Zerodol Aceclofenac Tablets

Zerodol

Aceclofenac TabIets 100 mg

 

For the use only of a registered Medical Practitioner or a Hospital or a Laboratory

 

DESCRIPTION

Aceclofenac is an orally administered phenylacetic add derivative with effects on a variety of inflammatory mediators. It is from the class of non-steroidal anti-inflammatory drug (NSAID), related to diclofenac. Through its analgesic and anti-inflammatory properties, aceclofenac provides symptomatic relief in a variety of painful conditions.

 

COMPOSITION

Each film-coated tablet contains:

Aceclofenac BP 100mg

 

PHARMACOLOGY

The mode of action of aceclofenac is largely based on the inhibition of prostaglandin synthesis Aceclofenac is a potent inhibitor of the enzyme cyclo-oxygenase, which is involved in the production of prostaglandins. Aceclofenac has been shown to exert effects on a variety of mediators of inflammation. The drug inhibits synthesis of the inflammatory cytokines interleukin (IL)-1 and tumour necrosis factor and inhibits prostaglandin E2 (PGE2) production. Effects on cell adhesion molecules from neutrophils have also been noted. In vitro data indicate inhibition of cyclo-oxygenase (COX)-1 and 2 by aceclofenac in whole blood assays, with selectivity for COX-2 being evident.

In contrast to some other NSAIDs, aceclofenac has shown stimulatory effects on cartilage matrix synthesis, that may be linked to the ability of the drug to inhibit IL-1 activity. In vitro data indicate stimulation by the drug of synthesis of gIycosaminoglycan in osteoarthritic cartilage. There is also evidence that aceclofenac stimulates the synthesis of IL-1 receptor antagonist in human articular chondrocytes subjected to inflammatory stimuli and that 4’-hydroxyacclofenac has chondroprotective properties attributable to supression of IL-1 mediated promatrix metaIIoproteinase production and proteoglycan release.

In patients with osteoarthritis of the knee, aceclofenac decrease pain, reduces severity and improves the functional capacity of the knee. It redices joint inflammation, pain intensity and the duration of morning stiffness in patients with rheumatoid arthritiss. The duration of morning stiffness and pain intensity are reduced and spinal mobility improved, by aceclofenac in patients with ankylosing spondylitis.

 

PHARMACOKINETICS

Aceclofenac is rapidly and completely absorbed after oral administration. Peak plasma concentrations are reached 1 to 3 hours after an oral dose. The drug is highly protein bound (>99%). The presence of food does not alter the extent of absorption of aceclofenac but the absorption rate is reduced. The plasma concentration of aceclofenac was approximately twice that in synovial fluid after multiple doses of the drug in patients with kneel pain and synovial fluid effusion.

Aceclofenac is metabolised to a major metabolite, 4’- hydroxyaceclofenac and to a number of other metabolites including 5- hydroxyaceclofenac, 4’-hydroxyaceclofenac, diclofenac and 5- hydroxydiclofenac. These other metabolites account for the fate of approximately 20% of each dose of aceclofenac. Renal excretion is the main route of elimination of aceclofenac with 70 to 80% of an administered dose found in the urine, mainly as the glucuronides of aceclofenac and its metabolites. Of each dose of aceclofenac, 20% is excreted in the faeces. The plasma elimination half life of the drug is approximately 4 hours.

 

INDICATIONS

Aceclofenac is indicated for the relief of pain and inflammation associated with rheumatoid arthritis, osteoarthntis or ankylosing spondylitis.

 

CONTRAINDICATIONS

Aceclofenac should not be administered to patients hypersensitive to aceclofenac or other NSAIDs, or patients with a history of aspirin or NSAID-related allergic or anaphylaptic reactions or with peptic ulcers or GI bleeding, moderate or severe renal impairment.

