Salofalk Enema 2g

Each enema contains 2g mesalazine in 59 ml of suspension.

For a full list of excipients, see section 6.1.

Enema

Therapy and prophylaxis of acute attacks of mild ulcerative colitis, especially in the rectum and sigmoid colon and also in the descending colon.

Method of administration: Rectal

Adults and the Elderly: 1 enema once a day at bedtime. The action of Salofalk is enhanced if the patient lies on the left side when introducing the enema. The dosage should be adjusted to suit the progress of the condition. Do not discontinue treatment suddenly.

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

Severe impairment of renal or hepatic function. Known hypersensitivity to salicylates or the excipients.

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

If the findings are normal, further testing should be carried out every 3 months. If additional symptoms occur, tests should be performed immediately.

Caution is recommended in patients with impaired hepatic function.

Salofalk enemas are not recommended 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 enemas.

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

Specific interaction studies have not been performed.

Interactions may occur during treatment with Salofalk enemas and concomitant administration of the following medicinal products. Most of these possible interactions are based on theoretical reasons:

In patients who are concomitantly treated with azathioprine or 6-mercaptopurine, possible enhanced myelosuppressive effects of azathioprine or 6-mercaptopurine should be taken into account.

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 (2-4 g, 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, embryonal/fetal 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 like diarrhoea cannot be excluded. Therefore, Salofalk enemas should only be used during breast-feeding if the potential benefit outweighs the possible risk. If the suckling neonate develops diarrhoea, the breast-feeding should be discontinued.

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

The following side effects have been reported with the use of mesalazine:

No cases of intoxication have been reported to date and no specific antidotes are known.

If necessary, intravenous infusion of electrolytes (forced diuresis) should be considered in cases of overdose.

Pharmacotherapeutic group: Aminosalicylic acid and similar agents

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 in 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 demonstrated good rectal tolerance, no preclinical studies have been performed with Salofalk rectal preparations.

Preclinical data on mesalazine 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.

Salofalk Enema 2g contains the following excipients:

Carbomer, disodium edetate, potassium acetate (E261), potassium metabisulphite (E224), purified water, sodium benzoate (E211), xanthan gum (E415).

None known.

24 months.

Store at room temperature (15-25°C) and protect from light.

Low density concertina shaped polythene bottle with a low density polythene application nozzle packed in cartons containing seven individually blister packed bottles.

None stated

Dr Falk Pharma UK Ltd, Unit k, Bourne End Business Park

Cores End Road, Bourne End, Bucks, SL8 5AS

United Kingdom

PL 10341/0008

31^st December 2004

August 2010