PENTASA MESALAZINE ENEMA 1G

Active substance: MESALAZINE

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PRODUCT SUMMARY
1.

NAME OF THE MEDICINAL PRODUCT

Pentasa® Mesalazine Enema.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each enema bottle contains mesalazine 1g in 100ml.

3.

PHARMACEUTICAL FORM
Rectal suspension.
Each bottle contains 100ml of a colourless to faint yellow suspension
containing 1g mesalazine.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications
Pentasa Mesalazine Enema is indicated for the treatment of ulcerative colitis
affecting the distal colon and rectum.

4.2.

Posology and method of administration
Adults: The recommended dosage is one enema at bedtime.
Chlldren: Not recommended.
Pentasa Mesalazine Enemas are for rectal administration

4.3.

Contraindications
Pentasa is contraindicated in:
- patients with known sensitivity to salicylates
- patients with severe liver and/or renal impairment
- patients allergic to any of the ingredients

4.4.

Special warnings and precautions for use
Serious blood dyscrasias have been reported rarely with mesalazine.
Haematological investigations should be performed if the patient develops
unexplained bleeding, bruising, purpura, anaemia, fever or sore throat.
Treatment should be stopped if there is suspicion or evidence of blood
dyscrasia.
Most patients who are intolerant or hypersensitive to sulphasalazine are able to
use Pentasa without risk of similar reactions. However, caution is
recommended when treating patients allergic to sulphasalazine (risk of allergy
to salicylates). Caution is recommended in patients with impaired liver
function.
It is recommended that mesalazine is used with extreme caution in patients
with mild to moderate renal impairement (see section 4.3).
If a patient develops dehydration while on treatment with mesalazine, normal
electrolyte levels and fluid balance should be restored as soon as possible.
Mesalazine induced cardiac hypersensitivity reactions (myocarditis and
pericarditis) have been reported rarely. Treatment should be discontinued on
suspicion or evidence of these reactions.

4.5.

Interaction with other medicinal products and other forms of interaction
The concurrent use of mesalazine with other known nephrotoxic agents, such
as NSAIDs and azathioprine, may increase the risk of renal reactions (see
section 4.4)
Concomitant treatment with mesalazine can increase the risk of blood
dyscrasia in patients receiving azathioprine or 6-mercaptopurine.

4.6.

Pregnancy and lactation
Pentasa® should be used with caution during pregnancy and lactation and only
if the potential benefit outweighs the possible hazards in the opinion of the
physician.
Mesalazine is known to cross the placental barrier, but the limited data
available on its use in pregnant women do not allow assessment of possible
adverse effects. No teratogenic effects have been observed in animal studies.

Blood disorders (leucopenia, thrombocytopenia, anaemia) have been reported
in new-borns of mothers being treated with PENTASA.
Mesalazine is excreted in breast milk. The mesalazine concentration in breast
milk is lower than in maternal blood, whereas the metabolite, acetyl
mesalazine appears in similar or increased concentrations. There is limited
experience of the use of oral mesalazine in lactating women. No controlled
studies with PENTASA during breast-feeding have been carried out.
Hypersensitivity reactions like diarrhoea in the infant cannot be excluded.

4.7.

Effects on ability to drive and use machines
No adverse effects.

4.8.

Undesirable effects
Mesalazine may be associated with an exacerbation of the symptoms of colitis
in those patients who have previously had such problems with sulphasalazine.
Undesirable effects are as follows:
Common
(≥1% and <10%)

Gastrointestinal disorders:
Nausea, vomiting, diarrhoea, abdominal pain
Skin disorders:
Rash (including urticaria and erythematous rash)
General:
Headache

Rare
(≥0.01% and <0.1%)

Blood disorders:
Leucopenia (including granulocytopenia), neutropenia,
agranulocytosis, aplastic anaemia, thrombocytopema
Nervous system disorders:
Peripheral neuropathy
Cardiac disorders:
Myocarditis, pericarditis
Respiratory disorders:
Allergic lung reactions (including dyspnoea, coughing,
allergic alveolitis, pulmonary eosinophilia, pulmonary
infiltration, pneumonitis)
Gastrointestinal disorders:

Pancreatitis, increased amylase
Liver:
Abnormalities of hepatic function and hepatotoxicity
(including, hepatitis, cirrhosis, hepatic failure)
Urogenital:
Abnormal renal function (including interstitial nephritis,
nephrotic syndrome), urine discolouration (*see
additional text).
Collagen disorders:
Lupus erythematosus-like reactions

Very rare(<0.01%)

Blood disorders:
Anaemia, eosinophilia (as part of an allergic reaction)
and pancytopenia
Liver:
Increased liver enzymes and bilirubin
Skin disorders:
Reversible alopecia, bullous skin reactions including
erthema multiforme and Stevens-Johnson syndrome.
Musculo-skeletal disorders:
Myalgia, arthralgia
Allergic reactions:
Hypersensitivity reactions, drug fever.

