Gladio 100 mg Film-coated Tablets is indicated for the relief of pain and inflammation in
osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults.

Posology
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 dose is 200 mg daily, taken as two separate 100 mg doses, one tablet in
the morning and one in the evening.
Children
There are no clinical data on the use of Aceclofenac 100 mg Tablets in children and
therefore it is not recommended for use in children.

Elderly
The elderly, who are more likely to be suffering from impaired renal, cardiovascular or
hepatic function and receiving concomitant medication, 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.

The pharmacokinetics of Gladio 100mg Tablets are not altered in elderly patients, therefore
it is not considered necessary to modify the dose or dose frequency.
Patients with renal impairment
There is no evidence that the dosage of Aceclofenac 100 mg Tablets needs to be modified
in patients with mild renal impairment, but as with other NSAIDs caution should be
exercised (see section4.4).
Patients with liver impairment
There is some evidence that the dose of Aceclofenac 100 mg Tablets should be reduced in
patients with hepatic impairment and it is suggested that an initial daily dose of 100 mg be
used.
Method of administration
Gladio 100 mg Film-coated Tablets are supplied for oral administration and should be
swallowed whole with a sufficient quantity of liquid.
To be taken preferably with or after food. When Aceclofenac 100 mg Tablets was
administered to fasting and fed healthy volunteers only the rate and not the extent of
aceclofenac absorption was affected

Hypersensitivity to aceclofenac or to any of the excipients listed in section 6.1 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. Patients with active bleeding or bleeding diathesis. Severe hepatic failure and renal failure (see section 4.4). Established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease. History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Aceclofenac 100 mg Tablets should not be prescribed during pregnancy, especially during the last trimester of pregnancy, in women attempting to conceive and lactation unless there are compelling reasons for doing so. The lowest effective dosage should be used (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 Gladio 100 mg Tablets with concomitant NSAIDs including cyclooxygenase-2
selective inhibitors should be avoided (see section 4.5).
Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs especially
gastrointestinal bleeding and perforation which may be fatal (see section 4.2).
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, Renal and Hepatic Impairment:
The administration of an NSAID 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).
Renal:
The importance of prostaglandins in maintaining renal blood flow should be taken into
account in patients with impaired cardiac or renal function, those being treated with
diuretics or recovering from major surgery. Effects on renal function are usually reversible
on withdrawal of Gladio 100 mg Tablets.

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), Aceclofenac
100 mg Tablets should be discontinued. Close medical surveillance is necessary in patients
suffering from mild to moderate impairment of hepatic function. Hepatitis may occur
without prodromal symptoms.
Use of Gladio 100 mg Tablets in patients with hepatic porphyria may trigger an attack.
Cardiovascular and cerebrovascular effects:
Patients with congestive heart failure (NYHA-I) and patients with significant risk factors
for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking)
should only be treated with aceclofenac after careful consideration.
Appropriate monitoring and advice are required for patients with a history of hypertension
and/or mild congestive heart failure (NYHA-I) as fluid retention and oedema have been
reported in association with NSAID therapy.
As the cardiovascular risks of aceclofenac 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.

