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 minimized 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.

Children

For children of 12 years and over, the recommended daily dose is 75 – 100 mg in two or three divided doses. Diclofenac Potassium 50 mg tablets should not be indicated for use in children less than 12 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.

Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4)

• Hypersensitivity to Diclofenac 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. • 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). • This product contains soya. If you are allergic to peanut or soya, do not use this medicinal product.

Warnings

Undesirable effects may be minimized 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 effect (see section 4.5).

Elderly:

The elderly have increased frequency of adverse reactions to NSAIDs especially gastro intestinal bleeding and perforation which may be fatal (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, with ulcerative colitis, or with Crohn's disease as these conditions may be exacerbated (see section 4.8 Undesirable effects).

Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding).

Gastrointestinal bleeding, ulceration and perforation:

GI bleeding, 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.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAlD 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 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).

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 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.

NSAlDs 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).

Hepatic

Close medical surveillance is imperative in patients suffering from severe impairment of hepatic function.

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).

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).

Precautions

Cardiovascular, Renal and Hepatic Impairment:

The administration of an NSAlD may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3).

Hepatic

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 “Interactions”). 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

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.

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. 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 should only be treated with Diclofenac after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, and smoking).

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 NSAlDs (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.

Other analgesics   including   cyclooxygenase-2    selective    inhibitors    and corticosteroid:administration of diclofenac with other systemic NSAlDs or

corticosteroid may increase the risk gastrointestinal bleeding or ulceration.

Avoid concomitant use of two or more NSAlDs (including aspirin) as this may increase the risk of adverse effects (see section 4.4).

Diuretics and antihypertensive agents: like other NSAlDs , concomitant use of diclofenac diuretics or antihypertensive agents(e.g beta-blockers, angiotensin converting enzyme                      (AOI          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 give 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 drugs may be associated with increased serum potassium leve which should therefore be monitored frequently Digoxin: if use concomitantly,diclofenac may raise plasma concentrations of digoxin monitoring of the serum digoxin level is recommended.

Anti-hypertensives: Reduced anti-hypertensive effect.

Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Cardiac glycosides: NSAlDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Lithium: if use concomitantly,diclofenac may raise plasma concentrations of lithium Decreased elimination of lithium. Monitoring of the serum lithium level is recommended.

Methotrexate: Diclofenac,can inhibit the tubular renal clearance of methotrexate increasing methotrexate level .caution is recommended when NSAIDs, including diclofenac,administrered less than 24 hours before or after treatment with methotrexate, since blood concentration of methotrexate may rise and the toxicity of this substance be increased. Cases serious toxicity have been reported when methotrexate an 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: Diclofenace, like other NSAlDs,may lncreased the nephrotoxicity of ciclosporin due to the effect on renal prostaglandine. Therefore,it should be given at doses lower than that would be used in patient not receiving

 

ciclosprin..

Mifepristone: NSAlDs should not be used for 8-12 days after mifepristone administration as NSAlDs can reduce the effect of mifepristone.

Corticosteroids: lncreased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Anti-coagulants and Anti-platelet agents: caution is recommended since concomitant administration could increase the risk of bleeding ( see section 4.4). Although clinical investigation do not appear to indicate that diclofenac affects the action of anticoagulants, there are isolated report of an increased risk of haemorrhage in patients receiving diclofenac and anticoagulant concomitantly. Close monitoring of such patient is therefore recommended to be certain that change in anticoagulant dosage is required. As with other nonsteroidal anti-inflammatory agent diclofenac in a high dose can reversibly inhibit platelet aggregation also NSAlDs may enhance the effects of anti- coagulants, such as warfarin (see section 4.4).

Quinolone antibiotics: Animal data indicate that NSAlDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAlDs and quinolones may have an increased risk of developing convulsions.“Therefore, caution should be exercised when considering the use of quinolone in patients who are already receiving as NSAID.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRls): lncreased risk of gastrointestinal bleeding (see section 4.4).

Tacrolimus: Possible increased risk of nephrotoxicity when NSAlDs are given with tacrolimus.this might be mediated through renal antiprostaglandin effects of both NSAID and calcineual inhibitor.

Phenytoin: when using phenytoin concomitantly with diclofenac, monitoring pf phenytoin plasma concentration is recommended due to an expected increase in exposure to phenytoin.

Potent CYP2C9 inhibitor: caution is recommended when co-prescribing diclofenac with potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole), which could result in significant increase in peak plasma concentration and exposure to diclofenac due to inhibition diclofenac metabolism.

Zidovudine: lncreased risk of haematological toxicity when NSAlDs 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.

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.

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 cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increase from less 1% to approximately 1.5%.

The risk is believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality.

In addition, increase incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period during the first and second trimester of pregnancy, diclofenc should not be given unless clear necessary. If diclofenac is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to:

-cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension), renal dysfunction, which may progress to renal failure with oligo-hydroamniosis, their 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

In limited studies so far available, NSAlDs can appear in breast milk in very low concentrations. NSAlDs should, if possible, be avoided when breastfeeding.

Like other NSAIDs, diclofenac passes into the breast milk in small amounts. therefore, diclofenac 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 difficultied conceiving or who are undergoing investigation of infertility, withdrawal of diclofenac should be considered.

See section 4.4 Special warnings and precautions for use, 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.

If serious side-effects occur, Diclofenac Potassium tablets should be withdrawn.

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 section 4.4)

Gastrointestinal: The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (See section 4.4) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Other adverse reactions reported less commonly include:

Renal: Nephrotoxicity in various forms, including interstitial nephritis, nephritic syndrome and renal failure.

Hepatic: abnormal liver function, hepatitis and jaundice.

Neurological and special senses: Visual disturbances, optic neuritis, headaches, paraesthesia, reports of 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) , depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Haematological: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.

Dermatological: Bullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity.

Cardiovascular    system:    In    isolated    cases,    Palpitations,    chest    pain, hypertension, congestive heart failure.

Other organ systems: Impotence (very rare).

 

To report any side effect(s):

•Saudi Arabia:

The National Pharmacovigilance Center (NPC):

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa Website: https://ade.sfda.gov.sa/

•United Arab of Emirates:

Pharmacovigilance and Medical Device Section P.O. Box: 1853, Tel: 80011111

Email: pv@mohap.gov.ae

Drug Department, Ministry of Health & Prevention Dubai-UAE.

•Other GCC States:

Please contact the relevant competent authority.

a)   Symptoms

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, 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.

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.

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

“Special measures such as forced dieresis, dialysis or haemo-perfusion are probably of no help in eliminating NSAIDs, including diclofenac,due to high protein binding any extensive metabolism“

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.

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 3.9µmol/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 fertility, pregnancy and lactation)

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.

Lactose monohydrate, maize starch, microcrystalline cellulose, sodium starch glycolate, talc, Povidone V, magnesium Stearate, opadry OYL white, red iron oxide, polyethylene glycol.

Not applicable

3 Years.

No special storage precautions. Store below 30°C

Dolvic-K® 50 mg tablets are round, deep convex, reddish brown, non-scored film coated tablets engraved with PhI on one side & NC2 embossed on the other. Packed in PVC/TE/PVDC/Alu blisters, intended for oral use.

Pack sizes: 20 Film Coated Tablets.

Not applicable.