Each sachet of Salofalk 1.5g granules contains 1.5 g mesalazine.
Excipients/Inactive Ingredients: Each tablet also contains the following excipients: Sodium carbonate, eudragit L/dibutylphthalate, talcum, poly(vinyl-2-pyrrolidone), microcrystalline cellulose, carboxymethylcellulose sodium, glycine, calcium stearate, silica, hydroxypropylmethylcellulose, eudragit E, macrogol 6000, titanium dioxide (E171), yellow iron oxide (E172).
Each sachet of Salofalk 1.5g granules contains 3.0 mg aspartame.
Granules: Aspartame (E 951); Carmellose sodium; Citric acid; Colloidal anhydrous silica; Hypromellose; Magnesium stearate; Methacrylic acid-methyl methacrylate copolymer (1:1) ((MW approx. 135000)) (Eudragit L 100); Methylcellulose; Microcrystalline Cellulose; Polyacrylate dispersion 40 % (Eudragit NE 40 D containing 2 % Nonoxynol 100); Povidone K 25; Simeticone; Sorbic acid; Talc; Titanium dioxide (E 171); Triethyl citrate; Vanilla custard flavouring; Ethanol (only present as residue in the final product, up to 1.25 %).
Each suppository also contains the following excipients: Hard fat, docusate sodium and cetyl alcohol.
The enema also contains the following excipients: Sodium benzoate (0.03
g), potassium metabisulfite (max. 0.14 g), disodium edetate, carbomer, potassium acetate, xanthan gum.
Pharmacotherapeutic group: Aminosalicylic acid and similar agents. ATC code: A07EC02.
Pharmacology: Pharmacodynamics: 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 submucosal 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 are therefore of no relevance for therapeutic efficacy, but rather a factor for safety. In order to realise this, Salofalk granules are gastric juice resistant and release mesalazine in a pH dependent manner, due to an Eudragit L coating, and prolonged manner, due to the matrix granule structure.
Pharmacokinetics: General considerations of mesalazine: Absorption: Mesalazine absorption is highest in proximal 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 %, depending on the 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 the total orally administered mesalazine dose is excreted into the breast milk mainly as N-Ac-5-ASA.
Salofalk Granules specific: Distribution: Owing to the granule size of approx. 1 mm, transit from the stomach to the small intestine is fast. A combined pharmacoscintigraphic/pharmacokinetic study showed that the compound reaches the ileocaecal region within approx. 3 hours and the ascending colon within approx. 4 hours. The total transit time in the colon amounts to about 20 hours. Approximately 80 % of an administered oral dose is estimated to be available in the colon, sigmoid colon and rectum.
Absorption: Mesalazine release from Salofalk granules starts after a lag phase of about 2-3 hours. Peak plasma concentrations are reached at about 4-5 hours. The systemic bioavailability of mesalazine after oral administration is estimated to be approximately 15-25 %. Food intake delays absorption by 1 to 2 hours but does not change the rate and extent of absorption.
Elimination: From a 3 x 500 mg daily mesalazine dose in long-term therapy, a total renal elimination of mesalazine and N-Ac-5-ASA under steady state conditions was calculated to be about 25 %. The unmetabolised excreted mesalazine part was less than 1 % of the oral dose. The elimination half-life in this study was 4.4 hours.
Toxicology: Preclinical safety data: 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.
Tablet: Ulcerative colitis (treatment of acute attack, prevention of recurrence), Crohn's disease (treatment of acute attack).
Granules: For the treatment of acute episodes and the maintenance of remission of
Suppository: Ulcerative colitis, proctitis and inflammation of the anal canal.
Enema: Treatment of mild and moderate attacks of ulcerative colitis, above all those in the rectum and sigmoid colon.
Tablet: For treatment of inflammatory bowel diseases (Crohn's disease, ulcerative colitis), Salofalk 250- and 500-mg tablets are available.
