Dr. Falk Pharma UK Ltd

Salofalk 250mg Gastro-Resistant Tablets

Each tablet contains 250 mg of mesalazine.

For a full list of excipients, see section 6.1.

Gastro-resistant tablet

Round, biconvex, yellow tablets.

As an anti-inflammatory in the management of ulcerative colitis, and in the treatment of Crohn's disease.

Salofalk Tablets are for oral administration.

Adults including the elderly:

When symptoms of acute inflammation are present, 2 Salofalk 250 tablets should be taken with ample fluid in the morning, afternoon and evening after meals, unless otherwise prescribed. In severe cases of the diseases the dosage may be doubled. (Generally an acute attack endures 8 – 12 weeks. A high dose therapy with Salofalk 250 should not last longer).

As maintenance therapy to prevent recurrence, 2 tablets should be taken in the morning, afternoon and evening.

Children: There is only limited documentation for an effect in children (age 6 -18 years).

Children 6 years of age and older:

Active disease: To be determined individually, starting with 30-50mg/kg/day in divided doses. Maximum dose: 75mg/kg/day. The total dose should not exceed the maximum dose for adults.

Maintenance treatment: To be determined individually, starting with 15-30mg/kg/day in divided doses. The total dose should not exceed the recommended dose for adults.

It is generally recommended that half the adult dose may be given to children up to a body weight of 40kg and the normal adult dose to those above 40kg.

Salofalk is contraindicated in cases of:

Known hypersensitivity to salicylates or any of the excipients

Sever 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 250mg tablets 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 tablets.

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 250mg tablets. Should Salofalk 250mg tablets cause acute intolerance reactions such as abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.

This product contains 48mg of sodium per tablet. To be taken into consideration by patients on a sodium controlled diet.

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 tablets 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 tablets 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 tablets 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.

Mesalazine, orally administered, acts predominantly locally at the gut mucosa and in the submucous tissue from the luminal side of the intestine. It is important, therefore, that mesalazine is available at the regions of inflammation. Systemic bioavailability/plasma concentrations of mesalazine therefore are of no relevance for therapeutic efficacy, but rather a factor for safety. In order to fulfil these criteria Salofalk tablets are coated with Eudragit L; they are thus gastro-resistant and release of mesalazine is pH dependent.

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.

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.

Anhydrous sodium carbonate (E500)

Glycine

Povidone

Microcrystalline cellulose

Colloidal anhydrous silica

Calcium stearate

Coating agents:

Hypromellose

Eudragit L/P [Poly (methacrylic acid, methyl methacrylate]

Talc

Titanium dioxide (E171)

Yellow ferric oxide (E172)

Basic Butylated Methacrylate Copolymer [Eudragit E]

Macrogol 6000

Not applicable.

3 years.

Do not store above 25°C.

PVC/PVDC/aluminium blister packs packed in cardboard cartons containing 100 or 300 tablets.

Not all pack sizes may be marketed.

No special requirements.

Dr. Falk Pharma GmbH

Leinenweberstr. 5

79108 Freiburg

Germany

PA 573/4/3

Date of first authorisation: 11 October 1989

Date of last renewal: 11 October 2009

02/2012