Alace

COMPOSITION

Each Film coated tablet contains:

Aceclofenac BP...........100 mg

DESCRIPTION

Aceclofenac is an orally administered phenylacetic acid derivative with effects on a variety of inflammatory mediators. It is from the class of non-steroidal anti-inflammatory drug (NSAID), related to diclofenac.

PHARMACOLOGY

Pharmacodynamics
Aceclofenac is a novel 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.        Aceclofenac directly blocks PGE₂ secretion at the site of inflammation. Aceclofenac has been demonstrated to inhibit cyclooxygenase (COX) activity and to suppress the PGE₂ production by inflammatory cells, which are likely to be a primary source of PGE₂.

2.        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.

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

Pharmacokinetics
Absorption: After oral administration, aceclofenac is rapidly absorbed and the bioavailability is almost 100%. Peak plasma concentrations are reached approximately 1.25 to 3 hours following ingestion. T_max is delayed with concomitant food intake whereas the degree of absorption is not influenced.

Distribution: Aceclofenac is highly protein-bound (> 99.7%). Aceclofenac penetrates into the synovial fluid where the concentrations reach approximately 60% of those in plasma. The volume of distribution is approximately 30L.

Metabolism: Aceclofenac is probably metabolized via CYP2C9 to the main metabolite 4-hydroxyaceclofenac. The mean plasma elimination half-life is 4-4.3 hours.

Excretion: Approximately two-thirds of the administered dose is excreted via the urine, mainly as conjugated hydroxymetabolites . Only 1% of an oral single dose is excreted unchanged.

INDICATIONS

ALACE is indicated for the treatment of acute painful inflammatory conditions with or without associated fever.

DOSAGE AND ADMINISTRATION

ALACE tablets are supplied for oral administration in adults. The maximum recommended dose of ALACE is two tablets daily, taken as one tablet in the morning and one in the evening.

CONTRAINDICATIONS

• Hypersensitivity to Aceclofenac or any component of the tablet.
• In patients in whom substances with a similar action (e.g. aspirin, or other NSAIDs), precipitate attacks of asthma, bronchospasm, acute rhinitis or urticaria or patients are hypersensitive to these drugs.
• Severe heart failure or severely impaired hepatic or renal organ function and during the last three months of pregnancy.

DRUG INTERACTIONS

·         Aceclofenac may increase plasma concentrations of lithium, digoxin and methotrexate.

·         Aceclofenac may increase the activity of anticoagulants, inhibit the activity of diuretics, enhance cyclosporin nephrotoxicity and precipitate convulsions when co-administered with quinolone antibiotics. When concomitant administration with potassium sparing diuretics is employed, serum potassium should be monitored.

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

WARNINGS AND PRECAUTIONS

General

• Aceclofenac should be given with caution to elderly patients with renal, hepatic or cardiovascular impairment and to those receiving other medication. The lowest effective dose should be used and renal function monitored regularly.
• Renal and hepatic function and blood counts should be monitored during long term treatment. Persistently elevated hepatic enzyme levels necessitate withdrawal of aceclofenac.

Renal impairment

Patients with mild 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.

Hepatic impairment

The recommended initial dose of ALACE should be reduced to one tablet daily in patients with impaired hepatic function.

Pregnancy
The drug in not recommended in pregnant women.

Lactation
The drug in not recommended in breast-feeding women.

Paediatric use

There are no clinical data on the use of aceclofenac in children.

Geriatric use

Generally no dose reduction is necessary, however, consider the precautions.

ADVERSE EFFECTS

The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn`s disease have been reported following administration.