Alace

Rx                 ALACE

COMPOSITION:

ALACE  TAB

Each film coated tab contains

Aceclofenac Potassium 100mg

DESCRIPTION:

ALACE (Aceclofenac) is a widely used non-steroidal anti-inflammatory drug. It is a phenylacetic acid derivative and is similar to diclofenac although it appears to have a lower tendency to cause gastrointestinal effects. It is White to off-white, round shaped, biconvex, film-coated tablet.

ALACE (Aceclofenac) is a non-steroidal agent with anti-inflammatory and analgesic properties. Its mode of action is largely based on inhibition of prostaglandin synthesis. ALACE is a potent inhibitor of the enzyme cyclooxygenase, which is involved in the production of prostaglandins. It also stimulates cartilage matrix (glycosaminoglycans) synthesis. 

PHARMACODYNAMICS:

ALACE (Aceclofenac) is an NSAID known to exhibit multifactor mechanism of action. Aceclofenac was developed in order to provide a highly effective pain relieving therapy with a reduced side effect profile.

1. ALACE (Aceclofenac) directly blocks PGE 2 secretion at the site of inflammation by inhibiting IL-Beta & TNF in the inflammatory cells (Intracellular Action). Aceclofenac has been demonstrated to inhibit cyclooxygenase (COX) activity and to suppress the PGE 2 production by inflammatory cells, which are likely to be a primary source of PGE 2. Inflammatory cells release IL-1 and TNF, which produce PGE 2 by induction of COX-2. Aceclofenac and 4`- hydroxyaceclofenac penetrate the inflammatory cells like polymorphonuclears, monocytes and rheumatoid synovial cells and get hydrolyzed to the active metabolites diclofenac and 4`-hydroxydiclofenac which inhibit IL-1 and TNF released by the inflammatory cells and therefore suppress production of PGE 2 at the site of inflammation.

2. ALACE (Aceclofenac) stimulates the synthesis of the extracellular matrix of the Human Articular Cartilages. Aceclofenac blocks degeneration and stimulates synthesis of extracellular matrix of cartilages by inhibiting the action of different cytokines. Aceclofenac and the metabolites inhibit IL-6 production by human chondrocytes. This leads to inhibition of increase of inflammatory cells in synovial tissue, inhibition of IL-1 amplification, inhibition of increased MMP synthesis and thus ensuring proteoglycan production. Aceclofenac also inhibits IL-1 and TNF production by human chondrocytes, inflammatory cells and synovial cells and therefore blocks suppression of GAG and collagen synthesis and stimulates growth factor mediated synthesis of GAG and collagen. 4`-hydroxyaceclofenac, a metabolite of aceclofenac inhibits pro MMP1 and pro MMP3 produced by synovial cells (Rheumatoid Synovial Cells) in serum and in synovial fluid and thus inhibits progressive joint destruction by MMPs.

3. ALACE (Aceclofenac) inhibits Neutrophil Adhesion & Accumulation at the inflammatory site in the early phase and thus blocks the pro-inflammatory actions of Neutrophils.

PHARMACOKINETICS

Absorption:

ALACE (Aceclofenac) is rapidly and completely absorbed after oral administration. Peak plasma concentrations are reached 1 to 3 hours after an oral dose. T max is delayed with concomitant food intake whereas the degree of absorption is not influenced.

Distribution:

ALACE (Aceclofenac) is highly protein-bound (>99%).The plasma concentration of aceclofenac was approximately twice that in synovial fluid after multiple doses of the drug in-patient with knee pain and synovial fluid effusion. The volume of distribution is approximately 30L.

Metabolism:

ALACE (Aceclofenac) is probably metabolized via CYP2C9 to a major metabolite 4'-hydroxyaceclofenac and to a number of other metabolites including 5-hydroxyaceclofenac, 4'-hydroxydiclofenac, diclofenac and 5-hydroxydiclofenac.

Excretion:

 Renal excretion is the main route of elimination of ALACE (Aceclofenac). 70 to 80% of administered dose were found in the urine, mainly as conjugated hydroxyl metabolites. 20% is excreted in the feces. Only 1% of an oral single dose is excreted unchanged. The plasma elimination half-life of the drug is approximately 4 hours.

