SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Salofalk Enema 2g.

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

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

For the full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM Enema.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

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

4.2    Posology and method of administration

Posology

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.

Paediatric population

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

Method of administration:

Rectal

4.3 Contraindications

Salofalk is contraindicated in cases of:

•    Severe impairment of hepatic or renal function.

•    Hypersensitivity to the active substance, salicylates or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

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 three months. If additional symptoms occur, these tests should be performed immediately.

Caution is recommended in patients with impaired hepatic function.

Salofalk 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.

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. Should Salofalk cause acute intolerance reactions such as abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.

This medicine contains sodium benzoate, which may be mildly irritant to the skin, eyes and mucous membranes

4.5 Interaction with other medicinal products and other forms of interaction

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.

4.6 Fertility, pregnancy and lactation

Pregnancy

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 the 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 (24g, 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/fetal development, parturition or postnatal development.

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

Breastfeeding

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 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.

4.7 Effects on ability to drive and use machines

Salofalk Enema 2g have no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

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

Organ Class System	Frequency According to MedDRA Convention
	Rare (> 1/10,000; <1/1,000)	Very rare (< 1/ 10,000)
Blood and lymphatic		Altered blood counts (aplastic

system disorders		anaemia, agranulocytosis, pancytopenia, neutropenia, leukopenia, thrombocytopenia)
Nervous system disorders	Headache, dizziness	peripheral neuropathy
Cardiac disorders	Myocarditis, Pericarditis
Respiratory, thoracic and mediastinal disorders		Allergic and fibrotic lung reactions (including dyspnoea, cough, bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis)
Gastrointestinal disorders	Abdominal pain, diarrhoea, flatulence, nausea, vomiting, constipation	Acute pancreatitis
Renal and urinary disorders		Impairment of renal function including acute and chronic interstitial nephritis and renal insufficiency
Skin and subcutaneous tissue disorders		Alopecia
Musculoskeletal and connective tissue disorders		Myalgia, arthralgia
Immune system disorders		Hypersensitivity reactions such as allergic exanthema, drug fever, lupus erythematosus syndrome, pancolitis
Hepatobiliary disorders		Changes in liver function parameters (increase in transaminases and cholestasis parameters), hepatitis, cholestatic hepatitis
Reproductive system disorders		Oligospermia (reversible)

Reporting of suspected adverse reactions

Reporting of suspected reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

4.9 Overdose

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.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

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.

5.2    Pharmacokinetic properties

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.

Preclinical safety data

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.

6    PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Salofalk Enema 2g contains the following excipients:

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

6.2.    Incompatibilities

None known.

6.3.    Shelf Life

24 months.

6.4    Special precautions for storage

Do not store above 30°C. Protect from light.

6.5. Nature and Contents of Container

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

Special precautions for disposal

No special requirements. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7.    MARKETING AUTHORISATION HOLDER

Dr Falk Pharma UK Ltd Unit K

Bourne End Business Park Cores End Road Bourne End

Bucks SL8 5AS United Kingdom

8. MARKETING AUTHORISATION NUMBER

PL 10341/0008

9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

31^st December 2004

10 DATE OF REVISION OF THE TEXT

20/05/2015