Adults and elderly
Relief of all grades of pain and inflammation in a wide range of conditions, including:
(i) arthritic conditions: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout,
(ii) acute musculo-skeletal disorders such as periarthritis (for example frozen shoulder), tendinitis,
tenosynovitis, bursitis,
(iii) other painful conditions resulting from trauma, including fracture, low back pain, sprains, strains,
dislocations,orthopaedic, dental and other minor surgery.
Children
Rumafen 50 mg tablets are not suitable for children.

Posology
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to
controlsymptoms (see section 4.4).
Adults: 75 mg to 150 mg daily in two or three divided doses.
The recommended maximum daily dose of diclofenac sodium is 150mg.
Special populations
Elderly:
Although the pharmacokinetics of Diclofenac sodium are not impaired to any clinically relevant extent in
elderly patients, nonsteroidal anti-inflammatory drugs should be used with particular caution in such patients
who generally are more prone to adverse reactions. In particular it is recommended that the lowest effective
dosage be used in frail elderly patients or those with a low body weight (see also precautions) and the patient
should be monitored for GI bleeding during NSAID therapy.
Cardiovascular and significant cardiovascular risk factors
Diclofenac is contraindicated in patients with established congestive heart failure (NYHA II-IV), ischemic heart
disease, peripheral arterial disease and/or cerebrovascular disease (see section 4.3 Contraindications).
Patients with congestive heart failure (NYHA-I) or significant risk factors for cardiovascular disease should be
treated with diclofenac only after careful consideration. Since cardiovascular risks with diclofenac may increase
with dose andduration of exposure, the lowest effective daily dose should be used and for the shortest duration
possible (see section4.4 Special warnings and precautions for use).
Renal impairment: Diclofenac is contraindicated in patients with renal failure (see section 4.3
Contraindications). Nospecific studies have been carried out in patients with renal impairment, therefore, no
specific dose adjustmentrecommendations can be made. Caution is advised when administering diclofenac to
patients with mild to moderaterenal impairment (see section 4.4 Special warnings and precautions for use).
Hepatic impairment: Diclofenac is contraindicated in patients with hepatic failure (see section 4.3
Contraindications).
No specific studies have been carried out in patients with hepatic impairment, therefore, no specific dose
adjustment recommendations can be made. Caution is advised when administering diclofenac to patients with
mild to moderate hepatic impairment (see section 4.4 Special warnings and precautions for use).
Paediatric population:
Rumafen 50 mg tablets are not suitable for children.
Method of administration
For oral administration.
To be taken whole with liquid, preferably with or after food.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Active, or gastric or intestinal ulcer, bleeding or perforation. • History of gastrointestinal bleeding or perforation, relating to previous NSAIDs therapy. • Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding). • Last trimester of pregnancy (see section 4.6) • Hepatic failure • Renal failure • Established congestive heart failure (NYHA-II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease. • Like other non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac is also contraindicated in patients in whom attacks of asthma, angiodema, urticaria.

General
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 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 (see section 4.5).
Caution is indicated in the elderly on basic medical grounds. 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).
As with other nonsteroidal anti-inflammatory drugs including diclofenac, allergic reactions, including
anaphylactic/anaphylactoid reactions, can also occur without earlier exposure to the drug (see section
4.8).Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result
in myocardial infarction. Presenting symptoms of such reactions can include chest pain occurring in association
with an allergic reaction to diclofenac.
Like other NSAIDs, diclofenac may mask the signs and symptoms of infection due to its pharmacodynamic
properties.
This medicine contains lactose and therefore is not recommended for patients with rare hereditary problems of
galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
Gastrointestinal effects
Gastrointestinal bleeding (haematemesis, melaena), ulceration or perforation, which can be fatal has been
reported with all NSAIDs including diclofenac, and may occur at any time during treatment, with or without
warning symptoms or a previous history of serious gastrointestinal (GI) events. They generally have more
serious consequences in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving
diclofenac, the medicinal product should be withdrawn.
As with all NSAIDs, including diclofenac, close medical surveillance is imperative and particular caution
should be exercised when prescribing diclofenac in patients with symptoms indicative of gastrointestinal
disorders or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation (see section 4.8).
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses including diclofenac
and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation.
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding
and perforation which may be fatal (see section 4.2).
To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if complicated with
haemorrhage or perforation, and in the elderly, the treatment should be initiated and maintained at the lowest
effective dose.
Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered
for these patients, and also for patients requiring concomitant use of medicinal products containing low dose
acetylsalicylic acid (ASA/aspirin), or other medicinal products likely to increase gastrointestinal risk (see below
and section 4.5).
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 such as warfarin, selective serotoninreuptake
inhibitors (SSRIs) or anti-platelet agents such as acetylsalicylic acid (see section 4.5).
Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn's
disease, as their condition may be exacerbated (see section 4.8).
NSAIDs, including diclofenac, may be associated with increased risk of gastro-intestinal anastomotic leak.
Close medical surveillance and caution are recommended when using diclofenac after gastro-intestinal surgery.
Hepatic impairment
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 should be discontinued.
Hepatitis may occur with diclofenac without prodromal symptoms.
Caution is called for when using diclofenac in patients with hepatic porphyria, since it may trigger an attack.
Renal impairment
As fluid retention and oedema have been reported in association with NSAID 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 in those patients with substantial extracellular volume depletion from any cause, e.g.
before or after major surgery (see4.3). 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.
Skin 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.
Diclofenac sodium tablets should be discontinued at the first appearance of skin rash, mucosal lesions or any
other signs of hypersensitivity.
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 and cerebrovascular effects
Patients with congestive heart failure (NYHA-1) or patients with significant risk factors for cardiovascular
events (e.g., Hypertension, 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.
Appropriate monitoring and advice are required for patients with a history of hypertension and congestive heart
failure (NYHA-1) as fluid retention and oedema have been reported in association with NSAID therapy
including diclofenac.
Clinical trial and epidemiological data consistently point towards 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.
Patients should remain alert for the signs and symptoms of serious arteriothrombotic events (e.g. chest pain,
shortness of breath, weakness, slurring of speech), which can occur without warnings. Patients should be
instructed to see a physician immediately in case of such an event.
Haematological effects
During prolonged treatment with diclofenac, as with other NSAIDs, monitoring of the blood count is
recommended.
Diclofenac may reversibly inhibit platelet aggregation (see anticoagulants in section 4.5). Patients with defects
haemostasias, bleeding diathesis or haematological abnormalities should be carefully monitored.
Pre-existing asthma
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.
Female fertility:
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 4.6).

