Instructions for use Salofalk gastro-resistant granules prolonged release 500 mg Granu-Stix sachet No. 50
Composition
active ingredient: mesalazine;
1 sachet (930 mg granules) contains 500 mg of mesalazine;
Excipients: microcrystalline cellulose, hypromellose, colloidal anhydrous silica, polyacrylate dispersion, magnesium stearate, simethicone emulsion, methacrylate copolymer (type A), triethyl citrate, talc, titanium dioxide (E 171), sodium carboxymethylcellulose, aspartame (E 951), anhydrous citric acid, sweet vanilla flavor, povidone.
Dosage form
Gastro-resistant granules, prolonged action.
Main physicochemical properties: rounded particles of elongated or rounded shape, grayish-white in color, packaged in aluminum foil bags.
Pharmacotherapeutic group
Gastrointestinal tract and metabolism. Antidiarrheals, intestinal anti-inflammatory/antimicrobial drugs. Intestinal anti-inflammatory drugs. Aminosalicylic acid and similar agents. Mesalazine.
ATX code A07ES02.
Pharmacological properties
Pharmacodynamics
Pharmacodynamic effect
Mesalazine, when administered orally, acts predominantly locally on the intestinal mucosa and on the submucosal tissue on the luminal side of the intestine. It is therefore important that mesalazine is available in areas of inflammation. Systemic bioavailability and plasma concentrations are therefore not essential for determining the therapeutic effect, but rather are factors for determining the degree of safety. Salofalk granules are resistant to gastric juice, and mesalazine is released from them depending on the pH of the medium due to the coating with Eudragit L; prolonged release is provided by the structure of the granule matrix.
Preclinical data reveal no special hazard for humans based on conventional studies of safety, pharmacology, genotoxicity, carcinogenicity (in rats) or toxicity to reproduction.
Renal toxicity (renal papillary necrosis and epithelial damage in the proximal tubule (Pars convoluta) or the entire nephron) has been observed in toxicity studies with repeated high oral doses of mesalazine. The clinical significance of these findings is unknown.
Pharmacokinetics
General properties of mesalazine
Absorption
Absorption of mesalazine is highest in the proximal part of the intestine and lowest in its distal part.
Biotransformation
Mesalazine is metabolized both presystemically in the intestinal mucosa and in the liver to the pharmacologically inactive N-acetyl-5-aminosalicylic acid (N-Acetyl-5-ASA). Acetylation is apparently independent of the acetylation phenotype. Some acetylation also occurs by colonic bacteria. The protein binding of mesalazine and N-Acetyl-5-ASA is 43% and 78%, respectively.
Excretion
Mesalazine and its metabolite N-Ac-5-ASA are excreted in the faeces (major part), renally (varying between 20% and 50% depending on the type of administration, pharmaceutical form and route of release of mesalazine) and biliary (minor part). Renal excretion occurs mainly in the form of N-Ac-5-ASA. About 1% of the total orally administered dose of mesalazine passes into breast milk, mainly in the form of N-Ac-5-ASA.
Features of Salofalk granules
Distribution
Due to the size of the granules, about 1 mm, they pass from the stomach to the duodenum quickly.
A combined pharmaco-scintigraphic/pharmacokinetic study showed that the compound reaches the ileocecal region within 3 hours and the ascending colon after approximately 4 hours. The total transit time through the large intestine is approximately 20 hours.
About 80% of an administered oral dose is available in the colon, sigmoid colon, and rectum.
Absorption
The release of mesalazine from Salofalk granules begins after a lag phase lasting about 2-3 hours. Peak plasma concentrations are reached after about 4-5 hours. The systemic bioavailability of mesalazine after oral administration is approximately 15-25%.
Food intake delays absorption by 1–2 hours, but does not alter its rate or extent.
Breeding
When mesalazine was administered at a daily dose of 3 × 500 mg, the total renal excretion rate of mesalazine and N-Ac-5-ASA under steady-state conditions was approximately 25%. The fraction of unmetabolized mesalazine was approximately 1% of the oral dose. The half-life in this study was 4.4 hours.
Indication
Treatment of exacerbations and prevention of relapses of ulcerative colitis.
Contraindication
Hypersensitivity to mesalazine, to any of the components of the drug or to salicylates, gastric and duodenal ulcer in the acute stage, severe hepatic and/or renal failure, hemorrhagic diathesis.
Interaction with other medicinal products and other types of interactions
During complex treatment with Salofalk and azathioprine, 6-mercaptopurine or thioguanine, some studies have shown a higher frequency of myelosuppressive effects, which supposedly indicates the presence of an interaction, but the mechanism of interaction is not fully established. It is recommended to regularly monitor the level of leukocytes, and the dosage regimen of thiopurines should be adjusted.