 

WARNINGS

Close medical surveillance is imperative in patients with symptoms indicative of gastrointestinal disorders, with a history suggestive of gastrointestinal ulceration, with ulcerative colitis or with Crohn’s disease, bleeding diathesis or haematological abnormalities.

Gastrointestinal bleeding or ulcerative perforation, haematemesis and melaena have in general more serious consequences in the elderly. They can occur at any time during treatment, with or without warning symptoms or a previous history. In the rare instances, where gastrointestinal bleeding or ulceration occurs in patients receiving aceclofenac, the drug should be withdrawn.

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

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur without earlier exposure to the drug.

 

PRECAUTIONS

Patients with mild renal or cardiac impairment and the elderly should be kept under surveillance, since the use of NSAIDs may result in deterioration of renal function. The lowest effective dose should be used and renal function monitored regularly.

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 diuretic or recovering from major surgery. Effects on renal function are usually reversible on withdrawal of aceclofenac.

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 should be discontinued. Hepatitis may occur without prodromal symptoms. Use of aceclofenac in patients with hepatic porphyria may trigger an attack.
Aceclofenac may reversibly inhibit platelet aggregation.

Caution should also be exercised in patients with history of coagulation defects and history of liver dysfunction.

Renal and hepatic function and blood counts should be monitored during long term treatment.

NSAIDs should be given with care to patients with a history of heart failure or hypertension since oedema has been reported in association with NSAID administration.
Use with caution in patients suffering from or with a history of bronchial asthma since NSAIDs have been known to cause bronchospasm in such patients.

Effects on ability to drive and use machines

Patients suffering from dizziness, vertigo, or other central nervous system disorders whilst taking NSAIDs should refrain from driving or handling dangerous machinery.

Usage in pregnancy and lactation

The drug is not recommended in pregnant or breast feeding women.

Usage in paediatrics

There are no clinical data on the use of aceclofenac in children and therefore aceclofenac is not recommended for use in children.

Usage in geriatrics

The pharmacokinetics of aceclofenac are not altered in elderly patients, therefore it is not considered necessary to modify the dose or dose frequency.

As with other non-steroidal anti-inflammatory drugs (NSAIDs), caution should be exercised in the treatment of elderly patients, who are generally more prone to adverse reactions, and who are more likely to be suffering from impaired renal, cardiovascular or hepatic function and receiving concomitant medication. The elderly should be monitored for Gl bleeding for 4 weeks following initiation of NSAID therapy.

Lithium

Aceclofenac, like many NSAIDs, may increase plasma concentration of lithium.

Cardiac glycosides

Through their renal effects, NSAIDs may increase plasma glycoside (including digoxin) levels, exacerbate cardiac failure and reduce the glomerular filtration rate in patients receiving glycosides.

Diuretics

Aceclofenac, like other NSAIDs may inhibit the activity of diuretics. 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. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Anticoagulants

Like other NSAIDs, aceclofenac may enhance the activity of anticoagulants. Close monitoring of patients on combined anticoagulant and aceclofenac therapy should be undertaken.

Antidiabetic agents

There have been isolated reports of hypoglycaemic and hyperglycaemic effects. Thus with aceclofenac, consideration should be given to adjustment of the dosage of hypoglycaemic agents.

Methotrexate

Caution should be exercised if NSAIDs and methotrexate are administered within 24 hours of each other, since NSAIDs may increase methotrexate 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.

Other NSAIDs and Steroids

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

Cyclosporin

Cyclosporin nephrotoxicity may be increased by the effect of NSAIDs on renal prostaglandins.

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 a NSAID.

 

ADVERSE DRUG REACTIONS

Aceclofenac is well tolerated, with most adverse events being minor and reversible.
The most frequent are gastrointestinal disorders, in particular dyspepsia, abdominal pain, nausea and diarrhea, and occasional occurrence of dizziness. Dermatological complaints including pruritus and rash and abnormal hepatic enzyme and serum creatinine levels have also been reported. If serious reactions occur, aceclofenac should be withdrawn.

