Composition
Each lm-coated tablet contains: Aceclofenac EP ………… 100 mg
Excipients:
Microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, stearic acid, opadry white, isopropyl alcohol and dichloromethane.

THERAPEUTIC INDICATIONS Diclotol is indicated for the relief of pain and inammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.
RECOMMENDED DOSE Adults:
The recommended dose is 200 mg daily, taken as two separate 100 mg doses, one tablet in the morning and one tablet in the evening.
Children:
No clinical data on the use of Aceclofenac 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 is not altered in elderly patients, therefore it is not necessary to modify the dose or dose frequency.
Renal insufficiency:
There is no evidence that the dosage of Aceclofenac needs to be modied in patients with mild renal impairment, but as with other NSAIDs caution should be exercised.
Hepatic insufficiency:
There is some evidence that the dose of Aceclofenac should be reduced in patients with hepatic impairment and it is suggested that an initial daily dose of 100 mg be used.
MODE OF ADMINISTRATION
Diclotol tablets should be swallowed whole with a sufcient quantity of liquid.
To be taken preferably with or after food.

UNDESIRABLE EFFECTS
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. Nausea, vomiting, diarrhoea, atulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease 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-specic 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.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events.
The majority of adverse reactions reported have been reversible and of a minor nature. The most frequent are gastro-intestinal disorders, in particular dyspepsia, abdominal pain, nausea and diarrhoea, and occasional occurrence of dizziness. Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.
Investigations:
Abnormal hepatic enzyme and serum creatinine levels have also been reported. Other adverse reactions reported less commonly include:

Renal:
Nephrotoxicity in various forms, including interstitial nephritis, nephrotic 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 with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation, depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.
Haematological:
Agranulocytosis, aplastic anaemia and haemolytic anaemia.
Dermatological:
Bullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity.
If serious adverse reactions occur, Diclotol should be withdrawn.
The following is a table of adverse reactions reported during clinical studies and after authorization, grouped by System-Organ Class and estimated frequencies

SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms. The use of Diclotol with concomitant NSAIDs including cyclooxygenase- 2 selective inhibitors should be avoided.
Elderly:The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
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.
Renal:
The importance of prostaglandins in maintaining renal blood ow 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. Hepatic:
If abnormal liver function tests persist or worsen, clinical signs or symptoms consistent with liver disease develop or if other manifestations occur, Aceclofenac 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 Aceclofenac in patients with hepatic porphyria may trigger an attack.
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 uid retention and oedema have been reported in association with NSAID therapy.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with aceclofenac after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
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 gastro-intestinal 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, 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.
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.
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 as these conditions may be exacerbated.
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.
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. Aceclofenac should be discontinued at the rst appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Impaired female fertility:
The use of Aceclofenac may impair female fertility and is not recommended in women attempting to conceive. In women who have difculties conceiving or who are undergoing investigation of infertility, withdrawal of Aceclofenac should be considered.
Hypersensitivity reactions:
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur without earlier exposure to the drug.

FERTILITY, PREGNANCY AND LACTATION
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 rst 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 rst 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.
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 Preservex should therefore be avoided in pregnancy and lactation unless the potential benets to the other outweigh the possible risks to the foetus.
Fertility:
The use of Diclotol may impair female fertility and is not recommended in women attempting to conceive. In women who have difculties conceiving or who are undergoing investigation of infertility, withdrawal of Preservex should be considered
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Undesirable effects such as dizziness, drowsiness, vertigo, fatigue, visual disturbances or other central nervous system disorders are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.

OVERDOSES AND TREATMENT
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 signicant poisoning acute renal failure and liver damage are possible.
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.
Specic 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.
CONTRAINDICATIONS
Hypersensitivity to aceclofenac or to any of the excipients.
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-inammatory drugs.
Severe heart failure, hepatic failure and renal failure.
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Aceclofenac should not be prescribed during pregnancy, especially during the last trimester of pregnancy, unless there are compelling reasons for doing so. The lowest effective dosage should be used

PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic Group:
Non Steroidal Anti inammatory & Antirheumatic
ATC CODE:
M01AB16
Pharmacodynamic 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.
Pharmacokinetic Properties:
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 uid, 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 protein bound (>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. No changes in the pharmacokinetics of aceclofenac have been detected in the elderly.
THERAPEUTIC INDICATIONS
Diclotol is indicated for the relief of pain and inammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.
STORAGE CONDITION
Store below 30°C.
SHELF LIFE
3 years
DOSAGE FORMS AND PACKAGING AVAILABLE
Alu/Alu blister of 14 tablets, 2 or 10 blisters in a carton box.
Alu/Alu blister of 10 tablets, 10 blisters in a carton box.
NAME AND ADDRESS OF MANUFACTURER
Kusum Healthcare Pvt. Ltd.
SP 289(A), RIICO Indl. Area,
Chopanki, Bhiwadi (Rajasthan), India
DATE OF REVISION OF PACKAGE INSERT
Not Applicable
MM Reg. No.: 1903AA 7529 14070003461705