Mezavant XL - Medicines Management

January 2010
Mezavant
N O RT H S TA F F O R D S H I R E
AREA PRESCRIBING COMMITTEE
MEDICINE REVIEW SUMMARY
N O R T H S T A F F O R D S H I R E H E A L T H E C O N O M Y P U B L I C A T I O N
Efficacy.
A multicentre, randomised, double-blind, doubledummy,
parallel-group study investigated the efficacy
and safety of Mezavant XL® compared with Asacol
MR® for the maintenance of left-sided ulcerative
colitis in adults. 334 patients were randomised
equally to receive either 2.4g Mezavant XL® in the
morning or 1.6g Asacol MR® in the morning and
800mg in the evening. At 12 months there was no
significant difference in the proportion of patients
who were in clinical remission, and clinical and
endoscopic remission. Both treatments were similarly
tolerated.
Dose and administration.
a) Induction of remission:
In adults, including the elderly, the recommended
dose is 2.4 to 4.8g (two to four tablets) taken once
daily. The highest dose of 4.8g/day is recommended
for patients not responding to lower doses of
mesalazine. When using 4.8g/day, the effect of the
Mezavant XL® (Mesalazine MR)
Verdict.
• Mezavant XL® is to be included within the North Staffordshire Joint Formulary and will
have a GREEN traffic light.
• Mezavant XL® is licensed in adults over 18 years for the induction of clinical and endoscopic
remission in patients with mild to moderate, active ulcerative colitis, and for the maintenance
of remission. However it has been agreed with the local gastroenterology clinicians that it
will be used for the maintenance of remission of ulcerative colitis.
• Mezavant XL® contains a core of mesalazine 1.2g formulated in a multi-matrix system. This is
designed to dissolve at pH 7 and above, facilitating the extended delivery of effective
concentrations of mesalazine through the entire colon with limited systemic absorption.
• Mesalazine is an aminosalicylate. It appears that its mechanism of action is topical and
involves diminishing inflammation by blocking cyclooxygenase and inhibiting prostaglandin
production in the colon.
• Mesalazine preparations release active drug at different sites along the gastrointestinal tract.
Consequently they should be prescribed according to their mode and site of action and the
brand name should be specified.
• Mezavant XL® has the advantage of once-daily dosing. It is therefore an option in poorly
compliant patients on Asacol MR® for maintenance therapy.
treatment should be evaluated at 8 weeks.
b) Maintenance of remission:
The recommended dose in adults is 2.4g (two tablets)
taken once daily.
The tablets must not be crushed or chewed and
should be taken with food.
The manufacturer states that specific studies have not
been performed to investigate Mezavant XL® in
patients with hepatic or renal impairment.
Safety.
Contraindications include history of hypersensitivity
to salicylates (including mesalazine) or any of the
excipients of Mezavant XL®. Mezavant XL® is also
contraindicated in severe renal impairment (GFR

Mezavant XL® (Mesalazine MR)
N O R T H S T A F F O R D S H I R E H E A L T H E C O N O M Y P U B L I C A T I O N
Reports of renal impairment (nephropathy, acute/
chronic interstitial nephritis) have been associated
with mesalazine preparations and pro-drugs of
mesalazine. Mezavant XL® should be used with
caution in patients with confirmed mild to moderate
renal impairment. It is recommended that renal
function is checked in all patients prior to initiation
of therapy and at least twice a year.
Patients with chronic lung function impairment,
especially asthma, are at risk of hypersensitivity
reactions and should be closely monitored.
Serious blood dyscrasias have been reported rarely.
If the patient develops unexplained bleeding,
bruising, purpura, anaemia, fever or sore throat,
haematological investigations should be performed
and if suspected treatment should be terminated.
Mesalazine induced cardiac hypersensitivity reactions
have been reported rarely. Mezavant XL® should be
used with caution in patients with conditions
predisposing to myo- or pericarditis. If suspected,
mesalazine preparations must not be restarted.
Mesalazine has been associated with an acute
intolerance syndrome that may be difficult to
distinguish from a flare of inflammatory bowel
disease. If suspected, treatment must be stopped and
not reintroduced.
There has been Requires reports no dose of mesalazine adjustment increasing from CFCcontaining
therefore inhalers. it should Same steroid be used dose with
liver
enzyme levels
caution in given. patients with liver impairment.
Mesalazine is excreted in breast milk at low
concentration. Acetylated form of mesalazine is
excreted in breast milk at higher concentration.
Caution should be exercised if using mesalazine
while breast-feeding and only if the benefit
outweighs the risks. Sporadically acute diarrhoea
has been reported in breast fed infants.
The manufacturer states that data on mesalazine
show no sustained effect on male fertility.
The manufacturer states that the most commonly
reported adverse drug reactions during acute
treatment were flatulence, nausea or headache,
which were not dose related and occurred in less
than 3% of patients receiving Mezavant XL®.
Interactions.
The manufacturer states that no investigations
have been performed on interactions between
Mezavant XL® and other drugs. However, there
have been reports of interactions between other
mesalazine containing products and other drugs.
Caution is recommended for the concomitant use
of mesalazine with known nephrotoxic agents,
including NSAIDs and azathioprine as these may
increase the risk of renal adverse reactions.
Mesalazine inhibits QVAR thiopurine methyltransferase.
Requires In patients 50-60% on azathioprine dose reduction or 6-mercaptopurine,
from CFC
-containing caution is recommended inhalers. for concurrent use can
increase the potential for blood dyscrasias.
Metered dose inhalers (MDIs) only. Metered dose inhalers (MDIs), and inhalers.
Caution should be exercised when treating patients Administration with coumarin-type anticoagulants
allergic to sulphasalazine due to the potential risk of e.g. warfarin, could result in decreased
cross sensitivity 50mcg, reactions 100mcg, with 200mcg mesalazine. and 250mcg 50mcg anticoagulant and 100mcg activity. strengths available The manufacturer
due
strengths available.
to recommends lower dose needed. that prothrombin time is closely
The manufacturer states that limited experience with monitored if this combination is essential.
mesalazine
Use
in
with
pregnancy
.
does not indicate an
Use with .
increased Black risk triangle of drug status (established induced congenital drug but No Cost black analysis.
triangle status (>7 years experience
The in cost UK). of Mezavant XL® in primary care is
malformations. new formulation Mesalazine in crosses UK). the placental
barrier, but provides foetal concentrations much £62.44 (60 tablets). Therefore, in primary care,
lower than Licensed those seen in adults with and adult children therapeutic (any age) use. Licensed in adults, but not licensed in children