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Algic

Phillips Pharmaceuticals Limited
Plot 122-132, Apapa-Oshodi Expressway, Afprint Ind. Est., Iyano-Osolo B/stop, Lagos Nigeria.
Email: mktng.phillips@gmail.com, info@phillipsnigeria.com
Tel: 0805-6292409; 0803-6761764
Website: http://phillipspharma.com

Brand Name

Algic

Manufacturer

MSN Laboratories Limited

Plot No 42. Anrich Industrial Estate, Bollaram, Medak Dist. 502 325, AP, India

Therapeutic Class

Non-steroidal anti-inflammatory drugs (NSAIDs), Systemic

Dosage Form, Composition & NAFDAC Registration Number (NRN)

Tablets (NRN: B-4-0160): Each film coated tablet contains Aceclofenac BP - 100 mg. Colour: Titanium dioxide

Pack Size: Aceclofenac tablets in PVC-PVDC Blister pack of 10 Tablets.

Algic

Pharmacology

The chemical name for Aceclofenac is 2-[2-[2-(2,6-Dichlorophenyl) amino phenyl] acetyl] oxyacetic acid:

The empirical formula for Aceclofenac is C16H13Cl2N04 and molecular weight is 354.19.

PHARMACEUTICAL FORM:
Aceclofenac film-coated tablets 100 mg are presented as white round film-coated tablets with plain surface on both side.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamic properties
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

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.

Preclinical safety data

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.

Indications

Aceclofenac belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). It is indicated for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.

CLINICAL PARTICULARS:

Posology and method of administration-

Aceclofenac 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 was administered to fasting and fed healthy volunteers only the rate and not the extent of aceclofenac absorption was affected. Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms

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 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 Aceclofenac are not altered in elderly patients, therefore it Is not considered 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 (see also Precautions).

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.

Contra-indications

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. The lowest effective dosage should be used.

Precautions/Warnings

Undesirable effects may be minimised by using the lowest eff9l'live dose for the shortest duration necessary to control symptoms, and GI and cardiovascular risks below). The use of Aceclofenac with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.

Elderly:

The elderly have an increased frequency of adverse reactions to NSA1Ds especially gastrointestinal bleeding and perforation which may be fatal.

Respiratory disorders:

Caution is required 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 of Aceclofenac.

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 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.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for aceclofenac.

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 ii 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. 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.

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. 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, mucosa/ 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.

Haematological:

Aceclofenac may reversibly inhibit platelet aggregation (see anticoagulants under interactions).

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. Interaction with other medicinal products and other forms of interaction

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 (SSRls):

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.

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.

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. Special warnings and precautions for use, regarding female fertility. 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.

Interactions

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.

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, angioedema 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 (for example myocardial infarction or stroke).

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.

Dermatological complaints including pruritus and rash and Investigations: Abnormal hepatic enzyme and serum creatinine levels have also been reported.

Adverse 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, angioedema 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 (for example myocardial infarction or stroke).

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.

Dermatological complaints including pruritus and rash and 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 (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, depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.

Haematological: Thrombocytopenia, neutropenia, 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, Aceclofenac 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.

MedDRa SOC Common <10% - >1% Uncommon <1% - >10% Rare <G1% - >0.01% Very rare/ isolated reports <0.01%
Blood and lymphatic system disorder     Anaemia Granulocytopenia, Thrombocytopenia, Neutropenia, Haemolytic anaemia
Immune system disorder     Anaphylactic reaction (including shock) Hypersensitivity  
Metabolism and nutrition disorder       Hyperkalemia
Psychiatric disorder       Depression, Abnormal dreams, Insomnia
Nervous system disorder Dizziness     Paraesthesia, Tremor, Somnolence, Headache, Dysgeusia (abnormal taste)
Eye disorder     Visual disturbance  
Ear and labyrinth disorder       Vertigo
Cardiac disorder       Palpitations
Vascular disorder       Flushing, Hot flush
Respiratory, thoracic and mediastinal disorders     Dyspnoea Bronchospasm, Stridor
Gastrointestinal disorders Dyspepsia, Abdominal pain, Nausea, Diarrhoea Flatulence, Gastritis, Constipation, Vomiting, Mouth ulceration Melaena Stomatitis Haematemesis Gastrointestinal haemorrhage, Gastric ulcer, Pancreatitis
Hepatobiliary disorders       Hepatitis, Jaundice
Skin and subcutaneous tissue disorders   Pruritus, Rash, Dermatitis, Urticaria Face oedema Purpura, Dermatitis bullous
Renal and urinary disorders       Renal insufficiency, Nephrotic syndrome
General disorders and administration site conditions       Oedema Fatigue, Cramps in legs
Investigations Hepatic enzyme increased Blood urea increased, Blood creatinine increased   Blood alkaninie phosphatase increased, Weight increase

Dosage & Administration

The recommended dose is 200 mg daily for adults, taken as two separate 100 mg doses, one tablet in the morning and one in the evening.

OVERDOSE

There are no human data available on the consequences of Aceclofenac overdose.

a) Symptoms

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, tainting, 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 Itta-threatening overdose.
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. Frequent or prolonged convulsions should be treated with intravenous diazepam.

Other measures may be indicated by the patient's clinical condition.

Specific therapies such as forced diuresis, dialysis or haemopertusion are probably of no help in eliminating NSAIDs due to their high rate of protein binding and extensive metabolism.

Storage/Handling Recommendations

SHELF LIFE 2 YEARS

Store below 30°C.

Review Date

2016-10-17 10:00:14