SALOFALK Mesalazine 250mg Rectal Suppository 30's

Indications/Uses

Tablet: Salofalk is used for the treatment of: Ulcerative colitis and proctitis (treatment of acute attack or to prevent relapse); Crohn's disease (treatment of acute attack).
Granules: Treatment of acute episodes and the maintenance of remission of ulcerative colitis.
Enema: Treatment of acute episodes and maintenance of remission of ulcerative colitis that is limited to the rectum.
Suppository: Treatment of acute episodes and prevention of further episodes (recurrence) of a chronic inflammatory disease limited to the rectum (back passage) known by doctors as ulcerative colitis.

Dosage/Direction for Use

Tablet: Adults and elderly: Depending upon the clinical requirements in individual cases, the following daily doses are recommended: See table.

Salofalk 500 mg gastro-resistant tablets should be taken in the morning, at midday and in the evening, 1 hour before meals. They should be swallowed whole, not chewed, and taken with plenty of fluid.
The duration of therapy is determined by the physician.
In patients with bowel resection of the ileocoecal region with resection of the ileocoecal valve, in rare cases it was observed that Salofalk 500 mg gastro-resistant tablets were excreted undissolved with the faeces due to the too fast intestinal passage. In case of this observation, please contact the physician.
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/day in divided doses.
Maximum dose: 75 mg/kg/day. The total dose should not exceed the maximum adult dose.
Maintenance treatment (ulcerative colitis): To be determined individually, starting with 15-30 mg/kg/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.
Granules: Adults and the Elderly: Treatment of Acute Episodes of Ulcerative Colitis: Once daily, 1-2 sachets of Salofalk 1.5 g granules (equivalent to mesalazine 1.5-3 g 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 3 divided doses if this is more convenient to the patient.
Maintenance of Remission of Ulcerative Colitis: The standard treatment is mesalazine 0.5 g 3 times daily (in the morning, at midday and in the evening) corresponding to a total dose of mesalazine 1.5 g/day. For patients known to be at increased risk for relapse for medical reasons or due to difficulties to adhere to application of 3 daily doses, the dosing schedule can be adapted to mesalazine 3 g given as a single daily dose, preferably in the morning.
Children: There is only limited documentation for an effect in children (6-18 years).
Children ≥6 years: Active Disease: To be determined individually, starting with 30-50 mg/kg body weight/day once daily preferably in the morning or in divided doses. Maximum Dose: 75 mg/kg body weight/day. The total dose should not exceed the maximum adult dose.
Maintenance Treatment: To be determined individually, starting with 15-30 mg/kg body weight/day in divided doses. The total dose should not exceed the recommended adult dose.
It is generally recommended that ½ the adult dose may be given to children up to a body weight of 40 kg and the normal adult dose to those >40 kg.
Enema: Unless otherwise prescribed, the contents of 1 enema bottle (60-g suspension) are instilled in the rectum once every evening before bedtime. The best results are achieved if the bowels are evacuated prior to instillation of Salofalk 4 g/60 mL enema.
Suppository: Adults and Elderly: For the treatment of acute symptoms of inflammation, insert 2 Salofalk 250 mg suppositories into the rectum 3 times daily (in the morning, at midday and at bedtime) (equivalent to 1500 mg mesalazine daily).
In long-term treatment to prevent recurrences, insert 1 Salofalk 250 mg suppository into the rectum 3 times daily (equivalent to 750 mg mesalazine daily).
Missed Dose: Do not take larger amount than normal dose of Salofalk 250 mg suppository, continue treatment at the prescribed dosage.
Use in Children: There is little experience and only limited documentation for an effect in children.
Duration of Treatment: Physician will decide how long does the patient need to continue the treatment with this medicine. This will depend on the patient's condition.
To obtain the maximum benefit from this medicine, use Salofalk 250 mg suppositories regularly and consistently, as directed.
Administration: Tablet: 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 with sufficient liquid.
Granules: 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.
Enema: Shake well before use to homogenize the suspension.
Remove the protective cap and hold the vial vertically to avoid spilling the contents. Lie on the left side, stretch out the left leg and pull the right leg in at an angle to keep balance. Insert the applicator, which is coated with a lubricant for easy insertion into the rectum, holding the vial pointed towards the navel.
Holding the vial tightly, bend slightly so that the applicator is pointing towards the back.
Press the plastic vial slowly to avoid triggering off a passage of stool. After use, remove the empty vial from the rectum.
Keep lying in the same position for 30 min to enable the enema to spread evenly into the intestines. The best effect is obtained by letting the enema work overnight.
The duration of therapy is determined by the physician.
In general, the acute attack disappears after 8-12 weeks. Do not use Salofalk enemas after the acute attack is over.
Suppository: This medicine may only be used rectally, so it has to be inserted through the anus. Do not take by mouth.