Indications:

ALACE (Aceclofenac) is indicated for the relief of pain and inflammation in both acute and chronic pain like osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, dental pain, post-traumatic pain, low back pain, gynaecological pain etc.

CONTRAINDICATIONS:

Ø  ALACE (Aceclofenac) is contraindicated in patients previously sensitive to aceclofenac or aspirin or other NSAIDs.

Ø  It should not be administered to patients with active or suspected peptic ulcer or gastrointestinal bleeding and moderate to severe renal impairment.

WARNING AND PRECAUTIONS:

ALACE (Aceclofenac) should be administered with caution to patients with symptoms indicative of gastrointestinal disorders, with a history of peptic ulceration, ulcerative colitis, Crohn's disease, hepatic porphyria, and coagulation disorders. Patients suffering from severe hepatic impairment must be monitored.

·         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 of Aceclofenac Tablets.

·         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 Tablets 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.

·         Haematological:

Aceclofenac Tablets may reversibly inhibit platelet aggregation.

USE IN PREGNANCY AND LACTATION:

Pregnancy: There is no information on the use of ALACE (Aceclofenac) during pregnancy. Aceclofenac should not be administered during pregnancy, unless there are compelling reasons for doing so. The lowest effective dose should be administered.

Lactation: There is no information on the secretion of aceclofenac in breast milk. The use of aceclofenac should therefore be avoided during lactation unless the potential benefits to the mother outweigh the possible risks to the children.

DRUG INTERACTIONS:

Lithium and Digoxin: ALACE (Aceclofenac), like many NSAIDs may increase plasma concentrations of lithium and Digoxin.

Diuretics: ALACE (Aceclofenac), like other NSAIDs, may interact the activity of diuretics.

Anticoagulants: Like other NSAIDs, ALACE (Aceclofenac) may enhance the activity of anticoagulant. Close monitoring of patients on combined anticoagulants and Aceclofenac therapy should be undertaken.

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.

Cyclosporin: Enhances Cyclosporin nephrotoxicity.

Quinolone antibiotics: It precipitate convulsion when co-administered with quinolone antibiotics.

Antidiabetic drugs: Hypo or hyperglycaemia may result from the concomitant administration of aceclofenac and antidiabetic drugs, although this is rare.

 NSAIDS of corticosteroids: Co administration of aceclofenac with other NSAIDS of corticosteroids may

             results in increased frequency of adverse event.

                   

ADVERSE EFFECTS:

ALACE (Aceclofenac) is well tolerated, with most adverse events being minor and reversible and affecting mainly the GI system. Most common events include dyspepsia (7.5%), abdominal pain (6.2%), nausea (1.5%), diarrhea (1.5%), flatulence (0.8%), gastritis (0.6%), constipation (0.5%), vomiting (0.5%), ulcerative stomatitis (0.1%), pancreatitis (0.1%). Withdrawal rates due to these events were significantly lower in aceclofenac than with ketoprofen and tenoxicam.

Other adverse effect, which is not common such as dizziness (1%), vertigo (0.3%), and rare cases: par aesthesia and tremor.

DOSAGE AND ADMINISTRATION:

Adults: The maximum 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 is no clinical data on the use of ALACE (Aceclofenac) in children.

Elderly: The pharmacokinetics of ALACE (Aceclofenac) are not altered in elderly patients, therefore it is not considered necessary to modify the dose and dose frequency.

Renal insufficiency: There is no evidence that the dosage of ALACE (Aceclofenac) needs to be modified in patients with mild renal impairment.

Hepatic insufficiency: The dose of ALACE (Aceclofenac) should be reduced in patients with hepatic impairment. An initial daily dose of 100 mg should be administered.

OVERDOSAGE:

There is no human data available on the consequences of ALACE (Aceclofenac) overdosage. After overdosage, following therapeutic measures to be taken: absorption should be prevented as soon as possible by means of gastric lavage and treatment with activated charcoal. Supportive and symptomatic treatment should be given for complications.

STORAGE:
Store in a cool and dry place

COMMERCIAL PACKAGING:

Ø  10 Blisters of 10 Tablets