.