Aceclofenac should also be administered with caution and under close medical surveillance
to patients with a history of cerebrovascular 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.
Close medical surveillance is imperative in patients with symptoms indicative of gastrointestinal
disorders, with a history suggestive of gastro-intestinal ulceration, with ulcerative
colitis or with Crohn's disease, bleeding diathesis or haematological abnormalities.
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 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 could
increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such
as warfarin, selective serotonin-reuptake inhibitors or antiplatelet agents such as aspirin
(see section 4.5).
When GI bleeding or ulceration occurs in patients receiving aceclofenac, the treatment
should be withdrawn.
NSAIDs should be given with care to patients with a history of gastrointestinal disease
(ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section
4.8).
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).
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. Aceclofenac 100 mg Film-coated
Tablets should be discontinued at the first appearance of skin rash, mucosal lesions, or any
other sign of hypersensitivity.
Exceptionally, varicella can trigger serious cutaneous and soft tissues infections
complications. To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use of aceclofenac in case of
varicella.
Impaired female fertility:
The use of Aceclofenac 100 mg Tablets 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 Aceclofenac
100 mg Film-coated Tablets should be considered.
Hypersensitivity reactions:
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions,
can also occur without earlier exposure to the drug.
Haematological:
Aceclofenac 100 mg Tablets may reversibly inhibit platelet aggregation (see anticoagulants
under 'Interactions').
Aceclofenac should be avoided in patients who have developed anaemia, agranulocytosis
or thrombocytopenia secondary to NSAIDs or metamizol.
Long term treatment:
All patients who are receiving NSAIDs should be monitored as a precautionary measure
e.g. renal failure, hepatic function (elevation of liver enzymes may occur) and blood
counts.

Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use
of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects
(see section 4.4).
Anti-hypertensives: Reduced anti-hypertensive effect. The risk of acute renal insufficiency,
which is usually reversible, may be increased in some patients with compromised renal
function (e.g. dehydrated patients or elderly patients) when ACE- inhibitors or angiotensin
II receptor antagonists are combined with NSAIDs. Therefore, the combination should be
administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of
concomitant therapy, and periodically thereafter.
Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of
NSAIDs. Although it was not shown to affect blood pressure control when co-administered
with bendrofluazide, interactions with other diuretics cannot be ruled out. When
concomitant administration with potassium-sparing diuretics is employed, serum potassium
should be monitored.
Cardiac glycosides like digoxin:: NSAIDs may exacerbate cardiac failure, reduce GFR
(glomerular filtration rate) and increase plasma glycoside levels. The combination should
be avoided unless frequent monitoring of glycoside levels can be performed.
Lithium: Several NSAIDs drugs inhibit the renal clearance of lithium, resulting in increased
serum concentration of lithium. The combination should be avoided unless frequent
monitoring of lithium can be performed.
Methotrexate: The possible interaction between NSAIDs and methotrexate should be born
in mind also when low doses of methotrexate are used, especially in patients with
decreased renal function. When combination therapy has to be used, the renal function
should be monitored. Caution should be exercised if NSAIDs and methotrexate are
administered within 24 hours of each other, since NSAIDs may increase plasma levels,
resulting in increased toxicity.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration
as NSAIDs can reduce the effect of mifepristone.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see
section 4.4). Close monitoring of patients on combined anti-coagulants and Aceclofenac
100 mg Film-coated Tablets therapy should be undertaken.
Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of
convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones
may have an increased risk of developing convulsions. Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of
gastrointestinal bleeding (see section 4.4).
Ciclosporin,tacrolimus: Administration of NSAID drugs together with cyclosporin or
tacrolimus is thought to increase the risk of nephrotoxicity due to decreased synthesis of
prostacyclin in the kidney. During combination therapy it is therefore important to carefully
monitor renal function.
Zidovudine: Increased 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 can be given together with
oral antidiabetic agents without influencing their clinical effect. However, there have been
isolated reports of hypoglycaemic and hyperglycaemic effects. Thus with Aceclofenac 100
mg Film-coated Tablets, consideration should be given to adjustment of the dosage of
hypoglycaemic agents.
Other NSAIDs: Concomitant therapy with aspirin or other NSAIDs may increase the
frequency of adverse reactions, including the risk of GI bleeding.