Overdosage

Granules: There are rare data on overdosage (eg, 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.

Administration

Should be taken on an empty stomach: Take 1 hr before meals. Swallow whole, do not chew/crush.

Contraindications

Hypersensitivity to salicylic acid, salicylates and its derivatives or any of the ingredients. Severe hepatic and renal diseases/impairment.
Tablet/Enema/Suppository: Salofalk suppositories should not be used in babies and infants. It should not be used in the case of pathological propensity to bleeding.
Enema: Bronchial asthmatics should not be treated with Salofalk 4-g enemas since sulfite contained in the enemas may cause hypersensitivity reactions.

Special Precautions

Tablet: Blood tests (differential blood count; liver function parameters such as transaminases; serum creatinine) and urine status (dip sticks/sediments) should be checked before and during treatment, at the discretion of the doctor. As a guideline, controls are recommended 14 days after starting treatment, then a further two to three times at intervals of 4 weeks.
If the findings are normal, follow-up tests are required every three months. If additional symptoms develop, tests must be performed immediately. The recommended kidney function tests are serum urea (BUN) and creatinine assay as well as urine sediment test.
Caution is recommended in patients with impaired hepatic function.
Salofalk 500 mg enteric coated tablets should not be used in patients with impaired renal function. Mesalazine-induced renal toxicity should be considered, if renal function deteriorates during treatment.
In patients with pulmonary function disturbances, in particular asthma, close medical supervision is necessary during treatment with drugs containing mesalazine.
Treatment with Salofalk 500 mg Enteric-coated tablet should only be started under medical supervision in patients with known hypersensitivity to preparations containing sulphasalazine. If acute signs of intolerability e.g. cramps, acute abdominal pain, fever, severe headache and skin rash occur, treatment must be withdrawn immediately.
Enema: Salofalk should be taken under medical supervision. A blood count and urine status should be performed at the attending physician's discretion during treatment. As a general guideline, tests are recommended 14 days after beginning of treatment and then another 2-3 times at 4-weekly intervals.
If the findings are normal, follow-up tests are required every 3 months or if additional signs of illness occur. The recommended kidney function tests are serum urea (BUN) and creatinine assays as well as urine sediment tests.
Patients should be monitored for elevated methemoglobin values.
In patients with pulmonary function disturbances, in particular asthma, close medical supervision is necessary during treatment with drugs containing mesalazine (5-aminosalicylic acid).
Treatment with Salofalk should only be started under medical supervision in patients with known hypersensitivity to preparations containing sulfasalazine. If acute signs of intolerability eg, cramps, acute abdominal pain, fever, severe headache and skin rash occur, treatment must be withdrawn immediately.
Use in Children: Salofalk should not be used to treat infants and small children because of insufficient experience with this age group.
Granules: Blood tests (differential blood count; liver function parameters eg, 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 2-3 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 granules 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 granules.
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 granules. Should Salofalk granules cause acute intolerance reactions eg, abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.
In patients with phenylketonuria, it should be kept in mind that Salofalk granules contain aspartame as a sweetening agent, equivalent to 1.68 mg (Salofalk 1.5 g granules).
Effects on the Ability to Drive or Operate Machinery: Granules/Suppository: Salofalk have no influence on the ability to drive and use machines.