There is evidence that mesalazine may reduce the anticoagulant effect of warfarin.
Possible enhancement of the hypoglycemic effect of sulfonylurea derivatives, toxic effects of methotrexate. The activity of furosemide, spironolactone, sulfonamides, rifampicin, uricosuric drugs (probenecid and sulfinpyrazone) may be weakened. Mesalazine may potentiate the undesirable effect of glucocorticoids on the gastric mucosa, reduce the absorption of digoxin.
There may be a reduction in the release of mesalazine from the granules due to a decrease in pH caused by the metabolism of lactulose by bacteria.
Application features
At the discretion of the physician, blood tests (formed elements; liver function parameters such as ALT or AST; serum creatinine) and urine tests (test strips, sediment) should be performed during and after treatment. It is recommended that tests be performed approximately 14 days after the start of treatment and then 2–3 times at 4-week intervals. If the test results are normal, preventive checks can be performed every three months. If other additional symptoms appear, tests should be performed urgently.
It should be used with caution in patients with impaired liver function.
Salofalk granules should be used with caution in patients with impaired renal function. Renal function should be monitored regularly, namely by measuring the level of blood urea nitrogen and creatinine in patients with proteinuria.
If renal function deteriorates during treatment, mesalazine-induced renal toxicity should be considered.
Cases of nephrolithiasis, including the formation of stones with a 100% mesalazine content, have been reported with the use of mesalazine. It is recommended to ensure adequate hydration during treatment.
Patients with lung diseases, in particular asthma, should be monitored during treatment with Salofalk granules.
Patients who have had hypersensitivity reactions to drugs containing sulfasalazine should be under medical supervision from the very beginning of the course of treatment with Salofalk granules. If acute symptoms of intolerance appear, such as cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.
Salofalk 500 mg and 1000 mg granules contain 1 mg and 2 mg aspartame respectively. Aspartame is a source of phenylalanine. This may be harmful for patients with phenylketonuria (PKU). There is no need to reduce the dose in elderly patients.
Salofalk granules contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose/galactose malabsorption or sucrase/isomaltase insufficiency should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per sachet, i.e. essentially 'sodium-free'.
Ability to influence reaction speed when driving vehicles or other mechanisms
In general, no effect on the ability to drive or use machines has been observed. If dizziness occurs during treatment with the drug, you should refrain from driving or using other machinery.
Use during pregnancy or breastfeeding
There are no adequate data from the use of Salofalk prolonged-release enteric-coated granules in pregnant women, but data from a limited number of pregnant women indicate no adverse effects of mesalazine on pregnancy or on the health of the foetus and/or newborn. No other epidemiological data are available to date. A single case of renal failure has been reported in a newborn whose mother had taken mesalazine at high doses (2-4 g orally) for a long time during pregnancy. There have been reports of blood disorders (leukopenia, thrombocytopenia, anaemia) in newborns whose mothers had taken mesalazine.
Animal studies with oral administration of mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.
Salofalk granules should only be taken during pregnancy if the expected benefit outweighs the risk.
N-acetyl-5-aminosalicylic acid and, to a lesser extent, mesalazine pass into breast milk. There is currently only limited experience of use in women during breastfeeding. Hypersensitivity reactions, such as diarrhoea, in infants cannot be excluded. Therefore, Salofalk granules should only be used during breastfeeding if the expected benefit outweighs the risk. If diarrhoea develops in the breast-fed infant, breastfeeding should be discontinued.
Method of administration and doses
Adults and elderly patients
Take 3 sachets of Salofalk 500 mg or 3 sachets of Salofalk 1000 mg (equivalent to 1.5–3.0 g of mesalazine daily) once daily, preferably in the morning, according to individual clinical need.
For convenience, you can also divide the prescribed daily dose into 3 doses (1 sachet of Salofalk 500 mg granules 3 times a day or 1 sachet of Salofalk 1000 mg granules 3 times a day).
To prevent relapses of ulcerative colitis (maintenance of remission)
Take 1 sachet of Salofalk 500 mg 3 times a day, which is equivalent to 1.5 g of mesalazine per day.
For patients who are at increased risk of relapse for medical reasons or because of difficulties in adhering to the three daily doses, the dosage regimen can be changed to 3.0 g of mesalazine as a single daily dose, preferably in the morning.
Children under 6 years old
Salofalk granules should not be used in children under 6 years of age due to lack of experience with the drug in this age group.