The following interactions include those observed with diclofenac gastro-resistant tablets and/or other
pharmaceutical forms of diclofenac.
Lithium: If used concomitantly, diclofenac may raise plasma concentrations of lithium. Monitoring of the serum
lithium level is recommended.
Digoxin: If used concomitantly, diclofenac may raise plasma concentrations of digoxin. Monitoring of the
serum digoxin level is recommended.
Diuretics and Anti-hypertensive 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 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 and periodically
thereafter, particularly for diuretics and ACE inhibitors due to the increased risk of nephrotoxicity.
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).
Anticoagulants 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 affects the action of anticoagulants, there are reports of an increased risk of haemorrhage in patients
receiving diclofenac and anticoagulants 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 high dose can reversibly inhibit platelet aggregation.
Other NSAIDS including cyclo-oxygenase-2selective inhibitors and corticosteroids: Co-administration of
diclofenac and 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).
Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of SSRIs may increase the risk of
gastrointestinal bleeding (see section 4.4).
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 hypoglycaemic and
hyperglycemic effects necessitating changes in the dosage of the antidiabetic agents during treatment with
diclofenac. For this reason, monitoring of the blood glucose level is recommended as a precautionary measure
during concomitant therapy.
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 increased.
Cases of serious toxicity have been reported when methotrexate and NSAIDs including diclofenac are given
within 24hours of each other. This interaction is mediated through accumulation of methotrexate resulting from
impairment ofrenal 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.
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 antimicrobials: 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.
Cardiac glycosides: Concomitant use of cardiac glycosides and NSAIDs in patients may exacerbate cardiac
failure, reduce GFR and increase plasma glycoside levels.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can
reduce the effect of mifepristone.
Potent CYP2C9 inhibitors: “Caution is recommended when co-prescribing diclofenac with potent CYP2C9
inhibitors (such as sulfinpyrazone and voriconazole), which could result in a significant increase in peak plasma
concentration and exposure to diclofenac due to inhibition of diclofenac metabolism.

Pregnancy and Breastfeeding
From the 20th week of pregnancy on ward, Rumafen use may cause oligohydramnios resulting from
foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon
discontinuation, in addition there have been reports of ductus arteriosus constriction following treatment
in the second trimester, most of which resolve after treatment cessation. Therefore, during the first and
second trimesters of pregnancy, Rumafen should not be given unless clearly necessary. If Rumafen is used by
a woman trying to conceive, or during the first and second trimesters of pregnancy, the dose should be kept low
and the duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and ductus
arteriosus constriction should be considered after exposure to Rumafen for several days from gestational
week 20 onwards. Rumafen should be discontinued if hypoamniotic fluid or ductus arteriosus
constriction is found.
During the last trimester of pregnancy, all inhibitors of fetal prostaglandin synthesis may expose the foetus to:
• cardiopulmonary toxicity (with premature constriction/closure of the ductus arteriosus and pulmonary
hypertension).
• Renal impairment (see above)
Mother and 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, Rumafen is contraindicated during the third trimester of pregnancy (see sections 4.3 and 5.3)
Female 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 (see also section 4.4 regarding female fertility).