Use In Pregnancy & Lactation

Use in Pregnancy: Tablet: There are no adequate data on the use of Salofalk 500 mg enteric coated 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 (2-4 g, orally) during pregnancy, renal failure in a neonate was reported. Salofalk 500 mg Enteric-coated tablet should only be used during pregnancy on medical advise since only your doctor can undertake the necessary assessment of likely benefits versus the potential risks.
Enema: In the first 3 months of pregnancy, mesalazine should only be used if strictly indicated. Whenever possible, women wishing to have children should wait for a phase when as little as possible or no medication is required before beginning pregnancy. If the individual's condition allows, treatment should be interrupted in the last 2-4 weeks of pregnancy. As yet, there is insufficient experience with Salofalk during breastfeeding. If treatment becomes necessary during lactation, the child should be weaned.
Granules: There are no adequate data on the use of Salofalk granules 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 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, embryonic/foetal development, parturition or postnatal development.
Salofalk granules should only be used during pregnancy if the potential benefit outweighs the possible risk.
Use in Lactation: Tablet: Only limited experience is available on the use of mesalazine-containing drugs during breast-feeding. The active substance is excreted in small amount into breast milk. Therefore, hypersensitivity reactions in the infant cannot be ruled out. To date, these have merely consisted of single cases of diarrhea. If the baby develops diarrhea during the use of Salofalk while breast-feeding, breast-feeding should be discontinued.
The patient should only use Salofalk 500 mg enteric coated tablets during breast-feeding, if the doctor tells the patient to since only the doctor can undertake the necessary assessment of likely benefits versus the potential risks.
Granules: 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 diarrhea in the infant, cannot be excluded. Therefore, Salofalk granules should only be used during breastfeeding if the potential benefit outweighs the possible risk. If the infant develops diarrhea, the breastfeeding should be discontinued.

Adverse Reactions

Tab/Granules: Abdominal pain, diarrhea, flatulence, nausea, vomiting; headache, dizziness. Tab: Peripheral neuropathy; renal impairment including acute & chronic interstitial nephritis & renal insufficiency; exanthema, drug fever, bronchospasm, pericarditis & myocarditis, pancreatitis, allergic & fibrotic lung reactions (including dyspnoea, cough, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis), butterfly rash (lupus erythematosus syndrome), pancolitis; myalgia, arthralgia; aplastic anaemia, agranulocytosis, pancytopenia, neutropenia, leucopenia, thrombocytopenia; raised transaminase & parameters of cholestasis, hepatitis, cholestatic hepatitis; alopecia; reversible oligospermia. Enema: Allergic exanthema, drug fever; bronchospasm; lupus erythematosus-like syndrome. Granules: Pericarditis. Supp: Allergic skin rash, fever, breathing difficulty.

Drug Interactions

Tablet: 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.
Enema/Suppository: The hypoglycemic action of the sulfonylureas can be intensified, as can gastrointestinal hemorrhage caused by coumarins. The toxicity of methotrexate can be increased. The uricosuric action of probenecid and sulfinpyrazone can be decreased, as can the diuretic action of furosemide and the action of spironolactone. The antituberculosis action of rifampicin can also be diminished. The gastric side effects of glucocorticoids can be increased.
One case of pancytopenia has been reported during treatment with 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 of lactulose.
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.

Storage

Tablet: Store at temperatures not exceeding 25°C.
Enema/Suppository: Do not store at temperatures exceeding 25°C (77°F). Protect from light.
Granules: Store at temperatures not exceeding 30°C.
Shelf-Life: 48 months.