Children aged 6 and over
Depending on the severity of the disease, during an exacerbation, 30–50 mg mesalazine/kg body weight/day should be given once a day, preferably in the morning, or this dose should be divided into 3 doses. The maximum dose is 75 mg/kg body weight/day. The total dose should not exceed the maximum adult dose.
For relapse prevention (maintenance treatment), a dose of 15–30 mg mesalazine/kg body weight/day should be used, divided into several doses.
Children weighing up to 40 kg are recommended to take half the adult dose, and children weighing more than 40 kg are recommended to take the usual adult dose.
Salofalk granules should not be chewed. The contents of a 500 mg or 1000 mg Granu-Stix sachet should be poured onto the tongue and swallowed with a sufficient amount of liquid without chewing.
Both in the treatment of exacerbations of inflammation and during long-term treatment, Salofalk granules should be used regularly and continuously to achieve the desired therapeutic effect.
The duration of use is determined by the doctor.
Children
Salofalk granules should not be used in children under 6 years of age due to lack of experience in this age group. There are limited data on use in children 6–18 years of age.
Overdose
There are reports of cases of overdose (e.g. intentional suicide by taking a high oral dose of mesalazine) that do not indicate renal or hepatic toxicity. To date, no cases of intoxication and specific antidotes have been reported. There is no specific antidote, treatment should be symptomatic and supportive. If necessary, intravenous electrolyte infusion (forced diuresis) should be used.
Adverse reactions
| Organ system classes | Frequency according to MedDRA | | | | |
Often (≥ 1/10 to < 1/10) | Infrequently (≥ 1/1000 to < 1/100) | rare (≥ 1/10,000; < 1/1,000) | very rare (< 1/10,000) | Frequency not known (cannot be estimated from the available data) | |
| Blood system and lymphatic system | | | | Changes in blood composition (aplastic anemia, agranulocytosis, pancytopenia, neutropenia, leukopenia, thrombocytopenia) | |
| Immune system | | | | Hypersensitivity reactions, including allergic rashes, drug fever, lupus-like syndrome, pancolitis, angioedema | |
| Nervous system | Headache | | dizziness | Peripheral neuropathy | |
| Cardiovascular system | | | Myocarditis, pericarditis | | |
| Respiratory, thoracic and mediastinal organs | | | | Allergic and fibrotic pulmonary reactions (including dyspnea, cough, bronchospasm, alveolitis, pulmonary eosinophilia, pulmonary infiltration, pneumonitis) | |
| Gastrointestinal tract | | Abdominal pain, diarrhea, dyspepsia, flatulence, nausea, vomiting, acute pancreatitis | | | |
| Hepatobiliary system | | | Cholestatic hepatitis | Hepatitis | |
| Leather and its derivatives | | | Increased sensitivity to sunlight and artificial ultraviolet radiation (photosensitivity) | Alopecia | |
| Musculoskeletal system and connective tissues | | | arthralgia | Myalgia, cramps | |
| Renal and urinary disorders | | | | Renal impairment, including acute and chronic interstitial nephritis and renal failure | Nephrolithiasis* |
| Reproductive system | | | | Oligospermia (reversible) | |
| General disorders | | | Asthenia, fatigue | | |
| Research | | Changes in liver function tests (increased transaminases and cholestasis parameters), changes in pancreatic enzymes (lipase and amylase increased), increased eosinophil count | | | |
*More detailed information is provided in the "Application Features" section.
Photosensitivity
The mechanism of myocarditis, pericarditis, pancreatitis, nephritis and hepatitis associated with mesalazine is unknown; it may have an allergic etiology.
It should be noted that some of these disorders can be explained by intestinal inflammation itself.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after a medicinal product has been authorised is very important. This allows the benefit/risk balance of the medicinal product to be continuously monitored. Healthcare professionals are asked to report any suspected adverse reactions via
Bundesinstitut für Arzneimittel und Medizinprodukte
(Federal Institute of Medicines and Medical Devices)
Pharmacovigilance Department
Kurt-Georg-Kiesinger-Allee 3
53175 Bonn
www.bfarm.de
Expiration date
4 years.
Do not use after the expiration date indicated on the package.
Storage conditions
Does not require any special storage conditions. Keep out of the reach of children.
Packaging
Salofalk, granules. 500 mg:
930 mg granules in Granu-Stix sachets; 50 sachets in a cardboard box.
Vacation category
According to the recipe.
Producer
Dr. Falk Pharma GmbH.
Location of the manufacturer and its business address
Leinenweberstrasse 5, 79108 Freiburg, Germany.