Pregnancy:
There is no information on the use of aceclofenac during pregnancy. Inhibition of
prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/fetal
development. Data from epidemiological studies suggest an increased risk of miscarriage,
cardiac malformation or gastroschisis after use of prostaglandin synthesis inhibitor in early
pregnancy. The absolute risk for cardiovascular malformation was increased from less than
1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of
therapy.
In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in
increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased
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, aceclofenac should not be given unless clearly
necessary. If aceclofenac 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 as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose
the foetus to:
- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary
hypertension);
- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;
the 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, aceclofenac is contraindicated during the third trimester of pregnancy (see
section 4.3).
Lactation
There is no information on the secretion of aceclofenac to breast milk; there was however
no notable transfer of radio labelled (14C) aceclofenac to the milk of lactating rats.
The use of aceclofenac should therefore be avoided in pregnancy and lactation unless the
potential benefits to the other outweigh the possible risks to the foetus.
Fertility
The use of aceclofenac 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 Aceclofenac 100 mg Film-coated Tablets should
be considered.

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are
possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

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, diarrhoea, 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).
Cardiovascular and cerebrovascular: Oedema, hypertension and cardiac failure have been
reported in association with NSAID treatment.
Aceclofenac is both structurally related and metabolised to diclofenac for which a greater
amount of clinical and epidemiological data consistently point towards an increased risk of
general arterial thrombotic events (myocardial infarction or stroke, particularly at high
doses and in long treatment). Epidemiological data has also found an increased risk of
acute coronary syndrome and myocardial infarction associated with the use of aceclofenac,
(see section 4.3 and 4.4).
Exceptionally, occurrence of serious cutaneous and soft tissues infections complications
during varicella has been reported in association with NSAID treatment.
Other adverse reactions reported less commonly include:
Renal: Interstitial nephritis.
Hepatic: abnormal liver function, hepatitis and jaundice.
Neurological and special senses: Optic neuritis, reports of aseptic meningitis (especially in
patients with existing auto immune 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), confusion, hallucinations, and drowsiness.
Haematological: Agranulocytosis, aplastic anaemia.
Dermatological: Bullous reactions including Stevens Johnson Syndrome and Toxic
Epidermal Necrolysis (very rare). Photosensitivity.
If serious adverse reactions occur, Aceclofenac 100 mg film-coated Tablets should be
withdrawn.
Within the system organ classes, undesirable effects are listed under headings of frequency,
using the following categories: very common ((≥1/10); common (≥1/100 to <1/10);
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not
known (cannot be estimated from the available data). Within each frequency grouping,
undesirable effects are presented in order of decreasing seriousness.

System organ
class
Common
(≥1/100 to
<1/10)
Uncommon
(≥1/1,000 to
<1/100)
Rare
(≥1/10,000 to
<1/1,000)
Very rare/ isolated reports
(<1/10,000)
Blood and
lymphatic
system
disorders
Anaemia Granulocytopenia
Thrombocytopenia
Neutropenia
Haemolytic anaemia
Immune
system
disorders
Anaphylactic
reaction
(including
shock)
Hypersensitivity
Metabolism
and nutrition
disorders
Hyperkalemia
Psychiatric
disorders
Depression
Abnormal dreams
Insomnia
Nervous
system
disorders
Dizziness Paraesthesia, Tremor
Somnolence, Headache
Dysgeusia (abnormal taste)
Eye disorders Visual
disturbance

Ear and
labyrinth
disorders
Vertigo
Tinnitus
Cardiac
disorders
Cardiac failure Palpitations
Vascular
disorders
Hypertension Flushing
Hot flush
Vasculitis
Respiratory,
thoracic and
mediastinal
disorders
Dyspnoea Bronchospasm
Stridor
Gastrointestinal
disorders
Dyspepsia
Abdominal
pain
Nausea
Diarrhoea
Flatulence
Gastritis
Constipation
Vomiting
Mouth
ulceration
Melaena
Gastrointestinal
haemorrhage
Gastrointestinal
ulceration
Stomatitis
Intestinal perforation
Exacerbation of Crohn's
disease and Colitis Ulcerative
Haematemesis
Pancreatitis
Hepatobiliary
disorders
Hepatic
enzyme
increased
Hepatic injury (including
hepatitis)
Jaundice
Blood alkaline phosphatase
increased
Skin and
subcutaneous
tissue disorders
Pruritus
Rash
Dermatitis
Urticaria
Angioedema Purpura
Severe mucocutaneous skin
reaction (including Stevens
Johnson Syndrome and Toxic
Epidermal Necrolysis)
Renal and
urinary
disorders
Blood urea
increased
Blood
creatinine
increased
Renal failure
Nephrotic syndrome
General
disorders and
administration
site conditions
Oedema
Fatigue
Cramps in legs
Investigations Weight increase