With a dosage recommendation of mesalazine 1.5 g/day, 3 x two 250-mg tab can be taken. If the recommended dosage is mesalazine >1.5 g/day, Salofalk 500-mg tabs should be taken, if possible. Depending on the clinical requirements in the individual case, the following dosages are recommended: Crohn's Disease: Acute Attack: 1.5-4.5 g.
Ulcerative Colitis: Acute Attack: 1.5-3 g. Remission/Long-Term Treatment: 1.5 g.
The required number of tablets shall be taken 1 hr before meals in the morning, at midday and in the evening. The tablets shall be swallowed whole with sufficient liquid.
In patients with bowel resection of the ileocoecal region with resection of the ileocoecal valve, it was observed in rare cases that Salofalk 500-mg tabs were excreted undissolved with the faeces due to the too fast intestinal passage. In case of this observation, contact the physician.
Granules: Posology: Adults and the elderly: For the treatment of acute episodes of ulcerative colitis: Once daily, 1 sachet of Salofalk 3g granules, 1-2 sachets of Salofalk 1.5g granules, 3 sachets of Salofalk 1000mg granules or 3 sachets of Salofalk 500mg granules (equivalent to 1.5-3.0 g mesalazine daily) preferably to be taken in the morning according to the individual clinical requirement.
It is also possible to take the prescribed daily dose in three divided doses (1 sachet of Salofalk 500mg granules 3 times daily or 1 sachet of Salofalk 1000mg granules 3 times daily) if this is more convenient to the patient.
For the maintenance of remission of ulcerative colitis: The standard treatment is 0.5 g mesalazine 3 times daily (in the morning, at midday and in the evening) corresponding to a total dose of 1.5 g mesalazine per day.
For patients known to be at increased risk for relapse for medical reasons or due to difficulties to adhere to application of three daily doses, the dosing schedule can be adapted to 3.0 g mesalazine given as a single daily dose, preferably in the morning.
Paediatric population: 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 30-50 mg/kg bw/day once daily preferably in the morning or in divided doses. Maximum dose: 75 mg/kg bw/day. The total dose should not exceed the maximum adult dose.
Maintenance treatment: To be determined individually, starting with 15-30 mg/kg bw/day in divided doses. The total dose should not exceed the recommended adult dose.
It is generally recommended that half the adult dose may be given to children up to a body weight of 40 kg and the normal adult dose to those above 40 kg.
Method of administration: The contents of the sachets of Salofalk granules should not be chewed.
The granules should be taken on the tongue and swallowed, without chewing, with plenty of liquid.
Both in the treatment of acute inflammatory episodes and during long term treatment, Salofalk granules should be used on a regular basis and consistently in order to achieve the desired therapeutic effects.
The duration of use is determined by the physician.
This product is not interchangeable with other brand or dosage form of products containing mesalazine.
Suppository: Insert one 500-mg supp into the anus in the morning, at midday and in the evening when acute signs of inflammation are present.
As soon as remission occurs, the dose should be reduced to one 250-mg supp 3 times daily to avoid recurrences.
Enema: Unless otherwise prescribed, the contents of 2 enemas (2 x 30-mL susp) is given once daily rectally before retiring. If there are problems to retain the large quantity of liquid, the enema may also be applied in 2 doses eg, during the night (after a bowel movement which discharges the 1st dose) or early in the morning.
The duration of Salofalk therapy is determined by the physician.
Treatment with Salofalk demands reliability and consistency from the side of the patient both on the acute inflammatory stage and during long-term therapy to enable therapeutic success.
Tablet: Even following ingestion at high dose, no symptoms of intoxication should be expected because of the substance-specific pharmacokinetic properties of mesalazine. Symptoms similar to those known in salicylate intoxication should be in principle occur. However, since higher absorption rates do not occur at high mesalazine doses, intoxication is unlikely.
Granules: 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.
Suppository/Enema: Owing to the biopharmaceutical properties of Salofalk suppository/enema and the substance-specific pharmacokinetic properties of mesalazine, only small amounts of the active principle are available for systemic action. For this reason, signs of intoxication are thus not to be reckoned with even when very high doses are taken. In principle, similar symptoms would have to occur to those which are familiar in salicylate intoxications: Mixed acidosis-alkalosis, hyperventilation, pulmonary oedema, dehydration by sweating and vomiting, hypoglycaemia.
