COMPOSITION

Each film-coated tablet contains:

Aceclofenac BP ………… 100 mg

ADDITIONAL INGREDIENTS

Excipients:

Microcrystalline Cellulose, Croscarmellose Sodium, Colloidal Anhydrous Silica, Stearic Acid, Opadry white, Isopriopyl Alcohol, Dichloromethane.

Composition of Opadry White YS-1-7027- Hypermellose, Titanium dioxide, Triacetin

INDICATIONS

Aceclofenac is indicated for the relief of pain and inflammation 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 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

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 modified 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 sufficient 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, flatulence, 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-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.

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.

ADVERSE DRUG REACTIONS:

*”Inform doctors about unexpected reactions after using drugs.”

INTERACTIONS WITH OTHER MEDICINAL PRODUCTS

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.

Anti-hypertensives:

Reduced anti-hypertensive effect.

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: NSAIDs may exacerbate cardiac failure, reduce GFR (glomerular filtration rate) and increase plasma glycoside levels.

Lithium:

Decreased elimination of lithium

Methotrexate:

Decreased elimination of methotrexate. 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.

Ciclosporin: Increased risk of nephrotoxicity.

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.

Anti-coagulants:

NSAIDs may enhance the effects of anti-coagulants, such as warfarin. Close monitoring of patients on combined anti-coagulants and Aceclofenac 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.

Tacrolimus:

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

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.

Other NSAIDs:

Concomitant therapy with aspirin or other NSAIDs may increase the frequency of adverse reactions, including the risk of GI bleeding.

PREGNANCY AND LACTATION

Pregnancy:

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) and on the possible risk of persistent pulmonary hypertension of the new born, use in the last trimester of pregnancy is contraindicated. The regular use of NSAIDs during the last trimester of pregnancy may decrease uterine tone and contraction. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child. 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 the foetus.

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 foetuses.

Lactation:

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

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.

Effects on ability to drive and use machines

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

WARNINGS AND PRECAUTIONS

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 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.

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 fluid 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 first 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 difficulties 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.

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-inflammatory 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.

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 NSAIDs essentially consists of supportive and symptomatic measures.

PHARMACEUTICAL FORM

Film coated Tablets

PHARMACOTHERAPEUTIC GROUP:

Non Steroid Anti inflammatory & Antirheumatic

ATC CODE: M01AB16.

PHARMACOLOGICAL PROPERTIES:

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 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 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.

STORAGE CONDITION

Store below 30°C.

DOSAGE FORMS AND PACKAGING AVAILABLE

Diclotol Tablets will be packed in Alu/Alu foil blister Packs

14 tablets in blister, 2 blisters of 14’s in a carton along with pack insert.

NAME AND ADDRESS OF MANUFACTURER

Kusum Healthcare Pvt Ltd

Sp 289(A), Riico Industrial Area,

Chopanki, Bhiwadi (Raj.),

India.

DATE OF REVISION OF PACKAGE INSERT

Not Applicable