Reporting of suspected adverse reactions
To Report any side effect (s):
The National Pharmacovigilance and Drug Safety Centre (NPC)
o Fax: +966-11-205-7662
o Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
o Toll free phone: 8002490000
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc

Management of acute poisoning with NSAIDs essentially consists of supportive and
symptomatic measures.
a) Symptoms
Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal irritation,
gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness,
dizziness, tinnitus, hypotension, respiratory depression, fainting, occasionally convulsions.
In 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.
Specific therapies such as dialysis or haemoperfusion are probable of no help in eliminating
NSAIDs due to their high rate of protein binding and extensive metabolism.
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.
In case of frequent or prolonged convulsions, patients should be treated with intravenous
diazepam.

Other measures may be indicated by the patient's clinical condition.
Management of acute poisoning with oral aceclofenac essentially consists of supportive
and symptomatic measures for complications such as hypotension, renal failure,
convulsions, gastro-intestinal irritation, and respiratory depression.

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antiinflammatory and antirheumatic products, non-steroids,
acetic acid derivatives and related substances
ATC code: M01AB16.
Aceclofenac is a non-steroidal agent with marked anti-inflammatory and analgesic
properties.
The mode of action of aceclofenac is largely based on the inhibition to prostaglandin
synthesis. Aceclofenac is a potent inhibitor of the enzyme cyclo-oxygenase, which is
involved in the production of prostaglandins.

After oral administration, aceclofenac is rapidly and completely absorbed as unchanged
drug. Peak plasma concentrations are reached approximately 1.25 to 3.00 hours following
ingestion. Aceclofenac penetrates into the synovial fluid, where the concentrations reach
approximately 57% of those in plasma. The volume of distribution is approximately 25 L.
The mean plasma elimination half-life is around 4 hours. Aceclofenac is highly proteinbound
(>99%). Aceclofenac circulates mainly as unchanged drug. 4'- Hydroxyaceclofenac
is the main metabolite detected in plasma. Approximately two- thirds of the administered
dose is excreted via the urine, mainly as hydroxymetabolites.
Aceclofenac is partially metabolised to diclofenac.
No changes in the pharmacokinetics of aceclofenac have been detected in the elderly.

The results from preclinical studies conducted with aceclofenac are consistent with those
expected for NSAIDs. The principal target organ was the gastro-intestinal tract. No
unexpected findings were recorded.

Aceclofenac was not considered to have any mutagenic activity in three in vitro studies and
an in vivo study in the mouse.
Aceclofenac was not found to be carcinogenic in either the mouse or rat.
Animal studies indicate that there was no evidence of teratogenesis in rats although the
systemic exposure was low and in rabbits treatment with aceclofenac (10 mg/kg/day)
resulted in a series of morphological changes in some fetuses.

6.1 List of excipients
In active ingrediants
Microcrystalline Cellulose
Croscarmellose Sodium
Povidone K-30
Magnesium Stearate
Ethanol
Film Coating
Opadry II (OY-LS-28908 White)
Purified Water

None known

24 months

Do not Store above 30°C.
Use this product within 90 days from the first opening.
Do not use after the expiry date stated on the label.
Do not use if there is any physical change on the product.
Keep out of reach of children.

Gladio is available as 20’s tablets packed in HDPE plastic bottle sealed with child proof
cap, packed along with leaflet in printed carton box.

No special instructions.