*Renal failure has been reported. Mesalazine-induced nephrotoxicity should
be suspected in patients developing renal dysfunction during treatment.
The mechanism of mesalazine induced myocarditis, pericarditis, pancreatitis,
nephritis and hepatitis is unknown, but it might be of allergic origin.
Following rectal administration local reactions such as pruritus, rectal
discomfort and urge may occur.

4.9.

Overdose
Acute experience in animals:

Single oral doses of mesalazine of up to 5g/kg in pigs or a single intravenous
dose of mesalazine at 920mg/kg in rats were not lethal.
Human experience:
No cases of overdose have been reported.
Management of overdose in man:
Symptomatic treatment at hospital. Close monitoring of renal function.
Intravenous infusion of electrolytes may be used to promote diuresis.

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic properties
Pharmacotherapeutic group: Intestinal anti-inflammatory agents.
Mechanism of action and pharmacodynamic effects:
Mesalazine is recognised as the active moiety of sulphasalazine in the
treatment of ulcerative colitis. It is thought to act locally on the gut wall in
inflammatory bowel disease, although its precise mechanism of action has not
been fully elucidated.
Increased leucocyte migration, abnormal cytokine production, increased
production of arachidonic acid metabolites, particularly leukotriene B4 and
increased free radical formation in the inflamed intestinal tissue are all present
in patients with inflammatory bowel disease. Mesalazine has in-vitro and invivo pharmacological effects that inhibit leucocyte chemotaxis, decrease
cytokine and leukotriene production and scavenge for free radicals. It is
currently unknown which, if any of these mechanisms play a predominant role
in the clinical efficacy of mesalazine.

5.2.

Pharmacokinetic properties
General characteristics of the active substance
Disposition and local availability:
Pentasa® enemas are designed to provide the distal part of the intestinal tract
with high concentrations of mesalazine and a low systemic absorption. The
enemas have been shown to reach and cover the descending colon.
Biotransformation:

Mesalazine is metabolised both pre-systemically by the intestinal mucosa and
systemically in the liver to N-acetyl mesalazine (acetyl mesalazine). The
acetylation seems to be independent of the acetylator phenotype of the patient.
Some acetylation also occurs through the action of colonic bacteria.
Acetyl mesalazine is thought to be clinically as well as toxicologically
inactive, although this remains to be confirmed.
Absorption:
The absorption following rectal administration is low, but depends on the
dose, the formulation and the extent of spread. Based on urine recoveries in
healthy volunteers under steady-state conditions given a daily dose of 2g (1g x
2), about 15-20% of the dose is absorbed after administration of enemas.
Distribution:
Mesalazine and acetyl mesalazine do not cross the blood brain barrier. Protein
binding of mesalazine is approximately 50% and of acetyl mesalazine about
80%.
Elimination:
The plasma half-life of pure mesalazine is approximately 40 minutes and for
acetyl mesalazine approximately 70 minutes. Both substances are excreted in
urine and faeces. The urinary excretion consists mainly of acetyl mesalazine.
Characteristics in patients:
The systemic absorption following administration of Pentasa® enemas has
been shown to be significantly decreased in patients with active ulcerative
colitis compared to those in remission.
In patients with impaired liver and kidney functions, the resultant decrease in
the rate of elimination and increased systemic concentration of mesalazine
may constitute an increased risk of nephrotoxic adverse reactions.

5.3.

Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are
additional to that already included in other sections of the SPC.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of excipients
Disodium Edetate
Sodium Metabisulphite
Sodium Acetate

Hydrochloric Acid, concentrated
Purified Water

6.2.

Incompatibilities
None known.

6.3.

Shelf life
24 months.

6.4.

Special precautions for storage
Do not store above 25°C. Keep bottle in outer carton.

6.5.

Nature and contents of container
Polyethylene enema bottles fitted with a tip and valve for rectal application,
supplied in nitrogen-filled aluminium-foil bags. Presented in cartons
containing 7 x 100ml bottles individually foil-wrapped.

6.6.

Instructions for use, handling and disposal
None.

7

MARKETING AUTHORISATION HOLDER
Ferring Pharmaceuticals Ltd
The Courtyard
Waterside Drive
Langley
Berkshire
SL3 6EZ
United Kingdom

8.

MARKETING AUTHORISATION NUMBER

PL 03194/0027

9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
15th November 1988 / 4th February 1999

10.

DATE OF REVISION OF TEXT
October 2004

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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