Action

Pharmacotherapeutic Group: Aminosalicylic acid and similar agents. ATC Code: A07EC02.
The mode of action to date is still not understood. It is, however, interesting that both salicylazosulfapyridine and 5-aminosalicylic acid inhibit prostaglandin synthesis and that prostaglandin-like substances appear in the feces and venous blood of the colon in ulcerative colitis. Prostaglandins are involved in inflammatory processes.
Hence, it has been suggested that salicylazosulfapyridine inhibits prostaglandin synthesis and reduces the breakdown of these substances. It is not as yet known which prostanoid is affected.
Pharmacology: Pharmacodynamics: Mechanism of Action: Granules: 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 realize 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 the proximal regions and lowest in the distal regions of the intestine.
Biotransformation: Mesalazine is metabolised pre-systemically to the pharmacologically inactive N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) in both the intestinal mucosa and the liver. Acetylation appears to be independent of the patient's acetylator phenotype. Some of the mesalazine is also acetylated by the bacteria of the large intestine. 43% of mesalazine and 78% of N-Ac-5-ASA are protein-bound.
Elimination/Excretion: Mesalazine and its metabolite N-Ac-5-ASA, are excreted in the faeces (major fraction), renally (the amount varies between 20% and 50%, depending on the method of administration, the pharmaceutical form and the associated mode of release of mesalazine) and via the biliary route (minor fraction). Renal excretion is mainly in the form of N-Ac-5-ASA. Approximately 1% of the orally administered mesalazine dose passes into breast milk, mainly as N-Ac-5-ASA.
Tablet: Absorption: Mesalazine absorption is highest in the proximal regions and lowest in the distal regions of the intestine.
Biotransformation: Mesalazine is metabolised pre-systematically to the pharmacologically inactive N-acetyl-5-aminosalicylic (N-Ac-5-ASA) in both the intestinal mucosa and the liver. Acetylation appears to be dependent on the patient's acetylator phenotype. Some of the mesalazine is also acetylated by the bacteria of the large intestine. 43% of mesalazine and 78% of N-Ac-5-ASA are protein-bound.
Elimination/Excretion: Mesalazine and its metabolite N-Ac-5-ASA, are excreted in the faeces (major fraction), renally (the amount varies between 20% and 50%, depending on the method of administration, the pharmaceutical form and the associated mode of release of mesalazine) and via the biliary route (minor fraction). Renal excretion is mainly in the form of N-Ac-5-ASA. Approximately 1% of the orally administered mesalazine dose passes into breast milk, mainly as N-Ac-5-ASA.
Specific aspects of Salofalk 500 mg gastro-resistant tablets: Distribution: A combined pharmacoscintigraphic/pharmacokinetic study has shown that in fasting patients, Salofalk 500 mg gastro-resistant tablets reach the ileocoecal region within approximately 3-4 hours in fasting subjects and the ascending colon within approximately 4-5 hours. In the colon, the total transit time is around 17 hours.
Absorption: Release of mesalazine from Salofalk 500 mg gastro-resistant tablets begins after a lag phase of approximately 3–4 hours. Peak plasma concentrations are reached after approximately 5 hours (ileocoecal region), and are 3.0 ±1.6 μg/mL for mesalazine and 3.4 ±1.6 μg/mL for the N-Ac-5-ASA metabolite following administration of 3 x 500 mg mesalazine/day under steady-state conditions.
Elimination: With multiple dosing (3 x 1 Salofalk 500 mg gastro-resistant tablets taken over 2 days; 1 gastro-resistant tablet on the third day = day of investigation), the total renal elimination rate of mesalazine and N-Ac-5-ASA over 24 hours was approximately 60%. When administered orally, the non-metabolised mesalazine fraction was approximately 10%.
Salofalk Granules Specific: Distribution: Owing to the granule size of approximately 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 approximately 3 hrs and the ascending colon within approximately 4 hrs. The total transit time in the colon amounts to about 20 hrs.
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 hrs. Peak plasma concentrations are reached at about 4-5 hrs. The systemic bioavailability of mesalazine after oral administration is estimated to be approximately 15-25%.
Food intake delays absorption by 1-2 hrs 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 unmetabolized excreted mesalazine part was <1% of the oral dose. The elimination half-life (t_½) in this study was 4.4 hrs.
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.

MedsGo Class

GIT Regulators, Antiflatulents & Anti-Inflammatories