Source: Registered Drug Product Database (NG) Publisher: Ajanta Pharma Limited, Ajanta House, Charkop, Kandivli (West), Mumbai - 400 067, India Manufacturing site address: Ajanta Pharma Limited, B-4/5/6, M.I.D.C. Area, Paithan, Dist. Aurangabad, Maharashtra, India, Telephone: (0091) 2431232123, Fax: (0091) 2431232088, e-mail: info@ajantapharma.com
Aceclofenac and Paracetamol combination is contraindicated in
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
The use of Aceclofenac with concomitant NSAIDs including cyclooxygenase2 selective inhibitors should be avoided.
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
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.
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 or recovering from major surgery, and the elderly. The importance of prostaglandins in maintaining renal blood flow should be taken into account in these patients. Renal function should be monitored in these patients.
Patients with mild to moderate renal impairment 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. 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. 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.
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). Aceclofenac should also be administered with caution and under close medical surveillance to patients with a history of cerebrovascular bleeding.
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 involving either the upper or lower gastrointestinal tract, with a history suggestive of gastrointestinal ulceration, bleeding or perforation, with ulcerative colitis or with Crohn’s disease, or haematological abnormalities, as these conditions may be exacerbated.
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.
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 systemic 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.
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
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. 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 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.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur without earlier exposure to the drug.
Aceclofenac may reversibly inhibit platelet aggregation.
All patients who are receiving NSAIDs should be monitored as a precautionary measure e.g. renal, hepatic function (elevation of liver enzymes may occur) and blood counts.
Cases of hepatic dysfunction/failure have been reported in patients with depleted glutathione levels, such as those who are severely malnourished, anorexic, have a low body mass index or are chronic heavy users of alcohol.
In patients with glutathione depleted states such as sepsis, the use of paracetamol may increase the risk of metabolic acidosis.
Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazard of overdose is greater in those with noncirrhotic alcoholic liver disease.
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.
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. Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication.
Drug interactions associated with Actinac Plus (Aceclofenac 100 mg and Paracetamol 500 mg Tablets) are similar to those observed with other NSAIDs.
Other analgesics including cyclooxygenase2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects, including GI bleeding.
Antihypertensives: NSAID’s may reduce the effect of antihypertensives. 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: Aceclofenac, like other NSAIDs, may inhibit the activity of diuretics. Diuretics can increase the risk of nephrotoxicity of NSAIDs. Although it was not shown to affect blood pressure control when coadministered 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 inhibit the renal clearance of glycosides, resulting in increased plasma glycoside levels. The combination should be avoided unless frequent monitoring of glycoside levels can be performed.
Lithium: Several NSAID drugs inhibit the renal clearance of lithium, resulting in increased serum concentrations 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 both an NSAID and methotrexate are administered within 24 hours of each other, since NSAIDs may increase plasma levels of methotrexate, 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.
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin. Close monitoring of patients on combined anticoagulants 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.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding
Cyclosporine, tacrolimus: Administration of NSAID drugs together with cyclosporine 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 are indications 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 with influencing their clinical effect. However, 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.
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
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. During the first and second trimester of pregnancy, aceclofenac should not be given unless clearly necessary. Consequently, aceclofenac is contraindicated during the third trimester of pregnancy.
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 Actinac Plus (Aceclofenac 100 mg and Paracetamol 500 mg Tablets) should therefore be avoided in pregnancy and lactation unless the potential benefits to the other outweigh the possible risks to the foetus.
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. 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) nonspecific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or © 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
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.
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, confusion, hallucinations, malaise and drowsiness.
Haematological: agranulocytosis, aplastic anemia.
Dermatological: Bullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity.
If serious adverse reactions occur, aceclofenac should be withdrawn.
Adverse events of paracetamol from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system class.
Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.
Post marketing data:
| Body System | Undesirable effect |
|---|---|
| Blood and lymphatic system disorders | Thrombocytopenia Agranulocytosis |
| Immune system disorders | Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angiodema and Stevens Johnson syndrome/toxic epidermal necrolysis |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm* |
| Hepatobiliary disorders | Hepatic dysfunction |
* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
Not applicable.
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