Dr. Falk Pharma UK Ltd

Salofalk 4g/60ml Enemas

Each Salofalk Enema contains 4.0g of Mesalazine (5-aminosalicylic acid) in 60.0ml of suspension (60g = 60ml).

Excipients: Sodium benzoate and Potassium metabisulphite

For a full list of excipients, see section 6.1.

Rectal suspension (Enema).

Creamy coloured rectal suspension with lubricated applicator.

As an anti-inflammatory in the management of ulcerative colitis, alone or, particularly in the acute phase, with corticosteriods

Salofalk enemas are for rectal administration.

Adults including the elderly:

Unless prescribed otherwise, the contents of one enema vial (60ml suspension) are given once per day rectally before retiring. The best results are obtained if gut lavage is carried out prior to the Salofalk enema.

Shake well before use to homogenise the suspension.

Children:

There is little experience and only limited documentation for an effect in children.

Salofalk is contraindicated in cases of:

Known hypersensitivity to salicylates or any of the excipients.

Severe impairment of hepatic or renal function.

Blood tests (differential blood count; liver function parameters such as ALT or AST; serum creatinine) and urinary status (dip sticks) should be determined prior to and during treatment, at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after commencement of treatment, then a further two to three tests at intervals of 4 weeks.

If the findings are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.

Caution is recommended in patients with impaired hepatic function.

Salofalk enemas should not be used in patients with impaired renal function.

Mesalazine-induced renal toxicity should be considered if renal function deteriorates during treatment.

Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment with Salofalk enema.

Patients with a history of adverse drug reactions to preparations containing sulfasalazine should be kept under close medical surveillance on commencement of a course of treatment with Salofalk enema. Should Salofalk enema cause acute intolerance reactions such as abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.

Due to their content of potassium metabisulphite, Salofalk 4g/60 mL enemas may cause allergic reactions with anaphylactic symptoms and bronchial constriction (bronchospasm) in sensitive patients, particularly in those with asthma or a history of allergies.

Because the product contains sodium benzoate, it may cause hypersensitivity reactions in suitably predisposed patients in the form of irritation of the skin, eyes and mucous membranes.

Specific interaction studies have not been performed.

In patients who are concomitantly treated with azathioprine, 6-mercaptopurine or thioguanine, a possible increase in the myelosuppressive effects of azathioprine, 6-mercaptopurine or thioguanine should be taken into account.

There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.

There are no adequate data from the use of Salofalk enemas in pregnant women.

However, data on a limited number of exposed pregnancies indicate no adverse effect of mesalazine on pregnancy or on the health of the foetus/newborn child. To date no other relevant epidemiologic data are available.

In one single case after long-term use of a high dose mesalazine (2-4g, orally) during pregnancy, renal failure in a neonate was reported.

Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development.

Salofalk enemas should only be used during pregnancy if the potential benefit outweighs the possible risk.

N-acetyl-5-aminosalicylic acid and to a lesser degree mesalazine are excreted in breast milk. Only limited experience during lactation in women is available to date. Hypersensitivity reactions such as diarrhoea in the infant cannot be excluded. Therefore, Salofalk enemas should only be used during breast-feeding if the potential benefit outweighs the possible risk. If the infant develops diarrhoea, breast-feeding should be discontinued.

No effects on the ability to drive and use machines have been observed.

There are rare data on overdosage (e.g. intended suicide with high oral doses of mesalazine), which do not indicate renal or hepatic toxicity. There is no specific antidote and treatment is symptomatic and supportive.

Pharmacotherapeutic group: Intestinal anti-inflammatory agent

ATC Code: A07EC02

The mechanism of the anti-inflammatory action is unknown. The results of in vitro studies indicate that inhibition of lipoxygenase may play a role.

Effects on prostaglandin concentrations in the intestinal mucosa have also been demonstrated. Mesalazine (5-aminosalicylic acid/5-ASA) may also function as a radical scavenger of reactive oxygen compounds.

On reaching the intestinal lumen, rectally administered mesalazine has largely local effects on the intestinal mucosa and submucosal tissue.

General considerations of mesalazine:

Absorption:

Mesalazine absorption is highest in proximal gut regions and lowest in distal gut areas.

Biotransformation:

Mesalazine is metabolised both pre-systemically by the intestinal mucosa and the liver to the pharmacologically inactive N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). The acetylation seems to be independent of the acetylator phenotype of the patient. Some acetylation also occurs through the action of colonic bacteria. Protein binding of mesalazine and N-Ac-5-ASA is 43 % and 78 %, respectively.

Elimination:

Mesalazine and its metabolite N-Ac-5-ASA are eliminated via the faeces (major part), renally (varies between 20 and 50 %, dependent on kind of application, pharmaceutical preparation and route of mesalazine release, respectively), and biliary (minor part). Renal excretion predominantly occurs as N-Ac-5-ASA. About 1 % of total orally administered mesalazine dose is excreted into the breast milk mainly as N-Ac-5-ASA.

With the exception of a local tolerance study in dogs, which showed good rectal tolerance, no preclinical studies have been performed with Salofalk rectal preparations.

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity, carcinogenicity (rat) or toxicity to reproduction.

Kidney toxicity (renal papillary necrosis and epithelial damage in the proximal convoluted tubule or the whole nephron) has been seen in repeat-dose toxicity studies with high oral doses of mesalazine. The clinical relevance of this finding is unknown.

Sodium benzoate (E211)

Potassium metabisulphite (E224)

Carbomer

Disodium edetate

Potassium acetate (E261)

Xanthan gum

Purified water

Not applicable.

2 years

Do not store above 25°C

Store in the original package in order to protect from light

Cardboard box containing 7 x 60ml white opaque low density polyethylene squeeze bottles with lubricated applicators. Each bottle is packed in a separate airtight seal.

Shake well before use

Dr Falk Pharma GmbH

Leinenweberstr. 5

79108 Freiburg

Germany

PA 573/4/1

Date of first authorisation: 08 Feb 1989

Date of last renewal: 8^th February 2009

February 2012