Although the incidence of GI adverse events with aceclofenac was similar to those of comparator NSAIDs in individual clinical trials, withdrawal rates due to these events were significantly lower with aceclofenac than with ketoprofen and tenoxicam. Costs incurred as a result of adverse event management are lower with aceclofenac than with a range of comparator NSAIDs. Although statistical analyses were not consistently available, faecal bleeding and endoscopy studies in humans have indicated overall less GI bleeding and GI mucosaI damage with aceclofenac than with naproxen or diclofenac.

The following adverse events [described as common (<10% -> 1%), uncommon (<1 %->0.1%), rare (<0.1% – >0.01%) and very rare/isolated reports (<0.01%)] were reported in clinical studies and post marketing surveillance.

Blood and lymphatic system disorders

Rare: Anaemia. Very rare: Granulacytopenia, thrombocytopenia, neutropenia, haemolytic anaemia

Immune system disorders

Rare: Anaphylactic reaction (including shock), hypersensitivity

Metabolism and nutrition disorders

Very rare: Hyperkalemia

Psychiatric disorders

Very rare: Depression, abnormal dreams, insomnia

Nervous system disorders

Common: Dizziness. Very rare: Paraesthesia, tremor, somnolence, headache, dysgeusia (abnormal taste)

Eye disorders

Rare: Visual disturbance

Ear and labyrinth disorders

Very rarer: Vertigo

Cardiac disorders

Very rare: Palpitations

Vascular disorders

Very rare: Flushing, hotflush

Respiratory, thoracic and mediastinal disorders

Rare: dyspnoea. Very rare: Bronchospasm, stridor

Gastrointestinal disorders

Common: Dyspepsia, abdominal pain, nausea and diarrhea. Uncommon: Flatulence, gastritis, constipation, vomiting, mouth ulceration. Rare: Melaena. Very rare: Stomatitis, haematemesis, gastrointestinal haemorrhage, gastric ulcer, pancreatitis

Hepatobiliary disorders

Very rare: Hepatitis, jaundice

Skin and subcutaneous tissue disorders

Uncommon: Pruritus, rash, dermatitis, urticaria. Rare: Face oedema. Very rare: Purpura, bullous dermatitis

Renal and urinary disorders

Very rare: Renal insufficiency, nephrotic syndrome

General disorders and administration site conditions

Very rare: Oedema, fatigue, cramps in legs

Laboratory investigations

Common: Increased hepatic enzyme. Uncommon: Increased blood urea, increased blood creatinine. Very rare: Increased blood alkaline phosphatase, weight increase.

 

DOSAGE AND ADMINISTRATION

Aceclofenac tablets should be swallowed whole with a sufficient quantity of liquid. When aceclofenac was administered to fasting and fed healthy volunteers only the rate and not the extent of aceclofenac absorption was affected and as such aceclofenac should be taken preferably with or after food.

The usual dose aceclofenac is 100 mg given twice daily by mouth. One tablet in the morning and one in the evening.

Renal impairment

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 impairment

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.

 

OVERDOSAGE

Management of acute poisoning with NSAIDs essentially consists of supportive and symptomatic measures.

There are no human data available on the consequences of aceclofenac overdosage. The therapeutic measures to be taken are: absorption should be prevented, as soon as possible after overdosage by means of gastric lavage and treatment with activated charcoaI; supportive and symptomatic treatment should be given for complications such as hypotension, renaI failure, convulsions, gastrointestinal irritation, and respiratory depression, specific therapies such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating NSAIDs due to their high rate of protein binding and extensive metabolism.

 

PRESENTATION

Blister strip of 10 tablets

 

STORAGE

Store below 30oC, in a dry place

KEEP OUT OF REACH OF CHILDREN

 

Made in India by

Ipca Laboratories Ltd.

Regd. Off.: 48, Kandivli Ind. Estate,

Mumbai 400 067

Advertisements

Leave a Reply