 Arrox
COMPOSITION
Each tablet contains Meloxicam 7.5mg
PHARMACODYNAMICS
Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the
oxicam family, with anti-inflammatory, analgesic and antipyretic properties.
The anti-inflammatory activity of meloxicam has been proven in classical
models of inflammation. As with other NSAIDs, its precise mechanism
of action remains unknown. However, there is at least one common
mode of action shared by all NSAIDs (including meloxicam) : inhibition
of the biosynthesis of prostaglandins, known inflammation mediators.
PHARMACOKINETICS
Absorption: Meloxicam is well absorbed from the gastrointestinal tract,
which is reflected by a high absolute bioavailability of 89% following oral
administration (capsule). Tablets, oral suspension and capsules were
shown to he bioequivalent. Following single dose administration of
meloxicam, mean maximum plasma concentrations are achieved within
5-6 hours with capsules and tablets. With multiple dosing, steady state
conditions were reached within 3 to 5 days. Once daily dosing leads to
drug plasma concentrations with a relatively small peak-trough fluctuation
in the range of 0.4 - 1.0
µg/mL for 7.5 mg doses and 0.8 - 2.0
µg/mL for
15 mg doses, respectively (Cmin and Cmax at steady state, respectively).
Maximum plasma concentrations of meloxicam at steady state, are
achieved within five to six hours. Continuous treatment for periods of
more than one year results in similar drug concentrations to those seen
once steady state is first achieved. Extent of absorption for meloxicam
following oral administration is not altered by concomitant food intake.
Distribution: Meloxicam is very strongly bound to plasma proteins,
essentially albumin (99%). Meloxicam penetrates into synovial fluid to
give concentrations approximately half of those in plasma.
Biotransformation: Meloxicam undergoes extensive hepatic
biotransformation. Four different metabolites of meloxicam were identified
in urine, which are all pharmacodynamically inactive. The major metabolite,
5'-carboxymeloxicam (60% of dose), is formed by oxidation of an
intermediate metabolite 5'- hydroxymethylmeloxicam, which is also
excreted to a lesser extent (9% of dose). In vitro studies suggest that
CYP 2C9 plays an important role in this metabolic pathway, with a minor
contribution from the CYP 3A4 isoenzyme. The patient's peroxidase
activity is probably responsible for the other two metabolites, which
account for 16% and 4% of the administered dose respectively.
Elimination: Meloxicam is excreted predominantly in the form of
metabolites and occurs to equal extents in urine and faeces. Less than
5% of the daily dose is excreted unchanged in faeces, while only traces
of the parent compound are excreted in urine. The mean elimination
half-life is about 20 hours. Total plasma clearance amounts on average
8 mL/min.
Special populations: Hepatic/renal insufficiency: Neither hepatic, mild
nor moderate renal insufficiency have a substantial effect on meloxicam
pharmacokinetics. In terminal renal failure, the increase in the volume
of distribution may result in higher free meloxicam concentrations, and
a daily dose of 7.5 mg must not be exceeded (see section Recommended
Dose).
Elderly: Mean plasma clearance at steady state in elderly subjects
was slightly lower than that reported for younger subjects.
INDICATIONS
Symptomatic treatment of:
• painful osteoarthritis (arthrosis, degenerative joint disease)
• rheumatoid arthritis
• ankylosing spondylitis
RECOMMENDED DOSE
Exacerbations of osteoarthrosis : 7.5 mg/day (one 7.5 mg tablet). If
necessary, in the absence of improvement, the dose may be increased
to 15 mg/day (two 7.5 mg tablets).
Rheumatoid arthritis, ankylosing spondylitis : 15 mg/day (two 7.5 mg
tablets).
(See also 'special populations'). According to the therapeutic response,
the dose may be reduced to 7.5 mg/day (one 7.5 mg tablet). DO NOT
EXCEED THE DOSE OF 15 MG/DAY. The total daily amount should be
taken as a single dose, with water or another liquid, during a meal.
Special populations
Elderly patients and patients with increased risks for adverse reaction:
The recommended dose for long term treatment of rheumatoid arthritis
and ankylosing spondylitis in elderly patients is 7.5 mg per day. Patients
with increased risks for adverse reactions should start treatment with
7.5 mg per day.
Renal impairment: In dialysis patients with severe renal failure, the dose
should not exceed 7.5 mg per day. No dose reduction is required in
patients with mild to moderate renal impairment (i.e. patients with a creatinine clearance of greater than 25 ml/min).
Hepatic impairment: No dose reduction is required in patients with mild
to moderate hepatic impairment
Children: Arrox should not be used in children aged under 15. This
medicinal product exists in other dosages, which may be more appropriate.
CONTRAINDICATIONS
This medicinal product is contra-indicated in the following situations:
• pregnancy and lactation (See section 'Pregnancy and lactation')
• hypersensitivity to meloxicam or to one of the excipients or
hypersensitivity to substances with a similar action, e.g. NSAIDs,
aspirin. Arrox should not be given to patients who have developed
signs of asthma, nasal polyps, angioneurotic oedema or urticaria
following the administration of aspirin or other NSAIDs.
• active gastro-intestinal ulcer or history of recurrent gastro-intestinal
ulcer;
• severely impaired liver function;
non-dialysed severe renal failure;
• gastrointestinal bleeding, cerebrovascular bleeding or other bleeding
disorders;
• severe uncontrolled heart failure.
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