Patients who experience visual disturbances, dizziness, vertigo, somnolence, central nervous system
disturbances, drowsiness or fatigue while taking NSAIDs should refrain from driving or operating machinery.

Adverse reactions are ranked under the 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, <1/1000); very rare (<1/10,000); not known: cannot be estimated from available data.
The following undesirable effects include those reported with other short-term or long-term use.
Table 1

* The frequency reflects data from long-term treatment with a high dose (150 mg/day). 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 doses (150 mg daily)
and in long term treatment (see sections 4.3 and 4.4 for Contraindications and Special warnings and special
precautions for use).

Reporting of suspected adverse reactions
The National Pharmacovigilance Center (NPC):
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Ext 2317-2356-2340
SFDA Call Center: 19999
E-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa

Symptoms
There is no typical clinical picture resulting from diclofenac over dosage. Over dosage can cause symptoms
such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhoea, dizziness,
disorientation, excitation, coma, drowsiness, tinnitus, fainting or convulsions. In the case of significant
poisoning acute renal failure and liver damage are possible.
Therapeutic measures
Management of acute poisoning with NSAIDs, including diclofenac, essentially consists of supportive measures
and symptomatic treatment. Supportive measures and symptomatic treatment should be given for complications
such as hypotension, renal failure, convulsions, gastrointestinal disorder, and respiratory depression.
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.
Activated charcoal may be considered after ingestion of a potentially toxic overdose, and gastric
decontamination (e.g. vomiting, gastric lavage) after ingestion of a potentially life threatening overdos

Pharmacotherapeutic group
Non-steroidal anti-inflammatory drugs (NSAlDs).
Mechanism of action
Rumafen is a non-steroidal agent with marked analgesic/anti-inflammatory properties. It is an inhibitor of
prostaglandin synthetase, (cyclo-oxygenase).
Diclofenac sodium in vitro does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent
to the concentrations reached in human beings.

Absorption
Absorption is complete but onset is delayed until passage through the stomach, which may be affected by food
which delays stomach emptying. The mean peak plasma diclofenac concentration reached at about 2 hours
(50mg dose produces 1511± 466 ng/ml ).
Bioavailability:
About half of the administered diclofenac is metabolised during its first passage through the liver ("first-pass"
effect), the area under the concentrations curve (AUC) following oral administration is about half that following
an equivalent parenteral dose.
Pharmacokinetic behaviour does not change on repeated administration. Accumulation does not occur, provided
the recommended dosage intervals are observed.
Distribution
The active substance is 99.7% protein bound, mainly to albumin (99.4%).
Diclofenac enters the synovial fluid, where maximum concentrations are measured 2-4 hours after the peak
plasma values have been attained. The apparent half-life for elimination from the synovial fluid is 3-6 hours.
Two hours after reaching the peak plasma values, concentrations of the active substance are already higher in
the synovial fluid than they are in the plasma and remain higher for up to 12 hours.
Diclofenac was detected in a low concentration (100 ng/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).
Metabolism
Biotransformation of diclofenac takes place partly by glucuronidation of the intact molecule, but mainly by
single and multiple hydroxylation and methoxylation, resulting in several phenolic metabolites, most of which
are converted to glucuronide conjugates. Two phenolic metabolites are biologically active, but to a much lesser
extent than diclofenac.
Elimination
The total systemic clearance of diclofenac in plasma is 263 ± 56 mL/min (mean value ± SD). The terminal halflife
in plasma is 1-2 hours. Four of the metabolites, including the two active ones, also have short plasma halflives
of 1-3 hours.
About 60% of the administered dose is excreted in the urine in the form of the glucuronide conjugate of the
intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% is
excreted as unchanged substance. The rest of the dose is eliminated as metabolites through the bile in the faeces.
Characteristics in patients
Elderly: No relevant age-dependent differences in the drug's absorption, metabolism, or excretion have been
observed, other than the finding that in five elderly patients, a 15-minute iv infusion resulted in 50% higher
plasma concentrations than expected with young healthy subjects.
Patients with renal impairment: 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> 10ml/min the calculated steady-state plasma levels of the hydroxy metabolites are
about 4 times higher than in normal subjects. However, the metabolites are ultimately cleared through the bile.
Patients with hepatic disease: In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics
and metabolism of diclofenac are the same as in patients without liver disease.

None stated.

Core: -
Microcrystalline cellulose (PH101)
Lactose (100 MESH)
Maize starch
Povidone (K30)
Magnesium stearate
Enteric coat: -
Eudragit L30D-55 (Methacrylic acid copolymer)
Triethyl citrate
Titanium dioxide
Purified talc

None known.

Three years

Store below 30 °C.
Store in original package in order to protect from light.

Each (transparent PVC-PVDC film/ Alu) blister contains 10 tablets

Not applicable.