SALOFALK 500 MG SUPPOSITORIES - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Salofalk Suppositories 500mg.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each suppository contains 500mg mesalazine

Excipient with known effect:

Each suppository contains 18 mg cetyl alcohol.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Suppository.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Management of mild and moderate episodes of ulcerative colitis that is limited to the rectum.

4.2 Posology and method of administration

Posology

Adults and the Elderly: 1 to 2 suppositories, 2 to 3 times daily.

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:

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

Severe impairment of renal or hepatic function.

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

Caution is recommended in patients with impaired hepatic function.

Salofalk suppositories should not be used in patients with impaired renal function. Mesalazine-induced renal toxicity should be considered if renal function deteriorates during treatment.

Cases of nephrolithiasis have been reported with the use of mesalazine including stones with a 100% mesalazine content. It is recommended to ensure adequate fluid intake during treatment.

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

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment.

Mesalazine should be discontinued, at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity.

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

Salofalk suppositories 500mg contain cetyl alcohol. Cetyl alcohol may cause local skin reactions (e.g. contact dermatitis).

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

Fertility

There are no adequate data from the use of Salofalk suppositories 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 (2–4g/day, 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.

Pregnancy

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

Breast-feeding

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 suppositories should only be used during breast-feeding if the potential benefit outweighs the possible risk. If the infant develops diarrhoea, breastfeeding should be discontinued.

4.7 Effects on ability to drive and use machines

Salofalk Suppositories 500mg have no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

* see section 4.4 for further information

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment (see section 4.4).

Photosensitivity

More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.

Reporting of suspected adverse reactions

Reporting suspected adverse 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 the Yellow Card Scheme website at: https://yellowcard.mhra.gov.uk or search for MHRA Yellow Card in the Google Play or Apple App Store

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.

5.3 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 Suppositories.

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 Suppositories 500mg contain the following excipients:

Hard Fat

Docusate sodium

Cetyl alcohol

6.2. Incompatibilities

None known.

6.3. Shelf Life

36 months.

6.4 Special precautions for storage

Do not store above 30°C. Store in the original container in order to protect contents from light.

6.5. Nature and Contents of Container

Cartons of ten or thirty suppositories in white, opaque PVC/PE moulded strips.

Each strip contains five suppositories.

6.6. Instruction for Use/Handling

None

7 MARKETING AUTHORISATION HOLDER

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

Cores End Road, Bourne End, SL8 5AS, United Kingdom

8.

MARKETING AUTHORISATION NUMBER

PL 10341/0009

9. DATE OF FIRST AUTHORISATION/RE­NEWAL OF AUTHORISATION

31st December 2004