Treatment: In Mixed Acidosis-Alkalosis: Restoration of the acid-base equilibrium in accordance with the situation, electrolyte substitution.
In dehydration by sweating and vomiting: Fluid administration.
In Hypoglycaemia: Glucose administration.
Hypersensitivity to the active substance, to salicylates, benzoates (for enema) or to any of the excipients.
Bronchial asthmatics should not be treated with Salofalk enemas since sulphite contained in the enemas may cause hypersensitivity reactions.
Severe impairment of hepatic or renal function; gastric and duodenal ulcers; haemorrhagic diathesis (predisposition to bleeding).
Use in children: Salofalk should not be used to treat infants and small children because of insufficient experience with this age group.
Granules: Unsuitable for phenyketonurics.
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, control examinations should be carried out every three months. If additional symptoms occur, control examinations should be performed immediately.
Caution is recommended in patients with impaired hepatic function.
are not recommended in patients with impaired renal function.
Mesalazine-induced renal toxicity should be considered if renal function
deteriorates during treatment.
Patients should be monitored for elevated methaemoglobin values.
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 sulfasalazine should be kept under close medical surveillance on commencement of a course of treatment with Salofalk. Should Salofalk cause acute intolerability reactions, such as abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately. In isolated cases, hypersensitivity reactions principally in the form of respiratory problems may also be experienced by non-asthmatics due to potassium sulphite content of the enema.
Granules: In patients with phenylketonuria, it should be kept in mind that Salofalk granules contain aspartame as a sweetening agent, equivalent to 0.56 mg (Salofalk 500mg granules), 1.12 mg (Salofalk 1000mg granules), 1.68 mg (Salofalk 1.5g granules) and 3.36 mg (Salofalk 3g granules) phenylalanine.
Photosensitivity: More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.
Effects on ability to drive and use machines:
Granules: No effects on the ability to drive and use machines have been observed.
Pregnancy: There are no adequate data from the use of Salofalk 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/foetal development, parturition or postnatal development.
Salofalk 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, like diarrhoea in the infant, can not be excluded.
Therefore, Salofalk should only be used during breastfeeding if the potential benefit outweighs the possible risk. If the suckling neonate develops diarrhoea, the breastfeeding should be discontinued.
The following undesirable effects have been observed after administration of mesalazine: (See table).
Click on icon to see table/diagram/image
Interactions may occur if the following drugs are given at the same time as Salofalk.
Anticoagulants: Possible potentiation of the anticoagulative action (increased risk of bleeding in the gastrointestinal tract).
Glucocorticoids: Possible increase in gastric side effects.
Sulphonylureas: Possible potentiation of the hypoglycaemic effect.
Methotrexate: Possible increase of the methotrexate toxicity.
Probenecid/Sulphinpyrazone: Possible reduction in uricosuric effects.
Spironolactone/Furosemide: Possible reduction in diuretic effects.
Rifampicin: Possible reduction in tuberculostatic effects.
Pancytopaenia occurred in one case under mesalazine in combination with mercaptopurine.
Granules: Specific interaction studies have not been performed.
Lactulose or similar preparations which lower stool pH: possible reduction of mesalazine release from granules due to decreased pH caused by bacterial metabolism.
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.
Special precautions for disposal: No special requirements.
Incompatibilities: Not applicable.
Do not store at temperatures above 25°C (77°F). Protect the suppository/enema from light.
Granules: Store below 30°C.
Shelf-Life: Tablet: 3 years.
Granules: 4 years.
A07EC02 - mesalazine ; Belongs to the class of aminosalicylic acid and similar antiinflammatory. Used in the treatment of intestinal inflammation.
Tab 250 mg x 100's. 500 mg (butter-yellow to ochre, lustreless with smooth surface) x 100's. PR granules (sachet) 1.5 g x 35's, 100's. Supp 250 mg x 30's. 500 mg x 30's. Enema 2 g/30 mL x 7's.